(-)-(2R,3R)-cis-8-chloro-5-<2-(dimethylamino)ethyl>-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one | 96125-57-4

• 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: (-)-(2R,3R)-cis-8-chloro-5-<2-(dimethylamino)ethyl>-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one
• 英文别名: (+)-cis-2-(4-methoxyphenyl)-3-hydroxy-5-[2-(dimethylamino)ethyl]-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one；(2R,3R)-8-chloro-5-[2-(dimethylamino)ethyl]-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4-one
• CAS: 96125-57-4
• 化学式: C₂₀H₂₃ClN₂O₃S
• 分子量: 406.933
• InChiKey: DWOKUCFPFUCSID-RBUKOAKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 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：

  (-)-(2R,3R)-cis-8-chloro-5-<2-(dimethylamino)ethyl>-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one 在 吡啶 、 乙酸酐 作用下， 生成 (-)-(2R,3R)-cis-3-acetoxy-8-chloro-5-<2-(dimethylamino)ethyl>2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one hydrochloride
  参考文献：
  名称：

  8-Chloro-1,5-benzothiazepine derivatives

  摘要：

  公开了通式为：##STR1##的8-氯-1,5-苯并硫氮杂卓衍生物，其中R1为氢、低级烷基或通式为R4CO-的基团，R2和R3各自为低级烷基，R4为氢或低级烷基，以及其药学上可接受的酸加成盐。所述衍生物（I）及其药学上可接受的酸加成盐可用作降压剂和/或冠状动脉或脑血管扩张剂。

  公开号：

  US04567175A1
• 作为产物：
  描述：

  5-氯-2-硝基苯硫醇 在 六甲基磷酰三胺 、 sodium tetrahydroborate 、 18-冠醚-6 、 sodium ethanolate 、 碳酸氢钠 、 potassium carbonate 、 tin(ll) chloride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 11.67h， 生成 (-)-(2R,3R)-cis-8-chloro-5-<2-(dimethylamino)ethyl>-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one
  参考文献：
  名称：

  A New Synthetic Route to 1,5-Benzothiazepines. Synthesis of Derivatives of Diltiazem.

  摘要：

  通过硫稳定苄基阴离子和酯羰基的碳-碳环闭合，然后立体选择性还原 1，5-苯并硫氮杂卓二酮的 C3-羰基，从草酸盐（6）合成了多种地尔硫卓衍生物（9a-c）（7）。

  DOI：

  10.1248/cpb.40.1986

文献信息

• 1,5-benzothiazepine derivatives and preparation thereof
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US05134139A1

  公开（公告）日：1992-07-28

  Novel 1,5-benzothiazepine derivatives of the formula: ##STR1## wherein X is hydrogen atom, a halogen atom or a lower alkyl group; R.sup.1 is a lower alkyl group or a lower alkoxy group; R.sup.2 is hydrogen atom, a lower alkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted phenyl-lower alkyl grup or a diphenyl-lower alkyl group; R.sup.3 is a lower alkyl group or a substituted or unsubstituted phenyl-lower alkyl group, Q is single bond, or an alkylene or lower alkenylene group which may optionally be substituted by a lower alkoxy group or oxo group; R.sup.4 is (i) hydrogen atom, (ii) a lower alkyl group, (iii) an N-phenyl-N-lower alkylamino group, (iv) a phenyl, phenyloxy, phenylthio, benzenesulfonylamino, 1,4-benzoquinonyl or benzylthio group which may optionally have substituent, or (v) a heterocyclic group which may optionally have substituent; and n is 2 or 3, or a pharmaceutically acceptable salt thereof, which are useful as a calcium antagonist, and the process for preparing thereof.

  1,5-苯并噻二唑衍生物的化学式如下：##STR1## 其中X是氢原子、卤素原子或较低的烷基基团；R.sup.1是较低的烷基基团或较低的烷氧基团；R.sup.2是氢原子、较低的烷基基团、取代或未取代的苯基团、取代或未取代的苯基-较低烷基基团或二苯基-较低烷基基团；R.sup.3是较低的烷基基团或取代或未取代的苯基-较低烷基基团；Q是单键，或者是一种可以选择地由较低的烷氧基团或氧基取代的烷基或较低的烯基基团；R.sup.4是(i)氢原子、(ii)较低的烷基基团、(iii)N-苯基-N-较低烷基氨基基团、(iv)苯基、苯氧基、苯硫基、苯磺酰氨基、1,4-苯醌基或苄硫基基团，可以选择地具有取代基，或者(v)可以选择地具有取代基的杂环基团；n为2或3，或其药学上可接受的盐，可用作钙拮抗剂，并且其制备方法。
• Synthesis of halogen-substituted 1,5-benzothiazepine derivatives and their vasodilating and hypotensive activities
  作者：Hirozumi Inoue、Mikihiko Konda、Tomiki Hashiyama、Hisao Otsuka、Kaoru Takahashi、Mitsunori Gaino、Tadamasa Date、Keiichi Aoe、Mikio Takeda

  DOI：10.1021/jm00106a032

  日期：1991.2

  its derivatives (2) with halogen substituents on the fused benzene ring were synthesized. These compounds were evaluated for their effects on vertebral and coronary blood flows and antihypertensive activity. The structure-activity relationships are discussed. The 8-chloro derivative ((+)-2b), the most potent compound in this series, was selected for clinical evaluation as a cerebral vasodilating and

