1-(2-bromoacetyl)-pyrrolidine-2,5-cis-dicarbonitrile | 866396-76-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1-(2-bromoacetyl)-pyrrolidine-2,5-cis-dicarbonitrile
• 英文别名: (2S,5R)-1-(2-bromoacetyl)pyrrolidine-2,5-dicarbonitrile
• CAS: 866396-76-1
• 化学式: C₈H₈BrN₃O
• 分子量: 242.075
• InChiKey: RTOYOAYPWNAATO-KNVOCYPGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-bromoacetyl)-pyrrolidine-2,5-cis-dicarbonitrile 、 叔戊基胺 以 乙腈 为溶剂， 反应 48.0h， 生成 (2R,5S)-1-[2-(1,1-Dimethyl-propylamino)-acetyl]-pyrrolidine-2,5-dicarbonitrile
  参考文献：
  名称：

  cis-2,5-Dicyanopyrrolidine Inhibitors of Dipeptidyl Peptidase IV:  Synthesis and in Vitro, in Vivo, and X-ray Crystallographic Characterization

  摘要：

  Inhibitors of the glucagon-like peptide-1 (GLP-1) degrading enzyme dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes in animal models and in human subjects. A novel series of cis-2,5-dicyanopyrrolidine alpha-amino amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. 1-({[1-(Hydroxymethyl) cyclopentyl] amino}acetyl) pyrrolidine-2,5-cis-dicarbonitrile (1c) is an achiral, slow-binding (time-dependent) inhibitor of DPP-IV that is selective for DPP-IV over other DPP isozymes and proline specific serine proteases, and which has oral bioavailability in preclinical species and in vivo efficacy in animal models. The mode of binding of the cis-2,5-dicyanopyrrolidine moiety was determined by X-ray crystallography. The hydrochloride salt of 1c was further profiled for development as a potential new treatment for type 2 diabetes.

  DOI：

  10.1021/jm0600085
• 作为产物：
  描述：

  1-benzhydryl-pyrrolidine-2,5-cis-dicarbonitrile 、 溴乙酰溴 以 乙腈 为溶剂， 反应 16.0h， 以99%的产率得到1-(2-bromoacetyl)-pyrrolidine-2,5-cis-dicarbonitrile
  参考文献：
  名称：

  cis-2,5-Dicyanopyrrolidine Inhibitors of Dipeptidyl Peptidase IV:  Synthesis and in Vitro, in Vivo, and X-ray Crystallographic Characterization

  摘要：

  Inhibitors of the glucagon-like peptide-1 (GLP-1) degrading enzyme dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes in animal models and in human subjects. A novel series of cis-2,5-dicyanopyrrolidine alpha-amino amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. 1-({[1-(Hydroxymethyl) cyclopentyl] amino}acetyl) pyrrolidine-2,5-cis-dicarbonitrile (1c) is an achiral, slow-binding (time-dependent) inhibitor of DPP-IV that is selective for DPP-IV over other DPP isozymes and proline specific serine proteases, and which has oral bioavailability in preclinical species and in vivo efficacy in animal models. The mode of binding of the cis-2,5-dicyanopyrrolidine moiety was determined by X-ray crystallography. The hydrochloride salt of 1c was further profiled for development as a potential new treatment for type 2 diabetes.

  DOI：

  10.1021/jm0600085

文献信息

• [EN] DICYANOPYRROLIDINES AS DIPEPTIDYL PEPTIDASE IV INHIBITORS<br/>[FR] DICYANOPYRROLIDINES INHIBITEURS DE LA DIPEPTIDYL PEPTIDASE IV
  申请人：PFIZER PROD INC

  公开号：WO2005095339A1

  公开（公告）日：2005-10-13

  The invention provides compounds of formula (I), the prodrugs and stereoisomers thereof, and the pharmaceutically acceptable salts of the compounds, prodrugs, and stereoisomers, wherein wherein R is as defined herein; pharmaceutical compositions thereof; combinations thereof; and uses thereof in the treatment of diabetic complications including diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, and the like.

  该发明提供了如下式（I）的化合物，其前药和立体异构体，以及该化合物、前药和立体异构体的药用可接受盐，其中R如本文所定义；其药物组合物；其组合物；以及在治疗糖尿病并发症包括糖尿病神经病变、糖尿病肾病、糖尿病微血管病变等方面的用途。
• <i>cis</i>-2,5-Dicyanopyrrolidine Inhibitors of Dipeptidyl Peptidase IV:  Synthesis and in Vitro, in Vivo, and X-ray Crystallographic Characterization
  作者：Stephen W. Wright、Mark J. Ammirati、Kim M. Andrews、Anne M. Brodeur、Dennis E. Danley、Shawn D. Doran、Jay S. Lillquist、Lester D. McClure、R. Kirk McPherson、Stephen J. Orena、Janice C. Parker、Jana Polivkova、Xiayang Qiu、Walter C. Soeller、Carolyn B. Soglia、Judith L. Treadway、Maria A. VanVolkenburg、Hong Wang、Donald C. Wilder、Thanh V. Olson

  DOI：10.1021/jm0600085

  日期：2006.6.1

  Inhibitors of the glucagon-like peptide-1 (GLP-1) degrading enzyme dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes in animal models and in human subjects. A novel series of cis-2,5-dicyanopyrrolidine alpha-amino amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. 1-([1-(Hydroxymethyl) cyclopentyl] amino}acetyl) pyrrolidine-2,5-cis-dicarbonitrile (1c) is an achiral, slow-binding (time-dependent) inhibitor of DPP-IV that is selective for DPP-IV over other DPP isozymes and proline specific serine proteases, and which has oral bioavailability in preclinical species and in vivo efficacy in animal models. The mode of binding of the cis-2,5-dicyanopyrrolidine moiety was determined by X-ray crystallography. The hydrochloride salt of 1c was further profiled for development as a potential new treatment for type 2 diabetes.