cis-(+/-)-2,3,3a,4,5,9b-hexahydro-9-bromo-3-(n-propyl)-1H-benz[e]indole | 149952-88-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: cis-(+/-)-2,3,3a,4,5,9b-hexahydro-9-bromo-3-(n-propyl)-1H-benz[e]indole
• 英文别名: cis-2,3,3a,4,5,9b-hexahydro-9-bromo-3-(n-propyl)-1H-benz[e]indole；cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-9-bromo-3-propyl-1H-benz[e]indole；(3aR,9bS)-9-bromo-3-propyl-1,2,3a,4,5,9b-hexahydrobenzo[e]indole
• CAS: 149952-88-5
• 化学式: C₁₅H₂₀BrN
• 分子量: 294.235
• InChiKey: VCEFUQAZQVYFKS-TZMCWYRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  二氧化碳 、 cis-(+/-)-2,3,3a,4,5,9b-hexahydro-9-bromo-3-(n-propyl)-1H-benz[e]indole 在 草酰氯 、 叔丁基锂 、 N,N-二甲基甲酰胺 作用下， 生成 cis-(3aR)-2,3,3a,4,5,9b-hexahydro-3-n-propyl-1H-benzindole-9-carboxylic acid chloride
  参考文献：
  名称：

  C-9 and N-Substituted Analogs of cis-(3aR)-(-)-2,3,3a,4,5,9b-Hexahydro-3-propyl-1H-benz[e]indole-9-carboxamide: 5-HT1A Receptor Agonists with Various Degrees of Metabolic Stability

  摘要：

  Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-LH-benz[e]indole-9-carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R(2)) were synthesized, and their serotonergic activity was evaluated in vitro and in vivo. Many of these compounds were incubated in the presence of rat hepatocytes, and the metabolic stability in vitro was compared to that of compound 1. Only the N-methyl and N-ethyl analogs ((-)-5a and (-)-5b) were more stable than compound 1, indicating that N-dealkylation is a major route of metabolism in this series. In addition, these analogs were found to be partial 5-HT1A receptor agonists in vivo. Modifications were also made to the carboxamide functionality of compound 1 (R(1) in 2) to yield substituted amides or ketones. Among these analogs, the methyl ketone (-)-15a was found to be a 5-HT1A agonist with full intrinsic activity in vivo and was approximately 20 times more potent than compound 1 and 5 times more potent than 8-OH-DPAT.

  DOI：

  10.1021/jm00004a018
• 作为产物：
  描述：

  cis-(3aR)-1,3,3a,4,5,9b-hexahydro-9-bromo-3-(1(R)-methylbenzyl)-1H-benzindole hydrochloride 在 甲醇 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 氯苯 为溶剂， 反应 49.0h， 生成 cis-(+/-)-2,3,3a,4,5,9b-hexahydro-9-bromo-3-(n-propyl)-1H-benz[e]indole
  参考文献：
  名称：

  顺式-（3aR）-（-）-2,3,3a，4,5,9b-六氢-3-丙基-1H-苯并[e]吲哚-9-羧酰胺的合成及生物活性：有力和选择性5 -HT1A受体激动剂，口服有效。

  摘要：

  顺式（3aR）-（-）-2,3,3a，4,5,9b-六氢-3-丙基-1H-苯并[e]吲哚-9-羧酰胺（（-）-在图3a）中描述了U93385。还合成并评估了顺式外消旋体及其对映体以及相应的反式对映体。这些类似物的合成是通过将9-羟基前体四步转化为9-羧酰胺或使用（R）-α-甲基苄基作为手性助剂的替代合成来实现的。发现顺式消旋体（+/-）-3a是选择性和有效的5-HT1A受体激动剂，其活性存在于顺式-（3aR）-对映体（-）-3a中。顺式（3aS）-对映体（+）-3a和反式-（3aR）-对映体（-）-3b显示部分5-HT1A激动剂活性，而其他反式-（3aS）-对映体（+）-3b没有显示活动。对映体（-）-3a在体外和体内生化/行为分析中均具有选择性。该化合物可有效降低小鼠的直肠温度，降低大鼠中脑血清素能神经元的放电速度，并抑制大鼠脑5-HT的合成。该化合物还减少了麻醉猫的交感神经放电和血压，

  DOI：

  10.1021/jm00067a018

文献信息

• Tricyclic compounds
  申请人：KYOWA HAKKO KOGYO CO., LTD.

  公开号：EP0312051A2

  公开（公告）日：1989-04-19

  Novel tricyclic compounds having a TXA2-antagonizing activity represented by formul (I): which strongly antagonize an action of thromboxane A2 and are expected to have preventive and therapeutic effects on ischemic diseases, cerebro-vascular diseases, etc.

  具有以式（I）为代表的 TXA2-拮抗活性的新型三环化合物： 它们能强烈拮抗血栓素 A2 的作用，有望对缺血性疾病、脑血管疾病等起到预防和治疗作用。
• Synthesis of isotopically labeled CIS-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-(N-propyl)-1H-benz[e]indole-9-carboxamide, a 5-HT1A receptor agonist
  作者：Wayne T. Stolle、John A. Easter、Mark J. Ackland、Susanne R. Haadsma-Svensson、Chiu-Hong Lin、Richard S. P. Hsi

  DOI：10.1002/(sici)1099-1344(199711)39:11<891::aid-jlcr34>3.0.co;2-q

  日期：1997.11

  The title compound is a potent and selective 5-HT1A receptor agonist with clinical potentials for treating anxiety and depression. It has been labeled with stable and radioactive isotopes to support ADME studies in animals and human subjects. Its carboxamide group was labeled with C-14, C-13, or C-13, N-15, and O-18. To provide a radioligand for investigating the receptor binding characteristics of the compound, we also labeled it with tritium in the N-propyl group to obtain the high specific activity of 86.7 Ci/mmol.
• CARBOXAMIDO-(1,2N)-CARBOCYCLIC-2-AMINOTETRALIN DERIVATIVES
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0586525B1

  公开（公告）日：1997-04-16
• US5486611A
  申请人：——

  公开号：US5486611A

  公开（公告）日：1996-01-23
• [EN] CARBOXAMIDO-(1,2N)-CARBOCYCLIC-2-AMINOTETRALIN DERIVATIVES
  申请人：THE UPJOHN COMPANY

  公开号：WO1992020655A1

  公开（公告）日：1992-11-26

  (EN) This invention is therapeutically useful tetralins and pharmaceutically acceptable acid addition salts thereof of formula (I), wherein X is -(CH2)n- or -C(R1)(H)-; R is C1-C8 alkyl; and R1 and R2 are the same or different and are selected from the group consisting of hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, aryl and benzyl. These compounds are useful to treat central nervous system disorders and are unexpectedly resistant to metabolism by the liver and have superior oral plasma bioavailability.(FR) Cette invention se rapporte à des tétralines à usage thérapeutique et à des sels d'addition d'acide pharmaceutiquement acceptables de la formule (I), où X représente -(CH2)n- ou -C(R1)(H)-; R représente alkyle C1-C8; et R1 et R2 sont identiques ou différents et sont choisis à partir du groupe composé d'hydrogène, d'alkyle C1-C8, d'alcényle C2-C8, d'alcynyle C2-C8, d'aryle et de benzyle. Ces compositions sont utilisées pour traiter des troubles du système nerveux central et opposent une résistance inattendue au métabolisme par le foie tout en présentant une biodisponibilité plasmatique orale supérieure.