  为了提高地尔硫卓（1）的作用效果和持续时间，合成了1，5-苯并硫氮杂卓钙通道阻滞剂，其衍生物（2）在稠合的苯环上具有卤素取代基。评估了这些化合物对椎骨和冠状动脉血流以及降压活性的影响。讨论了构效关系。选择该系列中最有效的化合物8-氯衍生物（（+）-2b）作为脑血管扩张和降压药进行临床评估。
• Novel 8-chloro-1,5-benzothiazepine derivatives, processes for preparing the same and pharmaceutical compositions
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：EP0127882A1

  公开（公告）日：1984-12-12

  Novel 8-chloro-1,5-benzothiazepine derivatives of the formula: wherein R' is hydrogen, lower alkyl or a group of the formula: R4CO-, each of R2 and R' is lower alkyl and R4 is hydrogen or lower alkyl, and a pharmaceutically acceptable acid addition salt thereof as well as a process for preparing the same are disclosed. Said derivative (I) and a pharmaceutically acceptable acid addition salt thereof in form of a pharmaceutical composition are useful as hypotensive agents and/or coronary or cerbral vasodilators.

  式中的新型 8-氯-1,5-苯并硫氮杂卓衍生物： 其中 R' 为氢、低级烷基或式中的基团：R4CO-, R2 和 R' 各为低级烷基，R4 为氢或低级烷基）的新型 8-氯-1,5-苯并硫氮杂卓衍生物及其药学上可接受的酸加成盐以及制备方法已被公开。以药物组合物形式存在的上述衍生物（I）及其药学上可接受的酸加成盐可用作降血压剂和/或冠状动脉或脑血管扩张剂。
• Benzothiazepine derivatives
  申请人：E.R. Squibb & Sons, Inc.

  公开号：EP0206540A1

  公开（公告）日：1986-12-30

  Vasodilating activity is exhibited by new compounds having the formula or a pharmaceutically acceptable salt thereof wherein n is 2 or 3; X is oxygen or sulfur; R, and R2 are each independently hydrogen, alkyl, cycloalkyl, or allyl, or R, and R2 together with the nitrogen atom to which they are attached are pyrrolidinyl, piperidinyl, or morpholinyl; R3 is alkyl, alkoxy, halogen, trifluoromethyl, or nitro; R4 is hydrogen, halogen, trifluoromethyl, or nitro; and R5 and R6 are each independently alkyl or cycloalkyl or R5 and R6 together with the nitrogen atom to which they are attached are pyrrolidinyl, piperidinyl, or morpholinyl.

  具有以下式子的新化合物具有血管扩张活性 或其药学上可接受的盐，其中 n为2或3； X为氧或硫； R和R2各自独立地是氢、烷基、环烷基或烯丙基，或R和R2连同它们所连接的氮原子是吡咯烷基、哌啶基或吗啉基； R3 是烷基、烷氧基、卤素、三氟甲基或硝基； R4 是氢、卤素、三氟甲基或硝基；以及 R5 和 R6 各自独立地为烷基或环烷基，或 R5 和 R6 与它们所连接的氮原子一起为吡咯烷基、哌啶基或吗啉基。
• 1,5-Benzothiazepine derivatives and preparation thereof
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP0416479A1

  公开（公告）日：1991-03-13

  Novel 1,5-benzothiazepine derivatives of the formula: wherein X is hydrogen atom, a halogen atom or a lower alkyl group; R1 is a lower alkyl group or a lower alkoxy group; R2 is hydrogen atom, a lower alkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted phenyl-lower alkyl group or a diphenyl-lower alkyl group; R3 is a lower alkyl group or a substituted or unsubstituted phenyl-lower alkyl group, Q is single bond, or an alkylene or lower alkenylene group which may optionally be substituted by a lower alkoxy group or oxo group; R4 is (i) hydrogen atom, (ii) a lower alkyl group, (iii) an N-phenyl-N-lower alkylamino group, (iv) a phenyl, phenyloxy, phenylthio, benzenesulfonylamino, 1,4-benzoquinonyl or benzylthio group which may optionally have substituent, or (v) a heterocyclic group which may optionally have substituent; and n is 2 or 3, or a pharmaceutically acceptable salt thereof, which are useful as a calcium antagonist, and the process for preparing thereof.

  式中的新型 1，5-苯并硫氮杂卓衍生物： 其中，X 是氢原子、卤素原子或低级烷基；R1 是低级烷基或低级烷氧基；R2 是氢原子、低级烷基、取代或未取代的苯基、取代或未取代的苯基-低级烷基或二苯基-低级烷基；R3 是低级烷基或取代或未取代的苯基-低级烷基，Q 是单键、亚烷基或低级烯基，可任选被低级烷氧基或氧代基团取代；R4 是(i)氢原子，(ii)低级烷基，(iii)N-苯基-N-低级烷基氨基，(iv)苯基、苯氧基、苯硫基、苯磺酰氨基、1,4-苯醌基或苄硫基，可选择具有取代基，或(v)杂环基，可选择具有取代基；以及 n 是 2 或 3，或其药学上可接受的盐，可用作钙拮抗剂及其制备方法。