1-acetyl-2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole | 422573-30-6

• 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: 1-acetyl-2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole
• 英文别名: 1-[2-(5-propyl-1H-1,2,4-triazol-3-yl)-2,3-dihydroindol-1-yl]ethanone
• CAS: 422573-30-6
• 化学式: C₁₅H₁₈N₄O
• 分子量: 270.334
• InChiKey: CURQCRZFDHOSJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-acetyl-2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole 在 盐酸 、 三氟乙酸 作用下， 生成 2-Amino-1-[2-(5-propyl-4H-[1,2,4]triazol-3-yl)-2,3-dihydro-indol-1-yl]-ethanone
  参考文献：
  名称：

  Tripeptidyl-peptidase II (TPP II) inhibitory activity of ( S )-2,3-dihydro-2-(1 H -imidazol-2-yl)-1 H -indoles, a systematic SAR evaluation. Part 2

  摘要：

  We have systematically explored the structure-activity relationship (SAR) for a series of compounds 2 as inhibitors of tripeptidyl-peptidase II (TPP II), a serine protease responsible for the degradation of cholecystokinin-8 (CCK-8). This SAR evaluation of the core structure 2 suggest a fairly restrictive pharmacophore for such related structures, but has yielded a limited set of compounds (2b, 2c, 2d, 2s, and 2t) with potent TPP II inhibitory activity (IC50 4-11 nM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.014
• 作为产物：
  描述：

  1-Acetyl-2,3-dihydro-1H-indole-2-carbonitrile 在 吡啶 、 硫化氢 、 三乙胺 作用下， 生成 1-acetyl-2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole
  参考文献：
  名称：

  Tripeptidyl-peptidase II (TPP II) inhibitory activity of ( S )-2,3-dihydro-2-(1 H -imidazol-2-yl)-1 H -indoles, a systematic SAR evaluation. Part 2

  摘要：

  We have systematically explored the structure-activity relationship (SAR) for a series of compounds 2 as inhibitors of tripeptidyl-peptidase II (TPP II), a serine protease responsible for the degradation of cholecystokinin-8 (CCK-8). This SAR evaluation of the core structure 2 suggest a fairly restrictive pharmacophore for such related structures, but has yielded a limited set of compounds (2b, 2c, 2d, 2s, and 2t) with potent TPP II inhibitory activity (IC50 4-11 nM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.014
• 作为试剂：
  描述：

  丁酰肼 、 1-acetyl-2,3-dihydro-1H-indole-2-carbothioamide 在 水 、 1-acetyl-2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole 作用下， 以 正丁醇 为溶剂， 反应 240.17h， 以to give 1-acetyl-2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole (compound 91)的产率得到1-acetyl-2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole
  参考文献：
  名称：

