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1. 发明申请

WO2008074966A1 CRTH2 ANTAGONISTS 审中-公开
公开(公告)号：WO2008074966A1
公开(公告)日：2008-06-26
申请号：PCT/GB2006/004856
申请日：2006-12-21
申请人： ARGENTA DISCOVERY LIMITED , HYND, George , RAY, Nicholas, Charles , FINCH, Harry , MIDDLEMISS, David , CRAMP, Michael, Colin , BLANEY, Paul, Matthew , WILLIAMS, Karen , GRIFFON, Yan , HARRISON, Trevor, Keith , CRACKETT, Peter
发明人： HYND, George , RAY, Nicholas, Charles , FINCH, Harry , MIDDLEMISS, David , CRAMP, Michael, Colin , BLANEY, Paul, Matthew , WILLIAMS, Karen , GRIFFON, Yan , HARRISON, Trevor, Keith , CRACKETT, Peter
IPC分类号： A61K31/437 , C07D471/04 , A61P37/08
CPC分类号： C07D471/04
摘要： The following compounds are CRTH2 antagonists, useful in treatment of respiratory disease: [3-(2,4-dichlorophenylsulfanyl)-6-fluoro-2-methylindolizin-1-yl]acetic acid, [6-fluoro-3-(2-fluoro-4-methanesulfonylphenylsulfanyl)-2-methylindolizin-1-yl]acetic acid, [6-fluoro-3-(4-methanesulfonyl-2-trifluoromethylphenylsulfanyl)-2-methylindolizin-1-yl]acetic acid, ( R )-2-[6-fluoro-3-(4-methanesulfonylphenylsulfanyl)-2-methylindolizin-1-yl]propionic acid, [3-(4-ethanesulfonylphenylsulfanyl)-6-fluoro-2-methylindolizin-1-yl]acetic acid, ( S )-2-[6-fluoro-3-(4-methanesulfonylphenylsulfanyl)-2-methylindolizin-1-yl]propionic acid, ethanesulfonylaminobenzenesulfonyl)-6-fluoro-2-methyiindolizin-1-yl]acetic acid, [7-chloro-6-fluoro-3-(4-methanesulfonylphenylsulfanyl)-2-methylindolizin-1-yl]acetic acid, [3-(2-chloro-4-methanesulfonylphenylsulfanyl)-7-cyano-2-methylindolizin-1-yl]acetic acid, [6-cyano-3-(4-methanesulfonylbenzyl)-2-methylindolizin-1-yl]acetic acid, [3-(4-chlorobenzyl)-7-cyano-2-methylindolizin-1-yl]acetic acid, [6-cyano-3-(6-fluoroquinolin-2-ylmethyl)-2-methylindolizin-1-yl]acetic acid, [6-fluoro-3-(4-methoxyphenylsulfanyl)-2-methylindolizin-1-yl]acetic acid, [7-chloro-6-fluoro-3-(4-methoxyphenylsulfanyl)-2-methylindolizin-1-yl]acetic acid, [3-(4-bromophenylsulfanyl)-6-fluoro-2-methylindolizin-1-yl]acetic acid, and [3-(4-cyclopropylsulfamoylphenylsulfanyl)-6-fluoro-2-methylindolizin-1-yl]acetic acid.
摘要翻译：以下化合物是可用于治疗呼吸系统疾病的CRTH2拮抗剂：[3-（2,4-二氯苯基硫烷基）-6-氟-2-甲基吲哚啉-1-基]乙酸[6-氟-3-（2- （4-甲基磺酰基-2-三氟甲基苯基硫烷基）-2-甲基吲哚哩啶-1-基]乙酸，（R） - （4-氟-4-甲磺酰基苯基硫烷基）-2-甲基吲哚啉-1-基] 2- [6-氟-3-（4-甲磺酰基苯基硫基）-2-甲基吲哚啉-1-基]丙酸，[3-（4-乙磺酰基苯基硫烷基）-6-氟-2-甲基吲哚啉-1-基]乙酸，（S）-2- [6-氟-3-（4-甲磺酰基苯基硫烷基）-2-甲基吲哚啉-1-基]丙酸，乙磺酰氨基苯磺酰基）-6-氟-2-甲基吲哚啉-1-基]乙酸[7 （4-甲磺酰基苯基硫烷基）-2-甲基吲哚哩啶-1-基]乙酸[3-（2-氯-4-甲磺酰基苯基硫烷基）-7-氰基-2-甲基吲哚啉-1-基] ]乙酸，[6-氰基-3-（4-甲磺酰基苄基）-2-甲基吲哚啉-1-基]乙酸[3-（4-氯苄基）-7-氰基-2-甲基吲哚吡啶-1-基]乙酸[6-氰基-3-（6-氟喹啉-2-基甲基）-2-甲基吲哚啉-1-基]乙酸[6-氟-3-（4-甲氧基苯基硫烷基） 2-甲基吲哚啉-1-基]乙酸，[7-氯-6-氟-3-（4-甲氧基苯基硫烷基）-2-甲基吲哚啉-1-基]乙酸，[3-（4-溴苯基硫烷基）-6- -2-氟-2-甲基吲哚啉-1-基]乙酸和[3-（4-环丙基氨磺酰基苯基硫烷基）-6-氟-2-甲基吲哚啉-1-基]乙酸。

