methyl 7-chloro-3-oxo-4-[3-(4-phenylpiperazin-1-yl)propyl]-3,4-dihydro-2H-1,5-benzoxathiepin-4-carboxylate | 99228-62-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: methyl 7-chloro-3-oxo-4-[3-(4-phenylpiperazin-1-yl)propyl]-3,4-dihydro-2H-1,5-benzoxathiepin-4-carboxylate
• 英文别名: methyl 7-chloro-3-oxo-4-[3-(4-phenylpiperazin-1-yl)propyl]3,4-dihydro-2H-1,5-benzoxathiepine-4-carboxylate；methyl 7-chloro-3-oxo-4-[3-(4-phenylpiperazin-1-yl)propyl]-1,5-benzoxathiepine-4-carboxylate
• CAS: 99228-62-3
• 化学式: C₂₄H₂₇ClN₂O₄S
• 分子量: 475.008
• InChiKey: PAISJJFSUFYPDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  84.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 7-chloro-3-oxo-4-[3-(4-phenylpiperazin-1-yl)propyl]-3,4-dihydro-2H-1,5-benzoxathiepin-4-carboxylate 、 硼氢化钠 以to give cis-isomer and trans-isomer of methyl 7-chloro-3-hydroxy-4-[3-(4-phenylpiperazin-1-yl)propyl]-3,4-dihydro-2H-1,5-benzoxathiepine-4-carboxylate的产率得到methyl 7-chloro-3-hydroxy-4-[3-(4-phenylpiperazin-1-yl)propyl]-3,4-dihydro-2H-1,5-benzoxathiepine-4-carboxylate
  参考文献：
  名称：

  Ophthalmic composition for lowering intraocular pressure

  摘要：

  一种眼科组合物，包括式中的化合物：##STR1##其中R.sup.1和R.sup.2各自为氢、卤素、羟基、低碳基或低烷氧基，R.sup.3和R.sup.4各自为氢、可选取代的低烷基、可选取代的环烷基或可选取代的芳基烷基，或与相邻氮原子形成可选取代的环；X为氢、可选取代的低烷基、可选取代的芳基或可选酯化或酰胺化羧基，Y为>C.dbd.O或>CH--OR.sup.5，其中R.sup.5为氢、酰基或可选取代的氨基甲酰基，m为0至2的整数，n为1至6的整数，或其盐，并提供一种治疗青光眼的方法，包括给予该化合物或其盐。

  公开号：

  US05538974A1
• 作为产物：
  描述：

  methyl 7-chloro-3-oxo-3,4-dihydro-2H-1,5-benzoxathiepine-4-carboxylate 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 10.0h， 生成 methyl 7-chloro-3-oxo-4-[3-(4-phenylpiperazin-1-yl)propyl]-3,4-dihydro-2H-1,5-benzoxathiepin-4-carboxylate
  参考文献：
  名称：

  1,5-Benzoxathiepin derivatives. II. Synthesis and serotonin S2-receptor-blocking activity of aminoalkyl-substituted 3,4-dihydro-2H-1,5-benzoxathiepin-3-ols and related compounds.

  摘要：

  新化合物1,5-苯并氧硫杂蒽衍生物，即3,4-二氢-2H-1,5-苯并氧硫杂蒽-3-醇，在2-、3-或4-位上具有氨基烷基团，被合成并评估其对血清素S2受体阻断活性和肾上腺素α1受体阻断活性的作用。甲基4-氨基烷基-3-羟基-3,4-二氢-2H-1,5-苯并氧硫杂蒽-4-羧酸酯显示出显著的S2受体阻断活性。研究了结构-活性关系（包括构象研究结果和骨架修饰）。在一系列1,5-苯并氧硫杂蒽、1-苯并氧杂蒽和1-苯并硫杂蒽衍生物中，甲基顺式-3-羟基-7-甲氧基-4-[3-(4-苯基-1-哌嗪基)丙基]-3,4-二氢-2H-1,5-苯并氧硫杂蒽-4-羧酸酯盐酸盐（CV-5197）在结合谱图上显示出最强的S2受体阻断活性和选择性，并被选作进一步药理评估的候选药物。

