(2S,4S)-4-fluoro-1-{2-[3-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-1,1-dimethyl-3-oxo-propylamino]-acetyl}-pyrrolidine-2-carbonitrile | 1186426-80-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,4S)-4-fluoro-1-{2-[3-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-1,1-dimethyl-3-oxo-propylamino]-acetyl}-pyrrolidine-2-carbonitrile
• 英文别名: (2S,4S)-4-fluoro-1-(2-(4-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)-2-methyl-4-oxobutan-2-ylamino)acetyl)pyrrolidine-2-carbonitrile；(2S,4S)-4-fluoro-1-[2-[[4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methyl-4-oxobutan-2-yl]amino]acetyl]pyrrolidine-2-carbonitrile
• CAS: 1186426-80-1
• 化学式: C₁₇H₂₇FN₄O₃
• 分子量: 354.425
• InChiKey: ORLJIXKKPRVJKG-IHRRRGAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  96.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (2S,4S)-1-(bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile 、 3-amino-1-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-3-methylbutan-1-one 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,4S)-4-fluoro-1-{2-[3-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-1,1-dimethyl-3-oxo-propylamino]-acetyl}-pyrrolidine-2-carbonitrile
  参考文献：
  名称：

  (2S,4S)-1-[2-(1,1-Dimethyl-3-oxo-3-pyrrolidin-1-yl-propylamino)acetyl]-4-fluoro-pyrrolidine-2-carbonitrile: A potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV

  摘要：

  A series of 2-[3-[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethylamino]-3-methyl-1-oxobutyl]-based DPP-IV inhibitors with various monocyclic amines were synthesized. The structure-activity relationships (SAR) led to the discovery of potent DPP-IV inhibitors, having IC(50) values of < 100 nM with excellent selectivity over the closely related enzymes, DPP-II, DPP8, DPP9 and FAP (IC(50) > 20 mu M). Of these compounds, the analogues 12a, 12h and 12i exhibited a long-lasting ex vivo DPP-IV inhibition in rats. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.124

文献信息

• PYRROLIDINE DERIVATIVES
  申请人：Jiaang Weir-Torn

  公开号：US20090227569A1

  公开（公告）日：2009-09-10

  Pyrrolidine compounds described herein and methods for using them to inhibit dipeptidyl peptidase IV and treat Type II diabetes.

  本文描述的吡咯烷化合物及其用于抑制二肽基肽酶IV和治疗II型糖尿病的方法。
• US8022096B2
  申请人：——

  公开号：US8022096B2

  公开（公告）日：2011-09-20
• (2S,4S)-1-[2-(1,1-Dimethyl-3-oxo-3-pyrrolidin-1-yl-propylamino)acetyl]-4-fluoro-pyrrolidine-2-carbonitrile: A potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV
  作者：Teng-Kuang Yeh、Ting-Yueh Tsai、Tsu Hsu、Jai-Hong Cheng、Xin Chen、Jen-Shin Song、Horng-Shing Shy、Mei-Chun Chiou、Chia-Hui Chien、Ya-Ju Tseng、Chung-Yu Huang、Kai-Chia Yeh、Yu-Lin Huang、Chih-Hsiang Huang、Yu-Wen Huang、Min-Hsien Wang、Hung-Kuan Tang、Yu-Sheng Chao、Chiung-Tong Chen、Weir-Torn Jiaang

  DOI：10.1016/j.bmcl.2010.04.124

  日期：2010.6

  A series of 2-[3-[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethylamino]-3-methyl-1-oxobutyl]-based DPP-IV inhibitors with various monocyclic amines were synthesized. The structure-activity relationships (SAR) led to the discovery of potent DPP-IV inhibitors, having IC(50) values of < 100 nM with excellent selectivity over the closely related enzymes, DPP-II, DPP8, DPP9 and FAP (IC(50) > 20 mu M). Of these compounds, the analogues 12a, 12h and 12i exhibited a long-lasting ex vivo DPP-IV inhibition in rats. (C) 2010 Elsevier Ltd. All rights reserved.