New Drug Approvals

Sumonerimod

DR ANTHONY MELVIN CRASTO Ph.D — Thu, 08 Oct 2026 07:59:57 +0000

Sumonerimod

CAS 2433782-42-2

MFC25H26F3NO3 MW445.5

3-(5-((4-cyclopentyl-3-(trifluoromethyl)benzyl)oxy)-3-methyl-1H-indol-2-yl)propanoic acid,

3-(5-{[4-cyclopentyl-3-(trifluoromethyl)phenyl]methoxy}-3-methyl-1Hindol-2-yl)propanoic acid
sphingosine-1-phosphate receptor 1 agonist, immunomodulator, S1P1 agonist 6, 49KZ2L5DUV, CBP-307, Icanbelimod, CBP 307

Sumonerimod is a selective Sphingosine-1-phosphate receptor 1 ($\text{S1P}_1$) agonist developed primarily for autoimmune and inflammatory diseases (such as ulcerative colitis and Crohn’s disease).

PAT

WO2020114475A1

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020114475&_cid=P12-MUZ8I1-71620-1

Reference Example 72: Preparation of Intermediate I-74

ntermediate I-73 (4.3 g) was dissolved in dichloromethane (30 mL). The reaction mixture was cooled to -40 °C, and a dichloromethane solution (50 mL) of N-bromosuccinimide (NBS, 1.98 g, 11.1 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was heated to 0 °C and stirred at 0 °C for 2 h. The reaction mixture was washed with water (20 mL), the organic phase was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by silica gel chromatography to obtain intermediate I-74.

[0395]

LC-MS(ESI)[M-H] ^–464。

[0396]Reference Example 73: Preparation of Intermediate I-75

Intermediate I-74 (1.0 g, 2.15 mmol) was dissolved in a mixture of 1,4-dioxane and water (10 mL, 4:1) at room temperature, followed by the addition of methylboric acid (1.29 g, 21.46 mmol), potassium carbonate (0.89 g, 6.44 mmol), and tetrakis(triphenylphosphine)palladium (243 mg, 0.21 mmol). The reaction mixture was stirred at 90 °C for 7 h under argon protection. The reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure to obtain the residue. The residue was dissolved in dichloromethane (20 mL), and water (10 mL) was added. The aqueous phase was separated and extracted with dichloromethane (20 mL × 2). The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the residue. The residue was purified by silica gel chromatography to obtain intermediate I-75.

[0399]

LC-MS(ESI)[M-H] ^–400.0.

[0400]Reference Example 74: Preparation of Intermediate I-76

Intermediate I-75 (470 mg, 1.17 mmol) was dissolved in tetrahydrofuran (10 mL) at room temperature, and ethoxycarbonylmethylene triphenylphosphine (490 mg, 1.41 mmol) was added. The reaction mixture was stirred at 80 °C for 15 h. After cooling the reaction solution to room temperature, the organic solvent was removed by concentration under reduced pressure to obtain the residue. The residue was purified by reversed-phase preparative liquid chromatography to obtain intermediate I-76.

[0403]

LC-MS(ESI)[M-H] ^–470.2.

[0404]Reference Example 75: Preparation of Intermediate I-77

Intermediate I-76 (110 mg, 0.23 mmol) was dissolved in ethyl acetate (2 mL), and PtO₂ (50 mg) was added

_. The reaction mixture was stirred at room temperature for 2 h under a hydrogen atmosphere. After filtration, the filtrate was concentrated under reduced pressure to give intermediate I-77.

[0407]

LC-MS(ESI)[M+H] ⁺474.2.

Example 16: Preparation of Compound 16

Intermediate I-77 (110 mg) was dissolved in tetrahydrofuran (2 mL), and lithium hydroxide monohydrate (29 mg, 0.70 mmol) and water (0.5 mL) were added. After stirring at room temperature for 3 h, the reaction solution was purified by preparative liquid chromatography to obtain compound 16.

[0809]

LC-MS(ESI)[M-H] ^–444.1.

[0810]

¹H NMR(400MHz,MeOH-d ₄)δ7.71(s,1H),7.66(d,J＝8.2Hz,1H),7.57(d,J＝8.2Hz,1H),7.13(d,J＝8.7Hz,1H),6.98(d,J＝2.3Hz,1H),6.76(dd,J＝8.7,2.4Hz,1H),5.10(s,2H),3.41–3.35(m,1H),3.00(t,J＝7.7Hz,2H),2.63(t,J＝7.7Hz,2H),2.18(s,3H),2.10–2.02(m,2H),1.95–1.86(m,2H),1.78–1.60(m,4H).

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References

///////////sumonerimod, anax labs, sphingosine-1-phosphate receptor 1 agonist, immunomodulator, S1P1 agonist 6, 49KZ2L5DUV, CBP-307, Icanbelimod, CBP 307

#sumonerimod, #anax labs, #sphingosine-1-phosphate receptor 1 agonist, #immunomodulator, #S1P1 agonist 6, #49KZ2L5DUV, #CBP-307, #Icanbelimod, #CBP 307

Sosimerasib

DR ANTHONY MELVIN CRASTO Ph.D — Sun, 04 Oct 2026 02:41:13 +0000

Sosimerasib

Cas 2839563-01-6

MF C36H39ClFN7O4 MW688.2 g/mol

(4R,7R)-16-chloro-9-[2-(dimethylamino)ethyl]-15-(2-fluoro-6-hydroxyphenyl)-4-methyl-12-(4-methyl-2-propan-2-yl-3-pyridinyl)-5-prop-2-enoyl-2,5,9,12,14-pentazatetracyclo[8.8.0.0^2,7.0^13,18]octadeca-1(10),13,15,17-tetraene-8,11-dione

(2R,4aR,8M)-11-chloro-6-[2-(dimethylamino)ethyl]-10-(2-fluoro-6-hydroxyphenyl)-2-methyl-8-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-3-(prop-2-enoyl)-2,3,4,4a,6,8-hexahydro-1Hpyrazino[1′,2′:4,5]pyrazino[2,3-c][1,8]naphthyridine-5,7-dione
Kirsten rat sarcoma viral oncogene homolog inhibitor, antineoplastic, HBI-2438, JMKX1899, HBI 2438, JMKX 1899, 2VHH89PP6W

Sosimerasib is an orally active KRAS^G12C inhibitor. Sosimerasib can be used in research related to non-small cell lung cancer.

Sosimerasib (also known as HBI-2438 or JMKX1899) is an orally active, covalent small molecule inhibitor that targets the KRAS G12C mutation. Developed natively in China, it secured conditional marketing approval from the National Medical Products Administration (NMPA) in February 2026, making it China’s first domestically discovered and registered KRAS G12C inhibitor.

The drug is designed to selectively lock the mutant KRAS protein in its inactive, GDP-bound state, preventing downstream oncogenic signaling pathways that drive tumor growth.

Mechanism and Clinical Indications

Sosimerasib specifically binds to the cysteine residue at position 12 of the mutated KRAS protein. It has shown distinct clinical advantages, including central nervous system (CNS) penetration, which makes it effective against brain metastases. Its primary therapeutic applications include:

Non-Small Cell Lung Cancer (NSCLC): It is indicated for patients with locally advanced or metastatic non-squamous NSCLC harboring the KRAS G12C mutation, particularly those who have progressed after receiving standard platinum-based chemotherapy or immune checkpoint inhibitors.
Colorectal Cancer (CRC) and Solid Tumors: It is being clinically evaluated as a monotherapy or combination treatment for other advanced solid tumors, showing promising anti-tumor activity in KRAS G12C-mutated colorectal cancer.

Efficacy Data

Data presented across recent oncology conferences highlight substantial therapeutic efficacy:

NSCLC Outcomes: In a pivotal Phase II trial involving 145 previously treated patients, a once-daily 500 mg dose of sosimerasib achieved an Objective Response Rate (ORR) of 52.4% and a Disease Control Rate (DCR) of 87.6%. The median progression-free survival (PFS) was documented at 7.2 months.
Colorectal Cancer Outcomes: Data from the 2026 ASCO Annual Meeting for advanced CRC patients demonstrated a confirmed ORR of 31.6% and a median PFS of 8.3 months.

Safety and Side Effects

Sosimerasib possesses a manageable safety profile, with rare occurrences of treatment discontinuations (around 1.8% to 2.1%) due to toxicity. The most common treatment-related adverse events (TRAEs) include:

Elevated liver enzymes (Alanine aminotransferase/ALT and Aspartate aminotransferase/AST increases)
Anaemia
Decreased white blood cell count or elevated gamma-glutamyl transferase

Commercial and Development Background

The compound was originally discovered by Shanghai Jiyu Pharmaceutical Technology. It is being co-developed and commercialized through partnerships with HUYA Bioscience International (Huyabio) and Zhejiang Hangyu Pharmaceutical. Within the Chinese market, it joins foreign-developed alternatives like sotorasib (Amgen) and adagrasib (Bristol Myers Squibb), marking a major milestone for independent biomedical innovation in the region. Ongoing Phase III trials are evaluating sosimerasib in combination regimens (such as with the FAK inhibitor IN10018) as a first-line treatment option.

PAT

[US20220389029]

https://patentscope.wipo.int/search/en/detail.jsf?docId=US380594568&_cid=P20-MUT7JP-65582-1

Embodiment 29: Preparation of Compound 29

Step 1: Preparation of Compound 29-1

Compound 25-3 (700 mg, 1 mmol) and cesium carbonate (977 mg, 3 mmol) were dissolved in N,N-dimethylformamide (20 mL), and compound 26-1 (432 mg, 3 mmol) was added thereto at room temperature (25° C.). After the addition was completed, under nitrogen atmosphere, the system was heated to 120° C. and stirred for 2 hours. The system was filtered and concentrated to obtain a crude product, the crude product was purified by silica gel column chromatography (dichloromethane/methanol (v/v)=1/10) to obtain compound 29-1.

MS (ESI) m/z (M+H) ⁺=778.2.

Step 2: Preparation of Compound 29-2

Compound 29-1 (150 mg, 0.2 mmol), hydrochloric acid (6N, 7 mL) were added to a mixed solution of methanol (0.6 mL) and tetrahydrofuran (6 mL). The system was heated to 55° C. and stirred for 10 min. The system was concentrated to obtain crude product compound 29-2, which was directly used in the next reaction without further purification.

MS (ESI) m/z (M+H) ⁺=634.2.

Step 3: Preparation of Compound 29

Compound 29-2 (140 mg, 0.2 mmol) was dissolved in dichloromethane (10 mL), and the system was cooled to 0° C., triethylamine (0.3 mL, 2.1 mmol) and acryloyl chloride (27 mg, 0.3 mmol) were added dropwise thereto, the reaction was carried out at 0° C. for 0.5 hours. The system was quenched with methanol and then concentrated to obtain a crude product. The crude product was dissolved in methanol (5 mL), potassium carbonate (140 mg) was added thereto, after the addition was completed, the system was stirred at room temperature (20° C.) for 30 min. The pH of the system was adjusted to 6 with hydrochloric acid, the mixture was extracted with dichloromethane (20 mL) and water (20 mL); and the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, the crude product was purified by high performance liquid chromatography (separation conditions: chromatographic column Welch Xtimate® C18 21.2×250 mm, 10 μm; column temperature: 25° C., mobile phase: water (10 mM/L NH ₄HCO ₃)-acetonitrile; acetonitrile 40%-60% 9 min; flow rate 30 mL/min) to obtain compound 29.

MS (ESI) m/z (M+H) ⁺=688.2.

Step 4: Preparation of Compounds 29A and 29B

Diastereoisomeric compound 29 was purified by SFC («Column_3»; mobile phase: [CO ₂-ethanol (0.1% ammonia)]; ethanol %: 25%; flow rate: 60 mL/min; column temperature: 38° C.). After concentration, compound 29A and compound 29B were obtained.

Compound 29A:

¹H NMR (400 MHz, DMSO-d ₆) δ 10.06 (brs, 1H), 8.37 (d, J=4.9 Hz, 1H), 8.18 (s, 1H), 7.29-7.05 (m, 2H), 6.97 (dd, J=16.8, 10.6 Hz, 0.75H), 6.79 (dd, J=16.7, 10.7 Hz, 0.25H), 6.69-6.46 (m, 2H), 6.07 (dd, J=16.8, 2.5 Hz, 1H), 5.68 (dd, J=10.5, 2.4 Hz, 1H), 4.95 (d, J=13.9 Hz, 0.25H), 4.82-4.66 (m, 0.75H), 4.54 (d, J=14.0 Hz, 1H), 4.40-4.12 (m, 2H), 3.94 (dd, J=20.5, 4.4 Hz, 1H), 3.68 (dd, J=14.2, 4.4 Hz, 1H), 3.14-2.90 (m, 1H), 2.43-2.34 (m, 2H), 2.27-2.08 (m, 2H), 1.97-1.82 (m, 9H), 1.56-1.45 (m, 3H), 0.97 (dd, J=6.6, 2.2 Hz, 3H), 0.78 (t, J=6.0 Hz, 3H).

MS (ESI) m/z (M+H) ⁺=688.3.

SFC 100% ee. Retention time was 3.559 min.

Separation conditions: chromatographic column: «Column_2»; mobile phase: [CO ₂-ethanol (0.05% DEA)]; ethanol %: 5%-40% 5 min, 40% 2.5 min, 5% 2.5 min; flow rate: 2.5 mL/min; column temperature: 35° C.

Compound 29B:

¹H NMR (400 MHz, DMSO-d ₆) δ 10.18 (brs, 1H), 8.45 (d, J=4.9 Hz, 1H), 8.26 (s, 1H), 7.29-7.20 (m, 2H), 7.04 (dd, J=16.8, 10.4 Hz, 0.75H), 6.86 (dd, J=17.6, 10.4 Hz, 0.25H), 6.72-6.60 (m, 2H), 6.14 (d, J=16.4 Hz, 1H), 5.75 (d, J=10.7 Hz, 1H), 5.03 (d, J=13.8 Hz, 0.25H), 4.80 (d, J=7.8 Hz, 0.75H), 4.61 (d, J=14.1 Hz, 1H), 4.43-4.30 (m, 1H), 4.28-4.15 (m, 1H), 4.04-3.89 (m, 1H), 3.75 (dd, J=14.5, 4.4 Hz, 1H), 3.28-3.10 (m, 2H), 2.75-2.65 (m, 1H), 2.39-2.28 (m, 1H), 2.28-2.17 (m, 1H), 2.06-1.96 (m, 6H), 1.81 (d, J=9.5 Hz, 3H), 1.53 (d, J=6.8 Hz, 3H), 1.11 (d, J=6.9 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H).

MS (ESI) m/z (M+H) ⁺=688.3.

HPLC retention time was 5.269 min.

Separation conditions: chromatographic column: Waters XBridge 4.6*100 mm, 3.5 μm; column temperature: 40° C.; mobile phase: water (10 mM ammonium bicarbonate)-acetonitrile; acetonitrile: 5%-95% 7 min; flow rate: 1.2 mL/min. SFC 100% ee. Retention time was 4.349 min.

