(2R)-1-{(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)-pyrrolidin-2-yl}carbonyl-N-((3S)-3-piperidylmethyl)pyrrolidine-2-carboxamide | 323182-20-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (2R)-1-{(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)-pyrrolidin-2-yl}carbonyl-N-((3S)-3-piperidylmethyl)pyrrolidine-2-carboxamide
• 英文别名: (2R)-1-{(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)pyrrolidin-2-yl}carbonyl-N-((3S)-3-piperidylmethyl)pyrrolidine-2-carboxamide；(2R)-1-[(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)pyrrolidine-2-carbonyl]-N-[[(3S)-piperidin-3-yl]methyl]pyrrolidine-2-carboxamide
• CAS: 323182-20-3
• 化学式: C₃₇H₄₄N₄O₄
• 分子量: 608.781
• InChiKey: NKECRNQFOBAVDC-FQVGEBPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-甲基丁醛 、 (2R)-1-{(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)-pyrrolidin-2-yl}carbonyl-N-((3S)-3-piperidylmethyl)pyrrolidine-2-carboxamide 生成 (2R)-1-{(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)-pyrrolidin-2-yl}carbonyl-N-{((3R)-1-(2-methylbutyl)-3-piperidyl)-methyl}pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Amide derivatives

  摘要：

  本发明涉及一种化合物，其由通式[I]表示[其中A代表以下式[ao]或[b0]Ar1的基团，Ar2和Ar3代表可选择取代的苯基；k代表0或1；m、n和s代表0、1或2；R1代表氢或可选择取代的低碳基；R2、R3、R4和R5要么代表氢或可选择取代的低碳基，要么R2和R3，或R4和R5一起代表三亚甲基等；R60代表氢、烷基或类似物；R61和R71要么代表烷基和类似物，要么一起代表三亚甲基等；X代表羰基或亚甲基；Y代表氮或甲烷基；Q-代表阴离子]等。本发明的化合物表现出对肌动蛋白M3受体的选择性拮抗作用，因此可用作治疗呼吸系统、泌尿系统和消化系统疾病的安全有效的药物，副作用小。

  公开号：

  US07452908B2
• 作为产物：
  描述：

  3,3,3-三苯基丙酸 在 sodium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 氯仿 为溶剂， 生成 (2R)-1-{(2S,4R)-4-hydroxy-1-(3,3,3-triphenylpropanoyl)-pyrrolidin-2-yl}carbonyl-N-((3S)-3-piperidylmethyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Identification of novel muscarinic M3 selective antagonists with a conformationally restricted Hyp-Pro spacer

  摘要：

  The identification of potent and selective muscarinic M-3 antagonists that are based on the recently discovered triphenylpropioamide derivative, 1, and have a unique amino acid spacer group is described. The introduction of a hydroxyproline-proline group to the spacer site and the use of a propyl or cyclopropylmethyl group as the piperidine N-substituent led to the discovery of the novel M-3 selective antagonists [8c, 8g; K-i < 2 nM (M-3), M-1/M-3 > 700-fold, M-2/M-3 > 180-fold], which have a more rigid structure than 1. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00843-0

文献信息

• Novel amide derivatives
  申请人：——

  公开号：US20040204369A1

  公开（公告）日：2004-10-14

  This invention relates to compounds which are represented by the general formula [I] 1 [in which A stands for a group of the following formula [a o ] or [b o ] 2 Ar 1 , Ar 2 and Ar 3 stand for optionally substituted phenyl; k stands for 0 or 1; m, n and s stand for 0, 1 or 2; R 1 stands for hydrogen or optionally substituted lower alkyl; R 2 , R 3 , R 4 and R 5 either stand for hydrogen or optionally substituted lower alkyl, or R 2 and R 3 , or R 4 and R 5 together stand for trimethylene and the like; R 60 stands for hydrogen, alkyl, or the like; R 61 and R 71 either stand for alkyl and the like, or together stand for trimethylene and the like; X stands for carbonyl or methylene; Y stands for nitrogen or methine; and Q − stands for anion], and the like. The compounds of the invention exhibit selective antagonism to muscarinic M 3 receptors, and therefore are useful as safe and effective agents showing little side effect, for treating diseases of the respiratory, urinary and digestive systems.

  本发明涉及由一般公式[I]1表示的化合物，其中A代表以下式[ao]或[bo]2Ar1的基团，Ar2和Ar3代表可选取代的苯基；k代表0或1；m、n和s代表0、1或2；R1代表氢或可选取代的低碳基；R2、R3、R4和R5要么代表氢或可选取代的低碳基，要么R2和R3，或者R4和R5一起代表三亚甲基等；R60代表氢、烷基或类似物；R61和R71要么代表烷基等，要么一起代表三亚甲基等；X代表羰基或亚甲基；Y代表氮或亚甲基；Q^-代表阴离子等。本发明的化合物表现出选择性的M3胆碱能受体拮抗作用，因此可用作治疗呼吸、泌尿和消化系统疾病的安全有效药物，副作用小。
• NOVEL AMIDE DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1213281B1

  公开（公告）日：2004-02-18
• Identification of a Novel 4-Aminomethylpiperidine Class of M₃ Muscarinic Receptor Antagonists and Structural Insight into Their M₃ Selectivity
  作者：Yufu Sagara、Takeshi Sagara、Minaho Uchiyama、Sachie Otsuki、Toshifumi Kimura、Toru Fujikawa、Kazuhito Noguchi、Norikazu Ohtake

  DOI：10.1021/jm051205r

  日期：2006.9.1

  Identification of a novel class of potent and highly selective M-3 muscarinic antagonists is described. First, the structure-activity relationship in the cationic amine core of our previously reported triphenylpropionamide class of M-3 selective antagonists was explored by a small diamine library constructed in solid phase. This led to the identification of M-3 antagonists with a novel piperidine pharmacophore and significantly improved subtype selectivity from a previously reported class. Successive modification on the terminal triphenylpropionamide part of the newly identified class gave 14a as a potent M-3 selective antagonist that had > 100-fold selectivity versus the M-1, M-2, M-4, and M-5 receptors (M-3: K-i = 0.30 nM, M-1/M-3 = 570-fold, M-2/M-3 = 1600-fold, M-4/M-3 = 140-fold, M-5/M-3 = 12000-fold). The possible rationale for its extraordinarily higher subtype selectivity than reported M-3 antagonists was hypothesized by sequence alignment of multiple muscarinic receptors and a computational docking of 14a into transmembrane domains of M-3 receptors.
• US6809108B1
  申请人：——

  公开号：US6809108B1

  公开（公告）日：2004-10-26
• US7452908B2
  申请人：——

  公开号：US7452908B2

  公开（公告）日：2008-11-18