(+)-cis-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-naphtho<1,2-b><1,4>thiazepin-4(5H)-one | 108383-87-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: (+)-cis-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-naphtho<1,2-b><1,4>thiazepin-4(5H)-one
• 英文别名: (2S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-5-[2-(dimethylamino)ethyl]naphtho[1,2-b][1,4]thiazepin-4(5H)-one；(-)-cis-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-5-[2-(dimethylamino)ethyl]naphtho[1,2-b]-1,4-thiazepin-4(5H)-one；(+)-cis-2,3-dihydro-3-hydroxy-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)naphtho[1,2-b][1,4]thiazepin-4(5H)-one；(+/-)-cis-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-5-(2-(dimethylamino)ethyl]naphtho[1,2-b][1,4]thiazepin-4(5H)-one；(2S,3S)-5-[2-(dimethylamino)ethyl]-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydrobenzo[i][1,5]benzothiazepin-4-one
• CAS: 108383-87-5
• 化学式: C₂₄H₂₆N₂O₃S
• 分子量: 422.548
• InChiKey: IGSREHOALYQNPA-YADHBBJMSA-N

物化性质

• 沸点：
  668.3±55.0 °C(Predicted)
• 密度：
  1.249±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  78.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+)-cis-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-naphtho<1,2-b><1,4>thiazepin-4(5H)-one 、 邻乙酰水杨酰氯 以 吡啶 为溶剂， 生成 (+/-)-cis-3-[[(2-acetyloxy)benzoyl]oxy]-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)naphtho[1,2-b][1,4]thiazepin-4(5H)-one
  参考文献：
  名称：

  Analogs of naphtho[1,2-.beta.] [1,4] thiazepin-4(5H)-one

  摘要：

  描述了式子##STR1##中的(+)-顺式化合物，其中R为较低的烷基；R.sub.1为##STR2##，其中R.sub.3为吡啶基，##STR3##或苯基，未取代或取代，取代基最多为3个，选自羟基、卤素、较低的烷氧基和较低的烷酰氧基；描述了(-)顺式对映体和(.+-.)-顺式外消旋体；或其药用可接受的酸盐。

  公开号：

  US04912102A1
• 作为产物：
  描述：

  2-aminonaphthalene-1-thiol 在 sodium hydroxide 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 乙醇 、 水 、 乙酸乙酯 、 甲苯 、 xylene 为溶剂， 反应 59.0h， 生成 (+)-cis-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-naphtho<1,2-b><1,4>thiazepin-4(5H)-one
  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

• Naphtho[1,2-b]-1,4-thiazepinones
  申请人：Hoffmann-La Roche Inc.

  公开号：US04652561A1

  公开（公告）日：1987-03-24

  Compounds of the formula ##STR1## wherein R.sub.1 is phenyl substituted with 1 to 3 lower alkoxy groups or 1 to 3 halogens; R.sub.2 is hydroxy, lower alkoxy, lower alkanoyloxy, lower cycloalkylcarbonyloxy; ##STR2## R.sub.3 and R.sub.4 are independently lower alkyl, phenyl lower alkyl or together form a piperidine or pyrrolidine ring; n is 2 to 4; m is 1 to 2; or pharmaceutically acceptable acid addition salts thereof are described. The compounds of formula I have activity as calcium channel blockers and accordingly, are useful as agents for lowering blood pressure, and as agents for treating ischemia.

  式为##STR1##的化合物，其中R.sub.1是苯基，其上取代有1至3个较低的烷氧基或1至3个卤素；R.sub.2是羟基、较低的烷氧基、较低的烷酰氧基、较低的环烷基羰基氧基；##STR2## R.sub.3和R.sub.4独立地是较低的烷基、苯基较低的烷基，或者一起形成哌啶或吡咯烷环；n为2至4；m为1至2；或其药学上可接受的酸盐。式I的化合物具有作为钙通道阻滞剂的活性，因此可用作降低血压的药物，并用作治疗缺血的药物。
• Process for making optically active
  申请人：Hoffmann-La Roche Inc.

  公开号：US04864058A1

  公开（公告）日：1989-09-05

  A process for preparing optically active naphtho[1,2-b][1,4]thiazepin-4(5H)-ones comprising resolution of rac-.beta.-[(2-amino-1-naphthalenyl)thio]-.alpha.-hydroxy-4-methoxybenzene propanoic acid and converting the optically active acids so obtained into final products is described. The end product naphtho[1,2-b][1,4]thiazepin-4(5H)-ones have activity as calcium channel blockers and accordingly are useful as agents for lowering blood pressure, and as agents for treating ischemia.

  本发明涉及一种制备光学活性的萘并[1,2-b][1,4]噻唑-4(5H)-酮的方法，包括将混合物中的rac-β-[(2-氨基-1-萘基)硫基]-α-羟基-4-甲氧基苯丙氨酸分离，并将得到的光学活性酸转化为最终产物。最终产物萘并[1,2-b][1,4]噻唑-4(5H)-酮具有作为钙通道阻滞剂的活性，因此可用作降低血压的药物和治疗缺血的药物。
• 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。
• 3-Acyloxy-5-aminoalkyl-2,3-dihydro-2-phenyl-naphtho[1,2-b][1,4]thiazepin-4(5H)-one derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0326906A1

  公开（公告）日：1989-08-09

  (+)-cis Compounds of the formula wherein R is lower alkyl and R₁ is pyridyl, one of the groups or phenyl or phenyl substituted by up to 3 substituents selected from the group consisting of nitro, hydroxy, halogen, lower alkoxy and lower alkanoyloxy, (-)-cis enantiomers, (±)-cis racemates and pharmaceuti­cally acceptable acid addition salts thereof are active as calcium antagonists, and accordingly, are useful as agents for lowering blood pressure and as agents for treating ischemia. They can be prepared from the corresponding 3-hydroxy compounds by reacting same with an appropriate acylating agent.

  式中的(+)-顺式化合物 其中 R 是低级烷基，R₁ 是吡啶基、基团之一 或苯基或最多被 3 个取代基取代的苯基，这些取代基选自由硝基、羟基、卤素、低级烷氧基和低级烷酰氧基组成的组、 (-)-顺式对映体、(±)-顺式外消旋体及其药学上可接受的酸加成盐具有钙拮抗剂的活性，因此可用作降血压药物和治疗缺血的药物。它们可以由相应的 3-羟基化合物与适当的酰化剂反应制备而成。
• US4652561A
  申请人：——

  公开号：US4652561A

  公开（公告）日：1987-03-24