All you want to know about drugs..by Dr Anthony Melvin Crasto, Worlddrugtracker, email me ........... amcrasto@gmail.com, call +91 9323115463 India
DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai), INDIA, worlddrugtracker, 29Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.8 Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contributionn, सुकून उतना ही देना प्रभू, जितने से जिंदगी चल जाये।औकात बस इतनी देना,कि औरों का भला हो जाये।...........P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
({(12'aR)-12'-[(11S)-7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-6',8'-dioxo-6',8',12',12'a-tetrahydro-1'H,4'H-spiro[cyclopropane-1,3'-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazin]-7'-yl}oxy)methyl methylcarbonate antiviral, GP 681, Jiangxi Qingfeng Pharmaceutical, influenza A, INFLUENZA B, Cap-dependent endonuclease-IN-3, A72V8WPZ9F
Suraxavir marboxil (GP681) is an oral antiviral prodrug developed by Jiangxi Qingfeng Pharmaceutical for treating acute, uncomplicated influenza A and B virus infections.
Key Details
Mechanism of Action: It converts into its active metabolite, GP1707D07, which acts as a cap-dependent endonuclease (CEN) inhibitor by targeting the polymerase acidic (PA) protein subunit of the influenza virus RNA polymerase. This stops viral gene transcription and replication.
Administration: Designed as a single-dose oral therapy (typically evaluated at 40 mg).
Efficacy: In phase 3 clinical trials, a single dose administered within 48 hours of symptom onset reduced the median time to symptom alleviation to 42.0 hours (compared to 63.0 hours for placebo) and rapidly lowered viral load.
Safety Profile: Adverse events are mostly mild to moderate and comparable to placebo, with low rates of acquired resistance (such as I38T PA variants).
Mechanism of ActionRNA-dependent RNA polymerase inhibitors
RegisteredInfluenza virus infections
28 Nov 2025Capital Medical University initiates enrolment in a phase III trial for Influenza virus infections (In children, In adults, In the elderly) in China (PO) (NCT07236814)
01 Aug 2025Jiangxi Kerui Pharmaceutical plans a phase III trial for Influenza virus infections (In Children) in August 2025 (PO, suspension) (NCT07113392)
Preparation of Compound of formula (10): Compound of formula (11) (388 mg, 1 mmol) was dissolved in 3 mL dichloromethane and added with 1 mL trifluoroacetic acid, and the mixture was stirred at room temperature for 3 hours. TLC showed the reaction was complete, and the mixture was added with 3N sodium hydroxide solution to adjust pH=9-10. The mixture was extracted with dichloromethane, and organic phases were merged, washed with saturated salt solution, dried, and concentrated to give 270 mg solid, which was directly used in the next step.
Preparation of Compound of formula (8): Compound of formula (9) (1.0 g, 7.8 mmol) was dissolved in 10 mL anhydrous tetrahydrofuran, and dropwise added with 2.5M n-butyllithium solution (3.1 mL, 7.8 mmol) slowly at −78° C. and under nitrogen protection. After addition, the mixture was stirred and reacted at the temperature for 2 hours. Then allyl formate (0.94 g, 7.8 mmol) was dropwise added. After addition, the mixture was stirred and reacted for 2 hours, and TLC showed the raw materials were substantially completely reacted, and then the reaction mixture was poured into saturated ammonium chloride solution to quench, and then extracted with ethyl acetate (15 mL×3). The organic phases were merged, dried over anhydrous sodium sulfate, and concentrated to dry to give 1.65 g oily product.
Preparation of Compound of formula (7): Compound of formula (8) (1.65 g, 7.8 mmol) was dissolved in 15 mL anhydrous tetrahydrofuran, and dropwise added with 1M diisobutylaluminum hydride solution (11.7 mL, 11.7 mmol) slowly at −78° C. and under nitrogen protection. After addition, the mixture was stirred and reacted at the temperature for 2 hours. TLC showed the raw materials were substantially completely reacted, and then the reaction mixture was poured into saturated potassium sodium tartrate solution to quench, and then extracted with ethyl acetate (20 mL×3). The organic phases were merged, dried over anhydrous sodium sulfate, and concentrated to dry to give 1.57 g oily product.
Preparation of Compound of formula (6): Compound of formula (7) (1.57 g, 7.4 mmol) was dissolved in 15 mL methanol, and p-toluenesulfonic acid monohydrate (140 mg, 0.74 mmol) was added, and the mixture was stirred at room temperature overnight. TLC showed the raw materials were substantially completely reacted, and then the mixture was added with saturated sodium bicarbonate solution to adjust to be neutral, and concentrated. The residue was separated by column chromatography to give 0.86 g yellow oily product.