PAT

US20230227472

https://patentscope.wipo.int/search/en/detail.jsf?docId=US402823590&_cid=P20-MUT7F9-60174-1

Step 3: Preparation of Compound 29

MS (ESI) m/z (M+H) ⁺=688.2.

Step 4: Preparation of Compounds 29A and 29B

Compound 29A:

MS (ESI) m/z (M+H) ⁺=688.3.

SFC 100% ee. Retention time was 3.559 min.

Compound 29B:

MS (ESI) m/z (M+H) ⁺=688.3.

HPLC retention time was 5.269 min.

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References

[1]. Jia Zhong, et al. Sosimerasib monotherapy in patients with previously treated KRAS G12C–mutated non-small cell lung cancer: Primary results of a phase 2 study. Journal of Clinical Oncology Volume 43, Number 16_suppl June 2025.

///////////sosimerasib, anax labs, Kirsten rat sarcoma viral oncogene homolog inhibitor, antineoplastic, HBI-2438, JMKX1899, HBI 2438, JMKX 1899, 2VHH89PP6W

#sosimerasib, #anax labs, #Kirsten rat sarcoma viral oncogene homolog inhibitor, #antineoplastic, #HBI-2438, #JMKX1899, #HBI 2438, #JMKX 1899, #2VHH89PP6W

Tiratricol

DR ANTHONY MELVIN CRASTO Ph.D — Fri, 02 Oct 2026 02:34:38 +0000

Tiratricol

CAS 51-24-1, 1477-04-9 (hydrochloride salt)

MFC₁₄H₉I₃O₄ MW621.93 g/mol

9/28/2026, Emcitate, FDA 2026, APPROVALS 2026, Triac

2-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]acetic acid

3,3′,5-TRIIODOTHYROACETIC ACID
Triiodothyroacetic acid

To treat peripheral thyrotoxicosis in patients with MCT8 deficiency

Tiratricol is a monocarboxylic acid that is (4-hydroxy-3,5-diiodophenyl)acetic acid in which the phenolic hydroxy group has been replaced by a 4-hydroxy-3-iodophenoxy group. It is a thyroid hormone analogue that has been used in the treatment of thyroid hormone resistance syndrome. It has a role as an antiviral agent, a nutraceutical, a thyroid hormone, an anti-obesity agent, an EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitor and a human metabolite. It is a monocarboxylic acid, a member of phenols, an aromatic ether and an organoiodine compound

Tiratricol (also known as TRIAC or triiodothyroacetic acid), sold under the brand name Emcitate, is a thyroid hormone analogue. Triiodothyroacetic acid is also a physiologic thyroid hormone that is present in the normal organism in low concentrations. Tiratricol is an analogue of a naturally circulating metabolite of the active thyroid hormone T3.^[1] MCT8 is a specific thyroid hormone transporter.^[1] While T3 and T4 thyroid hormones rely on MCT8 to enter several tissues such as the brain, tiratricol can enter cells independently of MCT8.^[1] Once inside cells, tiratricol activates the thyroid hormone receptor in a similar way to endogenous T3.^[1]

The most common side effects are excessive sweating, irritability, anxiety and nightmares.^[1]

Medical uses

Tiratricol is indicated in the management of thyroid hormone resistance syndrome.^[3]

In the United States, Tiratricol is indicated for the treatment of peripheral thyrotoxicosis in adults and pediatric patients with MCT8 deficiency (Allan–Herndon–Dudley syndrome).^[4]^[5]

Society and culture

Legal status

Tiratricol is not approved for sale in Canada. It was once an approved medication in Brazil, but its marketing authorization was suspended in 2003, effectively prohibiting its sale.^[6] Tiratricol is available in France for therapy of thyroid hormone resistance and adjuvant therapy of thyroid cancer.^[7]

In December 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Emcitate, intended for the treatment of MCT8 deficiency (Allan-Herndon-Dudley syndrome).^[1]^[8] The applicant for this medicinal product is Rare Thyroid Therapeutics International AB.^[1] Emcitate is a hybrid medicine of Téatrois, which has been authorized in France.^[1] Emcitate contains the same active substance as Téatrois but has a different indication.^[1] Tiratricol was authorized for medical use in the European Union in February 2025.^[1]^[2] Tiratricol was approved for medical use in the United States kn September 2026.^[5]

Research

Tiratricol has been investigated for use in reducing goiter.^[9]

It has also shown some effectiveness in reducing the atrophy caused when using corticosteroids.^[10]

Tiratricol has also been widely marketed, under various trade names, as a weight loss aid. In 1999 and 2000, the United States Food and Drug Administration and Health Canada both issued warnings to the public regarding the use of dietary supplements containing tiratricol.^[11]^[12]

LIT

C. E. Wilkinson (Biochem. J. 63, 601, 1956): The primary landmark study describing the controlled iodination approach to yield triiodothyroacetic acid.

Meltzer et al. (J. Org. Chem. 26, 1418, 1961): Advanced methods for the synthesis and purification of thyroacetic acid derivatives.

PAT

British Patent GB 803149 (1958)

https://patentscope.wipo.int/search/en/detail.jsf?docId=GB134699786&_cid=P10-MUQCJP-66503-1

EXAMPLE 1 3:5:31 – triiodo – 4 – (41 – hydroxyphenoxy)
phenyl acetic acid (Triac)
An aqueous solution of iodine (N: 40 mls.) was added dropwise with stirring during hour to a solution of 3:5-diiodo-4-(41hydroxyphenoxy)phenyl acetic acid (Diac) (9.92 g.; 0.02 mol.) in aqueous ethylamine (33%: 120 mls.). After a further hour the solution was acidified with hydrochloric acid (5N) at 10-15 (ice-bath cooling). The precipitate, which became gummy on filtration, was triturated with water containing a few drops of hydrochloric acid and again filtered.

The solid was then ground with water containing a little hydrochloric acid, filtered, washed with water and dried over phosphorus pentoxide (12.10 g.; m.p. 161-72 ). The crude product was dissolved in methanol (240 mls.) and stirred during the dropwise addition of water (180 mls.). After standing overnight, the mixture was decanted from the tarry material which had separated. Water (60 mls.) was added in one portion, and the milky solution allowed to stand several hours until crystallisation was complete. The product was collected and dried over phosphorus pentoxide, 7.1 g. (63%) m.p. 181-3 (after sinteringg at about 60 , effervescing at 100 and resolidifying at about 115 ). A sample from a previous experiment was dried by heating slowly to 100 in high vacuum over phosphorus pentoxide. Found: C, 27.3; H, 1.5; I, 61.2, C14H9O4I3 requires C, 27.0; H, 1.5; I, 61.2%.

To prepare the sodium salt of Triac 42.8 g. of Triac was dissolved in a hot solution of sodium carbonate (7.3 g.) in water (420 mis.) and filtered. A solution of salt (35%; 42 mis.) was added and the mixture cooled, finally in the refrigerator. The product was collected and dried to constant weight over phosphorus pentoxide (34.1 g.).

PAT

British Patent GB 805761 (1958)

PAT

US Patent US8071134B2

https://patentscope.wipo.int/search/en/detail.jsf?docId=US42563548&_cid=P10-MUQCHB-64862-1

PAT

Chinese Patent CN113181152B

https://patentscope.wipo.int/search/en/detail.jsf?docId=CN333439736&_cid=P10-MUQCEZ-62879-1

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References

“Emcitate EPAR”. European Medicines Agency (EMA). 12 December 2024. Retrieved 16 December 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
“Emcitate PI”. Union Register of medicinal products. 17 February 2025. Retrieved 27 February 2025.
Carvalho GA, Ramos HE (2004). “[Thyroid hormone resistance syndrome]” (PDF). Arq Bras Endocrinol Metabol (in Portuguese). 48 (1): 83–92. doi:10.1590/S0004-27302004000100010. PMID 15611821.
“EMCITATE — Now Approved”. EMCITATE® — Now Approved. Retrieved 29 September 2026.
“Egetis Therapeutics Announces U.S. FDA Approval of EMCITATE® (tiratricol) for Patients with MCT8 Deficiency”. Egetis Therapeutics. Retrieved 29 September 2026.
“Anvisa suspende Tiratricol” (in Portuguese). Brazilian Society of Endocrinology and Metabolism. Archived from the original on 9 October 2007. Retrieved 8 August 2007.
Laboratoires DB PHARMA: Teatrois Deprecated link archived 2015-01-19 at archive.today information
“First treatment for peripheral thyrotoxicosis in patients with Allan-Herndon-Dudley syndrome”. European Medicines Agency (EMA) (Press release). 13 December 2024. Retrieved 16 December 2024.
Brenta G, Schnitman M, Fretes O, et al. (November 2003). “Comparative efficacy and side effects of the treatment of euthyroid goiter with levo-thyroxine or triiodothyroacetic acid”. J. Clin. Endocrinol. Metab. 88 (11): 5287–92. doi:10.1210/jc.2003-030095. PMID 14602763.
Yazdanparast P, Carlsson B, Oikarinen A, Risteli J, Lavin T, Faergemann J (November 2006). “Action of topical thyroid hormone analogue, triiodothyroacetic acid in reversing glucocorticoid-induced skin atrophy in humans”. Thyroid. 16 (11): 1157–62. doi:10.1089/thy.2006.16.1157. PMID 17123343.
“FDA Warns Against Consuming Dietary Supplements Containing Tiratricol” (Press release). U.S. Food and Drug Administration. 21 November 2000. Archived from the original on 22 January 2001. Retrieved 8 August 2007.
“Health Canada issues warning on products containing Tiratricol (TRIAC)” (Press release). Health Canada. 2 December 1999. Retrieved 8 August 2007.

Clinical data


Trade names	Emcitate
Other names	3,3′,5-triiodothyroacetic acid TRIAC
AHFS/Drugs.com	International Drug Names
Drug class	Thyroid hormone
ATC code	H03AA04 (WHO) D11AX08 (WHO)
Legal status
Legal status	EU: Rx-only^[1]^[2]
Pharmacokinetic data
Metabolism	Liver glucuronidation
Excretion	Bile duct
Identifiers
IUPAC name
CAS Number	51-24-1
PubChem CID	5803
IUPHAR/BPS	2637
DrugBank	DB03604
ChemSpider	5598
UNII	29OQ9EU4R1
KEGG	D07214
ChEBI	CHEBI:40021
ChEMBL	ChEMBL41632
CompTox Dashboard (EPA)	DTXSID2045232
ECHA InfoCard	100.000.079
Chemical and physical data
Formula	C₁₄H₉I₃O₄
Molar mass	621.935 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES
InChI

//////////////tiratricol, anax labs, Emcitate, FDA 2026, APPROVALS 2026, Triac

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Zilurgisertib

DR ANTHONY MELVIN CRASTO Ph.D — Wed, 30 Sep 2026 02:34:35 +0000

Zilurgisertib

CAS 2173389-57-4

MW 502.6 g/mol MFC₃₀H₃₈N₄O₃

Atebrioz, FDA 2026, APPROVALS 2026, L5Z9S25HO2, INCB 000928

2-amino-N-(4-hydroxy-1-bicyclo[2.2.2]octanyl)-5-[4-[(1R,5S)-3-(oxan-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl]phenyl]pyridine-3-carboxamide

To reduce the volume of total new heterotopic ossification in adults and pediatric patients 12 years and older with fibrodysplasia ossificans progressiva

Zilurgisertib is an inhibitor of activin A receptor type 1 (activin receptor-like kinase 2; ALK2; ALK-2; ACVR1; ACTR-I), with potential anti-anemic and ossification suppressive activities. Upon administration, zilurgisertib targets, binds to and inhibits the activity of ALK-2. This prevents ALK2-mediated signaling and ALK2-mediated excessive bone morphogenetic protein (BMP) signaling. This may suppress heterotopic ossification (HO). As ALK-2 enhances the secretion of hepcidin, a peptide liver hormone and a key modulator of iron homeostasis, zilurgisertib is able to decrease hepcidin expression in the liver, thereby increasing and restoring plasma iron levels, enhancing erythropoiesis, and correcting anemia of chronic disease (ACD). ALK2, a serine/threonine receptor kinase and type I cell surface receptor for BMPs, is constitutively activated due to activating mutations in inflammatory conditions, various types of cancer, and in fibrodysplasia ossificans progressiva (FOP). Elevated serum hepcidin levels enhance storage of iron, reduce iron availability and causes iron deficiency anemia.

Zilurgisertib, sold under the brand name Atebrioz, is a medication used for the treatment of fibrodysplasia ossificans progressiva.^[1] It is an selective activin receptor-like kinase-2 (ALK2) inhibitor.^[1]^[2]

Zilurgisertib was approved for medical use in the United States in September of 2026.^[3]

Medical uses

Zilurgisertib is indicated to reduce the volume of total new heterotopic ossification (abrnomal bone formation) in people aged twelve years of age and older with fibrodysplasia ossificans progressiva.^[1]

Fibrodysplasia ossificans progressiva is a rare genetic disease caused certain mutations in the ACVR1/ALK2 gene which controls new bone growth.^[3] As a result, connective tissues such as muscle, tendons, and ligaments gradually turn into bone, causing limited movement, deformities, severe disability, and early death.^[3]

Adverse effects

Zilurgisertib can cause fetal harm based on data from animal studies.^[3]

The most common side effects include headache, joint pain, upper respiratory tract infection, nosebleeds, and nausea.^[3]

History

The effectiveness of zilurgisertib was evaluated in a randomized, double-blind, placebo‑controlled trial (NCT05090891) in which 63 participants with FOP were randomly assigned to receive zilurgisertib 100 mg or placebo once daily for 24 weeks followed by a 292-week, single-arm, open-label extension period during which participants received oral zilurgisertib 100 mg daily.^[3]

Society and culture

Legal status

Zilurgisertib was approved for medical use in the United States in September 2026.^[4] The US Food and Drug Administration granted the application for zilurgisertib fast track, priority review, and orphan drug designations for this indication.^[3]

Names

Zilurgisertib is the international nonproprietary name.^[5]

Zilurgisertib is sold under the brand name Atebrioz.^[3]

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US242623881&_cid=P22-MUNHEN-48106-1

Example 34: 2-amino-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-5-(4-((1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinamide (also named compound A herein)

To a solution of 2-amino-5-(4-((1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinic acid TFA salt (Intermediate 14a, 4.10 g, 8.14 mmol) and 4-aminobicyclo[2.2.2]octan-1-ol hydrochloride (2.17 g, 12.2 mmol) in anhydrous DMF (60 mL) was added N-methylmorpholine (2.24 mL, 20.4 mmol) and HATU (4.64 g, 12.2 mmol) under a nitrogen atmosphere at RT. The reaction mixture was stirred for 2 h and then diluted with a sat. aq. solution of NaHCO ₃ and extracted three times with EtOAc. The combined organic extracts were washed with brine, dried over MgSO ₄, filtered and concentrated under reduced pressure. The crude product was purified by reversed-phase chromatography (Method 3b). Pure fractions were treated with a sat. aq. NaHCO ₃ solution and extracted three times with EtOAc. The combined organic extracts were washed with brine, dried over MgSO ₄, filtered and concentrated under reduced pressure to give the title compound as an off-white solid. The absolute configuration as depicted was confirmed by X-ray crystallography of the title compound in a complex with the ALK-2 kinase domain. 1H NMR (400 MHz, DMSO-d6) δ 8.34 (d, 1H), 7.98 (d, 1H), 7.79 (s, 1H), 7.57 (d, 2H), 7.23 (d, 2H), 6.92 (s, 2H), 4.31 (s, 1H), 3.91-3.78 (m, 2H), 3.40 (bs, 1H), 3.33-3.24 (m, 2H), 3.11 (d, 1H), 2.57 (bs, 1H), 2.50-2.34 (m, 1H), 2.34 (bs, 1H), 2.12-1.94 (m, 6H), 1.90-1.72 (m, 3H), 1.71-1.51 (m, 6H), 1.51-1.34 (m, 2H), 1.31 (t, 1H), 0.82-0.68 (m, 1H). (UPLC-MS) t _R 0.54 min; ESI-MS 503 [M+H] ⁺. Chiral HPLC (ChiralPak Id, 5 μm, flow rate: 1 mL/min, detection wavelength: 270 nm, mobile phase: heptane:isopropanol 60:40 (+0.1% diethylamine)): t _R 18.7 min, 92.3% ee.

