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【结 构 式】 
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【药物名称】YM-176770 【化学名称】1-[6-[2-[3-(4-Biphenylyl)-5-methyl-4H-1,2,4-triazol-4-yl]phenoxy]hexyl]-4-methylpiperazine 【CA登记号】258878-50-1 【 分 子 式 】C32H39N5O 【 分 子 量 】509.70053 |
【开发单位】Yamanouchi (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, Hypertension, Treatment of, Vasopressin V1a Antagonists |
合成路线1
Acetylation of o-aminophenol (I) gives o-hydroxy acetanilide (II), which is then protected as the benzyl ether (III) with benzyl bromide and K2CO3. Treatment of acetamide (III) with P2S5 affords the corresponding thioamide (IV), and subsequent S-methylation of (IV) gives rise to the thioimidate (V). Cyclization of thioimidate (V) with 4-biphenylcarboxylic acid hydrazide (VI) in hot DMF leads to the triazole derivative (VII). After benzyl group hydrogenolysis in (VII), the resultant phenol (VIII) is alkylated with 1,6-dibromohexane (IX) to produce the bromohexyl ether (X). Finally, condensation of bromide (X) with N-methylpiperazine (XI) furnishes the title compound.
| 【1】 Kakefuda, A.; et al.; Synthesis and pharmacological evaluation of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives as a novel class of selective antagonists for the human vasopressin V1A receptor. J Med Chem 2002, 45, 12, 2589. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 18663 | o-aminophenol; 2-aminophenol | 95-55-6 | C6H7NO | 详情 | 详情 |
| (II) | 56976 | 2-Acetamidophenol; 2-Hydroxyacetanilide; o-Acetamidophenol; o-Hydroxyacetanilide | 614-80-2 | C8H9NO2 | 详情 | 详情 |
| (III) | 56977 | N-[2-(benzyloxy)phenyl]acetamide | C15H15NO2 | 详情 | 详情 | |
| (IV) | 56978 | N-[2-(benzyloxy)phenyl]ethanethioamide | C15H15NOS | 详情 | 详情 | |
| (V) | 56979 | methyl N-[2-(benzyloxy)phenyl]ethanimidothioate | C16H17NOS | 详情 | 详情 | |
| (VI) | 56980 | 4-Biphenylcarboxylic acid hydrazide; 4-Phenylbenzhydrazide | 18622-23-6 | C13H12N2O | 详情 | 详情 |
| (VII) | 56981 | benzyl 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenyl ether; 4-[2-(benzyloxy)phenyl]-3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazole | C28H23N3O | 详情 | 详情 | |
| (VIII) | 56982 | 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenol | C21H17N3O | 详情 | 详情 | |
| (IX) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (X) | 56983 | 3-[1,1'-biphenyl]-4-yl-4-{2-[(6-bromohexyl)oxy]phenyl}-5-methyl-4H-1,2,4-triazole; 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenyl 6-bromohexyl ether | C27H28BrN3O | 详情 | 详情 | |
| (XI) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |