(2-tert-Butoxycarbonylamino-5-trifluoromethyl-benzoylamino)-acetic acid | 439150-97-7

• 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: (2-tert-Butoxycarbonylamino-5-trifluoromethyl-benzoylamino)-acetic acid
• 英文别名: (2-tert-Butoxycarbonylamino-5-trifluoromethylbenzoylamino)acetic acid；2-[[2-[(2-Methylpropan-2-yl)oxycarbonylamino]-5-(trifluoromethyl)benzoyl]amino]acetic acid
• CAS: 439150-97-7
• 化学式: C₁₅H₁₇F₃N₂O₅
• 分子量: 362.306
• InChiKey: BXSDMRFAONTENY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2-tert-Butoxycarbonylamino-5-trifluoromethyl-benzoylamino)-acetic acid 、 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Discovery of an orally-bioavailable CC Chemokine Receptor 2 antagonist derived from an acyclic diaminoalcohol backbone

  摘要：

  We describe an isostere-driven approach to improve upon a previously-described series of capped dipeptide antagonists of CC Chemokine Receptor 2 (CCR2). Modification of the substitution around the isostere was combined with additional changes in a distal aromatic substituent to provide single-digit nanomolar antagonists of CCR2. These studies led to the identification of 18, a compound that was suitable for studies in murine models of CCR2 activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.007
• 作为产物：
  描述：

  甘氨酸苄酯对甲苯磺酸盐 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 2-叔丁氧基甲酰胺基-5-三氟甲基苯甲酸 在 盐酸 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2-tert-Butoxycarbonylamino-5-trifluoromethyl-benzoylamino)-acetic acid
  参考文献：
  名称：

  Cyclic derivatives as modulators of chemokine receptor activity

  摘要：

  本申请描述了公式（I）的MCP-1调节剂或其药用盐形式，用于预防风湿性关节炎、多发性硬化症、动脉粥样硬化、哮喘、再狭窄、器官移植和癌症。

  公开号：

  US20030216434A1

文献信息

• Synthesis and evaluation of cis-3,4-disubstituted piperidines as potent CC chemokine receptor 2 (CCR2) antagonists
  作者：Robert J. Cherney、David J. Nelson、Yvonne C. Lo、Gengjie Yang、Peggy A. Scherle、Heather Jezak、Kimberly A. Solomon、Percy H. Carter、Carl P. Decicco

  DOI：10.1016/j.bmcl.2008.07.123

  日期：2008.9

  4-disubstituted piperidines was synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. Compound 24 emerged with an attractive profile, possessing excellent binding (CCR2 IC(50)=3.4 nM) and functional antagonism (calcium flux IC(50)=2.0 nM and chemotaxis IC(50)=5.4 nM). Studies to explore the binding of these piperidine analogs utilized a key CCR2 receptor mutant (E291A) with compound 14 and revealed

  合成了一系列顺式3,4-二取代的哌啶，并将其评估为CC趋化因子受体2（CCR2）拮抗剂。化合物24呈现出有吸引力的轮廓，具有出色的结合力（CCR2 IC（50）= 3.4 nM）和功能拮抗作用（钙通量IC（50）= 2.0 nM和趋化性IC（50）= 5.4 nM）。探索这些哌啶类似物结合的研究利用了关键的CCR2受体突变体（E291A）与化合物14的结合，显示出对Glu291的结合非常依赖。
• Discovery of trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists
  作者：Robert J. Cherney、John B. Brogan、Ruowei Mo、Yvonne C. Lo、Gengjie Yang、Persymphonie B. Miller、Peggy A. Scherle、Bruce F. Molino、Percy H. Carter、Carl P. Decicco

  DOI：10.1016/j.bmcl.2008.12.062

  日期：2009.2

  A series of trisubstituted cyclohexanes was designed, synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. This led to the identification of two distinct substitution patterns about the cyclohexane ring as potent and selective CCR2 antagonists. Compound 36 exhibited excellent binding (CCR2 IC50 = 2.4 nM) and functional antagonism (calcium flux IC50 = 2.0 nM and chemotaxis IC50 = 5

  设计，合成和评估了一系列三取代的环己烷作为CC趋化因子受体2（CCR2）拮抗剂。这导致鉴定出关于环己烷环的两种不同的取代模式，它们是有效的和选择性的CCR2拮抗剂。化合物36表现出优异的结合（CCR2 IC 50  = 2.4 nM）和功能拮抗作用（钙通量IC 50  = 2.0 nM，趋化性IC 50  = 5.1 nM）。
• Cyclic derivatives as modulators of chemokine receptors activity
  申请人：Cherney J. Robert

  公开号：US20060135503A1

  公开（公告）日：2006-06-22

  The present application describes modulators of MCP-1 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of rheumatoid arthritis, multiple sclerosis, atherosclerosis, asthma, restinosis, organ transplantation, and cancer.

  本申请描述了MCP-1调节剂的化学式(I)或其药学上可接受的盐形式，可用于预防类风湿性关节炎、多发性硬化症、动脉粥样硬化、哮喘、再狭窄、器官移植和癌症。
• Novel sulfone-containing di- and trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists
  作者：Robert J. Cherney、Ruowei Mo、Dayton T. Meyer、Matthew E. Voss、Yvonne C. Lo、Gengjie Yang、Persymphonie B. Miller、Peggy A. Scherle、Andrew J. Tebben、Percy H. Carter、Carl P. Decicco

  DOI：10.1016/j.bmcl.2009.05.041

  日期：2009.7

  Potent sulfone-containing di- and trisubstituted cyclohexanes were synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. This led to the trisubstituted derivative 54, which exhibited excellent binding (CCR2 IC50 = 1.3 nM) and functional antagonism (calcium flux IC50 = 0.5 nM and chemotaxis IC50 = 0.2 nM). The superiority of the trisubstituted scaffold was rationalized to be the result of a conformational rigidification, which provided insight into the bioactive conformation of this chemotype. (C) 2009 Elsevier Ltd. All rights reserved.
• CYCLIC DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1343751A2

  公开（公告）日：2003-09-17