N^α-(tert-butyloxycarbonyl)-(R)-tryptophan di-n-pentylamide | 127369-12-4

• 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: N^α-(tert-butyloxycarbonyl)-(R)-tryptophan di-n-pentylamide
• 英文别名: tert-butyl N-[(2R)-1-(dipentylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate
• CAS: 127369-12-4
• 化学式: C₂₆H₄₁N₃O₃
• 分子量: 443.63
• InChiKey: WWIWVSOIOCCJGZ-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  32
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  74.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N^α-(tert-butyloxycarbonyl)-(R)-tryptophan di-n-pentylamide 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-[(2R)-1-(dipentylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-4-oxo-1H-quinoline-2-carboxamide
  参考文献：
  名称：

  Cholecystokinin (CCK) antagonists: (R)-tryptophan-based hybrid antagonists of high affinity and selectivity for CCK-A receptors

  摘要：

  The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a novel series of benzotript-based hybrid antagonists N-alpha-(3'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (9, A-67396), N-alpha-(4',8'-dihydroxy-2'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (23, A-70276), and N-alpha-(3'-quinolylcarbonyl)-(R)-5'-hydroxytryptophan di-n-pentylamide (36, A-71134) which possess respectively binding affinities of 23, 21, and 11 nM for the pancreatic CCK-A receptor and which inhibit CCK8-induced amylase secretion. Compound 9 possesses a selectivity of > 500-fold for the pancreatic CCK-A receptor over the CCK-B receptor 1.

  DOI：

  10.1021/jm00116a002
• 作为产物：
  描述：

  BOC-D-色氨酸 、 二戊胺 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以57%的产率得到N^α-(tert-butyloxycarbonyl)-(R)-tryptophan di-n-pentylamide
  参考文献：
  名称：

  Cholecystokinin (CCK) antagonists: (R)-tryptophan-based hybrid antagonists of high affinity and selectivity for CCK-A receptors

  摘要：

  The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a novel series of benzotript-based hybrid antagonists N-alpha-(3'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (9, A-67396), N-alpha-(4',8'-dihydroxy-2'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (23, A-70276), and N-alpha-(3'-quinolylcarbonyl)-(R)-5'-hydroxytryptophan di-n-pentylamide (36, A-71134) which possess respectively binding affinities of 23, 21, and 11 nM for the pancreatic CCK-A receptor and which inhibit CCK8-induced amylase secretion. Compound 9 possesses a selectivity of > 500-fold for the pancreatic CCK-A receptor over the CCK-B receptor 1.

  DOI：

  10.1021/jm00116a002

文献信息

• Derivatives of tryptophan as CCK antagonists
  申请人：ABBOTT LABORATORIES

  公开号：EP0336356A2

  公开（公告）日：1989-10-11

  A compound of the formula: wherein R₁ and R₂ are independently selected from hydrogen, loweralkyl, cycloalkyl, loweralkenyl, adamantyl, aryl, substituted aryl, heterocyclic group, substituted alkyl, substituted amide, functionalized carbonyl, and nitrogen containing ring wherein R₁, R₂ and the adjacent nitrogen atom form a ring; R₁₁ is hydrogen, loweralkyl, or loweralkenyl; R₂₀ is hydrogen, loweralkyl, or loweralkenyl; B is -(CH₂)m-, substituted alkenylene, -QCH₂- wherein Q is O, S, NH or substituted amino, -CH₂Q- wherein Q is as defined or B is NH; Z is C=O, S(O)₂, or C=S; Ar is a heterocyclic group, aryl or substituted aryl; D is unsubstituted or substituted indol-3-yl, indolin-3-yl or oxindol-3-yl; and m is 0 to 4; or a pharmaceutically acceptable salt thereof.

