3-[4-(N-Hydroxycarbamimidoyl)-3-methyl-phenyl]-propionic acid tert-butyl ester | 856165-68-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-[4-(N-Hydroxycarbamimidoyl)-3-methyl-phenyl]-propionic acid tert-butyl ester
• 英文别名: tert-butyl 3-[4-[(E)-N'-hydroxycarbamimidoyl]-3-methylphenyl]propanoate
• CAS: 856165-68-9
• 化学式: C₁₅H₂₂N₂O₃
• 分子量: 278.351
• InChiKey: DVCDZDJWEBEFSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[4-(N-Hydroxycarbamimidoyl)-3-methyl-phenyl]-propionic acid tert-butyl ester 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 14.0h， 生成 3-(4-{5-[4-((S)-sec-Butoxy)-3-cyano-phenyl]-[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：

  4-溴-2-甲基苯腈 在 palladium on activated charcoal bis(tri-tert-butylphosphine)palladium(0) 、 N-甲基二环己基胺 、 盐酸羟胺 、 氢气 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 20.0~70.0 ℃ 、103.42 kPa 条件下， 生成 3-[4-(N-Hydroxycarbamimidoyl)-3-methyl-phenyl]-propionic acid tert-butyl ester
  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

文献信息

• [EN] (3,4-DISUBSTITUTED)PROPANOIC CARBOXYLATES AS S1P (EDG) RECEPTOR AGONISTS<br/>[FR] CARBOXYLATES PROPANOIQUES 3,4-DISUSBSTITUES UTILISES EN TANT QU'AGONISTES DU RECEPTEUR S1P (EDG)
  申请人：MERCK & CO INC

  公开号：WO2005058848A1

  公开（公告）日：2005-06-30

  The present invention encompasses compounds of Formula A: A 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。
• [EN] TRIAZOLE OXADIAZOLES DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZOLES ET D'OXADIAZOLES
  申请人：MERCK SERONO SA

  公开号：WO2009080663A1

  公开（公告）日：2009-07-02

  The invention relates to compounds of formula (I), wherein R1, R2, Ra, Rb, X have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple sclerosis.

  该发明涉及公式（I）的化合物，其中R1、R2、Ra、Rb、X具有权利要求书中给定的含义。这些化合物可用于治疗自身免疫性疾病，如多发性硬化症。
• TRIAZOLE OXADIAZOLES DERIVATIVES
  申请人：Quattropani Anna

  公开号：US20100305092A1

  公开（公告）日：2010-12-02

  The invention relates to compounds of formula I: wherein R 1 , R 2 , R a , R b , X have the meanings given in claim 16 . The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple sclerosis.

  本发明涉及式I的化合物：其中R1、R2、Ra、Rb、X的含义如权利要求16所示。该化合物可用于治疗自身免疫性疾病，如多发性硬化症等。
• US8202856B2
  申请人：——

  公开号：US8202856B2

  公开（公告）日：2012-06-19