[8-chloro-4-difluoromethoxy-2-isopropyl-3-(4-methanesulfonylbenzyl)quinolin-5-yloxy]acetic acid methyl ester | 932708-41-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: [8-chloro-4-difluoromethoxy-2-isopropyl-3-(4-methanesulfonylbenzyl)quinolin-5-yloxy]acetic acid methyl ester
• 英文别名: methyl 2-[8-chloro-4-(difluoromethoxy)-3-[(4-methylsulfonylphenyl)methyl]-2-propan-2-ylquinolin-5-yl]oxyacetate
• CAS: 932708-41-3
• 化学式: C₂₄H₂₄ClF₂NO₆S
• 分子量: 527.973
• InChiKey: KNTOJDSEFNTRQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  100
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [8-chloro-4-difluoromethoxy-2-isopropyl-3-(4-methanesulfonylbenzyl)quinolin-5-yloxy]acetic acid methyl ester 在 lithium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 [8-chloro-4-difluoromethoxy-2-isopropyl-3-(4-methanesulfonylbenzyl)quinolin-5-yloxy]acetic acid
  参考文献：
  名称：

  WO2007/36743

  摘要：

  公开号：

文献信息

• Quinolines and their therapeutic use
  申请人：Pulmagen Therapeutics (Asthma) Limited

  公开号：US07858640B2

  公开（公告）日：2010-12-28

  Compounds of formula [1] are CRTH2 antagonists, useful in the treatment of conditions having an inflammatory components; in which: R1-R9 are various substituents; A is —CHR10—, —C(O)—, —S(O)n—, —O—, or —NR10— wherein n is an integer from 0-1 and R10 is selected from various substituents; B is a direct bond or a divalent radical; R11 and R12 are selected from cvarious substituents; X is a carboxylic acid, tetrazole, 3-hydroxyisoxazole, hydroxamic acid, phosphinate, phosphonate, phosphonamide, sulfonic acid group, or a group of formula C═(O)NHSO2R6 or SO2NHC(═O)R6; and Y is aryl, heteroaryl, aryl-fused-heterocycloalkyl, heteroaryl-fused-cycloalkyl, heteroaryl-fused-heterocycloalkyl or aryl-fused-cycloalkyl group.

  化合物的化学式[1]是CRTH2拮抗剂，可用于治疗具有炎症成分的疾病；其中：R1-R9是不同的取代基；A是-CHR10-，-C（O）-，-S（O）n-，-O-或-NR10-，其中n是0-1的整数，R10是选择的不同取代基；B是直接键或二价基团；R11和R12是选择的不同取代基；X是羧酸，四唑，3-羟基异噁唑，羟肟酸，磷酸酯，膦酸盐，膦酰胺，磺酸基或公式C =（O）NHSO2R6或SO2NHC（= O）R6的基团；Y是芳基，杂环芳基，芳基融合杂环烷基，杂环芳基融合环烷基，杂环芳基融合杂环烷基或芳基融合环烷基基团。
• Quinolines and Their Therapeutic Use
  申请人：Cramp Michael Colin

  公开号：US20090156600A1

  公开（公告）日：2009-06-18

  Compounds of formula [1] are CRTH2 antagonists, useful in the treatment of conditions having an inflammatory component; in which: R 1 , R 2 , R 3 , R 4 and R 5 are independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, cyclopropyl, halo, —S(O) n R 6 , —SO 2 NR 7 R 8 , —NR 7 R 8 , —NR 7 C(O)R 6 , —CO 2 R 7 , —C(O)NR 7 R 8 , —C(O)R 7 6 , —NO 2 , —CN or a group —OR 9 ; wherein each R 6 is independently C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, cycloalkyl, aryl, or heteroaryl; R 7 , R 8 are independently C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, cycloalkyl, cycloalkyl-(C 1 -C 6 alkyl)-, aryl, heteroaryl or hydrogen; R 9 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, cycloalkyl, cylcoalkyl-(C 1 -C 6 alkyl)-, or a group —SO 2 R 6 ; A is —CHR 10 —, —C(O)—, —S(O) n —, —O—, or —NR 10 — wherein n is an integer from 0-2 and R 10 is hydrogen C 1 -C 3 alkyl, or C 1 -C 6 -fluoroalkyl group; B is a direct bond, or a divalent radical selected from —CH 2 —, —CH 2 CH 2 —, —CHR 11 —, —CR 11 R 12 —, —CH 2 CHR 11 —, CH 2 CR 11 R 12 —, —CHR 11 CHR 12 —, and divalent radicals of formula —(CR 11 R 12 ) p -Z- wherein Z is attached to the ring carrying R 1 , R 2 and R 3 ; wherein R 11 is C 1 -C 3 alkyl, cyclopropyl, C 1 -C 6 -fluoroalkyl; R 12 is methyl or fluoromethyl; p is independently 1 or 2; and Z is —O—, —NH—, or —S(O) n —, wherein n is an integer from 0-2; X is a carboxylic acid, tetrazole, 3-hydroxyisoxazole, hydroxamic acid, phosphinate, phosphonate, phosphonamide, or sulfonic acid group, or a group of formula C(═O)NHSO 2 R 6 or SO 2 NHC(═O)R 6 ; and Y is aryl, heteroaryl, aryl-fused-heterocycloalkyl, heteroaryl-fused-cycloalkyl, heteroaryl-fused-heterocycloalkyl or aryl-fused-cycloalkyl group.

