[4-(4-Fluoro-phenyl)-2-(3'-trifluoromethoxy-biphenyl-2-ylmethyl)-thiazol-5-yl]-acetic acid | 870862-04-7

• 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: [4-(4-Fluoro-phenyl)-2-(3'-trifluoromethoxy-biphenyl-2-ylmethyl)-thiazol-5-yl]-acetic acid
• 英文别名: 2-[4-(4-fluorophenyl)-2-[[2-[3-(trifluoromethoxy)phenyl]phenyl]methyl]-1,3-thiazol-5-yl]acetic acid
• CAS: 870862-04-7
• 化学式: C₂₅H₁₇F₄NO₃S
• 分子量: 487.474
• InChiKey: GLTDPYBJGLZZJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  87.7
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(2-(2-Bromobenzyl)-4-(4-fluorophenyl)thiazol-5-yl)acetic acid 、 3-(三氟甲氧基)苯硼酸 生成 [4-(4-Fluoro-phenyl)-2-(3'-trifluoromethoxy-biphenyl-2-ylmethyl)-thiazol-5-yl]-acetic acid
  参考文献：
  名称：

  Substituted Thiazoleacetic Acid as Crth2 Ligands

  摘要：

  式(I)的化合物对于治疗对CRTH2受体活性调节敏感的疾病，如哮喘、鼻炎、过敏性气道综合症和过敏性鼻支气管炎是有用的；其中X1为—S—、—O—、—N═N—、—NR7—、—CR7═CR8—、—CR7═N—，其中R7和R8独立地为氢或C1-C3烷基；A为羧基—COOH，或羧基生物同位素；环Ar2和Ar3各自表示苯基或5-或6-成员单环杂芳基环，或由5-或6-成员碳环或杂环环组成的双环系统，该环或环系统可以选择性地被取代；环B与Ar2和Ar3的定义相同，或是一个可以选择性地被取代的N-吡咯烷基、N-哌啶基或N-氮杂环己基环；s为0或1；L1、L2和L4为描述中定义的连接基团；Q1和Q2表示描述中定义的取代基。

  公开号：

  US20080119456A1

文献信息

• Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 1
  作者：Øystein Rist、Marie Grimstrup、Jean-Marie Receveur、Thomas M. Frimurer、Trond Ulven、Evi Kostenis、Thomas Högberg

  DOI：10.1016/j.bmcl.2009.12.008

  日期：2010.2

  Structure-activity relationships of three related series of 4-phenylthiazol-5-ylacetic acids, derived from two hits emanating from a focused library obtained by in silico screening, have been explored as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Several compounds with double digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained in all subclasses. The most potent compound was [2-(4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl] acetic acid having an binding affinity of 3.7 nM and functional antagonistic effect of 66 nM in a BRET and 12 nM in a cAMP assay with no functional activity for the other PGD2 DP receptor (27 mu M in cAMP). (C) 2009 Elsevier Ltd. All rights reserved.
• Substituted Thiazoleacetic Acid as Crth2 Ligands
  申请人：Ulven Trond

  公开号：US20080119456A1

  公开（公告）日：2008-05-22

  Compounds of formula (I) are useful for the treatment of disease responsive to modulation of CRTH2 receptor activity, such as asthma, rhinitis, allergic airway syndrome, and allergic rhinobronchitis; wherein X 1 is —S—, —O—, —N═N—. —NR 7 —, —CR 7 ═CR 8 —, —CR 7 ═N—, wherein R 7 and R 8 are independently hydrogen or C 1 -C 3 alkyl; A is a carboxyl group —COOH, or a carboxyl bioisostere; rings Ar 2 and Ar 3 each independently represent a phenyl or 5- or 6-membered monocyclic heteroaryl ring, or a bicyclic ring system consisting of a 5- or 6-membered carbocyclic or heterocyclic ring which is benz-fused or fused to a 5- or 6-membered monocyclic heteroaryl ring, said ring or ring system being optionally substituted; ring B is as defined for Ar 2 and Ar 3 , or an optionally substituted N-pyrrolidinyl, N-piperidinyl or N-azepinyl ring; s is 0 or 1; L1, L2 and L4 are linker radicals as defined in the description; Q 1 and Q 2 represent substituents as defined in the description.

  式(I)的化合物对于治疗对CRTH2受体活性调节敏感的疾病，如哮喘、鼻炎、过敏性气道综合症和过敏性鼻支气管炎是有用的；其中X1为—S—、—O—、—N═N—、—NR7—、—CR7═CR8—、—CR7═N—，其中R7和R8独立地为氢或C1-C3烷基；A为羧基—COOH，或羧基生物同位素；环Ar2和Ar3各自表示苯基或5-或6-成员单环杂芳基环，或由5-或6-成员碳环或杂环环组成的双环系统，该环或环系统可以选择性地被取代；环B与Ar2和Ar3的定义相同，或是一个可以选择性地被取代的N-吡咯烷基、N-哌啶基或N-氮杂环己基环；s为0或1；L1、L2和L4为描述中定义的连接基团；Q1和Q2表示描述中定义的取代基。