Preparation of Compound of formula (5): Compound of formula (10) (270 mg, 0.94 mmol) and Compound of formula (6) (255 mg, 1.13 mmol) were dissolved in 5 mL acetonitrile. 1M solution of tin tetrachloride in dichloromethane (1.4 mL, 1.41 mmol) was added dropwise under nitrogen protection and at −20° C. After addition, the mixture was stirred and reacted at the temperature for 3 hours. The mixture was added with saturated sodium bicarbonate solution, stirred for 30 min, and stood to layer, and the aqueous phase was extracted with dichloromethane. The organic phases were merged, washed with saturated salt solution, dried, and concentrated to give 428 mg crude product.
Preparation of Compound of formula (4): Compound of formula (5) (428 mg, 0.89 mmol) was dissolved in 5 mL tetrahydrofuran, and tetrakis(triphenylphosphine)palladium (104 mg, 0.09 mmol) and morpholine (774 mg, 8.9 mmol) were added and reacted at room temperature for 2 hours. The reaction was shown complete through TLC spot plate analysis. The mixture was concentrated, and the residue was separated by column chromatography to give 216 mg product.
Preparation of Compound of formula (3): Compound of formula (4) (216 mg, 0.61 mmol) and Compound of formula (12) (242 mg, 0.92 mmol) were reacted at 100° C. for 3 hours in 3 mL solution of T 3P in ethyl acetate under airtight condition. The mixture was cooled, diluted with saturated NaHCO3, and then extracted with ethyl acetate. The organic phases were merged, dried and concentrated, and separated by column chromatography to give 200 mg crude product, which was separated by chiral column to give 40 mg product.
Preparation of Compound of formula (2): Compound of formula (3) (40 mg, 0.067 mmol) and lithium chloride (20 mg, 0.48 mmol) were reacted at 100° C. for 3 hours in 1 mL DMA. After the reaction finished, the mixture was diluted with 10 mL water, and added with 2N hydrochloric acid to adjust pH to 3-4. The mixture was filtered, and the solid was pumped to dry to give 25 mg product. 1HNMR (400 MHz, CDCl 3) δ: 7.05-7.15 (m, 5H), 6.85 (m, 1H), 6.70 (d, 1H, J=7.6 Hz), 5.78 (d, 1H, J=7.6 Hz), 5.3 (m, 2H), 4.69 (d, 1H, J=6.8 Hz), 4.17 (d, 1H, J=14 Hz), 4.09 (d, 1H, J=14 Hz), 3.90 (m, 1H), 3.69 (m, 1H), 3.44 (d, 1H, J=15.2 Hz), 0.95 (m, 1H), 0.74 (m, 3H); ESI-MS m/z (M+H) + 510.1.
Preparation of Compound of formula (1): Compound of formula (2) (40 mg, 0.08 mmol), chloromethyl methyl carbonate (25 mg, 0.2 mmol), potassium carbonate (28 mg, 0.2 mmol) and potassium iodide (3 mg, 0.02 mmol) were reacted at 60° C. for 5 hours in 1 mL N,N-dimethylacetamide. The reaction was shown complete through TLC spot plate analysis, the mixture was added with water to quench, and added with 1N diluted hydrochloric acid to adjust pH to 3-4. The solid was filtered, dried, and separated by column chromatography to give 35 mg product, which was the compound of formula (1), and the solid was analyzed to be amorphous and used as the starting material for preparing various crystal forms in subsequent embodiments. 1HNMR (400 MHz, DMSO-d6) δ: 7.40-7.42 (m, 2H), 7.25 (d, 1H, J=7.6 Hz), 7.15 (m, 1H), 7.10 (m, 1H), 7.00 (d, 1H, J=7.2 Hz), 6.84 (t, 1H, J=7.6 Hz), 5.75 (m, 4H), 5.43 (d, 1H, J=16.4 Hz), 4.57 (dd, 1H, J=3.2, 9.6 Hz), 3.96-4.03 (m, 3H), 3.73 (s, 3H), 3.51 (t, 1H, J=10.0 Hz), 3.41 (s, 1H), 0.75 (t, 2H, J=8.4 Hz), 0.50 (m, 2H); ESI-MS m/z (M+H) + 598.1.
No comments:
Post a Comment