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    • 3. 发明申请
      US20090156600A1 Quinolines and Their Therapeutic Use 有权
    • Quinolines and Their Therapeutic Use
    • 喹啉及其治疗用途
    • US20090156600A1
    • 2009-06-18
    • US12066603
    • 2006-09-29
    • Michael Colin Cramp , Rosa Arienzo , George Hynd , Peter Crackett , Yann Griffon , Trevor Keith Harrison , Nicholas Charles Ray , Harry Finch , John Gary Montana
    • Michael Colin Cramp , Rosa Arienzo , George Hynd , Peter Crackett , Yann Griffon , Trevor Keith Harrison , Nicholas Charles Ray , Harry Finch , John Gary Montana
    • A61K31/5377 , C07D215/233 , A61P11/06 , C07D413/14 , A61K31/47
    • C07D215/233 , A61K31/47 , C07D215/12 , C07D215/18 , C07D215/20 , C07D215/227 , C07D215/36 , C07D215/48 , C07D401/04 , C07D401/10 , C07D401/12
    • 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-C6-fluoroalkyl, cyclopropyl, halo, —S(O)nR6, —SO2NR7R8, —NR7R8, —NR7C(O)R6, —CO2R7, —C(O)NR7R8, —C(O)R76, —NO2, —CN or a group —OR9; wherein each R6 is independently C1-C6alkyl, C1-C6-fluoroalkyl, cycloalkyl, aryl, or heteroaryl; R7, R8 are independently C1-C6alkyl, C1-C6-fluoroalkyl, cycloalkyl, cycloalkyl-(C1-C6alkyl)-, aryl, heteroaryl or hydrogen; R9 is hydrogen, C1-C6alkyl, C1-C6-fluoroalkyl, cycloalkyl, cylcoalkyl-(C1-C6alkyl)-, or a group —SO2R6; A is —CHR10—, —C(O)—, —S(O)n—, —O—, or —NR10— wherein n is an integer from 0-2 and R10 is hydrogen C1-C3alkyl, or C1-C6-fluoroalkyl 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-C6-fluoroalkyl; R12 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)NHSO2R6 or SO2NHC(═O)R6; and Y is aryl, heteroaryl, aryl-fused-heterocycloalkyl, heteroaryl-fused-cycloalkyl, heteroaryl-fused-heterocycloalkyl or aryl-fused-cycloalkyl group.
    • 式[1]化合物是CRTH2拮抗剂，可用于治疗具有炎性成分的病症; 其中：R1，R2，R3，R4和R5独立地是氢，C1-C6烷基，C1-C6-氟烷基，环丙基，卤素，-S（O）nR6，-SO2NR7R8，-NR7R8，-NR7C（O） -C（O）NR 7 R 8，-C（O）R 76，-NO 2，-CN或-OR 9基团; 其中每个R 6独立地为C 1 -C 6烷基，C 1 -C 6 - 氟烷基，环烷基，芳基或杂芳基; R 7，R 8独立地是C 1 -C 6烷基，C 1 -C 6氟代烷基，环烷基，环烷基 - （C 1 -C 6烷基） - ，芳基，杂芳基或氢; R 9是氢，C 1 -C 6烷基，C 1 -C 6 - 氟代烷基，环烷基，环烷基 - （C 1 -C 6烷基） - 或-SO 2 R 6基团; A是-CHR 10 - ， - C（O） - ， - S（O）n - ， - O-或-NR 10 - ，其中n是0-2的整数，R 10是氢C1-C3烷基或C1-C6 氟烷基 或选自-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 - - 的二价基团和式 - （CR11R12）pZ- 其中Z连接到携带R1，R2和R3的环上; 其中R11是C1-C3烷基，环丙基，C1-C6-氟代烷基; R12是甲基或氟甲基; p独立地为1或2; 和Z是-O - ， - NH-或-S（O）n - ，其中n是0-2的整数; X是羧酸，四唑，3-羟基异恶唑，异羟肟酸，次膦酸盐，膦酸盐，膦酰胺或磺酸基，或式C（-O）NHSO 2 R 6或SO 2 NHC（-O）R 6的基团; 并且Y是芳基，杂芳基，芳基稠合 - 杂环烷基，杂芳基 - 稠合 - 环烷基，杂芳基 - 稠合 - 杂环烷基或芳基稠合 - 环烷基。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
    • 4. 发明授权
      US06680338B2 Hydroxamic and carboxylic acid derivatives 失效
    • Hydroxamic and carboxylic acid derivatives
    • US06680338B2
    • 2004-01-20
    • US09777522
    • 2001-02-06
    • John Gary Montana , Andrew Douglas Baxter , David Alan Owen , Robert John Watson
    • John Gary Montana , Andrew Douglas Baxter , David Alan Owen , Robert John Watson
    • A61K31351
    • C07D401/12 , C07C309/08 , C07D309/08
    • Compounds having therapeutic utility are of formula (I) B—X—(CH2)n—CR2R3—CR4R5—COY  (I) wherein n=0-1; X is S(O)0-2; Y is OR1 or NHOH; R2 and R4 are independently H or a group (optionally substituted with R10) selected from C1-6 alkyl, C2-6 alkenyl, aryl, C1-6 alkyl-aryl, heteroaryl, C1-6 alkyl-heteroaryl, heterocycloalkyl, C1-6 alkyl-heterocycloalkyl, cycloalkyl and C1-6 alkyl-cycloalkyl; and R1, R3 and R5 are independently H or C1-6 alkyl, provided that not more than two of R2, R3, R4 and R5 are H; or any of CR2R3, CR4R5 and CR2—CR4 is a cycloalkyl or heterocycloalkyl ring optionally substituted with R10 or a group (optionally substituted with R10) selected from C1-6 alkyl, aryl, C1-6 alkyl-aryl, heteroaryl and C1-6 alkyl-heteroaryl; B is heterocycloalkyl (optionally substituted by R6 or R7) bonded through carbon to X, or C1-6 alkyl-heterocycloalkyl (optionally substituted with R6 or R7), or a group (substituted with R6) selected from C1-8 alkyl, C2-6 alkenyl and C2-6 alkynyl; R6 is N(R7)2, OR7, COR7, C(═NOR9)R7, NR7R8, S(O)0-2R9 or SO2N(R7)2; R7 is H or a group selected from C1-6 alkyl, aryl, C1-6 alkyl-aryl, heteroaryl, C1-6 alkyl-heteroaryl, cycloalkyl, C1-6 alkyl-cycloalkyl, heterocycloalkyl and C1-6 alkyl-heterocycloalkyl, wherein said group is optionally substituted with R9, COR9, SO0-2R9, CO2R9, OR9, CONR1R9, NR1R9, halogen, CN, SO2NR1R9 or NO2, and for each case of N(R7)2 the R7 groups are the same or different or N(R7)2 is heterocycloalkyl optionally substituted with R9, COR9, SO0-2R9, CO2R9, OR9, CONR1R9, NR1R9, NR1R9 halogen, CN, SO2NR1R9 or NO2, R8 is COR7, CON(R7)2, CO2R9 or SO2R9; R9 is C1-6 alkyl, aryl, C1-6 alkyl-aryl, heteroaryl or C1-6 alkyl-heteroaryl; and R10 is OR7, COR7, CO2R1, CON(R7)2, NR7R8, S(O)0-2R9, SO2N(R7)2, CN, halogen or cycloimidyl (optionally substituted with R1); and the salts, solvates, hydrates, N-oxides, protected amino, protected carboxy and protected hydroxamic acid derivatives thereof.
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Espacenet 法律信息 同族专利 专利引用
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