1-[3-chloro-5-(ethoxycarbonyl)pyridin-2-yl]azetidine-3-carboxylic acid | 898227-25-3

• 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: 1-[3-chloro-5-(ethoxycarbonyl)pyridin-2-yl]azetidine-3-carboxylic acid
• 英文别名: 1-(3-chloro-5-ethoxycarbonylpyridin-2-yl)azetidine-3-carboxylic acid
• CAS: 898227-25-3
• 化学式: C₁₂H₁₃ClN₂O₄
• 分子量: 284.699
• InChiKey: MBQJQXSVUBSJDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-氯噻吩-5-磺酰胺 、 1-[3-chloro-5-(ethoxycarbonyl)pyridin-2-yl]azetidine-3-carboxylic acid 在 1-羟基苯并三唑 、 1,2-二氯乙烷 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.5h， 以56%的产率得到ethyl 5-chloro-6-[3-({[(5-chloro-2-thienyl)sulfonyl]amino}carbonyl)azetidin-1-yl]nicotinate
  参考文献：
  名称：

  Lead Optimization of Ethyl 6-Aminonicotinate Acyl Sulfonamides as Antagonists of the P2Y₁₂ Receptor. Separation of the Antithrombotic Effect and Bleeding for Candidate Drug AZD1283

  摘要：

  Synthesis and structure-activity relationships of ethyl 6-aminonicotinate acyl sulfonamides, which are potent antagonists of the P2Y(12) receptor, are presented. Shifting from 5-chlorothienyl to benzyl sulfonamides significantly increased the potency in the residual platelet count assay. Evaluation of PK parameters in vivo in dog for six compounds showed a 10-fold higher clearance for the azetidines than for the matched-pair piperidines. In a modified Folts model in dog, both piperidine 3 and azetidine 13 dose-dependently induced increases in blood flow and inhibition of ADP-induced platelet aggregation with antithrombotic ED50 values of 3.0 and 10 mu g/kg/min, respectively. The doses that induced a larger than 3-fold increase in bleeding time were 33 and 100 mu g/kg/min for 3 and 13, respectively. Thus, the therapeutic index (TI) was >= 10 for both compounds. On the basis of these data, compound 3 was progressed into human clinical trials as candidate drug AZD1283.

  DOI：

  10.1021/jm400820m
• 作为产物：
  描述：

  3-氨基-4-羟基吡啶盐酸盐 、 2-氮杂环丁烷-2-羧酸 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 18.0h， 以73%的产率得到1-[3-chloro-5-(ethoxycarbonyl)pyridin-2-yl]azetidine-3-carboxylic acid
  参考文献：
  名称：

  WO2006/73361

  摘要：

  公开号：

文献信息

• Novel Pyridine Compounds
  申请人：Bach Peter

  公开号：US20090227555A2

  公开（公告）日：2009-09-10

  The present invention relates to certain novel pyridin compounds of Formula (I) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-thrombotic agents etc, and processes for their preparation, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.

  本发明涉及某些新型的Formula (I)吡啶化合物，以及制备这些化合物的方法，它们作为P2Y12抑制剂和抗血栓剂等的用途，以及它们的制备过程，它们在心血管疾病中作为药物的用途，以及包含它们的制药组合物。
• NOVEL PYRIDINE COMPOUNDS
  申请人：AstraZeneca AB

  公开号：EP1836189A1

  公开（公告）日：2007-09-26
• [EN] NOVEL PYRIDINE COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES DE PYRIDINE
  申请人：ASTRAZENECA AB

  公开号：WO2006073361A1

  公开（公告）日：2006-07-13

  [EN] The present invention relates to certain novel pyridin compounds of Formula ( I ) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, and processes for their preparation, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.
  [FR] La présente invention concerne certains nouveaux composés de pyridine de formule (I); des méthodes de préparation desdits composés, leur utilisation comme inhibiteurs de P2Y12 ou comme agents thrombotiques, etc. Elle concerne également des méthodes de préparation et d'utilisation desdits composés comme médicaments dans des maladies cardiovasculaires; ainsi que des compositions pharmaceutiques contenant ces composés.
• WO2006/73361
  申请人：——

  公开号：——

  公开（公告）日：——
• Lead Optimization of Ethyl 6-Aminonicotinate Acyl Sulfonamides as Antagonists of the P2Y₁₂ Receptor. Separation of the Antithrombotic Effect and Bleeding for Candidate Drug AZD1283
  作者：Peter Bach、Thomas Antonsson、Ruth Bylund、Jan-Arne Björkman、Krister Österlund、Fabrizio Giordanetto、J. J. J. van Giezen、Søren M. Andersen、Helen Zachrisson、Fredrik Zetterberg

  DOI：10.1021/jm400820m

  日期：2013.9.12

  Synthesis and structure-activity relationships of ethyl 6-aminonicotinate acyl sulfonamides, which are potent antagonists of the P2Y(12) receptor, are presented. Shifting from 5-chlorothienyl to benzyl sulfonamides significantly increased the potency in the residual platelet count assay. Evaluation of PK parameters in vivo in dog for six compounds showed a 10-fold higher clearance for the azetidines than for the matched-pair piperidines. In a modified Folts model in dog, both piperidine 3 and azetidine 13 dose-dependently induced increases in blood flow and inhibition of ADP-induced platelet aggregation with antithrombotic ED50 values of 3.0 and 10 mu g/kg/min, respectively. The doses that induced a larger than 3-fold increase in bleeding time were 33 and 100 mu g/kg/min for 3 and 13, respectively. Thus, the therapeutic index (TI) was >= 10 for both compounds. On the basis of these data, compound 3 was progressed into human clinical trials as candidate drug AZD1283.