Alternative Example 34A: To a solution of 2-amino-5-(4-((1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinic acid hydrochloride (1 kg, 1.683 mol) and 4-aminobicyclo[2.2.2]octan-1-ol hydrochloride (343.9 g, 1.935 mol) in DMF (3500 mL) was added Et ₃N (681.2 g, 6.732 mol) and HATU (767.9 g, 2.019 mol) at RT. The reaction mixture was stirred at RT for 1 h. The mixture was heated to IT=45° C., 5% NH ₃.H ₂O solution (5200 g) was added. Stirred for about 30 min, another 5% NH ₃.H ₂O solution (1800 g) was added. The mixture was heated to IT=45° C. for 2 h. The mixture was cooled to IT=22° C. Filtered, the wet cake was washed with H ₂O (1500 mL×3). The wet cake was dried under vacuum at 45° C. for 24 h. The crude product was dissolved in acetone (3000 mL), then filtered to remove some undissolved solid. The filtrate was heated to IT=50° C. H ₂O (2000 mL) was added. The mixture was stirred at IT=50° C. for 30 min until a white precipitate formed. H ₂O (4000 mL) was added slowly. The mixture was stirred at IT=50° C. for 2 h. The mixture was cooled to IT=22° C. in 2 h, Filtered, the wet cake was washed with acetone:H ₂O=1:2 (v/v, 1000 mL×2). The wet cake was dried under vacuum at 45° C. for 24 h. total 760 g white solid was obtained (89% yield, 99.4% ee).

¹H NMR (DMSO-d6) δ: 8.32 (d, J=2.3 Hz, 1H), 7.97 (d, J=2.3 Hz, 1H), 7.77 (s, 1H), 7.54 (d, J=8.3 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 6.90 (s, 2H), 4.31 (s, 1H), 3.82 (m, 2H), 3.29 (m, 2H), 3.07 (d, J=8.5 Hz, 1H), 2.54 (d, J=8.3 Hz, 1H), 2.44 (dd, J=8.5, 3.5 Hz, 1H), 2.37 (m, 1H), 2.31 (td, J=10.2, 5.0 Hz, 1H), 2.04 (m, 6H), 1.80 (dt, J=7.9, 3.8 Hz, 1H), 1.71 (d, J=12.3 Hz, 1H), 1.65 (d, J=11.5 Hz, 1H), 1.62 (m, 6H), 1.38 (m, 1H), 1.34 (m, 1H), 1.29 (t, J=3.9 Hz, 1H), 0.73 (dd, J=7.9, 3.6 Hz, 1H).

¹³C NMR (DMSO-d6) δ: 167.80, 157.69, 148.28, 141.27, 134.91, 134.79, 126.40, 125.66, 123.53, 111.01, 66.22, 65.59, 59.10, 55.46, 52.04, 33.72, 31.92, 31.77, 30.59, 29.61, 24.14, 17.20.

MS(ESI-TOF): 503.3018 [M+H]+.

The starting material (hydrochloride salt) was obtained as follows:

Methyl 2-amino-5-(4-((1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinate dihydrochloride (10 g, 19.5 mmol, 1.0 eq) was suspended in MeOH (31.7 g). A solution of NaOH (2.9 g, 72.2 mmol, 3.7 eq) in H ₂O (10 g) was then added. The reaction mixture was heated to 45±5° C. and stirred for more than 3 h, yielding a suspension.

To another flask containing acetone (200 g), 5˜6 N HCl in i-PrOH (14.8 g, 97.6 mmol, 5 eq) was added. The solution was heated to 47±3° C. Then the above MeOH suspension was added to the mixture dropwise and stirred at 47±3° C. for 3 h. The mixture was cooled down to 23±3° C. and stirred for 3 h. After filtration, the wet cake was washed with acetone (40 g). The wet cake was dried under vacuum at 55° C. for 8 h. 2-Amino-5-(4-((1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinic acid hydrochloride (12.3 g, 99.3% HPLC purity, 62.1% assay yield) was obtained as an off-white solid.

¹H NMR (DMSO-d6) δ: 11.53 (br s, 1H), 8.64 (br s, 1H), 8.54 (br s, 1H), 7.72-8.42 (m, 2H), 7.64 (br d, J=7.9 Hz, 2H), 7.38 (br d, J=7.8 Hz, 2H), 3.85-4.04 (m, 3H), 3.40-3.73 (m, 4H), 3.15-3.33 (m, 2H), 2.18 (br d, J=3.9 Hz, 1H), 1.95-2.12 (m, 4H), 1.88 (br d, J=10.0 Hz, 1H), 1.05 (br t, J=6.4 Hz, 1H).

¹³C NMR (DMSO-d6) δ: 167.2, 155.8, 144.3, 142.0, 139.6, 133.8, 127.7, 126.3, 124.1, 110.0, 65.8, 62.5, 55.7, 53.2, 29.9, 28.8, 28.7, 23.5, 16.6.

MS(ESI-TOF): 380.1974 [M+H] ⁺.

The starting material, 2-Amino-5-(4-((1R,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinate dihydrochloride, was obtained as follows:

To a 500 mL round bottom flask were charged 1R,5S)-1-(4-bromophenyl)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-3-ium chloride (20 g, 1 eq), EA (200 mL), and 25% K ₂CO ₃ (62 g). The mixture was stirred for 30 min until all solids were dissolved. After phase separation, the organic layer was concentrated. 2-Methyl-2-butanol (48 g, 60 mL) was added. The organic layer was concentrated. 2-Methyl-2-butanol (144 g, 180 mL) was added.

The mixture was transferred to a 500 mL Redlay. K ₂CO ₃ (18.8 g, 2.5 eq) and methyl 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinate (16.8 g, 1.04 eq; see Intermediate 1e) were added. The mixture was degassed with N ₂ for three times. The mixture was heated to IT=50±5° C. within 1 h. Pd(dppf)Cl ₂ (1.2 g, 0.03 eq) was added. The mixture was heated to IT=70±3° C. and stirred for 2 h. After cooling to 22° C., H ₂O (120 g) and EA (180 g) were added and stirred for 30 min. MCC (6 g) was added and the mixture was filtered through MCC. The cake was washed with EA (54 g). After phase separation, the organic layer was washed with 5% NaCl (124 g). Quadrasil MP (Heavy metal scavenger from Johnson Matthey, 6 g) was then added to the organic layer. The mixture was heated to IT=55° C. for 8 h, filtered through MCC and washed with EA (54 g). Quadrasil MP (2 g) was added to the organic layer. The mixture was heated to IT=55° C. for 6 h, filtered through CMC and washed with EA (54 g). The organic layer was concentrated. Acetone (158 g, 200 mL) was added. After stirring at IT=22±3° C. for 30 min, the mixture was heated to IT=40±3° C. 15.5% HCl (38.4 g) was added dropwise with IT<50° C. The mixture was stirred at IT=45±3° C. for 1 h. The mixture was cooled to 22±3° C. The mixture was stirred at 22±3° C. for 1 h and filtered. The cake was washed with acetone (32 g×2). The wet cake was dried under vacuum at 50° C. for at least 8 h. The starting material was obtained, 22.5 g white solid (97.1% HPLC purity, 5.2% water content, 87% assay yield) was obtained.

¹H NMR (DMSO-d6) δ: 11.43 (br d, J=5.7 Hz, 1H), 8.62-8.80 (m, 2H), 7.85-8.58 (m, 2H), 7.67 (d, J=8.3 Hz, 2H), 7.39 (d, J=8.4 Hz, 2H), 3.85-4.06 (m, 6H), 3.60-3.69 (m, 2H), 3.50-3.59 (m, 1H), 3.44 (brd, J=7.7 Hz, 1H), 3.14-3.31 (m, 2H), 2.21 (dt, J=8.4, 4.2 Hz, 1H), 1.94-2.12 (m, 4H), 1.76-1.93 (m, 1H), 1.07 (br t, J=7.1 Hz, 1H).

¹³C NMR (DMSO-d6) δ: 165.0, 154.0, 143.5, 142.0, 140.1, 132.8, 127.7, 126.5, 124.2, 110.7, 65.8, 62.5, 55.6, 53.3, 53.3, 29.9, 28.9, 28.8, 23.6, 16.8.

MS(ESI-TOF): 394.2071 [M+H] ⁺.

The starting material, 1R,5S)-1-(4-bromophenyl)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-3-ium chloride, was obtained as follows:

To a 1 L Redlay were charged (1R,5S)-1-(4-bromophenyl)-3-azabicyclo[3.1.0]hexan-3-ium chloride (30 g, 1 eq), dihydro-2H-pyran-4(3H)-one (13.13 g, 1.2 eq) and THF (300 mL). The mixture was stirred at IT=22±5° C. for 1 h. NaBH(OAc) ₃ (30.1 g, 1.3 eq) was added portion wise while keeping IT<30° C. The mixture was stirred at IT=22±5° C. for 2 h. 6.2% HCl (93 g, 90 ml, 1.5 eq) was added while maintaining IT<30° C. and pH<2. The mixture was stirred for 10 min. 25% K ₂CO ₃ (259 g, 210 mL) was added to adjust pH=8-9. IPAc (300 mL) was added. The mixture was stirred for 10 min. After phase separation, H ₂O (150 g) was added to the organic layer. The mixture was stirred for 10 min. After phase separation, the organic layer was concentrated under vacuum (50-100 mbar, 50° C. water bath). IPA (120 g, 150 mL) was added. The organic layer was concentrated under vacuum (50-100 mbar, 50° C. water bath). IPA (144 g, 180 mL) was added. The mixture was filtered through CMC. The cake was washed with IPA (24 g×2). H ₂O (5 g) was added to the organic layer. 31% HCl (19.3 g) was added dropwise with IT<35° C. The mixture was stirred at IT=22±5° C. for 2 h and filtered. The cake was washed with IPA (48 g×2). The wet cake was dried under vacuum at 50° C. for at least 6 h. The desired product (31.4 g, 98% HPLC purity, 78% yield) was obtained as a white solid.

¹H NMR (DMSO-d6 and D ₂O) δ: 7.46 (br d, J=8.4 Hz, 2H), 7.15 (br d, J=8.4 Hz, 2H), 3.90 (br d, J=7.8 Hz, 3H), 3.62 (br s, 1H), 3.51 (br s, 2H), 3.16-3.38 (m, 3H), 2.05-2.21 (m, 1H), 1.93 (br s, 2H), 1.49-1.71 (m, 2H), 1.05-1.30 (m, 1H).

¹³C NMR (DMSO-d6) δ: 138.3, 131.9, 129.2, 120.4, 65.5, 62.3, 56.2, 53.9, 29.1, 28.9, 24.8, 23.0. MS(ESI-TOF): 322.0761 [M+H]+

The complete way of manufacture of Alternative Example 34 A is depicted in the following Reaction Scheme 34A:

The first compound in this scheme, A1, can be obtained as follows:

Step 1-2 Synthesis of 1c and 1d

PAT

Compound A [WO2021257532A1]

PAT

example 34 [US20210155606A1]

PAT

US10710980, Example 34

PAPERS

Discovery and Characterization of Zilurgisertib, a Potent and Selective Inhibitor of Activin Receptor-like Kinase-2 (ALK2) for the Treatment of Fibrodysplasia Ossificans ProgressivaPublication Name:ACS Medicinal Chemistry LettersPublication Date:2025-10-31PMCID:PMC12621050PMID:41256990DOI:10.1021/acsmedchemlett.5c00516
Pharmacokinetics of Zilurgisertib With and Without Food from Single and Multiple Ascending Dose Phase 1 Studies in Healthy AdultsPublication Name:European Journal of Drug Metabolism and PharmacokineticsPublication Date:2024-12-09PMCID:PMC11802711PMID:39652202DOI:10.1007/s13318-024-00926-z

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References

“Atebrioz FDA label” (PDF). files.mirumpharma.com.
Gangat N, Tefferi A (June 2025). “Emerging Pathogenetic Mechanisms and New Drugs for Anemia in Myelofibrosis and Myelodysplastic Syndromes”. American Journal of Hematology. 100 Suppl 4: 51–65. doi:10.1002/ajh.27659. PMID 40056069.
Center for Drug Evaluation and Research (25 September 2026). “FDA Approves Third Treatment for Fibrodysplasia Ossificans Progressiva”. U.S. Food and Drug Administration. U.S. Food and Drug Administration (FDA). Retrieved 27 September 2026. This article incorporates text from this source, which is in the public domain.
“Mirum Pharmaceuticals and Incyte Announce U.S. FDA Approval of Atebrioz (zilurgisertib) for Adult and Pediatric Patients with Fibrodysplasia Ossificans Progressiva” (Press release). Mirum Pharmaceuticals. 25 September 2026. Retrieved 27 September 2026 – via Business Wire.
World Health Organization (2022). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 88”. WHO Drug Information. 36 (3). hdl:10665/363551.

External links

“Zilurgisertib ( Code – C175551 )”. EVS Explore.
“Zilurgisertib Fumarate ( Code – C199021 )”. EVS Explore.
Clinical trial number NCT05090891 for “To Assess the Efficacy, Safety, and Tolerability of INCB000928 in Participants With Fibrodysplasia Ossificans Progressiva (Progress)” at ClinicalTrials.gov

Clinical data

Trade names	Atebrioz
Other names	INCB-000928, INCB000928
License data	US DailyMed: Zilurgisertib
Routes of administration	By mouth
Drug class	Kinase inhibitor (ALK2 selective)
ATC code	None
Legal status
Legal status	US: ℞-only^[1]
Identifiers
CAS Number	2173389-57-4 2173390-29-7
PubChem CID	138628908 162623634
IUPHAR/BPS	11888
UNII	L5Z9S25HO2 1R349830SB
KEGG	D12547 D12548
ChEMBL	ChEMBL5314579
Chemical and physical data
Formula	C₃₀H₃₈N₄O₃
Molar mass	502.659 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES
InChI

///////////zilurgisertib, anax labs, Atebrioz, FDA 2026, APPROVALS 2026, L5Z9S25HO2, INCB 000928

#zilurgisertib, #anax labs, #Atebrioz, #FDA 2026, #APPROVALS 2026, #L5Z9S25HO2, #INCB 000928

Tavapadon

DR ANTHONY MELVIN CRASTO Ph.D — Mon, 28 Sep 2026 03:07:41 +0000

Tavapadon

CAS No.:1643489-24-0
Formula:C₁₉H₁₆F₃N₃O₃
Molecular Weight:391.34

9/25/2026, Juvmo, FDA 2026, APPROVALS 2026, CEREVEL, CVL 751, PF 6649751, PF-06649751,

To treat Parkinson’s disease in adults

Tavapadon (PF-06649751) is an orally active and highly selective dopamine D1/D5 receptor partial agonist. Tavapadon is effective in enabling movement and reducing disability and has the potential for Parkinson’s disease.

