(+/-) {7-[[(4-fluorophenyl)sulfonyl](methyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (+/-) {7-[[(4-fluorophenyl)sulfonyl](methyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetic acid
• 英文别名: Crth2-IN-1；2-[7-[(4-fluorophenyl)sulfonyl-methylamino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetic acid
• 化学式: C₂₁H₂₁FN₂O₄S
• 分子量: 416.473
• InChiKey: JTCAGRAKUAAYDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  88
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-) {7-[[(4-fluorophenyl)sulfonyl](methyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetic acid 生成 (R)-2-(7-(4-氟-N-甲基苯基磺酰胺)-6,7,8,9-四氢吡啶并[1,2-a]吲哚-10-基)乙酸 、 MK-7246 S enantiomer
  参考文献：
  名称：

  Discovery of MK-7246, a selective CRTH2 antagonist for the treatment of respiratory diseases

  摘要：

  In this manuscript we wish to report the discovery of MK-7246 (4), a potent and selective CRTH2 (DP2) antagonist. SAR studies leading to MK-7246 along with two synthetic sequences enabling the preparation of this novel class of CRTH2 antagonist are reported. Finally, the pharmacokinetic and metabolic profile of MK-7246 is disclosed. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.015
• 作为产物：
  描述：

  (+/-)-methyl {7-[[(4-fluorophenyl)sulfonyl](methyl)amino]-6,7,8,9-tetrahydro-pyrido[1,2-a]indol-10-yl}acetate 在 lithium hydroxide 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.0h， 生成 (+/-) {7-[[(4-fluorophenyl)sulfonyl](methyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetic acid
  参考文献：
  名称：

  WO2007/19675

  摘要：

  公开号：

文献信息

• [EN] INDOLE DERIVATIVES AS CRTH2 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'INDOLE UTILISABLES EN TANT QU'ANTAGONISTES DU RÉCEPTEUR CRTH2
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2010031182A1

  公开（公告）日：2010-03-25

  The compound (+) 7R-[[(4-fluorophenyl)sulfonyl](methyl)ammo]-6,7,8,9-tetrahydropyrido[1,2-a]mdol-10-yl}acetic acid and pharmaceutically acceptable salts thereof are antagonists of the PGD2 receptor, CRTH2, and as such are useful in the treatment and/or prevention of CRTH2-meidated diseases such as asthma.

  (+)7R-[[(4-氟苯基)磺酰](甲基)氨基]-6,7,8,9-四氢吡啶并[1,2-a]吲哚-10-基}乙酸及其药用盐是PGD2受体CRTH2的拮抗剂，因此在治疗和/或预防CRTH2介导的疾病如哮喘中是有用的。
• Indole derivatives as crth2 receptor antagonists
  申请人：Wang Zhaoyin

  公开号：US20090286825A1

  公开（公告）日：2009-11-19

  Compounds according to formula (I) wherein the radicals R 1 , R 2 and R 3 are as herein defined, and wherein Ar represents an aryl group or heteroaryl group, preferably phenyl, n is 1 or 2, and the radical X represents a group selected from —C(R a )(R b )—, —C(R a )(R b )—C(R a )(R b )—, —C(R a )═C(R a )—, OC(R a )(R b )— or SC(R a )(R b )—. These compounds and their pharmaceutical acceptable salts are used in pharmaceutical compositions as prostaglandine D2 receptor antagonists useful in the treatment of CRTH2-mediated diseases such as respiratory, inflammatory or allergic conditions among others.

  化合物的公式为（I），其中基团R1、R2和R3如所定义，Ar代表芳基或杂芳基，优选苯基，n为1或2，基团X代表从—C（Ra）（Rb）—，—C（Ra）（Rb）—C（Ra）（Rb）—，—C（Ra）═C（Ra）—，OC（Ra）（Rb）—或SC（Ra）（Rb）—中选择的基团。这些化合物及其药学上可接受的盐用于制备药物组合物，作为前列腺素D2受体拮抗剂，对治疗CRTH2介导的疾病，如呼吸系统、炎症或过敏等病症有用。
• INDOLE DERIVATIVES AS CRTH2 RECEPTOR ANTAGONISTS
  申请人：Wang Zhaoyin

  公开号：US20110201641A1

  公开（公告）日：2011-08-18

  The compound (+) 7R-[[(4-fluorophenyl)sulfonyl] (methyl)ammo]-6,7,8,9-tetrahydropyrido[1,2-a]mdol-10-yl}acetic acid and pharmaceutically acceptable salts thereof are antagonists of the PGD2 receptor, CRTH2, and as such are useful in the treatment and/or prevention of CRTH2-meidated diseases such as asthma.

  复合物（+）7R-[[(4-氟苯基)磺酰基]（甲基）氨基]-6,7,8,9-四氢吡啶[1,2-a]咪唑-10-基}乙酸及其药学上可接受的盐是PGD2受体，CRTH2的拮抗剂，因此在治疗和/或预防CRTH2介导的疾病，如哮喘中有用。
• TRICYCLIC COMPOUNDS AS ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS
  申请人：Stearns Brian Andrew

  公开号：US20120004233A1

  公开（公告）日：2012-01-05

  Described herein are antagonists of PGD 2 receptors. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such antagonists of PGD 2 receptors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD 2 -dependent or PGD 2 -mediated conditions or diseases.

  本文描述了PGD2受体拮抗剂。还描述了包括本文所述化合物的制药组合物和药物，以及使用这些PGD2受体拮抗剂的方法，单独或与其他化合物结合，用于治疗呼吸系统、心血管系统和其他PGD2依赖性或PGD2介导的疾病或病症。
• Indole derivatives as CRTH2 receptor antagonists
  申请人：Merck Frosst Canada Ltd

  公开号：US07696222B2

  公开（公告）日：2010-04-13

  Compounds according to formula (I) wherein the radicals R1, R2 and R3 are as herein defined, and wherein Ar represents an aryl group or heteroaryl group, preferably phenyl, n is 1 or 2, and the radical X represents a group selected from —C(Ra)(Rb)—, —C(Ra)(Rb)—C(Ra)(Rb)—, —C(Ra)═C(Ra)—, OC(Ra)(Rb)— or SC(Ra)(Rb)—. These compounds and their pharmaceutical acceptable salts are used in pharmaceutical compositions as prostaglandine D2 receptor antagonists useful in the treatment of CRTH2-mediated diseases such as respiratory, inflammatory or allergic conditions among others.

  化合物的公式为（I），其中基团R1、R2和R3如本文所定义，其中Ar代表芳基或杂芳基，优选苯基，n为1或2，基团X代表从—C（Ra）（Rb）—，—C（Ra）（Rb）—C（Ra）（Rb）—，—C（Ra）═C（Ra）—，OC（Ra）（Rb）—或SC（Ra）（Rb）—中选择的基团。这些化合物及其药用盐可用于制备药物组合物，作为前列腺素D2受体拮抗剂，用于治疗CRTH2介导的疾病，如呼吸系统、炎症或过敏等情况。