4,5,6,7,8,8a-hexahydro-4,8-ethenocycloheptapyrrole-1,3(2H,3aH)-dione | 6705-94-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 4,5,6,7,8,8a-hexahydro-4,8-ethenocycloheptapyrrole-1,3(2H,3aH)-dione
• 英文别名: hexahydro-4,8-ethenocyclohepta[c]pyrrole-1,3-(2H3aH)dione；4,5,6,7,8,8a-hexahydro-4,8-ethenocyclohepta[c]pyrrole-1,3-(2H,3aH)-dione；4-Azatricyclo[5.3.2.02,6]dodec-11-ene-3,5-dione
• CAS: 6705-94-8
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: NCTZQEWQACWPOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,5,6,7,8,8a-hexahydro-4,8-ethenocycloheptapyrrole-1,3(2H,3aH)-dione 以85%的产率得到
  参考文献：
  名称：

  ABOU-GHARBIA, MAGID;PATEL, USHA R.;WEBB, MICHAEL B.;MOYER, JOHN A.;ANDREE+, J. MED. CHEM., 31,(1988) N 7, 1382-1392

  摘要：

  DOI：
• 作为产物：
  描述：

  马来酰亚胺 、 1,3-环庚二烯 以 xylene 为溶剂， 反应 3.0h， 以70%的产率得到4,5,6,7,8,8a-hexahydro-4,8-ethenocycloheptapyrrole-1,3(2H,3aH)-dione
  参考文献：
  名称：

  Polycyclic aryl- and heteroarylpiperazinyl imides as 5-HT1A receptor ligands and potential anxiolytic agents: synthesis and structure-activity relationship studies

  摘要：

  A series of polycyclic aryl- and heteroarylpiperazinyl imides were prepared and tested in various receptor-binding and behavioral tests. Parameters measured included in vitro inhibition of D2 and 5-HT1A receptor binding, inhibition of apomorphine (APO) induced stereotyped and climbing behavior, and activity in blocking conditioned avoidance responding (CAR). Several compounds demonstrated moderate to high affinity for the 5-HT1A receptor binding site; compounds 27 and 36 containing the serotonin mimetic (o-methoxyphenyl)piperazinyl moiety and compounds 42 and 50 containing the 2-pyrimidinylpiperazinyl moiety displayed the highest affinity, being equal to that of the 5-HT1A agonist 8-OH-DPAT (Ki = 1-1.3 nM). In addition to affinity at 5-HT1A binding sites, many compounds were active in blocking CAR. Compound 34, 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]hexahydro-4,7-etheno-1H- cyclobut[f]isoindole-1,3(2H)-dione, demonstrated 3 times the activity of buspirone, blocking CAR in rats with an AB50 of 13 mg/kg. It also displayed high affinity for the 5-HT1A receptor (Ki = 16 nM), which is at least 20 times higher than its affinity for D2 (Ki = 345 nM) and 5-HT2 (Ki = 458 nM) receptors. Compound 34 was selected for further preclinical and pharmacokinetic evaluations for possible development as an anxiolytic agent. Structure-activity relationships within this series are discussed.

  DOI：

  10.1021/jm00402a023

文献信息

• 1,4-diazine derivatives
  申请人：American Home Products Corporation

  公开号：US04851533A1

  公开（公告）日：1989-07-25

  The compounds: ##STR1## in which n is one of the integers 0 or 1; and when n is 1, R.sup.1 and R.sup.2 are hydrogen or alkyl of 1 to 3 carbon atoms, and R.sup.6 and R.sup.7, taken together, are tetramethylene, pentamethylene or hexamethylene; and when n is 0, R.sup.1 and R.sup.2, taken together, are ##STR2## where the dotted line represents optional unsaturation; p is one of the integers 2, 3, 4 or 5; q is one of the integers 1, 2 or 3; and R.sup.3 is ##STR3## where R.sup.4 is hydrogen, alkyl of 1 to 6 carbon atoms; alkoxy of 1 to 6 carbon atoms or halo; and R.sup.5 is hydrogen or halo; or a pharmaceutically acceptable salt thereof are antipsychotic and anxiolytic agents.

  化合物：##STR1## 其中n是0或1之一的整数；当n为1时，R.sup.1和R.sup.2为氢或1至3个碳原子的烷基，而R.sup.6和R.sup.7共同取自四亚甲基、五亚甲基或六亚甲基；当n为0时，R.sup.1和R.sup.2共同取自##STR2##其中点线表示可选不饱和度；p是2、3、4或5之一的整数；q是1、2或3之一的整数；而R.sup.3是##STR3##其中R.sup.4是氢、1至6个碳原子的烷基；1至6个碳原子的烷氧基或卤素；而R.sup.5是氢或卤素；或其药学上可接受的盐是抗精神病和抗焦虑剂。
• Fused bicyclic imides with psychotropic activity
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0220873A1

  公开（公告）日：1987-05-06

  There are disclosed compounds of the formula wherein R represents formula III or represents -CHR1-CHR2-wherein R1 and R2 taken together represent formula II or IV with the proviso that the sum of o and p in formula III and in formula IV where Y is -(CH2)0- is not zero; R3 is unsubstituted or substituted phenyl, 2-pyridinyl, 2-pyrimidinyl, 2-pyrazinyl or 3-pyridazinyl, where the substituents are selected from the group lower alkyl, lower alkoxy, halo, cyano, nitro and trifluoromethyl, with the proviso that when R1 and R2 taken together represent formula II in which X is O,methylene or dimethylene, R3 is other than unsubstituted or substituted phenyl, 2-pyridinyl or 2-pyrimidinyl; Y is -(CH2)0- or vinylene; X is lower alkylene, vinylene or O; m is 2-4; n is 1 - 3; o is 0 - 3; p is 0 - 4; .... represents a single or double bond; and the pharmaceutically acceptable salts thereof and their use as antipsychotic/ anxiolytic agents having a low liability for extrapyramidal side effects.

  公开了如下式的化合物 其中 R 代表式 III 或代表 -CHR1-CHR2- 其中 R1 和 R2 合在一起代表式 II 或 IV 但在式 III 和 Y 为-(CH2)0-的式 IV 中，o 和 p 之和不为零；R3 为未取代或取代的苯基、2-吡啶基、2-嘧啶基、2-吡嗪基或 3-哒嗪基，其中取代基选 自低级烷基、低级烷氧基、卤代、氰基、硝基和三氟甲基，但当 R1 和 R2 合在一起代表式 II（其中 X 为 O、亚甲基或二亚甲基）时，R3 不是未取代或取代的苯基、2-吡啶基或 2-嘧啶基； Y 是-(CH2)0-或亚乙烯； X 是低级亚烷基、亚乙烯基或 O； m 是 2-4； n 是 1 - 3 o 是 0 - 3 p 为 0 - 4； .... 代表单键或双键；及其药学上可接受的盐类，以及它们作为抗精神病药/抗焦虑药的用途，具有较低的锥体外系副作用。
• ABOU-GHARBIA, MAGID A.
  作者：ABOU-GHARBIA, MAGID A.

  DOI：——

  日期：——
• ABOU-GHARBIA, MAGID;PATEL, USHA R.;WEBB, MICHAEL B.;MOYER, JOHN A.;ANDREE+, J. MED. CHEM., 31,(1988) N 7, 1382-1392
  作者：ABOU-GHARBIA, MAGID、PATEL, USHA R.、WEBB, MICHAEL B.、MOYER, JOHN A.、ANDREE+

  DOI：——

  日期：——
• US4851533A
  申请人：——

  公开号：US4851533A

  公开（公告）日：1989-07-25