  公式[1]的化合物是CRTH2拮抗剂，在治疗具有炎症成分的疾病中有用；其中：R1、R2、R3、R4和R5分别独立地为氢、C1-C6烷基、C1-C6氟代烷基、环丙基、卤素、—S（O）nR6、—SO2NR7R8、—NR7R8、—NR7C（O）R6、—CO2R7、—C（O）NR7R8、—C（O）R76、—NO2、—CN或—OR9中的一个基团；其中每个R6独立地为C1-C6烷基、C1-C6氟代烷基、环烷基、芳基或杂环芳基；R7、R8独立地为C1-C6烷基、C1-C6氟代烷基、环烷基、环烷基-(C1-C6烷基)-、芳基、杂环芳基或氢；R9为氢、C1-C6烷基、C1-C6氟代烷基、环烷基、环烷基-(C1-C6烷基)-或—SO2R6中的一个基团；A为—CHR10—、—C（O）—、—S（O）n—、—O—或—NR10—，其中n为0-2的整数，R10为氢、C1-C3烷基或C1-C6氟代烷基；B为直接键或选择自—CH2—、— —、—CHR11—、—CR11R12—、— CHR11—、 CR11R12—、—CHR11CHR12—和公式—（CR11R12）p-Z-的二价基团，其中Z连接到携带R1、R2和R3的环上；其中R11为C1-C3烷基、环丙基或C1-C6氟代烷基；R12为甲基或氟甲基；p独立地为1或2；Z为—O—、—NH—或—S（O）n—，其中n为0-2的整数；X为羧酸、四唑、3-羟基异噁唑、羟肟酸、磷酸酯、膦酸酯、膦酰胺或磺酸基团，或公式C（═O）NHSO2R6或SO2NHC（═O）R6的基团；Y为芳基、杂环芳基、芳基融合杂环烷基、杂环烷基融合环烷基、杂环芳基融合杂环烷基或芳基融合环烷基的基团。
• QUINOLINES AND THEIR THERAPEUTIC USE
  申请人：Argenta Discovery Limited

  公开号：EP1928457A2

  公开（公告）日：2008-06-11
• US7858640B2
  申请人：——

  公开号：US7858640B2

  公开（公告）日：2010-12-28
• [EN] QUINOLINES AND THEIR THERAPEUTIC USE<br/>[FR] QUINOLEINES ET LEUR UTILISATION THERAPEUTIQUE
  申请人：ARGENTA DISCOVERY LTD

