(2S,5S,11bR)-2-(benzyloxycarbonyl)amino-5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino-<8,7-b>indole | 170552-57-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (2S,5S,11bR)-2-(benzyloxycarbonyl)amino-5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino-<8,7-b>indole
• 英文别名: (2S,5S,11bR)-2-(benzyloxycarbonyl)amino-5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole；(2S,5S,11bR)-3-oxo-2-(phenylmethoxycarbonylamino)-1,2,5,6,11,11b-hexahydroindolizino[8,7-b]indole-5-carboxylic acid
• CAS: 170552-57-5
• 化学式: C₂₃H₂₁N₃O₅
• 分子量: 419.437
• InChiKey: DYMLKQUGZUMYOI-OTWHNJEPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,5S,11bR)-2-(benzyloxycarbonyl)amino-5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino-<8,7-b>indole 在 TEA 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三氟乙酸 作用下， 生成 (S)-3-[((2S,5S,11bR)-2-Benzyloxycarbonylamino-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole-5-carbonyl)-amino]-4-phenyl-butyric acid
  参考文献：
  名称：

  Highly constrained dipeptoid analogues containing a type II′ β-turn mimic as novel and selective CCK-A receptor ligands

  摘要：

  Conformationally constrained dipeptoid analogues containing the type II' beta-turn mimic (2S,5S,11bR)-2-amino-3-oxohexahydroindolizino[8,7-b] indoled-carboxylate framework in place of the alpha-MeTrp residue, show high binding affinity and selectivity for CCK-A receptors, suggesting that a turn-like conformation could contribute to the bioactive conformation at this CCK receptor subtype. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00677-5
• 作为产物：
  描述：

  (2S,5S,11bR)-2-(benzyloxycarbonyl)amino-5-methoxycarbonyl-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino<8,7-b>indole 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以94%的产率得到(2S,5S,11bR)-2-(benzyloxycarbonyl)amino-5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino-<8,7-b>indole
  参考文献：
  名称：

  2-Amino-3-oxohexahydroindolizino[8,7-b]indole-5-carboxylate derivatives as new scaffolds for mimicking β-turn secondary structures. Molecular dynamics and stereoselective synthesis

  摘要：

  Highly constrained 2-amino-3-oxohexahydroindolizino[8-7-b]indole-5-carboxylate derivatives of general formula 1 have been developed as novel beta-turn mimetics. Molecular dynamics studies on model structures 2a and 2b have revealed that both indolizinoindole derivatives are able to adopt conformations close to those of ideal type II' beta-turn. The asymmetric synthesis of this heterocyclic system was accomplished from 1,3-di- and 1,2,3-trisubstituted tetrahydro-beta-carbolines, which were prepared in stereoselective or stereospecific way by application of the Pictet-Spengler reaction.

  DOI：

  10.1016/0040-4020(95)00402-t

文献信息

• β-Turned Dipeptoids as Potent and Selective CCK₁ Receptor Antagonists
  作者：Mercedes Martín-Martínez、Natalia De la Figuera、Miriam Latorre、Rosario Herranz、M. Teresa García-López、Edurne Cenarruzabeitia、Joaquín Del Río、Rosario González-Muñiz

  DOI：10.1021/jm000959x

  日期：2000.10.1

  approximately 6-fold higher CCK(1) selectivity than analogue 16a, with the type II mimetic. From these results, we propose that the presence of a beta-turn-like conformation within the peptide backbone of dipeptoids could contribute to their bioactive conformation at the CCK(1) receptor subtype. Concerning functional activity, compounds 15a and 16a behave as CCK(1) receptor antagonists.

  为了提高我们对CCK（1）拮抗剂的生物活性构象的认识，我们先前曾描述过用（2S，5S，11bR）-2-氨基-3-氧六氢吲哚并[8,7- b] indole-5-carbox ylate（IBTM）骨架，一种探测的II'型β-转弯模拟物，导致了受限的类似物（2S，5S，11bR，1'S）-和（2S，5S，11bR，1'R）- 2-（苄氧羰基）氨基-5- [1'-苄基-2'-（羧基）乙基]氨基甲酰基-3-氧代-2,3,5,6,11,11b-六氢-1H-吲哚并[8， 7-b]吲哚，1a，b，显示出对CCK（1）受体的高结合亲和力和选择性。在这份报告中，我们描述了化合物1的新类似物的合成和结合概况，旨在探索C末端残基的重要性以及受体结合亲和力和选择性的β转角类型的重要性。结构亲和关系的研究表明，C末端的游离羧酸和Phe和betaHph残基的S构型有利于CCK（1）受体识别。而且，该受体亚型的选择性
• Effects of the incorporation of IBTM β-turn mimetics into the dipeptoid CCK1 receptor agonist PD 170292
  作者：Mercedes Martı́n-Martı́nez、Miriam Latorre、M.Teresa Garcı́a-López、Edurne Cenarruzabeitia、Joaquı́n Del Rı́o、Rosario González-Muñiz

  DOI：10.1016/s0960-894x(01)00630-8

  日期：2002.1

  Replacement of the 2-Adoc-D-alphaMeTrp residue in the non-selective CCK1 receptor agonist PD 170292 by the Z-(2R,5R, 11bS)-IBTM skeleton, able to fix a type 11 beta-turn-like conformation, led to a conformationally restricted dipeptoid analogue, namely 3a, which exhibited a notable increase in the CCK1 selectivity and antagonist properties. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 2(S)-amino-3-oxo-11b(R)-hexahydroindolizino[8,7-b]indole-5(S)-carboxylate as a new type of β-turn dipeptide mimetic
  作者：Natalia de la Figuera、Isabel Rozas、M. Teresa García-López、Rosario González-Muñiz

  DOI：10.1039/c39940000613

  日期：——

  Molecular-modelling studies have shown that 2(S)-amino-3-oxo-11 b(R)-hexahydroindolizino[8,7-b]indole-5(S)-carboxylate, stereoselectively prepared by Pictet-Spengler reaction between H-Trp-OMe and Z-Asp(H)-OBz and subsequent gamma-lactamization, behaves as a type-ll' beta-turn inducing mimetic.