(S)-3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-((5-methylisoxazol-3-yl)methyl)-6,7-dihydro-5H-pyrrolo[3,4-b]-pyridin-5-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (S)-3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-((5-methylisoxazol-3-yl)methyl)-6,7-dihydro-5H-pyrrolo[3,4-b]-pyridin-5-one
• 英文别名: (S)-3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-((5-methylisoxazol-3-yl)methyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one；3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-[(5-methyl-1,2-oxazol-3-yl)methyl]-7H-pyrrolo[3,4-b]pyridin-5-one
• 化学式: C₂₀H₁₈Cl₂N₄O₂
• 分子量: 417.295
• InChiKey: RBLWOLKKTLUERQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  85.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-benzyl 5-ethyl 6-(chloromethyl)-4-(2,4-dichlorophenyl)-2-methylpyridine-3,5-dicarboxylate 在 sodium tetrahydroborate 、 palladium 10% on activated carbon 、 氢气 、 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 异丙醇 为溶剂， 生成 (S)-3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-((5-methylisoxazol-3-yl)methyl)-6,7-dihydro-5H-pyrrolo[3,4-b]-pyridin-5-one
  参考文献：
  名称：

  Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778)

  摘要：

  Optimization of a 5-oxopyrrolopyridine series based upon structure activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.

  DOI：

  10.1021/jm4008906

文献信息

• Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods
  申请人：Devasthale Pratik

  公开号：US20060264457A1

  公开（公告）日：2006-11-23

  Compounds are provided having the formula (I) wherein R, X, Y, Z, A and n are as defined herein, which are inhibitors of dipeptidyl peptidase IV and thus are useful in treating diabetes and related diseases.

  提供的化合物具有以下式(I)的结构，其中R、X、Y、Z、A和n的定义如本文所述，这些化合物是二肽基肽酶IV的抑制剂，因此在治疗糖尿病和相关疾病方面是有用的。
• PYRROLOPYRIDINE-BASED INHIBITORS OF DIPEPTIDYL PEPTIDASE IV AND METHODS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1888589B1

  公开（公告）日：2012-05-09
• US7521557B2
  申请人：——

  公开号：US7521557B2

  公开（公告）日：2009-04-21
• [EN] PYRROLOPYRIDINE-BASED INHIBITORS OF DIPEPTIDYL PEPTIDASE IV AND METHODS<br/>[FR] INHIBITEURS A BASE DE PYRROLOPYRIDINE, POUR INHIBER LA DIPEPTIDYL PEPTIDASE IV, ET PROCEDES CORRESPONDANTS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2006127287A2

  公开（公告）日：2006-11-30

  [EN] Compounds are provided having the formula (I): wherein R, X, Y, Z, A and n are as defined herein, which are inhibitors of dipeptidyl peptidase IV and thus are useful in treating diabetes and related diseases.
  [FR] La présente invention concerne des composés de formule (I) dans laquelle R, X, Y, Z, A et n sont tels que définis dans l'invention, ces composés étant des inhibiteurs de la dipeptidyl peptidase IV et s'avérant ainsi utiles pour traiter le diabète et des troubles associés.
• Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (<i>Sa</i>)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5<i>H</i>-pyrrolo[3,4-<i>b</i>]pyridin-6(7<i>H</i>)-yl)-<i>N</i>,<i>N</i>-dimethylacetamide (BMS-767778)
  作者：Pratik Devasthale、Ying Wang、Wei Wang、John Fevig、JianXin Feng、Aiying Wang、Tom Harrity、Don Egan、Nathan Morgan、Michael Cap、Aberra Fura、Herbert E. Klei、Kevin Kish、Carolyn Weigelt、Lucy Sun、Paul Levesque、Frederic Moulin、Yi-Xin Li、Robert Zahler、Mark S. Kirby、Lawrence G. Hamann

  DOI：10.1021/jm4008906

  日期：2013.9.26

  Optimization of a 5-oxopyrrolopyridine series based upon structure activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.