|
【结 构 式】 
|
【药物名称】Anatibant mesilate, LF-16-0687MS, LF-16-0687(free base) 【化学名称】N-[3-(4-Amidinobenzamido)propyl]-1-[2,4-dichloro-3-(2,4-dimethylquinolin-8-yloxymethyl)phenylsulfonyl]-L-prolinamide bis(methanesulfonate) 【CA登记号】209788-45-4 (diHCl), 209733-45-9 (free base) 【 分 子 式 】C36H44Cl2N6O11S3 【 分 子 量 】903.88368 |
【开发单位】Fournier (Orphan Drug), Fournier (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Neurologic Drugs (Miscellaneous), Stroke, Treatment of, Bradykinin B2 Antagonists, Non-Steroidal Antiinflammatory Drugs |
合成路线1
The title compound has been synthesized by condensation of amidino benzoic acid (I) with primary amine (II) using EDC and HOAt.
| 【1】 Dodey, P.; Bondoux, M.; Ou, K.; Barth, M.; Houziaux, P. (Fournier Industrie et Santé); Novel N-benzenesulphonyl-L-proline derivs., method for preparing and therapeutic use. EP 0944618; US 6063791; WO 9824783 . |
合成路线2
In an alternative procedure, amine (II) was condensed with 4-cyanobenzoic acid (III) to give amide (IV). Subsequent addition of hydroxylamine to the cyano group of (IV) afforded N-hydroxy amidine (V), which was acetylated with Ac2O to produce (VI). This compound was finally reduced to the target amidine by hydrogenation over Lindlar catalyst.
| 【1】 Dodey, P.; Bondoux, M.; Ou, K.; Barth, M.; Houziaux, P. (Fournier Industrie et Santé); Novel N-benzenesulphonyl-L-proline derivs., method for preparing and therapeutic use. EP 0944618; US 6063791; WO 9824783 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 37922 | (2S)-N-(3-aminopropyl)-1-[(2,4-dichloro-3-[[(2,4-dimethyl-8-quinolinyl)oxy]methyl]phenyl)sulfonyl]-2-pyrrolidinecarboxamide | C26H30Cl2N4O4S | 详情 | 详情 | |
| (III) | 36897 | 4-cyanobenzoic acid；4-Carboxybenzonitrile;p-Carboxybenzonitrile | 619-65-8 | C8H5NO2 | 详情 | 详情 |
| (IV) | 37923 | (2S)-N-[3-[(4-cyanobenzoyl)amino]propyl]-1-[(2,4-dichloro-3-[[(2,4-dimethyl-8-quinolinyl)oxy]methyl]phenyl)sulfonyl]-2-pyrrolidinecarboxamide | C34H33Cl2N5O5S | 详情 | 详情 | |
| (V) | 37924 | (2S)-N-[3-([4-[amino(hydroxyimino)methyl]benzoyl]amino)propyl]-1-[(2,4-dichloro-3-[[(2,4-dimethyl-8-quinolinyl)oxy]methyl]phenyl)sulfonyl]-2-pyrrolidinecarboxamide | C34H36Cl2N6O6S | 详情 | 详情 | |
| (VI) | 37925 | (2S)-N-[3-([4-[[(acetoxy)imino](amino)methyl]benzoyl]amino)propyl]-1-[(2,4-dichloro-3-[[(2,4-dimethyl-8-quinolinyl)oxy]methyl]phenyl)sulfonyl]-2-pyrrolidinecarboxamide | C36H38Cl2N6O7S | 详情 | 详情 |