Tavapadon (developmental code names CVL-751, PF-06649751) is a dopamine receptor agonist which is under development for the treatment of Parkinson’s disease.^[2]^[3]^[4] It is under development by Cerevel Therapeutics, which acquired tavapadon from Pfizer in 2018.^[2] It is taken by mouth.^[1]

Tavapadon acts as a highly selective partial agonist of the dopamine D₁ receptor (K_i = 9 nM; IATooltip Intrinsic activity = 65%) and the dopamine D₅ receptor (K_i = 13 nM; IA = 81%).^[3]^[4]^[1] It has no significant affinity or functional activity at the D₂-like receptors (D₂, D₃, D₄) (K_i ≥ 4,870 to 6,720 nM).^[1] Tavapadon also shows biased agonism for G_s-coupled signaling at the D₁-like receptors.^[1]^[3]

As of December 2024, tavapadon has completed phase 3 clinical trials for Parkinson’s disease.^[2]

OriginatorPfizer
DeveloperCerevel Therapeutics; Pfizer
ClassAntiparkinsonians; Small molecules
Mechanism of ActionDopamine D1 receptor agonists; Dopamine D5 receptor agonists
registrationParkinson’s disease
01 Dec 2025Cerevel Therapeutics completes a phase III TEMPO-4 trial in Parkinson Disease (In adults, In elderly in the US, Australia, Bulgaria, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Poland, Serbia, Spain, and Ukraine (PO) (NCT04760769)
28 Nov 2025No recent reports of development identified for phase-I development in Parkinson’s-disease(In volunteers) in USA (PO, Tablet)
26 Sep 2025Preregistration for Parkinson’s disease (Early-stage disease, In the elderly, In adults) in USA (PO)

The industrial synthesis of tavapadon typically proceeds via a convergent sequence:

Ether Formation: Coupling of a substituted phenol derivative (such as a 4-hydroxy-2-methylphenyl component) with a 2-halogenated-3-(trifluoromethyl)pyridine (e.g., 2-chloro-3-trifluoromethylpyridine) via nucleophilic aromatic substitution ($S_NAr$) or transition-metal-catalyzed cross-coupling to construct the biaryl ether framework.
Pyrimidine Ring Construction / Functionalization: Assembly or modification of the 1,5-dimethylpyrimidine-2,4-dione core onto the substituted aryl backbone, often utilizing base-catalyzed cyclizations (e.g., using methylating agents and urea/amide derivatives).
Chiral Resolution / Final Purification: Final isolation of the target enantiomer or specific crystalline form (as outlined in WO2023102087A1 and WO2023143321) to meet active pharmaceutical ingredient (API) regulatory grades.

PAT

W02014207601

Examples 7 and 8

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2014207601&_cid=P12-MUKNR1-83868-1

Step 1. Synthesis of tert-butyl 4-bromo-3,5-dimethyl-2,6-dioxo-3,6-dihydropyrimidine-1(2H)-carboxylate (C22).

Compound C2 (800 mg, 3.65 mmol), di-tert-butyl dicarbonate (99%, 966 mg, 4.38 mmol), triethylamine (0.62 mL, 4.4 mmol) and 4-(dimethylamino)pyridine (45 mg, 0.36 mmol) were combined in tetrahydrofuran (15 mL) and heated to 70 °C for 1 hour, then allowed to stir at room temperature for 18 hours. The reaction mixture was concentrated in vacuo, and the residue was purified via chromatography on silica gel (Gradient: 10% to 25% ethyl acetate in heptane) to provide the product as a white solid. Yield: 1.10 g, 3.45 mmol, 94%. ¹H NMR (400 MHz, CDCl₃) δ 3.64 (s, 3H), 2.12 (s, 3H), 1.61 (s, 9H).

Step 2. Synthesis of ten-butyl 4-[4-(benzyloxy)-2-methylphenyl]-3,5-dimethyl-2,6-dioxo-3,6-dihydropyrimidine-1(2H)-carboxylate ( C23).

A mixture of C22 (1.00 g, 3.13 mmol), [4-(benzyloxy)-2-methylphenyl]boronic acid (98%, 1.16 g, 4.68 mmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) – tert-butyl methyl ether adduct (S-Phos precatalyst) (119 mg, 0.156 mmol), and cesium carbonate (3.06 g, 9.39 mmol) in 2-methyltetrahydrofuran (10 mL) and water (3 mL) was heated at 50 °C for 66 hours. The reaction mixture was diluted with water and ethyl acetate, and then filtered to remove suspended solids. The filtrate was extracted several times with ethyl acetate, and the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was suspended in a 1:3 mixture of ethyl acetate and heptane, stirred for several minutes, and filtered, providing the product as a white solid. Yield: 970 mg, 2.22 mmol, 71%. LCMS m/z 337.2 [(M-Boc)+H]⁺. ¹H NMR (400 MHz, CDCl₃) δ 7.34-7.48 (m, 5H), 6.91-7.01 (m, 3H), 5.10 (s, 2H), 3.01 (s, 3H), 2.16 (br s, 3H), 1.66 (s, 9H), 1.64 (s, 3H).

Step 3. Synthesis of 6-(4-hydroxy-2-methylphenyl)-1,5-dimethylpyrimidine-2,4(1H,3H)-dione (C24).

Racemate C25 (1.30 g, 3.32 mmol) was separated into its atropenantiomers via chiral chromatography (Column: Phenomenex Lux Cellulose-2; Gradient: heptane / ethanol). The first-eluting atropenantiomer, obtained as a tan solid that exhibited a negative (-) rotation, was designated as Example 7. Yield: 536 mg, 1.37 mmol, 41%. The second-eluting atropenantiomer, also obtained as a tan solid but with a positive (+) rotation, was designated as Example 8. Yield: 553 mg, 1.41 mmol, 42%. 7: LCMS m/z 392.2 [M+H]⁺. ¹H NMR (400 MHz, CDCl₃) δ 8.34 (ddq, J=4.9, 1.9, 0.6 Hz, 1H), 8.30 (br s, 1H), 8.05 (ddq, J=7.6, 1.9, 0.7 Hz, 1H), 7.13-7.21 (m, 4H), 3.06 (s, 3H), 2.21 (br s, 3H), 1.69 (s, 3H). 8: LCMS m/z 392.2 [M+H]⁺. ¹H NMR (400 MHz, CDCl₃) δ 8.34 (br d, J=4.9 Hz, 1H), 8.30 (br s, 1H), 8.05 (br d, J=7.5 Hz, 1H), 7.13-7.22 (m, 4H), 3.06 (s, 3H), 2.21 (br s, 3H), 1.69 (s, 3H).

PAT

WO2015162084 SIMILAR

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2015162084&_cid=P12-MUKNEL-70374-1

PAT

US9334247

PAT

WO2023102087A1

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023102087&_cid=P12-MUKNKO-77090-1

Tavapadon, 1 , 5-dimethy I -6-(2-methy 1 -4- { [3 -(tri fluoromethyl)pyri din-2-yl]oxy}phenyl)pyrimidine-2,4(lH,3H)-dione has the following chemical structure:

and is described in International Publication No. W02014/207601. As disclosed in International Publication No. W02014/207601, the class of compounds encompassing Tavapadon, may exist as conformational isomers due to hindered rotation about a single bond, i.e., atropisomerism. In the case of Tavapadon, the atropenantiomers or atropisomers may be designated as (-)-Tavapadon or (+)-Tavapadon, depending on the optical rotation, and can include any mixture thereof, including a racemic mixture, wherein the racemic mixture can be designated as (±)-Tavapadon. According to International Publication No.

W02014/207601, the compound Tavapadon may be obtained as a racemate (i.e., (±)-Tavapadon), which may be separated by chiral chromatography into two atropenantiomers. The atropisomer exhibiting an anticlockwise (negative) rotation on a polarimeter is denoted the (-)-atropenantiomer [i.e., (-)-Tavapadon], and the atropisomer exhibiting a clockwise (positive) rotation on a polarimeter is denoted the (+)-atropenantiomer [i.e., (+)-Tavapadon],

PAT

WO2023143321 (or corresponding US20250145588A1 / CN115974803A equivalents)

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References

Clinical data

Other names	CVL-751; PF-6649751; PF-06649751
Routes of administration	By mouth^[1]
Drug class	Dopamine receptor agonist
Identifiers
IUPAC name
CAS Number	1643489-24-0
PubChem CID	86764100
ChemSpider	48062699
UNII	PT4P8MJP8L
KEGG	D11431
ChEMBL	ChEMBL3697617
CompTox Dashboard (EPA)	DTXSID301337071
Chemical and physical data
Formula	C₁₉H₁₆F₃N₃O₃
Molar mass	391.350 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES
InChI

References

Bezard E, Gray D, Kozak R, Leoni M, Combs C, Duvvuri S (2024). “Rationale and Development of Tavapadon, a D1/D5-Selective Partial Dopamine Agonist for the Treatment of Parkinson’s Disease”. CNS Neurol Disord Drug Targets. 23 (4): 476–487. doi:10.2174/1871527322666230331121028. PMC 10909821. PMID 36999711. Tavapadon is a highly selective partial agonist at D1 and D5 dopamine receptors, [52] with little to no functional activity at D2, D3, or D4 receptors in vitro (unpublished data). Assays measuring the displacement of radioligand binding in cell lines expressing recombinant human dopamine receptors have shown that tavapadon has a high affinity for both D1 (Ki = 9 nM) and D5 (Ki = 13 nM) (unpublished data). Conversely, tavapadon had a low affinity at D2 (Ki ≥ 6210 nM), D3 (Ki ≥ 6720 nM), and D4 (Ki ≥ 4870 nM) (unpublished data). […] In vitro assays of functional activity have confirmed that tavapadon acts as a partial agonist by binding at D1 and D5 receptors, corresponding to 65% and 81% of dopamine’s intrinsic activity, respectively, and inducing functional receptor activation, with half-maximal effective concentration (EC50) values of 19 nM and 17 nM (unpublished data).
“Tavapadon – Cerevel Therapeutics”. Adis Insight. Springer Nature Switzerland AG.
Cerri S, Blandini F (December 2020). “An update on the use of non-ergot dopamine agonists for the treatment of Parkinson’s disease”. Expert Opinion on Pharmacotherapy. 21 (18): 2279–2291. doi:10.1080/14656566.2020.1805432. PMID 32804544. S2CID 221163451.
Hall A, Provins L, Valade A (January 2019). “Novel Strategies To Activate the Dopamine D₁ Receptor: Recent Advances in Orthosteric Agonism and Positive Allosteric Modulation”. Journal of Medicinal Chemistry. 62 (1): 128–140. doi:10.1021/acs.jmedchem.8b01767. PMID 30525590. S2CID 54469910.

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Lirafugratinib

DR ANTHONY MELVIN CRASTO Ph.D — Sat, 26 Sep 2026 03:00:23 +0000

Lirafugratinib

CAS No.:2549174-42-5
Formula:C₂₈H₂₄FN₇O₂
Molecular Weight:509.53

FDA 2026, APPROVALS 2026, Lyrfigtu, RLY-4008, RLY 4008, 23SEPT2026

N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-
d]pyrimidin-6-yl)phenyl)methacrylamide (lirafugratinib)

To adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma harboring a fibroblast growth factor receptor 2 gene fusion or other rearrangement

Lirafugratinib (RLY-4008) is an orally active, irreversible and highly selective FGFR2 inhibitor with an IC₅₀ of 3 nM. Lirafugratinib covalently binds to Cys491. Lirafugratinib targets FGFR2 primary alterations and resistance mutations and induces tumor regression while sparing other FGFRs.

Lirafugratinib (Lyrfigtu) received FDA approval on September 23, 2026, for adults with previously treated, unresectable or metastatic cholangiocarcinoma involving FGFR2 gene fusions or rearrangements.

Overview & Mechanism

Drug Class: An oral, selective, and irreversible FGFR2 small-molecule inhibitor.
Developer/Marketed By: Developed by Relay Therapeutics and commercialized globally by Elevar Therapeutics.
How it Works: Covalently targets the FGFR2 kinase domain to inhibit tumor-driving signaling while sparing other FGFR proteins to limit off-target effects.

Efficacy

Clinical Trial: Assessed in the phase 1/2 REFOCUS trial (NCT04526106) involving 116 previously treated, FGFR-inhibitor-naive patients.
Key Metrics: Demonstrated an objective response rate of 46%, a median duration of response of 11.8 months, and a median progression-free survival of 11.3 months.

Dosing & Administration

Recommended Dose: 70 mg orally once daily on a continuous basis until disease progression or unacceptable toxicity.

Safety & Warnings

Common Adverse Events: Hand-foot syndrome, stomatitis, nail issues, and ocular/retinal toxicities.
Special Warnings: Includes precautions for ocular toxicity, hyperphosphatemia, soft tissue mineralization, and embryo-fetal risks

PAPER

https://pmc.ncbi.nlm.nih.gov/articles/PMC10861881

SEE https://pmc.ncbi.nlm.nih.gov/articles/instance/10861881/bin/pnas.2317756121.sapp.pdf

N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-yl)oxy)phenyl)-7-methyl-7Hpyrrolo[2,3-d]pyrimidin-6-yl)phenyl)methacrylamide (lirafugratinib)

5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

A round bottomed flask was charged with 5-bromo-7H-pyrrolo[2,3-d]pyrimidin-4-amine (10.0 g,
47.16 mmol), Cs2CO3 (22.99 g, 70.75 mmol), DMF (120 mL) and a stirbar. Iodomethane (8.03 g,
56.59 mmol) was added, and the solution was stirred for 1 h at room temperature. The reaction mixture was diluted with H2O (300 mL), and the aqueous phase was extracted with ethyl acetate
(300 mL) three times. The combined organic layers were washed with saturated brines, dried
over sodium sulfate, filtered, and concentrated in vacuo. The resulting crude material was
purified by HPLC. Concentration in vacuo resulted in 5-bromo-7-methyl-7H-pyrrolo[2,3-
d]pyrimidin-4-amine (5 g, 47.1 % ) as an off-white solid.