  Tripeptidyl peptidase inhibitors

  摘要：

  本发明涉及式（I）的新化合物，它们是膜三肽基肽酶的抑制剂，该酶负责失活内源性神经肽，如胆囊收缩素（CCKs）。

  公开号：

  US08247432B2

文献信息

• TRIPEPTIDYL PEPTIDASE INHIBITORS
  申请人：Breslin Joseph Henry

  公开号：US20080108653A1

  公开（公告）日：2008-05-08

  The present invention is concerned with novel compounds of formula (I) which are inhibitors of a membrane tripeptidyl peptidase responsible for the inactivation of endogenous neuropeptides such as cholecystokinis (CCKs). The invention further relates to methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use as a medicine of said compounds. wherein n is an integer 0 or 1; X represents O; S; or —(CR 4 R 5 ) m — wherein m is an integer 1 or 2; R 4 and R 5 are each independently from each other hydrogen or C 1-4 alkyl; R 1 is C 1-6 alkylcarbonyl optionally substituted with hydroxy; C 1-6 alkyloxycarbonyl; aminoC 1-6 alkylcarbonyl wherein the C 1-6 alkyl group is optionally substituted with C 3-6 cycloalkyl; mono- and di(C 1-4 alkyl)aminoC 1-6 alkylcarbonyl; aminocarbonyl substituted with aryl; C 1-6 alkylcarbonyloxyC 1-6 alkylcarbonyl; C 1-6 alkyloxycarbonylaminoC 1-6 alkylcarbonyl wherein the amino group is optionally substituted with C 1-4 alkyl; an amino acid; C 1-6 alkyl substituted with amino; or arylcarbonyl; R 2 is an optionally substituted 5-membered heterocycle, or R 2 is optionally substituted benzimidazole; R 3 is a bivalent radical —CH 2 CH 2 — optionally substituted with halo or phenylmethyl; or R 3 is a bivalent radical of formula

  本发明涉及公式（I）的新化合物，该化合物是膜三肽基肽酶的抑制剂，该酶负责失活内源性神经肽，如胆囊收缩素（CCK）。本发明还涉及制备此类化合物的方法，包括含有该化合物的制药组合物以及该化合物作为药物的用途。 其中，n是整数0或1；X代表O、S或-（CR4R5）m-，其中m是整数1或2；R4和R5各自独立于氢或C1-4烷基；R1是C1-6烷基羰基，可选地取代羟基；C1-6烷氧羰基；氨基C1-6烷基羰基，其中C1-6烷基基团可选地取代C3-6环烷基；单和双（C1-4烷基）氨基C1-6烷基羰基；取代芳基的氨基羰基；C1-6烷基羰氧基C1-6烷基羰基；C1-6烷氧羰基氨基C1-6烷基羰基，其中氨基可选地取代C1-4烷基；氨基酸；取代氨基的C1-6烷基；或芳基羰基；R2是可选取代的5-成员杂环，或R2是可选取代的苯并咪唑；R3是二价基团-CH2CH2-，可选地取代卤素或苯甲基；或R3是公式的二价基团
• US7125891B2
  申请人：——

  公开号：US7125891B2

  公开（公告）日：2006-10-24
• US7947713B2
  申请人：——

  公开号：US7947713B2

  公开（公告）日：2011-05-24
• US8247432B2
  申请人：——

  公开号：US8247432B2

  公开（公告）日：2012-08-21
• [EN] TRIPEPTIDYL PEPTIDASE INHIBITORS<br/>[FR] INHIBITEURS DE TRIPEPTIDYL PEPTIDASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2002036116A2

  公开（公告）日：2002-05-10

  The present invention is concerned with novel compounds of formula (I) which are inhibitors of a membrane tripeptidyl peptidase responsible for the inactivation of endogenous neuropeptides such as cholecystokinis (CCKs). The invention further relates to methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use as a medicine of said compounds. (I) wherein n is an integer (0) or (1); X represents O; S; or -(CR4R5)m- wherein m is an integer (1) or (2); R?4 and R5¿ are each independently from each other hydrogen or C¿1-4?alkyl; R?1¿ is C¿1-6?alkylcarbonyl optionally substituted with hydroxy; C1-6alkyloxycarbonyl; aminoC1-6alkylcarbonyl wherein the C1-6alkyl group is optionally substituted with C3-6cycloalkyl; mono- and di(C1-4alkyl)aminoC1-6alkylcarbonyl; aminocarbonyl substituted with aryl; C1-6alkylcarbonyloxyC1-6alkylcarbonyl; C1-6alkyloxycarbonylaminoC1-6alkylcarbonyl wherein the amino group is optionally substituted with C1-4alkyl; an amino acid; C1-6alkyl substituted with amino; or arylcarbonyl; R?2¿ is an optionally substituted (5)-membered heterocycle, or R2 is optionally substituted benzimidazole; R3 is a bivalent radical -CH¿2?CH2- optionally substituted with halo or phenylmethyl; or R?3¿ is a bivalent radical of formula (II).