tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate | 856166-30-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate
• 英文别名: Tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate；tert-butyl 3-[4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-3-methylphenyl]propanoate
• CAS: 856166-30-8
• 化学式: C₂₁H₂₁Cl₂N₃O₃
• 分子量: 434.322
• InChiKey: JJJJRJBPNHDWHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(4-{5-[5-Chloro-6-(2,2,2-trifluoro-1-methyl-ethoxy)-pyridin-3-yl]-[1,2,4]oxadiazol-3-yl}-3-methyl-phenyl)-propionic acid
  参考文献：
  名称：

  Discovery of 3-arylpropionic acids as potent agonists of sphingosine-1-phosphate receptor-1 (S1P1) with high selectivity against all other known S1P receptor subtypes

  摘要：

  A series of 3-arylpropionic acids were synthesized as S1P(1) receptor agonists. Structure-activity relationship studies on the pendant phenyl ring revealed several structural features offering selectivity of S1P(1) binding against S1P(2-5). These highly selective SIP, agonists induced peripheral blood lymphocyte lowering in mice and one of them was found to be efficacious in a rat skin transplantation model, supporting that S1P(1) agonism is primarily responsible for the immunosuppressive efficacy observed in preclinical animal models. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.084
• 作为产物：
  描述：

  2,3-二氯吡啶-5-羰酰氯 、 N-hydroxy-2-methyl-4-(2-(tert-butoxycarbonyl)ethyl)benzamidine 在 三乙胺 作用下， 以 1,1-二氯乙烷 为溶剂， 生成 tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate
  参考文献：
  名称：

  [EN] (3,4-DISUBSTITUTED)PROPANOIC CARBOXYLATES AS S1P (EDG) RECEPTOR AGONISTS
  [FR] CARBOXYLATES PROPANOIQUES 3,4-DISUSBSTITUES UTILISES EN TANT QU'AGONISTES DU RECEPTEUR S1P (EDG)

  摘要：

  本发明涵盖了化合物A的公式：A以及其药用可接受的盐。这些化合物是S1P1/Edg1受体激动剂，因此通过调节白细胞的运动、在次生淋巴组织中滞留淋巴细胞以及增强血管完整性而具有免疫抑制、抗炎和止血活性。该发明还涉及含有这些化合物的药物组合物以及治疗或预防的方法。

  公开号：

  WO2005058848A1

文献信息

• (3,4-Disubstituted)Propanoic Carboxylates as Sip (Edg) Receptor Agonists
  申请人：Colandrea Vincent J.

  公开号：US20080249093A1

  公开（公告）日：2008-10-09

  The present invention encompasses compounds of Formula I: as well as the pharmaceutically acceptable salts thereof. The compounds are S1P 1 /Edg1 receptor agonists and thus have immunosuppressive, anti-inflammatory and hemostatic activities by modulating leukocyte trafficking, sequestering lymphocytes in secondary lymphoid tissues, and enhancing vascular integrity. The invention is also directed to pharmaceutical compositions containing such compounds and methods of treatment or prevention.

  本发明涵盖以下I式化合物及其药学上可接受的盐。这些化合物是S1P1 / Edg1受体激动剂，因此通过调节白细胞的转移，将淋巴细胞隔离在二级淋巴组织中，并增强血管完整性，具有免疫抑制，抗炎和止血活性。本发明还涉及含有这些化合物的制药组合物和治疗或预防的方法。
• (3,4-disubstituted)propanoic carboxylates as S1P (Edg) receptor agonists
  申请人：Merck & Co., Inc.

  公开号：US07605171B2

  公开（公告）日：2009-10-20

  The present invention encompasses compounds of Formula I: as well as the pharmaceutically acceptable salts thereof. The compounds are S1P1/Edg1 receptor agonists and thus have immunosuppressive, anti-inflammatory and hemostatic activities by modulating leukocyte trafficking, sequestering lymphocytes in secondary lymphoid tissues, and enhancing vascular integrity. The invention is also directed to pharmaceutical compositions containing such compounds and methods of treatment or prevention.

  本发明涵盖公式I的化合物及其药学上可接受的盐。这些化合物是S1P1 / Edg1受体激动剂，因此通过调节白细胞转移，将淋巴细胞隔离在二级淋巴组织中并增强血管完整性，具有免疫抑制、抗炎和止血活性。本发明还涉及含有这种化合物的制药组合物和治疗或预防的方法。
• (3,4-DISUBSTITUTED)PROPANOIC CARBOXYLATES AS S1P (EDG) RECEPTOR AGONISTS
  申请人：Merck & Co., Inc.

  公开号：EP1697333A1

  公开（公告）日：2006-09-06
• EP1697333A4
  申请人：——

  公开号：EP1697333A4

  公开（公告）日：2009-07-08
• US7605171B2
  申请人：——

  公开号：US7605171B2

  公开（公告）日：2009-10-20