5-bromo-6-iodo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

A round bottomed flask was charged with 5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-
amine (5 g, 22.12 mmol), DCM (50 mL) and TFA (2 mL) and a stirbar. 1-iodopyrrolidine-2,5-
dione (5.97 g, 26.54 mmol) was added, and the solution was stirred for 2 h at room temperature.
The reaction mixture was diluted with Na2SO3 solution (200 mL), and the aqueous phase was
extracted with DCM (200 mL) three times. The combined organic layers were washed with
saturated brines, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting
crude material was purified by HPLC. Concentration in vacuo resulted in 5-bromo-6-iodo-7-
methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (4 g, 51.3 %) as a yellow solid.

tert-butyl (4-(4-amino-5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)carbamate

A resealable reaction vial was charged with 5-bromo-6-iodo-7-methyl-7H-pyrrolo[2,3-
d]pyrimidin-4-amine (4 g, 11.36 mmol), tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)phenyl)carbamate (4.35 g, 13.63 mmol), Pd(dppf)Cl2 (994.16 mg, 1.36 mmol), K3PO4 (7.22
g, 34.08 mmol), DMF (50 mL), H2O (6.25 mL) and a stir bar before being evacuated and purged
with nitrogen three times. The mixture was stirred for 2 h at 90 °C. The reaction mixture was
diluted with H2O (300 mL), and the aqueous phase was extracted with ethyl acetate (300 mL)
three times. The combined organic layers were washed with brines, dried over sodium sulfate,
filtered, and concentrated in vacuo. The resulting crude material was purified by silica gel
chromatography (eluting with MeOH/DCM = 1/40). Concentration in vacuo resulted in tert-butyl
(4-(4-amino-5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)carbamate (3 g, 63.4%)
as a yellow solid.

6-(4-aminophenyl)-5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

A round bottomed flask was charged with tert-butyl (4-(4-amino-5-bromo-7-methyl-7Hpyrrolo[2,3-d]pyrimidin-6-yl)phenyl)carbamate (3 g, 7.19 mmol), DCM (50 mL) and TFA (12.5mL) and a stirbar. The solution was stirred for 1 h at room temperature. The reaction mixture
was diluted with H2O (100 mL), and the aqueous phase was extracted with DCM (50 mL) three
times. The pH of aqueous phase was adjusted to 7~8, then the aqueous phase was extracted with
DCM (100 mL) three times. The combined organic layers were washed with saturated brines,
dried over sodium sulfate, filtered, and concentrated in vacuo resulted in 6-(4-aminophenyl)-5-
bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (2.1 g, 92.1%) as a yellow solid.

N-(4-(4-amino-5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)methacrylamide

A resealable reaction vial was charged with 6-(4-aminophenyl)-5-bromo-7-methyl-7Hpyrrolo[2,3-d]pyrimidin-4-amine (2.1 g, 6.62 mmol), pyridine (785 mg, 9.93 mmol), DCM (100
mL) and a stir bar before being evacuated and purged with nitrogen three times. Methacryloyl
chloride (757.3 mg, 7.28 mmol) was added slowly at 0 oC. Then the mixture was stirred for 2 h
at room temperature. The reaction mixture was diluted with H2O (100 mL), and the aqueous
phase was extracted with DCM (100 mL) three times. The combined organic layers were washed
with brines, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting crude
material was purified by silica gel chromatography (eluting with MeOH/DCM=1/40).
Concentration in vacuo resulted in N-(4-(4-amino-5-bromo-7-methyl-7H-pyrrolo[2,3-
d]pyrimidin-6-yl)phenyl)methacrylamide (1.8 g, 70.5%) as an off-white solid.

2-(4-bromo-2-fluorophenoxy)-4-methylpyrimidine

A round bottomed flask was charged with 4-bromo-2-fluorophenol (1.0 g, 5.24 mmol), 2-fluoro4-methylpyrimidine (704 mg, 6.28 mmol), Cs2CO3 (5.12 g, 15.7 mmol) and a stirbar. DMF (20
mL) was added, and the solution was stirred for 1 h at 100 oC. The reaction mixture was diluted
with H2O (100 mL), and the aqueous phase was extracted with ethyl acetate (100 mL) three
times. The combined organic layers were washed with saturated brines, dried over sodium
sulfate, filtered, and concentrated in vacuo. The resulting crude material was purified by HPLC.
Concentration in vacuo resulted in 2-(4-bromo-2-fluorophenoxy)-4-methylpyrimidine (1.48 g,
99.8 %) as an off-white amorphous solid.

2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine

A solution/mixture of 2-(4-bromo-2-fluorophenoxy)-4-methylpyrimidine (500.00 mg, 1.77
mmol), bis(pinacolato)diboron (672.75 mg, 2.65 mmol), KOAc (520 mg, 5.3 mmol) and
Pd(dppf)Cl2 (129.4 mg, 0.177 mmol) in DMF (10 mL) was stirred for 2 h at 80 oC under nitrogen
atmosphere. The resulting mixture was diluted with water and extracted with EA. The combined
organic layers were washed with brines, dried over anhydrous Na2SO4. After filtration, the
filtrate was concentrated under reduced pressure. The residue was purified by HPLC.
Concentration in vacuo resulted in 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)phenoxy)-4-methylpyrimidine (430 mg, 73.7%) as a yellow solid.

2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine

A resealable reaction vial was charged with N-(4-(4-amino-5-bromo-7-methyl-7H-pyrrolo[2,3-
d]pyrimidin-6-yl)phenyl)methacrylamide (100 mg, 0.259 mmol), 2-(2-fluoro-4-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-4-methylpyrimidine (102.6 mg, 0.310 mmol),
Pd(DtBPF)Cl2 (16.9 mg, 0.026 mmol), CsF (118 mg, 0.776 mmol), DMF (2 mL), H2O (0.25
mL) and a stir bar before being evacuated and purged with nitrogen three times. The mixture was
stirred for 1 h at 90 °C. The reaction mixture was diluted with H2O (10 mL), and the aqueousphase was extracted with DCM (10 mL) three times. The combined organic layers were washed
with brines, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting crude
material was purified by Pre-HPLC (Column: XBridge Prep C18 OBD Column, 19*150 mm,
5μm; Mobile Phase A: Water(10 mmol/L NH4HCO3), Mobile Phase B: ACN; Flow rate: 25
mL/min; Gradient: 25% B to 50% B in 7 min, 50% B; Wave Length: 254/220 nm; RT1(min):
6.5). Concentration in vacuo resulted in N-(4-(4-amino-5-(3-fluoro-4-((4-methylpyrimidin-2-
yl)oxy)phenyl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenyl)methacrylamide ( 27.2 mg,
20.6%) as an off-white solid. LC/MS(BAS1): [M+H]+= 510.20; tR =1.405 min. 1H NMR (400
MHz, DMSO-d6) δ 9.92 (s, 1H), 8.47 (d, J = 5.0 Hz, 1H), 8.21 (s, 1H), 7.79 – 7.72 (m, 2H), 7.38
– 7.28 (m, 3H), 7.22 – 7.14 (m, 2H), 7.10 (dd, J = 8.1, 2.1 Hz, 1H), 5.98 (s, 2H), 5.80 (s, 1H),
5.54 (d, J = 1.7 Hz, 1H), 3.59 (s, 3H), 2.42 (s, 3H), 1.95 (d, J = 1.2 Hz, 3H).

PAT

WIPO Patent Publication: WO2020231990A1 (and related family filings)

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020231990&_cid=P20-MUHRQT-01820-1

PAT

United States Patents: US11780845

PAT

US20230192709

https://patentscope.wipo.int/search/en/detail.jsf?docId=US399951539&_cid=P20-MUHRKD-96615-1

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References

[1]. Vivek Subbiah, et al. RLY-4008, the First Highly Selective FGFR2 Inhibitor with Activity across FGFR2 Alterations and Resistance Mutations. Cancer Discov. 2023 Sep 6;13(9):2012-2031. [Content Brief]

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Solangepras

DR ANTHONY MELVIN CRASTO Ph.D — Thu, 24 Sep 2026 02:38:16 +0000

Solangepras

CAS 2254706-21-1

MF C24H29F2N5O3 MW473.525 g/mol

ETHANONE, 1-(2-(4-(2,4-DIFLUOROPHENOXY)-1-PIPERIDINYL)-7,8-DIHYDRO-3-(((3R)-TETRAHYDRO-3-FURANYL)AMINO)PYRIDO(3,4-B)PYRAZIN-6(5H)-YL)-

1-(2-[4-(2,4-difluorophenoxy)piperidin-1-yl]-3-{[(3R)-oxolan-3-yl]amino}-7,8-dihydropyrido[3,4-b]pyrazin-6(5H)-yl)ethan-1-one
G protein-coupled receptor 6 (GCPR6) inverse agonist, antiparkinsonian, CVN 424, PHASE 3, Parkinson’s disease

Solangepras (developmental code name CVN-424, also spelled solengepras) is an investigational, orally active small molecule drug currently in Phase 3 clinical trials for the treatment of Parkinson’s disease. Developed by the biotech company Cerevance, it represents a potentially first-in-class non-dopaminergic therapy designed to improve motor control without the debilitating side effects often triggered by traditional dopamine replacements.

Mechanism of Action

Unlike standard Parkinson’s treatments (such as levodopa) that directly target and stimulate dopamine pathways, solangepras utilizes an innovative, highly targeted pathway:

GPR6 Inverse Agonist: It selectively targets the G protein-coupled receptor 6 (GPR6), an orphan receptor primarily localized in the striatopalidal medium spiny neurons of the basal ganglia.
Modulating the “Brake” Circuit: In Parkinson’s disease, the indirect brain circuit that inhibits unwanted movement acts as an overactive “brake”. By decreasing intracellular cyclic AMP (cAMP) levels, solangepras reduces this excessive inhibitory signaling.
Restoring Circuit Balance: It restores balance to the basal ganglia circuit, facilitating better motor function without causing dopamine-related side effects like levodopa-induced dyskinesia (involuntary movements).

Clinical Trial Status

Solangepras is being evaluated across different stages of Parkinson’s disease, shifting focus primarily toward combination therapy:

Clinical Trial / Phase	Treatment Type	Results & Focus
Phase 2 (ASCEND Trial)	Monotherapy (Early, untreated patients)	Missed its primary endpoint. It did not demonstrate superior efficacy alone for early-stage patients, though it showed positive trends in non-motor symptoms.
Phase 2 (NCT04191577)	Adjunctive Therapy (Combination with levodopa)	Successful. Demonstrated a clinically meaningful reduction in daily “OFF time” (periods when standard medication wears off and symptoms return) and increased “ON time” without dyskinesia.
Phase 3 (ARISE Trial)	Adjunctive Therapy	Ongoing. Dosing began late last year to assess efficacy in 330 patients experiencing motor fluctuations, focusing on long-term daily OFF-time reduction.

Chemical & Research Profile

In scientific and laboratory settings, the compound is detailed as follows:

Chemical Name: 1-[2-[4-(2, 4-difluorophenoxy)piperidin-1-yl]-3-[[(3R)-oxolan-3-yl, amino]-7,8-dihydro-5H-pyrido[3, 4-b, pyrazin-6-yl]ethanone.
Molecular Formula: C₂₄H₂₉F₂N₅O₃ with a molecular weight of 473.52 g/mol.
Identifiers: Registered under CAS number 2254706-21-1

OriginatorCerevance
ClassAntiparkinsonians; Cyclic ethers; Fluorobenzenes; Furans; Ketones; Phenyl ethers; Piperidines; Pyrazines; Pyridines; Small molecules
Mechanism of ActionGPR6 protein inhibitors
Phase IIIParkinson’s disease
20 Mar 2026Chemical structure information added.
05 Dec 2025Efficacy data from a phase II ASCEND trial in Parkinson’s disease released by Cerevance
01 Apr 2025Adverse events and efficacy data from a phase II ASCEND trial in Parkinson’s disease released by Cerevance

Solangepras (INNTooltip International Nonproprietary Name; developmental code name CVN-424), or solengepras (USANTooltip United States Adopted Name), is an inverse agonist of the orphan G protein-coupled receptor 6 (GPR6) which is under development for the treatment of Parkinson’s disease.^[1][2][3][4] It is a small molecule and is taken by mouth.^[1][4] Solangepras produces hyperlocomotion and reverses haloperidol-induced catalepsy in rodents.^[4] It is being developed by Cerevance.^[1][2] As of October 2024, solangepras is in phase 3 clinical trials.^[1][2]

PATENTS

WO 2015/095728 A1 (PCT Application)

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2015095728&_cid=P21-MUEWTH-04566-1

[00653] Example 149 (5)-l-(2-(4-(2,4-difluorophenoxy)piperidin-l-yl)-3-(tetrahydrofuran-3-ylamino)-7,8-dihydropyrido[3,4-/?]pyrazin-6(5H)-yl)ethanone

[00654] To a solution of (5)-2-(4-(2,4-difluorophenoxy)piperidin-l-yl)-N-(tetrahydrofuran-3-yl)pyrido[3,4-Z?]pyrazin-3-amine (2.0 g, 4.68 mmol) in dioxane:acetone (50 ml; 1.5: 1) was added Ac₂0 (4.8 mL, 50.9 mmol) and Pd/C (400 mg, 3.76 mmol); then, the reaction was stirred at 60 °C under ¾ atmosphere (345 kPa) for 72 h. The mixture was filtered through a pad of Celite and washed with EtOAc. The reaction solution was diluted with EtOAc (50 mL) and poured into sat. aqueous aHC0₃ (50 ml), then washed with brine (2 x 30 mL). The organic layer was dried over Na₂S0₄ and concentrated to give the crude product, which was purified by flash column chromatography to yield the title compound (193.4 mg) as an off-white solid. ^XH NMR (400 MHz, DMSO-i/6) δ ppm 1.88-1.89 (m, 4H), 2.05-2.09 (m, 4H), 2.60-2.90 (m, 4H), 3.30-3.40 (m, 4H), 3.55-3.57 (m, 1H), 3.68-3.74 (m, 2H), 3.85-3.95 (m, 2H), 4.38-4.51 (m, 4H), 5.91 (dd, J= 6.0, 4.4 Hz, 1H), 7.01 (m, 1H), 7.25-7.31 (m, 2H); ESI-MS m/z [M+H]⁺ 474.3.

PAT

US 10,406,157 B2 / US 2018/0360831 A1

https://patentscope.wipo.int/search/en/detail.jsf?docId=US235206887&_cid=P21-MUEX2M-11550-1.