  DOI：

  10.1248/cpb.35.1930

文献信息

• 1,5-benzoxathiepin derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04672064A1

  公开（公告）日：1987-06-09

  Novel 1,5-benzoxathiepin derivatives of the formula: ##STR1## [wherein R.sub.1 and R.sub.2 are independently hydrogen, halogen, hydroxy, lower alkyl or lower alkoxy; R.sub.3 and R.sub.4 are independently hydrogen, optionally substituted lower alkyl or optionally substituted cycloalkyl or optionally substituted aralkyl, or both jointly form an optionally substituted ring together with the adjacent nitrogen atom; X is hydrogen, optionally substituted lower alkyl, optionally substituted aryl or a carboxyl group which may be esterified or amidated; Y is ##STR2## (wherein R.sub.5 is hydrogen, acyl or optionally substituted carbamoyl); m is an integer of 0 to 2; n is an integer of 1 to 6] and salts thereof exhibit serotonin S.sub.2 receptor blocking activity, calcium antagonism, actions to relieve cerebral vasospasm and to improve renal circulation and diuretic and antithrombotic activities, and are of value as a prophylactic and therapeutic agent for ischemic cardiopathies, thrombosis, hypertension and cerebral circulatory disorders.

  式为：##STR1##的1,5-苯并噻吩衍生物 [其中R.sub.1和R.sub.2独立地为氢、卤素、羟基、低烷基或低烷氧基；R.sub.3和R.sub.4独立地为氢、可选择取代的低烷基、可选择取代的环烷基或可选择取代的芳基烷基，或与相邻的氮原子共同形成可选择取代的环；X为氢、可选择取代的低烷基、可选择取代的芳基或可酯化或酰胺化的羧基；Y为##STR2##（其中R.sub.5为氢、酰基或可选择取代的氨基甲酰基）；m为0至2的整数；n为1至6的整数]及其盐具有5-羟色胺S.sub.2受体阻滞活性、钙拮抗作用、缓解脑血管痉挛和改善肾循环和利尿和抗血栓活性，可作为缺血性心脏病、血栓形成、高血压和脑循环障碍的预防和治疗剂。
• 1,5-benzoxathiepin derivatives
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04751316A1

  公开（公告）日：1988-06-14

  Novel 1,5-benzoxathiepin derivatives of the formula: ##STR1## [wherein R.sub.1 and R.sub.2 are independently hydrogen, halogen, hydroxy, lower alkyl or lower alkoxy; R.sub.3 and R.sub.4 are independently hydrogen, optionally substituted lower alkyl or optionally substituted cycloalkyl or optionally substituted aralkyl, or both jointly form an optionally substituted ring together with the adjacent nitrogen atom; X is hydrogen, optionally substituted lower alkyl, optionally substituted aryl or a carboxyl group which may be esterified or amidated; Y is >C.dbd.O or >CH--OR.sub.5 (wherein R.sub.5 is hydrogen, acyl or optionally substituted carbamoyl); m is an integer of 0 to 2; n is an integer of 1 to 6] and salts thereof exhibit serotonin S.sub.2 receptor blocking activity, calcium antagonism, actions to relieve cerebral vasospasm and to improve renal circulation and diuretic and antithrombotic activities, and are of value as a prophylactic and therapeutic agent for ischemic cardiopathies, thrombosis, hypertension and cerebral circulatory disorders.

  式子为：##STR1## 的新型1,5-苯并噻吩衍生物，其中R.sub.1和R.sub.2独立地为氢、卤素、羟基、较低的烷基或较低的烷氧基；R.sub.3和R.sub.4独立地为氢、可选择的取代较低的烷基或可选择的取代环烷基或可选择的取代芳基烷基，或两者共同形成一个与相邻氮原子一起可选择取代的环；X为氢、可选择取代的较低烷基、可选择取代的芳基或可酯化或酰胺化的羧基；Y为>C.dbd.O或>CH--OR.sub.5（其中R.sub.5为氢、酰基或可选择取代的氨基甲酰基）；m为0到2的整数；n为1到6的整数。其盐具有血清素S.sub.2受体阻滞活性、钙拮抗作用、缓解脑血管痉挛和改善肾脏循环和利尿和抗血栓活性，是一种预防和治疗缺血性心脏病、血栓形成、高血压和脑循环障碍的有价值的药物。
• 1,5-Benzoxathiepin derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0145494A2

