(2S,3S)-5-[2-(二甲氨基)乙基]-2-(4-甲氧苯基)-4-羰基-2,3,4,5-四氢萘并[1,2-b][1,4]硫氮杂卓-3-基乙酸酯盐酸(1:1) | 108383-96-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 中文名称: (2S,3S)-5-[2-(二甲氨基)乙基]-2-(4-甲氧苯基)-4-羰基-2,3,4,5-四氢萘并[1,2-b][1,4]硫氮杂卓-3-基乙酸酯盐酸(1:1)
• 英文名称: (+)-cis-3-(acetyloxy)-2,3-dihydro-2-(4-methoxyphenyl)-5-<2-(dimethylamino)ethyl>naphtho<1,2-b><1,4>thiazepin-4(5H)-one hydrochloride
• 英文别名: (+/-)-cis-3-(acetyloxy)-2,3-dihydro-2-(4-methoxyphenyl)-5-[2-(dimethylamino)ethyl]naphtho[1,2-b]-1,4-thiazepin-4(5H)-one hydrochloride；(+)-cis-3-(acetyloxy)-2,3-dihydro-2-(4-methoxyphenyl)-5-[2-(dimethylamino)ethyl]naphtho[1,2-b][1,4]thiazepin-4(5H)-one hydrochloride；Naltiazem hydrochloride；[(2S,3S)-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3-dihydrobenzo[i][1,5]benzothiazepin-3-yl] acetate;hydrochloride
• CAS: 108383-96-6
• 化学式: C₂₆H₂₈N₂O₄S*ClH
• 分子量: 501.046
• InChiKey: SFTBZKFGODNAKF-ITNPDYSASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.94
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  84.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (2S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-naphtho<1,2-b><1,4>thiazepin-4(5H)one 在 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 16.0h， 生成 (2S,3S)-5-[2-(二甲氨基)乙基]-2-(4-甲氧苯基)-4-羰基-2,3,4,5-四氢萘并[1,2-b][1,4]硫氮杂卓-3-基乙酸酯盐酸(1:1)
  参考文献：
  名称：

  Enantioselective synthesis of calcium channel blockers of the diltiazem group

  摘要：

  A lipase-catalyzed kinetic resolution of racemic trans-2-phenylcyclohexanol readily provides the (-)-1R,2S enantiomer. This alcohol is employed as its chloroacetate 10a in a chiral auxiliary-induced asymmetric Darzens glycidic ester condensation with p-anisaldehyde (9). Crystallization of the Darzens product affords enantiomerically pure (1R,2S)-2-phenylcyclohexyl (1R,2S)-2-(p-methoxyphenyl)glycidate (11), the structure of which was established by X-ray crystallography. The use of this glycidic ester in syntheses of diltiazem (1) and naltiazem (8), members of the diltiazem group of calcium channel blockers, provides these drug substances directly in enantiomerically pure form.

  DOI：

  10.1021/jo00029a013

文献信息

• 2,3-Dihydro-2-phenyl-5-aminoalkyl-naphtho [1,2-b]-1,4-thiazepin-4(5H)-one derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0234561A2

  公开（公告）日：1987-09-02

  It has been found that the novel compounds of the formula wherein R, is phenyl substituted with 1 to 3 lower alkoxy groups or 1 to 3 halogens, R2 is hydroxy, lower alkoxv. lower alkanovloxv. lower cvcloalkvlcarbonvloxv. R3 and R, are, independently, lower alkyl, phenyl lower alkyl or, taken together, form a piperidine or pyrrolidine ring, n is 2 to 4 and m is 1 to 2, and pharmaceutically acceptable acid addition salts thereof have activity as calcium channel blockers and, accordingly, are useful as agents for treating ischemia and as agents for lowering blood pressure. They can be prepared by reacting a compound of the formula with a compound of the formula and optionally converting the compound thus obtained to a compound wherein R2 is other than hydroxy.

  发现式中的新型化合物 其中 R 是被 1 至 3 个低级烷氧基或 1 至 3 个卤素取代的苯基，R2 是羟基、低级烷氧基、低级烷烃氧基、低级环烷烃氧基、低级环羰基氧基。 R3和R, 独立地是低级烷基、苯基低级烷基，或共同形成哌啶或吡咯烷环，n为2至4，m为1至2、 及其药学上可接受的酸加成盐具有钙通道阻滞剂的活性，因此可用作治疗缺血和降低血压的药物。它们可以通过将式 与式 并选择性地将由此得到的化合物转化为 R2 为羟基以外的化合物。
• US4652561A
  申请人：——

  公开号：US4652561A

  公开（公告）日：1987-03-24
• Enantioselective synthesis of calcium channel blockers of the diltiazem group
  作者：Alan Schwartz、Pradeep B. Madan、Erno Mohacsi、Jay P. O'Brien、Louis J. Todaro、David L. Coffen

  DOI：10.1021/jo00029a013

  日期：1992.1

  A lipase-catalyzed kinetic resolution of racemic trans-2-phenylcyclohexanol readily provides the (-)-1R,2S enantiomer. This alcohol is employed as its chloroacetate 10a in a chiral auxiliary-induced asymmetric Darzens glycidic ester condensation with p-anisaldehyde (9). Crystallization of the Darzens product affords enantiomerically pure (1R,2S)-2-phenylcyclohexyl (1R,2S)-2-(p-methoxyphenyl)glycidate (11), the structure of which was established by X-ray crystallography. The use of this glycidic ester in syntheses of diltiazem (1) and naltiazem (8), members of the diltiazem group of calcium channel blockers, provides these drug substances directly in enantiomerically pure form.