Example 1: (R)-1-(2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-3-((tetrahydrofuran-3-yl)amino)-7,8-dihydropyrido[3,4-b]pyrazin-6(5H)-yl)ethan-1-one

To a flask charged with (R)-2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-N-(tetrahydrofuran-3-yl)pyrido[3,4-b]pyrazin-3-amine (16 g, 37.4 mmol) in HOAc (80 mL) and THF (80 mL) was added acetic anhydride (17.66 mL, 187 mmol) under nitrogen. Palladium on carbon (10%, Aldrich 205699-10G, Lot #MKBZ3284V) (3.19 g, 2.99 mmol) was added under nitrogen. The flask was connected to a hydrogen-filled balloon and was evacuated with house vacuum and refilled with hydrogen eight times. The reaction mixture was stirred under hydrogen for 40 hours and then filtered through a pad of CELITE®, taking care not to let the cake dry out. The flask and filter cake were rinsed with EtOAc (48 mL), methanol (48 mL) and EtOAc (48 mL). The filtrate was concentrated in vacuo to remove THF, EtOAc and methanol (bath temperature ≤40° C.). The solution was diluted with heptane (480 mL) and reconcentrated in vacuo to azetrope off HOAc (bath temperature ≤45° C.). The residue was taken up in iPrOAc (320 mL), washed with 10 wt % aqueous K2CO ₃ (320 mL, 230 mmol) (pH 13 before wash, pH 10 after wash) and brine (240 mL, pH 7 after wash), dried over MgSO ₄, concentrated in vacuo and dried under house vacuum for at least 1 hour to give a light yellow solid (16.71 g). The crude product was taken up in ethanol (84 mL) and was heated in an oil bath with stirring. After the solids were dissolved, the solution was allowed to cool slowly in the oil bath with stirring, during which a precipitate started to form, and the solution became cloudy. The mixture was allowed to cool to ambient temperature in the oil bath and was stirred overnight. Following recrystallization, the white solid was collected by vacuum filtration, rinsed with ice-cold ethanol, and dried under high vacuum to give the title compound as a white solid (13.34 g, 75%). ¹H NMR (500 MHz, DMSO-d ₆) δ ppm 1.81-2.00 (m, 3H), 2.02-2.12 (m, 5H), 2.14-2.24 (m, 1H), 2.60 (t, J=5.61 Hz, 1H), 2.72 (t, J=5.86 Hz, 1H), 2.84-2.96 (m, 2H), 3.26-3.32 (m, 2H), 3.56 (dt, J=8.79, 5.13 Hz, 1H), 3.65-3.78 (m, 3H), 3.81-3.94 (m, 2H), 4.33-4.47 (m, 3H), 4.52 (tt, J=8.18, 4.03 Hz, 1H), 5.91 (dd, J=13.42, 6.10 Hz, 1H), 6.97-7.05 (m, 1H), 7.24-7.36 (m, 2H); ESI-MS m/z [M+H] ⁺ 474; mp 150° C. (DSC peak); chiral purity (via chiral column chromatography)>98% ee.

PAT

WO 2018/209255 / US 10,406,157 B2

PAT

WO 2025/160132

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References

Clinical data

Other names	Solengepras; CVN-424; CVN424
Routes of administration	Oral^[1]
Drug class	GPR6 inverse agonist
Identifiers
IUPAC name
CAS Number	2254706-21-1
PubChem CID	137359492
DrugBank	DB18958
ChemSpider	114869317
UNII	XO01711URG
KEGG	D12980
ChEMBL	ChEMBL4778540
Chemical and physical data
Formula	C₂₄H₂₉F₂N₅O₃
Molar mass	473.525 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES
InChI

“Solengepras”. AdisInsight. 21 October 2024. Retrieved 25 February 2025.
“Delving into the Latest Updates on CVN-424 with Synapse”. Synapse. 5 February 2025. Retrieved 25 February 2025.
Gros P, Garcia LA, Fox SH (2025). “Experimental Therapeutics in Parkinson’s Disease”. Neurologic Clinics. 43 (2): 399–426. doi:10.1016/j.ncl.2024.12.013. PMID 40185528.
Brice NL, Schiffer HH, Monenschein H, Mulligan VJ, Page K, Powell J, et al. (June 2021). “Development of CVN424: A Selective and Novel GPR6 Inverse Agonist Effective in Models of Parkinson Disease”. The Journal of Pharmacology and Experimental Therapeutics. 377 (3): 407–416. doi:10.1124/jpet.120.000438. PMID 33795395.

External links

Solengepras (CVN424) – Cerevance

////////////solangepras, anax labs, G protein-coupled receptor 6 (GCPR6) inverse agonist, antiparkinsonian, CVN 424, PHASE 3, Parkinson’s disease

#solangepras, #anax labs, #G protein-coupled receptor 6 (GCPR6) inverse agonist, #antiparkinsonian, #CVN 424, #PHASE 3, #Parkinson’s disease

Soclenicant

DR ANTHONY MELVIN CRASTO Ph.D — Tue, 22 Sep 2026 02:35:27 +0000

Soclenicant

CAS 1020634-41-6

MFC24H26N4O3 MW418.5 g/mol

6-(2,3-dihydro-1H-inden-2-ylamino)-1-ethyl-3-(morpholine-4-carbonyl)-1,8-naphthyridin-4-one

6-[(2,3-dihydro-1H-inden-2-yl)amino]-1-ethyl-3-(morpholine4-carbonyl)-1,8-naphthyridin-4(1H)-one
nicotinic acetylcholine receptor negative allosteric, modulator, anxiolytic, BNC210, IW-2143, BNC 210, IW 2143, QP49AY37OY

BNC-210 is under investigation in clinical trial NCT04951076 (A Phase 2b Study of BNC210 Tablet Formulation in Adults With Post-traumatic Stress Disorder (PTSD)).

Soclenicant (also known by its developmental code names BNC210 and IW-2143) is an investigational, orally active small-molecule drug developed to treat anxiety and stressor-related disorders. It is chemically classified as a synthetic heterocyclic compound based on a 1,8-naphthyridin-4-one scaffold.

Unlike traditional anxiety medications like benzodiazepines, it is designed to provide targeted relief without causing side effects like sedation, motor impairment, memory issues, or physical dependence.

Mechanism of Action

Soclenicant functions as a highly selective negative allosteric modulator (NAM) of the α7-nicotinic acetylcholine receptor (α₇ nAChR).

It works by tuning down the electric currents induced by neurotransmitters like acetylcholine and nicotine specifically at this receptor subtype.
In preclinical rodent models, it demonstrated strong acute anxiolytic (anti-anxiety), anti-stress, and antidepressant-like behaviors.

Clinical Development Status

The drug was originally engineered by Bionomics and saw collaborative development alongside entities like Ironwood Pharmaceuticals. Bionomics was acquired by Neuphoria Therapeutics in late 2024.

However, the drug’s clinical pipeline faced a massive setback:

Social Anxiety Disorder (SAD) Flop: In late 2025, a Phase 3 clinical trial evaluating a single 225-mg dose of soclenicant for the acute treatment of social anxiety disorder failed to meet its primary endpoint. It showed no statistically significant improvement in patient distress levels during a public speaking challenge compared to a placebo.
Current Status: Following the Phase 3 failure, Neuphoria Therapeutics discontinued the social anxiety program and triggered a strategic corporate review. While it has historically been granted FDA Fast Track designation for generalized anxiety disorder (GAD) and explored for Post-Traumatic Stress Disorder (PTSD), the future development pipeline remains uncertain

Soclenicant (INNTooltip International Nonproprietary Name),^[3] also known by its developmental code names BNC210 and IW-2143, is an antinicotinic agent which is under development for the treatment of anxiety disorders such as social phobia and generalized anxiety disorder, as well as for treatment of agitation, post-traumatic stress disorder (PTSD), and depressive disorders.^[1]^[4]^[5] It is taken by mouth.^[4]

The drug acts as a highly selective negative allosteric modulator (NAM) of the α₇-nicotinic acetylcholine receptor (α₇-nAChR).^[1]^[6]^[4]^[5] It produces anxiolytic-, anti-stress-, and antidepressant-like effects without causing sedation, memory or motor impairment, or physical dependence in rodents.^[6] Chemically, soclenicant is a synthetic heterocyclic small-molecule compound based on a 1,8-naphthyridin-4-one scaffold, bearing amide and amine functionalities.^[7]

Soclenicant is being developed by Bionomics.^[4] It has also been developed by Ironwood Pharmaceuticals and EmpathBio.^[4]^[5] Bionomics was acquired by Neuphoria Therapeutics in December 2024.^[4] As of December 2024, soclenicant is in phase 3 clinical trials for anxiety disorders, phase 2 trials for agitation and PTSD, and no recent development has been reported for depressive disorders.^[4]^[5] The drug received Fast Track designation from the United States Food and Drug Administration (FDA) in 2019.^[8] It was first described in the literature, in a conference abstract, by 2007.^[2]

Efficacy of BNC210 in Acute, As-needed Treatment of Anxiety in Social Anxiety Disorder – 1CTID:NCT06510504Phase:Phase 3Status:CompletedDate:2026-05-19
A Phase 2 Study of BNC210 for the Acute Treatment of Social Anxiety DisorderCTID:NCT05193409Phase:Phase 2Status:CompletedDate:2025-03-18
A Phase 2b Study of BNC210 Tablet Formulation in Adults With Post-Traumatic Stress Disorder (PTSD)CTID:NCT04951076Phase:Phase 2Status:CompletedDate:2025-02-06
Phase II Study of BNC210 in PTSDCTID:NCT02933606Phase:Phase 2Status:CompletedDate:2023-02-27
A Study of BNC210 in Elderly Patients With AgitationCTID:NCT03548194Phase:Phase 2Status:CompletedDate:2020-07-09

SYNTHETIC

The Pathway to Proof‐of‐Concept for BNC210, a Negative Allosteric Modulator of the Alpha‐7 Nicotinic Acetylcholine Receptor (nAChR), for Treatment of Psychiatric DiseasePublication Name:Clinical Pharmacology in Drug DevelopmentPublication Date:2025-09-27PMCID:PMC12856972PMID:41014090DOI:10.1002/cpdd.1609
BNC210, a negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor, demonstrates anxiolytic- and antidepressant-like effects in rodentsPublication Name:NeuropharmacologyPublication Date:2024-03-15PMID:38185416DOI:10.1016/j.neuropharm.2024.109836
BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disordersPublication Name:Expert Opinion on Investigational DrugsPublication Date:2023-03-20PMID:36927202DOI:10.1080/13543784.2023.2192922
Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety DisorderPublication Name:Biological PsychiatryPublication Date:2020-05-15PMCID:PMC7198974PMID:32107005DOI:10.1016/j.biopsych.2019.12.013

INTERMEDIATES

PAT

WO2012151640

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2012151640&_cid=P11-MUC1WO-96887-1

N-1

1-Ethyl-6-(indan-2-ylamino)-4-oxo-1,8-naphthyridine-3-cal-boxylic acid:

Ethanol (42.0 L) was added to reactor at 25-30 °C, followed by ethyl 1 -ethyl-6-(indan-2-ylamino)-4-oxo- 1 ,8-naphthyridine-3-carboxylate (4.20 kg) with stirring. Aqueous sodium hydroxide solution (prepared by dissolving 3.4 kg of sodium hydroxide into 42.0 L of water) was added to reaction mixture at 25-30 °C and reactor temperature was raised to 50-55 °C. The reaction mixture was stirred at 50-55 °C for 2 h and reaction progress was monitored by TLC. After completion of hydrolysis (~3 h), the reaction mass was cooled to 25-30 °C and pH was adjusted to 5-6 by addition of citric acid solution (prepared by dissolving 5.2 kg of citric acid in 47.0 L of water). The reaction mass was stirred for 20-25 minutes at 25-30 °C and filtered, the solid mass was washed with water (42.0 L) and acetone (21 .0 L). The material was transferred to drying trays and dried with hot-air dryer at 70-75 °C until the water content decreased to 1 .0%, yielding the desired compound (90%) as a solid. Ή NMR (DMSO-d6, 500MHz): 1.40(3H, t, J = 7.0Hz), 2.86-2.90(2H, m), 3.37-3.41 (2H, m), 4.38(1 H, d, J = 5.5 Hz), 4.62(2H_? q, J = 7.0Hz), 7.06( 1 H, d, J = 6.0Hz), 7.17-7.18(2H. m), 7.26-7.27(2H, m), 7.60(1 H, d, J = 2.5 Hz), 8.52(1 H, d, J =2.0 Hz), 9.00 (1 H, s), 15.30(1 H, s). ¹³C NMR (DMSO-d6, 125MHz): 15.19, 46.92, 52.92, 107.12, 109.42, 121.58, 124.63, 126.41 , 140.1 1 , 141.12, 143.33, 143.43, 145.93, 166.12, 177.53.

FINAL

6-(2 ,3-Dihydro-1H-inden-2-ylamino)-1-ethyl-3-(morpholin-4-ylcarbonyl)-1,8-naphthyridin-4(1H)-one

Step 1 : 160.0 L of dichloromethane (water content should be no more than 0.1%), 1 -ethyl-6-(indan-2-ylamino)-4-oxo-l ,8-naphthyridine-3-carboxylic acid (4.0 kg) and triethylamine (3.5 kg) were sequentially added to reactor at 25-30°C under nitrogen atmosphere and the reaction mixture was cooled to 10-15 °C. Pivaloyl chloride (4.1 kg) was slowly added to reaction mixture keeping the reaction temperature at 10-15°C. Then, the reaction temperature was raised to 25-30 °C and stirred. The reaction progress was monitored by TLC for disappearance of starting material. After completion of reaction (3-4 h), the reaction mixture was again cooled to 15-20 °C and morpholine (6.0 kg) was added with stirring, keeping the reaction temperature at 1 5-20 °C. N,N-Dimethyl-4-aminopyridine ( 194 g) and DMF (2.0 L) were added to the reaction mixture at 15-20 °C and heated to reflux. The reaction progress was monitored by TLC for the disappearance of intermediate pivaloyl ester and found to be complete within 12-13 h. The reaction mixture was cooled to 15-20 °C and then quenched by addition of aqueous sodium bicarbonate solution (prepared by dissolving 5.6 kg of sodium bicarbonate in 56.0 L of water) with stirring. The organic layer was separated and washed with aqueous sodium chloride solution (prepared by dissolving 23.0 kg of sodium chloride in 57.0 L of water). The organic layer was separated and dried by stirring with anhydrous sodium sulphate (4.0 kg). The organic layer was filtered through a Nutsche filter and the sodium sulphate was washed with dichloromethane. The filtrate was transferred into a flask and evaporated under vacuum below 40 °C. The resulting material in the flask was cooled to 25-30 °C and suspended in diethyl ether (40.0 L). The solid separated was filtered using a Nutsche filter and washed with diethyl ether (8.0 L) and the isolated wet solid was dissolved in dichloromethane (20.0 L). The solution (10.0 L) was then filtered through a silica gel plug (10.0 kg) with dichloromethane (36.0 L), followed by 10 L of 10% methanol in dichloromethane. The silica gel filter was dried under vacuum. Similarly, the remaining portion of solution ( 10.0 L) was filtered through another silica gel plug (10.0 kg). The combined filtrate was evaporated under vacuum below 40 °C and then residual solid was suspended in ethyl acetate (20.0 L) with stirring at 25-30 °C. The solid separated was filtered through Nutsche filter and washed with ethyl acetate (4.0 L). The filter was dried under vacuum and then material was transferred to drying trays and dried at 40-45 °C. Yield (2.36 Kg). ¹H NMR (DMSO-d6, 500MHz): 1.49 (3H, t, J = 7.2Hz), 2.91 (2H, dd, J = 3.5Hz, 16.0 Hz), 3.42-3.47(4H, m), 3.80(6H, s), 4.25-4.26(1H, bd), 4.40-4.48(3H, m), 7.20-7.25(4H, m),

7.82(1H, d, J = 3.0Hz), 8.09 (1H, s), 8.18(1 H, d, J = 3.0Hz). ¹³C NMR (CDCl₃, 150MHz): 15.27, 39.87, 43.05, 46.66, 48.09, 53.93, 66.80, 67.40, 1 13.27, 1 16.71 , 123.22, 124.92, 126.78, 140.87, 141 .46, 141.83, 141.90, 143.84, 166.27, 173.38.

