Methanesulfonic acid 2-(2,8-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yloxy)-ethyl ester | 1026804-76-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: Methanesulfonic acid 2-(2,8-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yloxy)-ethyl ester
• 英文别名: 2-[(6,13-Dichloro-2-tricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaenyl)oxy]ethyl methanesulfonate
• CAS: 1026804-76-1
• 化学式: C₁₈H₁₈Cl₂O₄S
• 分子量: 401.311
• InChiKey: AACXEQGBWHQQHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methanesulfonic acid 2-(2,8-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yloxy)-ethyl ester 在 lithium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 79.0h， 生成 1-<2-<(2,8-dichloro-10,11-dihydro-5H-dibenzocyclohepten-5-yl)oxy>ethyl>-3-piperidinecarboxylic acid
  参考文献：
  名称：

  Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake

  摘要：

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

  DOI：

  10.1021/jm00100a032
• 作为产物：
  描述：

  3-氯苄溴 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 三氯化铝 、 dilithium tetrachlorocuprate 、 sodium hydride 、 magnesium 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二硫化碳 、 乙醚 、 二氯甲烷 、 异丙醇 为溶剂， 反应 68.25h， 生成 Methanesulfonic acid 2-(2,8-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yloxy)-ethyl ester
  参考文献：
  名称：

  Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake

  摘要：

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

  DOI：

  10.1021/jm00100a032

文献信息

• Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake
  作者：Michael R. Pavia、Sandra J. Lobbestael、David Nugiel、Daniel R. Mayhugh、Vlad E. Gregor、Charles P. Taylor、Roy D. Schwarz、Laura Brahce、Mark G. Vartanian

  DOI：10.1021/jm00100a032

  日期：1992.10

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.