methyl 2-(3-chloropropyl)-8-methoxy-3-oxo-2,3,4,5-tetrahydro-1-benzoxepin-2-carboxylate | 108495-61-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噁庚英
• 英文名称: methyl 2-(3-chloropropyl)-8-methoxy-3-oxo-2,3,4,5-tetrahydro-1-benzoxepin-2-carboxylate
• 英文别名: methyl 2-(3-chloropropyl)-8-methoxy-3-oxo-4,5-dihydro-1-benzoxepine-2-carboxylate
• CAS: 108495-61-0
• 化学式: C₁₆H₁₉ClO₅
• 分子量: 326.777
• InChiKey: BEIHZPYXNUJOET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(3-chloropropyl)-8-methoxy-3-oxo-2,3,4,5-tetrahydro-1-benzoxepin-2-carboxylate 在 sodium tetrahydroborate 、 potassium iodide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 methyl cis-3-hydroxy-8-methoxy-2-<3-(4-phenyl-1-piperazinyl)propyl>-2,3,4,5-tetrahydro-1-benzoxepin-2-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
• 作为产物：
  描述：

  methyl 3-(4-methoxy-2-methoxycarbonylmethyloxyphenyl)propionate 在 sodium hydride 、 potassium carbonate 、 potassium iodide 作用下， 以 甲苯 、 乙腈 、 叔丁醇 为溶剂， 反应 3.5h， 生成 methyl 2-(3-chloropropyl)-8-methoxy-3-oxo-2,3,4,5-tetrahydro-1-benzoxepin-2-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

• 2-(piperazinylalkyl)-1-benzothiepin, 1-benzoxepin, and 1,5-benzodioxepin
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04736031A1

  公开（公告）日：1988-04-05

  Novel condensed seven-membered heterocyclic compounds 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, 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 in which R.sub.5 is hydrogen, acyl or optionally substituted carbamoyl, A is oxygen atom or sulfur atom, E is oxygen atom or methylene, and G is lower alkylene, provided that when A is sulfur atom, E is methylene, and salts thereof exhibit serotonin S.sub.2 receptor blocking activity, actions to relieve cerebral vasospasm and antithrombotic activity, and are of value as a prophylactic and therapeutic agent for ischemic cardiopathies, thrombosis, hypertension and cerebral circulatory disorders.

  本发明涉及一种化合物，其为七元杂环化合物，化学式为：##STR1## 其中R.sub.1和R.sub.2分别为氢、卤素、羟基、低碳基或低烷氧基；R.sub.3和R.sub.4分别为氢、可选取代的低碳基、可选取代的环烷基或可选取代的芳基烷基；或者两者共同形成一个可选取代的环，与相邻的氮原子一起；X为氢、可选取代的低碳基、可选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、酰基或可选取代的氨基甲酰基；A为氧原子或硫原子；E为氧原子或亚甲基；G为低碳基亚烷基。当A为硫原子时，E为亚甲基。该化合物的盐表现出5-羟色胺S.sub.2受体阻断活性，缓解脑血管痉挛和抗血栓活性，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。
• Condensed seven-membered heterocyclic compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0205264A1

  公开（公告）日：1986-12-17

  Novel condensed seven-membered heterocyclic compounds of the formula: wherein R, and R2 are independently hydrogen, halogen, hydroxy, lower alkyl or lower alkoxy, R3 and R4 are independently hydrogen, optionally substituted lower alkyl, 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=O or CH-OR5 in which Rs is hydrogen, acyl or optioinally substituted carbamoyl, A is an oxygen atom or sulfur atome, E is an oxygen atom or methylene, and G is lower alkylene, provided that when A is a sulfur atom, E is methylene, and salts thereof exhibit serotonin S2 receptor blocking activity, actions to relieve cerebral vasospasm and antithrombotic activity, and are of value as a prophylactic and therapeutic agent for ischemic cardiopathies, thrombosis, hypertension and cerebral circulatory disorders.

  式中的新型缩合七元杂环化合物： 其中 R 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、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 是氢、任选取代的低级烷基、任选取代的芳基或可酯化或酰胺化的羧基、 Y 是 C=O 或 CH-OR5，其中 Rs 是氢、酰基或被选择取代的氨基甲酰基、 A 是氧原子或硫原子，E 是氧原子或亚甲基，以及 G 是低级亚烷基，条件是当 A 是硫原子时，E 是亚甲基、 及其盐类具有 5-羟色胺 S2 受体阻断活性、缓解脑血管痉挛的作用和抗血栓活性，具有作为 具有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价值。
• SUGIHARA, HIROSADA;MABUCHI, HIROSHI;HIRATA, MINORU;IMAMOTO, TETSUJI;KAWAM+, CHEM. AND PHARM. BULL., 35,(1987) N 5, 1930-1952
  作者：SUGIHARA, HIROSADA、MABUCHI, HIROSHI、HIRATA, MINORU、IMAMOTO, TETSUJI、KAWAM+

  DOI：——

  日期：——
• US4736031A
  申请人：——

  公开号：US4736031A

  公开（公告）日：1988-04-05
• 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.
  作者：HIROSADA SUGIHARA、HIROSHI MABUCHI、MINORU HIRATA、TETSUJI IMAMOTO、YUTAKA KAWAMATSU

  DOI：10.1248/cpb.35.1930

  日期：——

  Novel 1, 5-benzoxathiepin derivatives, 3, 4-dihydro-2H-1, 5-benzoxathiepin-3-ols with an aminoalkyl group at the 2-, 3- or 4-position, were synthesized and evaluated for serotonin S2-receptor-blocking activity and adrenergic α1-receptor-blocking activity. Methyl 4-aminoalky1-3-hydroxy-3, 4-dihydro-2H-1, 5-benzoxathiepin-4-carboxylates showed significant S2-receptor-block-ing activities. Structure-activity relationships (including the results of a conformational study and skeletal modifications) were examined. In the series of 1, 5-benzoxathiepin, 1-benzoxepin and 1-benzothiepin derivatives, methyl cis-3-hydroxy-7-methoxy-4- [3- (4-phenyl -1-piperazinyl) propyl] -3, 4-dihydro-2H-1, 5-benzoxathiepin-4-carboxylatehydrochloride (CV-5197) showed the most potent and the most selective S2-receptor-blocking activity in the binding profile, and was chosen as a candidate for further pharmacological evaluation.

  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。