PAT

WO2014138772

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2014138772&_cid=P11-MUC1WO-96887-2

United States Patent Number 8,293,737, the entirety of which is incorporated herein by reference, describes certain 1,8-naphthyridin-4(1H)-one compounds which are useful as anxiolytic agents. Such compounds include 1-ethyl-6-(indan-2-ylamino)-3-(morphoIine-4-carbonyl)-1 ,8-naphthyridin-4-one (compound 1).

PAT

Novel anxiolytic compoundsPublication Number:EP-2540722-A1Priority Date:2006-10-16
Novel anxiolytic compoundsPublication Number:WO-2008046135-A1Priority Date:2006-10-16
Novel anxiolytic compoundsPublication Number:EP-2540722-B1Priority Date:2006-10-16Grant Date:2016-06-08
Anxiolytic compoundsPublication Number:US-10954231-B2Priority Date:2006-10-16Grant Date:2021-03-23
Anxiolytic compoundsPublication Number:US-10233181-B2Priority Date:2006-10-16Grant Date:2019-03-19
Novel anxiolytic compoundsPublication Number:US-2013012509-A1Priority Date:2006-10-16
Novel anxiolytic compoundsPublication Number:US-2018105524-A1Priority Date:2006-10-16
Novel anxiolytic compoundsPublication Number:US-2017183347-A1Priority Date:2006-10-16
Anxiolytic compoundsPublication Number:US-8906912-B2Priority Date:2006-10-16Grant Date:2014-12-09

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References

Hampsey E, Perkins A, Young AH (April 2023). “BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disorders”. Expert Opin Investig Drugs. 32 (4): 277–282. doi:10.1080/13543784.2023.2192922. PMID 36927202.
Andriambeloson, E., Wagner, S., Huyard, B., Sleebs, B., Quasi, N., Bui, C., … & Street, I. (2007, September). BNC210: A Novel Compound with Potent Anxiolytic Activity. In Behavioral Pharmacology (Vol. 18, pp. S16–S16). https://neurofit.com/im-posters/2008-ebps-bnc210.pdf
https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl132.pdf#page=198 soclenicantum soclenicant 6-[(2,3-dihydro-1H-inden-2-yl)amino]-1-ethyl-3-(morpholine4-carbonyl)-1,8-naphthyridin-4(1H)-one nicotinic acetylcholine receptor negative allosteric modulator, anxiolytic
“BNC 210”. AdisInsight. 30 December 2024. Retrieved 22 February 2025.
“Delving into the Latest Updates on BNC-210 with Synapse”. Synapse. 23 January 2025. Retrieved 22 February 2025.
O’Connor SM, Sleebs BE, Street IP, Flynn BL, Baell JB, Coles C, Quazi N, Paul D, Poiraud E, Huyard B, Wagner S, Andriambeloson E, de Souza EB (March 2024). “BNC210, a negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor, demonstrates anxiolytic- and antidepressant-like effects in rodents”. Neuropharmacology. 246 109836. doi:10.1016/j.neuropharm.2024.109836. hdl:11343/348285. PMID 38185416.
“CID 24772165”. PubChem. Retrieved 5 January 2026.
Bionomics Limited Press Release (2019-11-04). “Bionomics Announces Fast Track Designation Granted by U.S. FDA to BNC210 Development Program for the Treatment of PTSD”. BusinessWire. Retrieved 2020-09-09.

Clinical data

Other names	BNC210; BNC-210; IW2143; IW-2143
Routes of administration	Oral
Drug class	α₇-Nicotinic acetylcholine receptor negative allosteric modulator
ATC code	None
Legal status
Legal status	Investigational
Pharmacokinetic data
Bioavailability	69.4% (rat)^[1]^[2]
Protein binding	70–88%^[1]^[2]
Elimination half-life	6.2 hours (rat)^[1]^[2]
Identifiers
IUPAC name
CAS Number	1020634-41-6
PubChem CID	24772165
UNII	QP49AY37OY
KEGG	D13360
Chemical and physical data
Formula	C₂₄H₂₆N₄O₃
Molar mass	418.497 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES
InChI

//////soclenicant, anax labs, nicotinic acetylcholine receptor negative allosteric, modulator, anxiolytic, BNC210, IW-2143, BNC 210, IW 2143, QP49AY37OY

#soclenicant, #anax labs, #nicotinic acetylcholine receptor negative allosteric, #modulator, #anxiolytic, #BNC210, #IW-2143, #BNC 210, #IW 2143, #QP49AY37OY

Simedeutirom

DR ANTHONY MELVIN CRASTO Ph.D — Sun, 20 Sep 2026 02:33:42 +0000

Simedeutirom

CAS 2403721-24-2

MF C18H92H3Cl2N6O4 MW 450.25

2-[3,5-Dichloro-4-[[(7R)-2,5,6,7-tetrahydro-7-(methyl-d3)-1-oxo-1H-cyclopenta[d]pyridazin-4-yl]oxy]phenyl]-2,3,4,5-tetrahydro-3,5-dioxo-1,2,4-triazine-6-carbonitrile

2-[3,5-dichloro-4-[[(7R)-1-oxo-7-(trideuteriomethyl)-2,5,6,7-tetrahydrocyclopenta[d]pyridazin-4-yl]oxy]phenyl]-3,5-dioxo-1,2,4-triazine-6-carbonitrile

2-(3,5-dichloro-4-{[(7R)-7-(2H3)methyl-1-oxo-2,5,6,7-tetrahydro-1Hcyclopenta[d]pyridazin-4-yl]oxy}phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile
thyroid hormone beta receptor agonist, 4G7Z7KQ8GV

Simedeutirom is a selective, synthetic, deuterium-labeled thyroid hormone receptor beta (THR-β) agonist. It features a novel cyclopenta $d$ 𝑑pyridazine core and is primarily utilized as a specialized tool compound in the biochemical research of metabolic diseases, including obesity, type 2 diabetes mellitus, and related metabolic disorders.

Core Structural & Pharmacological Profile

Target Selectivity: It functions as a potent agonist specifically targeting the thyroid hormone receptor beta (THR-β), with an half-maximal effective concentration (EC₅₀) ranging between 0.1 to 1 μM. THR-β activation plays a foundational role in modulating hepatic lipid metabolism, lowering cholesterol, and regulating overall energy expenditure without heavily triggering the alpha receptor (THR-α), which is associated with adverse cardiac side effects.
Deuterium Labeling: The compound incorporates deuterium (a stable isotope of hydrogen) into its chemical architecture, specifically modified as a trideuteriomethyl group. Isotopic modification or “deuteration” is an established medicinal chemistry approach frequently evaluated to slow metabolic clearance and increase structural stability.
Chemical Identifiers:
- Molecular Formula: C₁₈H₁₂Cl₂N₆O₄
- Molecular Weight: 450.25 g/mol
- CAS Registry Number: 2403721-24-2
- FDA UNII Code: 4G7Z7KQ8GV

Research Context & Status

Simedeutirom is categorized under the International Nonproprietary Name (INN) database. However, it is fundamentally classified for in vitro and in vivo research use only. It has not been approved for clinical therapeutic use or direct distribution to patients.

PAT

WO 2019240938

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019240938&_cid=P11-MU978W-22170-1

PAT

US20250179050

https://patentscope.wipo.int/search/en/detail.jsf;jsessionid=B04410250978C4E0B0F323AD027AC8B8.wapp1nB?docId=US457344867&_cid=P11-MU96YW-11754-1

Example 1 Preparation of crude free base of compound I

Step 1: preparation of compound b

N-(3,5-dichloro-4-((7-(methyl-d3)-1-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [d]pyridazin-4-yl)oxy)phenyl)benzamid

4.62 kg of compound a was completely dissolved in 25.0 L of glacial acetic acid and added to a 100 L reaction kettle, 3300 g of benzoic anhydride was added, and the mixture was reacted at room temperature for about 4 hours with stirring turned on. The reaction was monitored by TLC (n-hexane/ethyl acetate=5/1) until compound a disappeared, then 2722 g of anhydrous sodium acetate was additionally added and the temperature was increased to 120° C. for a reaction under stirring for about 18 hours.

The reaction solution was cooled to 60-65° C., and concentrated under reduced pressure to remove most of the acetic acid. After the concentration was completed, 10 L of anhydrous ethanol was added to the residue and uniformly mixed. Then the mixed solution was slowly added to 250 L of water, while maintaining the rapid stirring, and a large amount of solid precipitated during the addition, and stirring was continued for about 0.5 hours after the addition, followed by centrifugation. The filter cake was washed with purified water (20 L×2) to give compound b in 100% yield, which went directly to the next step.

1H NMR (400 MHZ, DMSO) δ 12.07 (s, 1H), 10.55 (s, 1H), 8.04 (s, 2H), 7.98-7.95 (m, 2H), 7.63-7.50 (m, 3H), 3.29-3.25 (m, 1H), 3.02-2.90 (m, 2H), 2.39-2.36 (m, 1H), 1.75-1.72 (m, 1H).

LCMS m/z=433.1 [M+1]+

Step 2: preparation of compound c

4-(4-amino-2,6-dichlorophenoxy)-7-(methyl-d3)-2,5,6,7-tetrahydro-1H-cyclopenta [d]pyridazin-1-on

To a 100 L reaction kettle, 5.76 kg of the crude compound b from the previous step, a potassium hydroxide solution (2606 g KOH dissolved in 19.5 L of purified water) and 6.0 L of anhydrous ethanol were added under stirring. After the complete addition, the mixture was heated to reflux and reacted for about 16 hours, and the raw material was controlled for a complete reaction.

The temperature was reduced to 25° C., 30 L of water was added, the pH was adjusted to 8-9 with an ammonium chloride solid, and 35.0 L of ethyl acetate was added and stirred. The solution was phase-separated. The aqueous phase was extracted with ethyl acetate (15.0 L×2). The organic phases were combined and washed with a 5% aqueous sodium chloride solution (25 L×2). The organic phase was dried over 3.0 Kg of anhydrous sodium sulfate, filtered, and concentrated until no significant distillate flowed out, so as to obtain a crude product.

The crude product and 7.0 L of an aqueous 10% dioxane solution were heated for complete dissolution, cooled to room temperature, and crystallized with stirring for about 16 hours, followed by filtration to obtain a wet product, which was repeated purified twice and dried under vacuum at 50° C. for about 12 hours to give 1507 g of compound c.

1H NMR (400 MHZ, DMSO) δ 11.98 (s, 1H), 6.67 (m, 2H), 5.60 (s, 2H), 3.30-3.19 (m, 1H), 3.03-2.93 (m, 1H), 2.90-2.70 (m, 1H), 2.35 (m, 1H), 1.69 (m, 1H).

LCMS m/z=329.0 [M+1]+

Step 3: preparation of compound d

(R)-4-(4-amino-2,6-dichlorophenoxy)-7-(methyl-d3)-2,5,6,7-tetrahydro-1H-cyclopenta [d]pyridazin-1-one

3298 g of racemate c was subjected to chiral resolution to give, two optical isomers from separation:

Compound d (retention time: 1.583 min, 1230 g, off-white solid, ee %=99.60%, yield 37.3%); and compound d-1 (retention time: 1.926 min, 1255 g, off-white solid, ee %=99.76%, yield 38.1%).

Resolution conditions:

Instrument: MG III preparative SFC; column: Whelk 01 (S, S), 300× 50 mm I.D., 10 um; mobile phase: A: CO2, B: methanol; gradient: B 40%; flow rate: 200 mL/min; back pressure: 100 bar; column temperature: 38° C.; wavelength: 220 nm; period: 4.5 min; sample preparation: the racemate was dissolved in methanol/dichloromethane to achieve 50 mg/ml; and injection: 17 ml/injection.

Compound d

1H NMR (400 MHZ, DMSO) δ 11.98 (s, 1H), 6.67 (s, 2H), 5.60 (s, 2H), 3.30-3.19 (m, 1H), 3.03-2.93 (m, 1H), 2.90-2.70 (m, 1H), 2.35 (dtd,1H), 1.69 (ddt, 1H).

LCMS m/z=329.1 [M+1]+

Compound d-1

1H NMR (400 MHZ, DMSO) δ 11.98 (s, 1H), 6.68 (d, 2H), 5.60 (s, 2H), 3.29-3.18 (m, 1H), 2.97 (tdd, 1H), 2.90-2.72 (m, 1H), 2.35 (dtd, 1H), 1.69 (ddt, 1H).

LCMS m/z=329.0 [M+1]+

Step 4: preparation of compound e

Ethyl(R,Z)-(2-cyano-2-(2-(3,5-dichloro-4-((7-(methyl-d3)-1-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [d]pyridazin-4-yl)oxy)phenyl) hydrazineylidene) acetyl) carbamate

To a 100 L reaction kettle, 16.0 kg of acetic acid, 4.0 kg of purified water and 2.0 kg of compound d were added with stirring. The temperature was reduced to 0+5° C., then 2.36 kg of hydrochloric acid was added, and after the addition, the temperature was maintained at 0+5° C. with stirring for about 20 minutes. A sodium nitrite solution (0.5 kg of sodium nitrite dissolved in 1.0 kg of purified water) was dropwise added with the temperature being controlled at 0+5° C., and after the addition, the temperature was maintained at 0+5° C. for reaction for 2 hours. The temperature was controlled at 5+5° C. and a sodium acetate solution (1.5 kg of sodium acetate dissolved in 6.0 kg of purified water) was added dropwise, then 0.99 kg of N-cyanoacetourethane was added, and then the temperature was increased to 10+5° C. for a reaction for about 2 hours. Then a sample was taken for HPLC monitoring, after which time samples were taken at each about 2-hour interval, and the reaction was not stopped until the content of compound d was determined by HPLC to be≤1.0%.

After the completion of the reaction, the temperature was controlled to 10+5° C., and 30.0 kg of purified water was added to the reaction kettle. After the addition, the temperature was controlled at 10+5° C. with stirring continued for 1 hour, followed by filtration, and the cake was washed with 3.0 kg of purified water. The filter cake and 12.6 kg of anhydrous ethanol were added to a 100 L reaction kettle, heated to 50±5° C., and stirred for about 1 hour. The mixture was cooled to 20±5° C., stirred for 0.5 hours and filtered, and the filter cake was washed once with 1.26 kg of anhydrous ethanol.

The filter cake was dried at 55+5° C. with vacuum≤−0.07 MPa for about 17 hours, and compound e was obtained and collected, weighing 2.6327 kg.

1H NMR (400 MHZ, DMSO) δ 12.08 (d, 2H), 10.88 (s, 1H), 7.99 (s, 2H), 4.21 (q, 2H), 3.30-3.17 (m, 1H), 3.08-2.95 (m, 1H), 2.95-2.80 (m, 1H), 2.38 (ddd, 1H), 1.78-1.63 (m, 1H), 1.28 (t, 3H).