  式中的化合物 其中 R₁ 和 R₂ 独立选自氢、低级烷基、环烷基、低级烯基、金刚烷基、芳基、取代的芳基、杂环基团、取代的烷基、取代的酰胺、官能化羰基和含氮环，其中 R₁、R₂ 和相邻的氮原子形成一个环； R₁₁ 是氢、低级烷基或低级烯基； R₂₀ 是氢、低级烷基或低级烯基； B 是-(CH₂)m-、取代烯基、-QCH₂-（其中 Q 是 O、S、NH 或取代氨基）、-CH₂Q-（其中 Q 如所定义）或 B 是 NH； Z 是 C=O、S(O)₂ 或 C=S； Ar 是杂环基团、芳基或取代的芳基； D 是未取代或取代的吲哚-3-基、吲哚啉-3-基或氧杂吲哚-3-基；以及 m 是 0 至 4； 或其药学上可接受的盐。
• EP0442878A4
  申请人：——

  公开号：EP0442878A4

  公开（公告）日：1991-10-23
• DERIVATIVES OF TRYPTOPHAN AS CCK ANTAGONISTS
  申请人：ABBOTT LABORATORIES

  公开号：EP0442878A1

  公开（公告）日：1991-08-28
• [EN] DERIVATIVES OF TRYPTOPHAN AS CCK ANTAGONISTS
  申请人：ABBOTT LABORATORIES

  公开号：WO1989010355A1

  公开（公告）日：1989-11-02

  (EN) A compound of formula (I) wherein R1 and R2 are independently selected from hydrogen, loweralkyl, cycloalkyl, loweralkenyl, adamantyl, aryl, substituted aryl, heterocyclic group, substituted alkyl, substituted amide, functionalized carbonyl, and nitrogen containing ring wherein R1, R2 and the adjacent nitrogen atom form a ring; R11 is hydrogen, loweralkyl, or loweralkenyl; R20 is hydrogen, loweralkyl, or loweralkenyl; B is -(CH2)m-, substituted alkenylene, -QCH2- wherein Q is O, S, NH or substituted amino, -CH2Q- wherein Q is as defined or B is NH; Z is C=O, S(O)2, or C=S; Ar is a heterocyclic group, aryl or substituted aryl; D is unsubstituted or substituted indol-3-yl, indolin-3-yl or oxindol-3-yl; and m is 0 to 4; or a pharmaceutically acceptable salt thereof.(FR) L'invention concerne un composé de la formule (I), dans laquelle R1 et R2 sont sélectionnés indépendamment parmi l'hydrogène, un alkyle inférieur, un cycloalkyle, un alkényle inférieur, un adamantyle, un aryle, un aryle substitué, un groupe hétérocyclique, un alkyle substitué, un amide substitué, un carbonyle fonctionnalisé et un cycle contenant de l'azote dans lequel R1, R2 et l'atome d'azote adjacent forment un cycle; R11 représente un hydrogène, un alkyle inférieur ou un alkényle inférieur; R20 représente un hydrogène, un alkyle inférieur ou un alkényle inférieur; B représente -(CH2)m-, un alkénylène substitué, -QCH2- où Q représente O, S, NH ou un amino substitué, -CH2Q- où Q est tel qu'il est défini ci-dessus ou B représente NH; Z représente C=O, S(O)2, ou C=S; Ar est un groupe hétérocyclique, un aryle ou un aryle substitué; D est un oxindol-3-yl, indolin-3-yl ou indol-3-yl substitué ou non-substitué; et m est compris entre 0 et 4; ou un sel pharmaceutiquement acceptable de ce composé.
• Cholecystokinin (CCK) antagonists: (R)-tryptophan-based hybrid antagonists of high affinity and selectivity for CCK-A receptors
  作者：James F. Kerwin、Frank Wagenaar、Hana Kopecka、Chun Wel Lin、Thomas Miller、David Witte、Michael Stashko、Alex M. Nadzan

  DOI：10.1021/jm00116a002

  日期：1991.12

  The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a novel series of benzotript-based hybrid antagonists N-alpha-(3'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (9, A-67396), N-alpha-(4',8'-dihydroxy-2'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (23, A-70276), and N-alpha-(3'-quinolylcarbonyl)-(R)-5'-hydroxytryptophan di-n-pentylamide (36, A-71134) which possess respectively binding affinities of 23, 21, and 11 nM for the pancreatic CCK-A receptor and which inhibit CCK8-induced amylase secretion. Compound 9 possesses a selectivity of > 500-fold for the pancreatic CCK-A receptor over the CCK-B receptor 1.