  公开号：WO2007036743A2

  公开（公告）日：2007-04-05

  [EN] Compounds of formula [1] are CRTH2 antagonists, useful in the treatment of conditions having an inflammatory component; in which: R¹, R², R³, R⁴ and R⁵ are independently hydrogen, C₁-C₆alkyl, C₁- C₆fluoroalkyl, cyclopropyl, halo, -S(O)_nR⁶, -SO₂NR⁷R⁸, -NR⁷R⁸, -NR⁷C(O)R⁶, -CO₂R⁷, -C(O)NR⁷R⁸, -C(O)R⁶, -NO₂, -CN or a group -OR⁹; wherein each R⁶ is independently C₁-C₆alkyl, C₁-C₆fluoroalkyl, cycloalkyl, aryl, or heteroaryl; R⁷, R⁸ are independently C₁-C₆alkyl, C₁-C₆fluoroalkyl, cycloalkyl, cycloalkyl-(C₁-C₆alkyl)-, aryl, heteroaryl or hydrogen; R⁹ is hydrogen, C₁-C₆alkyl, C₁-C₆fluoroalkyl, cycloalkyl, cylcoalkyl-(C₁-C₆alkyl)-, or a group -SO₂R⁶; A is -CHR¹⁰-, -C(O)-, -S(O)_n-, -0-, or -NR¹⁰- wherein n is an integer from 0-2 and R¹⁰ is hydrogen, C₁-C₃alkyl, or C₁-C₆fluoroalkyl group; B is a direct bond, or a divalent radical selected from -CH₂-, -CH₂CH₂-, -CHR¹¹-, -CR¹¹R¹²-, -CH₂CHR¹¹-, -CH₂CR¹¹R¹²-, -CHR¹¹CHR¹²-, and divalent radicals of formula -(CR¹¹R¹²)_P-Z- wherein Z is attached to the ring carrying R¹, R² and R³; wherein R¹¹ is C₁-C₃alkyl, cyclopropyl, C₁-C₆fluoroalkyl; R¹² is methyl or fluoromethyl; p is independently 1 or 2; and Z is -0-, -NH-, or -S(O)_n-, wherein n is an integer from 0-2; X is a carboxylic acid, tetrazole, 3-hydroxyisoxazole, hydroxamic acid, phosphinate, phosphonate, phosphonamide, or sulfonic acid group, or a group of formula C(=O)NHSO₂R⁶or SO₂NHC(=O)R⁶; and Y is aryl, heteroaryl, aryl-fused- heterocycloalkyl, heteroaryl-fused-cycloalkyl, heteroaryl-fused-heterocycloalkyl or aryl-fused-cycloalkyl group.
  [FR] L'invention concerne des composés de formule [1] comme antagonistes du CRTH2, lesquels composés sont utiles dans le traitement d'états pathologiques présentant une composante inflammatoire, formule dans laquelle R¹, R², R³, R⁴ et R⁵ représentent indépendamment hydrogène, alkyle en C₁-C₆, fluoroalkyle en C₁-C₆, cyclopropyle, halo, -S(O)_nR⁶, -SO₂NR⁷R⁸, -NR⁷R⁸, -NR⁷C(O)R⁶, -CO₂R⁷, -(O)NR⁷R⁸, -C(O)R⁶, -NO₂, -CN ou un groupe -OR⁹, chaque R⁶ représentant indépendamment alkyle en C₁-C₆, fluoroalkyle en C₁-C₆, cycloalkyle, aryle ou hétéroaryle, R⁷ et R⁸ représentant indépendamment alkyle en C₁-C₆, fluoroalkyle en C₁-C₆, cycloalkyle, cycloalkyl-(C₁-C₆-alkyl)-, aryle, hétéroaryle ou hydrogène, R⁹ représentant hydrogène, alkyle en C₁-C₆, fluoroalkyle en C₁-C₆, cycloalkyle, cycloalkyl-(C₁-C₆-alkyl)- ou un groupe -SO₂R⁶ ; A = -CHR¹⁰-, -C(O)-, -S(O)_n-, -0- ou -NR¹⁰-, n étant un nombre entier de 0 à 2 et R¹⁰ représentant hydrogène, alkyle en C₁-C₃ ou un groupe fluoroalkyle en C₁-C₆ ; B est une liaison directe ou un radical divalent sélectionné parmi -CH₂-, -CH₂CH₂-, -CHR¹¹-, -CR¹¹R¹²-, -CH₂CHR¹¹-, -CH₂CR¹¹R¹²-, -CHR¹¹CHR¹²- et des radicaux divalents de formule -(CR¹¹R¹²)_P-Z-, dans laquelle Z est attaché au cycle portant R¹, R² et R³ ; R¹¹ représente alkyle en C₁-C₃, cyclopropyle, fluoroalkyle en C₁-C₆ ; R¹² représente méthyle ou fluorométhyle ; p représente indépendamment 1 ou 2 et Z = -0-, -NH- ou -S(O)_n-, n étant un nombre entier de 0 à 2 ; X est un acide carboxylique, tétrazole, 3-hydroxyisoxazole, acide hydroxamique, phosphinate, phosphonate, phosphonamide, ou groupe acide sulfonique ou un groupe de formule C(=O)NHSO₂R⁶ ou SO₂NHC(=O)R⁶ et Y représente aryle, hétéroaryle, hétérocycloalkyle aryle condensé, cycloalkyle hétéroaryle condensé, hétérocycloalkyle hétéroaryle condensé ou un groupe cycloalkyle aryle condensé.