公开(公告)号：US20090163534A1

公开(公告)日：2009-06-25

申请号：US11993412

申请日：2006-06-26

申请人： George Hynd ,  Nicholas Charles Ray ,  Harry Finch ,  David Middlemiss ,  Michael Colin Cramp ,  Paul Matthew Blaney ,  Karen Williams ,  Yan Griffon ,  Trevor Keith Harrison ,  Peter Crackett

发明人： George Hynd ,  Nicholas Charles Ray ,  Harry Finch ,  David Middlemiss ,  Michael Colin Cramp ,  Paul Matthew Blaney ,  Karen Williams ,  Yan Griffon ,  Trevor Keith Harrison ,  Peter Crackett

IPC分类号： A61K31/437 ,  C07D221/04 ,  A61P29/00

CPC分类号： C07D471/04

摘要： Compounds of formula (I) are ligands of the CRTH2 receptor and are useful in the treatment of respiratory disease: Formula (I) wherein R1, R2, R3 and R4 each independently are hydrogen, C1C6alkyl, fully or partially fluorinated C1C6alkyl, halo, —S(O)nR10, —SO2N(R10)2, —N(R10)2, —C(O)N(R10)2, —NR10C(O)R9, —CO2R10, —C(O)R9, —NO2, —CN or —OR11; wherein each R9 is independently C1C6alkyl, aryl, heteroaryl; R10 is independently hydrogen, C1C6alkyl, aryl, or heteroaryl; R11 is hydrogen, C1C6alkyl, fully or partially fluorinated C1C6alkyl or a group —SO2R9; n is 0, 1 or 2; R5 is C1C6alkyl, fully or partially fluorinated C1C6alkyl. C1C6alkenyl, C1C6alkynyl, optionally substituted aryl, or optionally substituted heteroaryl; R6 is hydrogen, C1C6alkyl or fully or partially fluorinated C1C6alkyl; R7 and R5 are independently hydrogen or C1C6alkyl, or R7 and R5 together with the atom to which they are attached form a cycloalkyl group; and X is —CHR6—, —S(O)n—, —NR6SO2— or —SO2NR6— wherein n is 0, 1 or 2.

摘要翻译： 式（I）化合物是CRTH2受体的配体，可用于治疗呼吸系统疾病：其中R 1，R 2，R 3和R 4各自独立地为氢，C 1 -C 6烷基，完全或部分氟化的C 1 -C 6烷基，卤素， S（O）nR10，-SO2N（R10）2，-N（R10）2，-C（O）N（R10）2，-NR10C（O）R9，-CO2R10，-C（O） ，-CN或-OR11; 其中每个R 9独立地为C 1 -C 6烷基，芳基，杂芳基; R 10独立地是氢，C 1 -C 6烷基，芳基或杂芳基; R 11是氢，C 1 -C 6烷基，完全或部分氟化的C 1 -C 6烷基或基团-SO 2 R 9; n为0,1或2; R5是C1C6烷基，完全或部分氟化的C1C6烷基。 C 1 -C 6烯基，C 1 -C 6炔基，任选取代的芳基或任选取代的杂芳基; R6是氢，C1C6烷基或完全或部分氟化的C 1 -C 6烷基; R 7和R 5独立地为氢或C 1 -C 6烷基，或者R 7和R 5与它们所连接的原子一起形成环烷基; 且X为-CHR 6 - ， - S（O）n - ， - NR 6 SO 2 - 或-SO 2 NR 6 - ，其中n为0,1或2。

公开(公告)号：US20090156600A1

公开(公告)日：2009-06-18

申请号：US12066603

申请日：2006-09-29

申请人： Michael Colin Cramp ,  Rosa Arienzo ,  George Hynd ,  Peter Crackett ,  Yann Griffon ,  Trevor Keith Harrison ,  Nicholas Charles Ray ,  Harry Finch ,  John Gary Montana

发明人： Michael Colin Cramp ,  Rosa Arienzo ,  George Hynd ,  Peter Crackett ,  Yann Griffon ,  Trevor Keith Harrison ,  Nicholas Charles Ray ,  Harry Finch ,  John Gary Montana

IPC分类号： A61K31/5377 ,  C07D215/233 ,  A61P11/06 ,  C07D413/14 ,  A61K31/47

CPC分类号： C07D215/233 ,  A61K31/47 ,  C07D215/12 ,  C07D215/18 ,  C07D215/20 ,  C07D215/227 ,  C07D215/36 ,  C07D215/48 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12

摘要： 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.

摘要翻译： 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。