  公开（公告）日：1985-06-19

  Novel 1,5-benzoxathiepin derivatives of the formula: [wherein R1 and R2 are independently hydrogen, halogen, hydroxy, lower alkyl or lower alkoxy; R3 and R4 are independently hydrogen, optionally substituted lower alkyl or optionally substituted cycloalkyl or optionally substituted aralkyl, or both jointly form an optionally substituted ring together with the adjacent nitrogen atom; X is hydrogen, optionally substituted lower alkyl, optionally substituted aryl or a carboxyl group which may be esterified or amidated; Y is or (wherein R5 is hydrogen, acyl or optionally substituted carbamoyl); m is an integer of 0 to 2; n is an integer of 1 to 6] and salts thereof exhibit serotonin S2 receptor blocking activity, calcium antagonism, actions to relieve cerebral vasospasm and to improve renal circulation and diuretic and antithrombotic activities, and are of value as a prophylactic and therapeutic agent for ischemic cardiopathies, thrombosis, hypertension and cerebral circulatory disorders.

  式中的新型 1,5-苯并噁噻啶衍生物： [其中 R1 和 R2 独立地为氢、卤素、羟基、低级烷基或低级烷氧基；R3 和 R4 独立地为氢、任选取代的低级烷基或任选取代的环烷基或任选取代的芳烷基，或两者与相邻的氮原子共同形成任选取代的环；X 为氢、任选取代的低级烷基、任选取代的芳基或可被酯化或酰胺化的羧基；Y 为 或 (其中 R5 是氢、酰基或任选取代的氨基甲酰基）；m 是 0 至 2 的整数；n 是 1 至 6 的整数]及其盐具有 5-羟色胺 S2 受体阻断活性、钙拮抗作用、缓解脑血管痉挛和改善肾循环的作用以及利尿和抗血栓活性，可作为缺血性心脏病、血栓形成、高血压和脑循环障碍的预防和治疗药物。
• Ophthalmic composition containing a 1,5-benzoxathiepine derivative for treating glaucoma
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP0667156A1

  公开（公告）日：1995-08-16

  An ophthalmic composition comprising a compound of the formula wherein R1 and R2 are each a hydrogen, a halogen, a hydroxyl, a lower alkyl or a lower alkoxy, R3 and R4 are each a hydrogen, an optionally substituted lower alkyl, an optionally substituted cycloalkyl or an optionally substituted aralkyl, or form, together with the adjacent nitrogen atom, an optionally substituted ring, X is a hydrogen, an optionally substituted lower alkyl, an optionally substituted aryl or an optionally esterified or amidized carboxyl, Y is >C=O or >CH-OR5 wherein R5 is a hydrogen, an acyl or an optionally substituted carbamoyl, m is an integer of from 0 to 2, and n is an integer of from 1 to 6, or a salt thereof, and a method for the prevention and treatment of eye diseases, comprising administering said compound or a salt thereof.

  一种包含式化合物的眼科组合物 其中 R1 和 R2 分别为氢、卤素、羟基、低级烷基或低级烷氧基，R3 和 R4 分别为氢、任选取代的低级烷基、任选取代的环烷基或任选取代的芳烷基，或与邻近的氮原子一起形成任选取代的环，X 为氢、任选取代的低级烷基、任选取代的芳烷基或任选酯化或酰胺化的羧基，Y 为 >C=O 或 >CH-OR5 其中 R1 和 R2 分别为氢、卤素、羟基、低级烷基或低级烷氧基、Y 是 >C=O 或 >CH-OR5 其中 R5 是氢、酰基或任选取代的氨基甲酰基，m 是 0 至 2 的整数，n 是 1 至 6 的整数，或其盐，以及一种预防和治疗眼疾的方法，包括施用所述化合物或其盐。
• US4672064A
  申请人：——

  公开号：US4672064A

  公开（公告）日：1987-06-09