LCMS m/z=496.1 [M+1]+

Step 5: preparation of compound of formula I

(R)-2-(3,5-dichloro-4-((7-(methyl-d3)-1-oxo-2,5,6,7-tetrahydro-1H-cyclopenta [d]pyridazin-4-yl)oxy)phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile

To a 100 L reaction kettle, 12.40 kg of N,N-dimethylacetamide, 2.6269 kg of compound e and 0.54 kg of sodium acetate were added with stirring. After the addition, the temperature was increased and the internal temperature was maintained at 115+5° C. for a reaction for about 2 hours. Then a sample was taken for HPLC monitoring, after which time samples were taken at each about 2-hour interval, and the reaction was not stopped until the content of compound e was determined by HPLC to be≤1.0%.

After the completion of the reaction, the temperature was reduced to 60±5° C., 0.788 kg of purified water was added to the reaction solution, and after the addition, the reaction solution was filtered while still hot and quickly added to 13.66 kg of purified water, and the temperature was lowered to 10+5° C. After filtration, the filter cake was added to 20 L of dimethyl sulfoxide and warmed for complete dissolution. 800 L of acetone was added and stirred for 0.5 to 1 h, and then filtered. The filter cake was dried at 55+5° C. with vacuum≤−0.07 MPa for about 20 hours to give the amorphous form of the compound of formula (I), weighing 1.56 kg.

1H NMR (400 MHZ, DMSO) δ 13.26 (s, 1H), 12.09 (s, 1H), 7.79 (s, 2H), 3.32-3.24 (m, 1H), 3.10-2.99 (m, 1H), 2.96-2.88 (m, 1H), 2.45-2.31 (m, 1H), 1.77-1.69 (m, 1H).

LCMS m/z=450.0 [M+1]+.

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References

Method for preparing (r)-1,4-dichloro-5-(methyl-d3)-6,7-dihydro-5h-cyclopenta[d]pyridazinePublication Number:WO-2025055949-A1Priority Date:2023-09-12
Polymorph as thyroid hormone receptor agonists and use thereofPublication Number:WO-2023147752-A1Priority Date:2022-02-07
Preparation method of pyridazinone derivative, and intermediate thereofPublication Number:TW-202342457-APriority Date:2022-02-07
Preparation method of pyridazinone derivative, and intermediate thereofPublication Number:WO-2023147779-A1Priority Date:2022-02-07
Polymorph as thyroid hormone receptor agonists and use thereofPublication Number:EP-4477652-A1Priority Date:2022-02-07

////////simedeutirom, anax labs, thyroid hormone beta receptor agonist, 4G7Z7KQ8GV

#simedeutirom, #anax labs, #thyroid hormone beta receptor agonist, #4G7Z7KQ8GV

Silevertinib

DR ANTHONY MELVIN CRASTO Ph.D — Fri, 18 Sep 2026 02:34:14 +0000

Silevertinib

CAS 2607829-38-7

MF C30H30ClFN6O2 MW561.0 g/mol

(E)-N-[4-(3-chloro-2-fluoroanilino)-7-[2-[(1R,5S)-3-methyl-3-azabicyclo[3.1.0]hexan-1-yl]ethynyl]quinazolin-6-yl]-4-morpholin-4-ylbut-2-enamide

(2E)-N-[4-(3-chloro-2-fluoroanilino)-7-{[(1R,5S)-3-methyl-3-azabicyclo[3.1.0]hexan-1-yl]ethynyl}quinazolin-6-yl]-4-(morpholin-4-yl)but-2-enamide
epidermal growth factor receptor tyrosine kinase inhibitor, antineoplastic, BDTX-1535, BDTX 1535, CANCER, Glioblastoma, Black Diamond Therapeutics, RP9F537KVY

Silevertinib is an investigational new drug that is being evaluated by Black Diamond Therapeutics for the treatment of glioblastoma and non-small cell lung cancer.^[1] It is a EGFR protein tyrosine kinase inhibitor.^[1][2]

Silevertinib (formerly known as BDTX-1535) is an investigational, orally bioavailable, fourth-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) developed by Black Diamond Therapeutics. It is specifically engineered to be brain-penetrant and to target a broad spectrum of both classical and non-classical EGFR mutations, as well as resistance mutations, while sparing wild-type EGFR to reduce side effects.

Silevertinib is an orally bioavailable, brain penetrating, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, silevertinib selectively targets, irreversibly binds to, and inhibits the activity of various EGFR alterations and mutations, including certain intrinsic and acquired resistance mutations. This prevents EGFR-mediated signaling in susceptible tumor cells. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.

Mechanism of Action

Silevertinib works by selectively and irreversibly binding to mutated EGFR receptors. EGFR is a receptor tyrosine kinase that, when mutated, triggers uncontrolled cell division and tumor vascularization. By shutting down this signaling cascade, silevertinib induces tumor cell death and inhibits further growth.

A major clinical advantage of the drug is its ability to cross the blood-brain barrier, allowing it to target central nervous system (CNS) tumors and brain metastases that many traditional therapies fail to reach.

Target Indications & Clinical Data

Silevertinib is primarily being studied for two aggressive types of cancer:

Non-Small Cell Lung Cancer (NSCLC): It targets frontline patients with classical and over 50 non-classical EGFR driver mutations, as well as patients who have developed the acquired C797S resistance mutation from prior treatments. Phase 2 clinical trial data presented at the American Society of Clinical Oncology (ASCO) 2026 Annual Meeting showcased robust efficacy:
- Objective Response Rate (ORR): 60% in treatment-naïve patients.
- CNS Response Rate: An impressive 86% intracranial ORR in patients presenting with brain metastases.
- Disease Control Rate (DCR): 91%.
Glioblastoma Multiforme (GBM): In May 2026, a randomized Phase 2 trial was initiated for newly diagnosed patients with EGFRvIII-positive, MGMT-negative glioblastoma, evaluating silevertinib in combination with temozolomide.

Safety Profile & Side Effects

The adverse events of silevertinib are consistent with the broader class of EGFR inhibitors. The most frequently reported treatment-related adverse events (TRAEs) include:

Rash
Diarrhea
Stomatitis (mouth sores)
Paronychia (nail bed inflammation)

While a high percentage of patients (up to 77–84%) require dose reductions to manage these side effects, data shows that 86% of responding patients maintained or deepened their clinical response even after dropping to a lower dose. The treatment discontinuation rate remains low at roughly 9–14%, indicating the drug is manageable for long-term therapy.

Regulatory Status

As an investigational drug, silevertinib is not yet approved for commercial use by global regulatory agencies. However, the manufacturer anticipates regulatory feedback from the US FDA regarding its registration pathway for first-line NSCLC therapy.

OriginatorBlack Diamond Therapeutics
Class2 ring heterocyclic compounds; Amides; Amines; Aniline compounds; Antineoplastics; Halogenated hydrocarbons; Morpholines; Quinazolines; Small molecules
Mechanism of ActionErbB receptor antagonists
Phase IIGlioblastoma
Phase I/IINon-small cell lung cancer
Phase 0Glioma
06 Aug 2026Black Diamond Therapeutics anticipates regulatory feedback from the US FDA on registration path of silevertinib for Non-small cell lung cancer (First-line therapy) in the fourth quarter of 2026 (Black Diamond pipeline, May 2026)
02 Jun 2026Efficcay and adverse event data from phase I/II trial in Non-small cell lung cancer presented at the 62nd Annual Meeting of the American Society of Clinical Oncology (ASCO-2026)
21 May 2026Efficacy and adverse events data from a phase I/II trial in Non small cell lung cancer released by Black Diamond Therapeutics

SYN

BDTX-1535 Goes after Osimertinib ResistancePublication Name:Cancer DiscoveryPublication Date:2021-12-01PMID:34702733DOI:10.1158/2159-8290.cd-nb2021-0395
Further characterization of a DNA polymerase activity in mouse sperm nucleiPublication Name:Biochimica et Biophysica Acta (BBA) – Nucleic Acids and Protein SynthesisPublication Date:1976-10-04PMID:10003DOI:10.1016/0005-2787(76)90342-7

PAT

[WO2021030711]

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021030711&_cid=P21-MU6CBO-49598-1

Example 33. Synthesis of Compound No. 37 ((E)-N-(4-((3-chloro-2-fluorophenyl)amino)-7-(((1R,5S)-3-methyl-3-azabicyclo[3.1.0]hexan-1-yl)ethynyl)quinazolin-6-yl)-4-morpholinobut-2-enamide)

PAT

WO2026064728

https://patentscope.wipo.int/search/en/detail.jsf;jsessionid=2A0850BB19B29C599F589233A4E61A49.wapp2nB?docId=WO2026064728&_cid=P21-MU6C38-37561-1

PAT

US20220298120

https://patentscope.wipo.int/search/en/detail.jsf?docId=US375116378&_cid=P21-MU6C60-41372-1

Example 33. Synthesis of Compound No. 37 ((E)-N-(4-((3-chloro-2-fluorophenyl)amino)-7-(((1R,5S)-3-methyl-3-azabicyclo[3.1.0]hexan-1-yl)ethynyl)quinazolin-6-yl)-4-morpholinobut-2-enamide)

Step 1. To a solution of (E)-4-bromobut-2-enoic acid (5.00 g, 30.3 mmol) and dimethylformamide (22.2 mg, 303 umol) in dichloromethane (20 mL) was added (COCl) ₂(3.85 g, 30.3 mmol) dropwise at 0° C. under N ₂. The mixture was stirred at 0-25° C. for 4 h. On completion, the reaction mixture was concentrated in vacuo to give (E)-4-bromobut-2-enoyl chloride (5.8 g, crude) as a yellow oil.

Step 2. To a solution of N4-(3-chloro-2-fluoro-phenyl)-7-[2-[(1S,5R)-3-methyl-3-azabicyclo[3.1.0]hexan-1-yl]ethynyl]quinazoline-4,6-diamine (4.00 g, 9.81 mmol) and triethylamine (2.98 g, 29.4 mmol) in dichloromethane (70 mL) was added a solution of (E)-4-bromobut-2-enoyl chloride (3.60 g, 19.6 mmol) in dichloromethane (15 mL) dropwise at 0° C. and the mixture was stirred at 0° C. for 10 min. On completion, the reaction mixture was concentrated under vacuum to give (E)-4-bromo-N-(4-((3-chloro-2-fluorophenyl)amino)-7-4(1R,5S)-3-methyl-3-azabicyclo[3.1.0]hexan-1-yl)ethynyl)quinazolin-6-yl)but-2-enamide (5.44 g, crude) as a yellow solid, which was used for next step directly. m/z ES+ [M+H] ⁺556.0

Step 3. A mixture of (E)-4-bromo-N-[4-(3-chloro-2-fluoro-anilino)-7-[2-[(1S,5R)-3-methyl-3-azabicyclo[3.1.0]hexan-1-yl]ethynyl]quinazolin-6-yl]but-2-enamide (5.44 g, 9.80 mmol), morpholine (1.71 g, 19.6 mmol), triethylamine (992 mg, 9.80 mmol) in dichloromethane (1.5 mL) was degassed and purged with N ₂for 3 times, and then the mixture was stirred at 25° C. for 12 hrs under N ₂atmosphere. On completion, the reaction mixture was concentrated in vacuo to give a residue. The residue was purified by reverse phase flash [acetonitrile/(0.1% formic acid in water), 0% to 90%] to give 2.8 g crude product. Then it was purified by Prep-HPLC [column: Waters Xbridge BEH C18 250*50 mm*10 um; mobile phase: [water (0.05% ammonium hydroxide v/v)-acetonitrile]; B %: 35%-55%, 22 min] to give 2.2 g crude product. Then the crude product was triturated with EA/petroleum ether=5/1 (200 mL) twice to give (E)-N-[4-(3-chloro-2-fluoro-anilino)-7-[2-[(1S,5R)-3-methyl-3-azabicyclo[3.1.0]hexan-1-yl]ethynyl]quinazolin-6-yl]-4-morpholino-but-2-enamide (1.84 g, 33% yield) as a yellow solid. m/z ES+ [M+H] ⁺561.3; ¹H NMR (400 MHz, DMSO-d ₆) δ 10.06 (s, 1H), 9.78 (s, 1H), 8.67 (s, 1H), 8.48 (s, 1H), 7.80 (s, 1H), 7.50 (s, 2H), 7.29 (t, J=7.6 Hz, 1H), 6.81 (td, J=5.6, 15.6 Hz, 1H), 6.45 (d, J=15.6 Hz, 1H), 3.65-3.60 (m, 4H), 3.17 (d, J=5.2 Hz, 2H), 3.11 (d, J=8.4 Hz, 1H), 2.93 (d, J=9.0 Hz, 1H), 2.46-2.38 (m, 6H), 2.26 (s, 3H), 1.98-1.90 (m, 1H), 1.38 (t, J=4.4 Hz, 1H), 1.03 (dd, J=4.0, 8.0 Hz, 1H).

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References

“Silevertinib”. AdisInsight. Springer Nature Switzerland AG. Retrieved 5 July 2026.
Joshi H, Sheikh MS (August 2025). “Cell Death, Molecular Targeted Therapies, and Metabolic Reprogramming in EGFR-Mutant Lung Cancer”. Cancers. 17 (17). Basel: 2791. doi:10.3390/cancers17172791. PMC 12427363. PMID 40940888.

PAT

Polymorphs as erbb inhibitorsPublication Number:EP-4405350-A1Priority Date:2021-09-21
Polymorphs as erbb inhibitorsPublication Number:US-2024425492-A1Priority Date:2021-09-21
Polymorphs as erbb inhibitorsPublication Number:WO-2023049168-A1Priority Date:2021-09-21
Method of treating cancers with alkyne substituted quinazoline derivativesPublication Number:WO-2022094464-A1Priority Date:2020-11-02
Alkynyl quinazoline compoundsPublication Number:EP-4013749-A1Priority Date:2019-08-15
Alkynyl quinazoline compoundsPublication Number:US-2022298120-A1Priority Date:2019-08-15
Alkynyl quinazoline compoundsPublication Number:US-2026049063-A1Priority Date:2019-08-15
Alkynyl quinazoline compoundsPublication Number:US-12435046-B2Priority Date:2019-08-15Grant Date:2025-10-07
Alkynyl quinazoline compoundsPublication Number:EP-4013749-B1Priority Date:2019-08-15Grant Date:2026-03-11
Alkynyl quinazoline compoundsPublication Number:WO-2021030711-A1Priority Date:2019-08-15

Clinical data

Other names	RVU-120
Identifiers
IUPAC name
CAS Number	2607829-38-7
PubChem CID	156071569
IUPHAR/BPS	13371
UNII	RP9F537KVY
KEGG	D13300
Chemical and physical data
Formula	C₃₀H₃₀ClFN₆O₂
Molar mass	561.06 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES
InChI

///////////silevertinib, anax labs, epidermal growth factor receptor tyrosine kinase inhibitor, antineoplastic, BDTX-1535, BDTX 1535, CANCER, Glioblastoma, Black Diamond Therapeutics, RP9F537KVY

#silevertinib, #anax labs, #epidermal growth factor receptor tyrosine kinase inhibitor, #antineoplastic, #BDTX-1535, #BDTX 1535, #CANCER, #Glioblastoma, #Black Diamond Therapeutics, #RP9F537KVY