2. 发明申请

WO2006136859A3 INDOLI ZINE DERIVATIVES AND THEIR USE AS CRTH2 ANTAGONISTS 审中-公开
标题翻译：吲哚嗪衍生物及其作为CRTH2拮抗剂的用途
公开(公告)号：WO2006136859A3
公开(公告)日：2007-04-05
申请号：PCT/GB2006002341
申请日：2006-06-26
申请人： ARGENTA DISCOVERY LTD , HYND GEORGE , RAY NICHOLAS CHARLES , FINCH HARRY , MIDDLEMISS DAVID , CRAMP MICHAEL COLIN , BLANEY PAUL MATTHEW , WILLIAMS KAREN , GRIFFON YAN , HARRISON TREVOR KEITH , CRACKETT PETER
发明人： HYND GEORGE , RAY NICHOLAS CHARLES , FINCH HARRY , MIDDLEMISS DAVID , CRAMP MICHAEL COLIN , BLANEY PAUL MATTHEW , WILLIAMS KAREN , GRIFFON YAN , HARRISON TREVOR KEITH , CRACKETT PETER
IPC分类号： C07D471/04 , A61K31/437 , A61P11/06 , A61P11/08 , A61P17/00 , A61P19/02 , A61P29/00 , A61P37/08
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 R 1 , R 2 , R 3 and R 4 each independently are hydrogen, C 1 C 6 alkyl, fully or partially fluorinated C 1 C 6 alkyl, halo, -S(O) n R 10 , -SO 2 N(R 10 ) 2 , -N(R 10 ) 2 , -C(O)N(R 10 ) 2 , -NR 10 C(O)R 9 , -CO 2 R 10 , -C(O)R 9 , -NO 2 , -CN or -OR 11 ; wherein each R 9 is independently C 1 C 6 alkyl, aryl, heteroaryl; R 10 is independently hydrogen, C 1 C 6 alkyl, aryl, or heteroaryl; R 11 is hydrogen, C 1 C 6 alkyl, fully or partially fluorinated C 1 C 6 alkyl or a group -SO 2 R 9 ; n is 0, 1 or 2; R5 is C 1 C 6 alkyl, fully or partially fluorinated C 1 C 6 alkyl , C 1 C 6 alkenyl , C 1 C 6 alkynyl, optionally substituted aryl, or optionally substituted heteroaryl; R 6 is hydrogen, C 1 C 6 alkyl or fully or partially fluorinated C 1 C 6 alkyl ; R 7 and R 8 are independently hydrogen or C 1 C 6 alkyl, or R 7 and R 8 together with the atom to which they are attached form a cycloalkyl group; and X is -CHR 6 -, -S(O) n -, -NR 6 SO 2 - or -SO 2 NR 6 - 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：式（I）其中R 1，R 2，R 2， > 3和R 4各自独立地是氢，C 1 -C 6烷基，完全或部分氟化的C 1 烷基，卤素，-S（O）n R 10，-SO 2 N， N（R 10）2，-N（R 10）2 - ， - C（O）N（R 10） R 10，-NR 10 C（O）R 9，-CO 2， -C（O）R 9，-NO 2，-CN或-OR 11， SUB>; 其中每个R 9独立地是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C 1 -C 6 烷基或基团-SO 2 R 9; n为0,1或2; R 5是C 1 -C 6烷基，完全或部分氟化C 1 -C 6烷基，C 1 -C 6烷基，C 1 -C 6烷基， 1个C 6链烯基，C 1 -C 6炔基，任选取代的芳基或任选取代的杂芳基; R 6是氢，C 1 -C 6烷基或完全或部分氟化的C 1 -C 6 烷基; R 7和R 8独立地是氢或C 1 -C 6烷基，或R 7， / SUB和R 8与它们所连接的原子一起形成环烷基; 和X是-CHR 6 - ， - S（O）n - ， - NR 6 SO 2 - 或-SO 2 NR 6 - ，其中n为0,1或2。

3. 发明申请

WO2006136859A2 INDOLIZINE DERIVATIVES 审中-公开
标题翻译：吲哚衍生物
公开(公告)号：WO2006136859A2
公开(公告)日：2006-12-28
申请号：PCT/GB2006/002341
申请日：2006-06-26
申请人： ARGENTA DISCOVERY LTD. , HYND, George , RAY, Nicholas, Charles , FINCH, Harry , MIDDLEMISS, David , CRAMP, Michael, Colin , BLANEY, Paul, Matthew , WILLIAMS, Karen , GRIFFON, Yan , HARRISON, Trevor, Keith , CRACKETT, Peter
发明人： HYND, George , RAY, Nicholas, Charles , FINCH, Harry , MIDDLEMISS, David , CRAMP, Michael, Colin , BLANEY, Paul, Matthew , WILLIAMS, Karen , GRIFFON, Yan , HARRISON, Trevor, Keith , CRACKETT, Peter
IPC分类号： C07D471/04
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 R 1 , R 2 , R 3 and R 4 each independently are hydrogen, C 1 C 6 alkyl, fully or partially fluorinated C 1 C 6 alkyl, halo, -S(O) n R 10 , -SO 2 N(R 10 ) 2 , -N(R 10 ) 2 , -C(O)N(R 10 ) 2 , -NR 10 C(O)R 9 , -CO 2 R 10 , -C(O)R 9 , -NO 2 , -CN or -OR 11 ; wherein each R 9 is independently C 1 C 6 alkyl, aryl, heteroaryl; R 10 is independently hydrogen, C 1 C 6 alkyl, aryl, or heteroaryl; R 11 is hydrogen, C 1 C 6 alkyl, fully or partially fluorinated C 1 C 6 alkyl or a group -SO 2 R 9 ; n is 0, 1 or 2; R5 is C 1 C 6 alkyl, fully or partially fluorinated C 1 C 6 alkyl , C 1 C 6 alkenyl , C 1 C 6 alkynyl, optionally substituted aryl, or optionally substituted heteroaryl; R 6 is hydrogen, C 1 C 6 alkyl or fully or partially fluorinated C 1 C 6 alkyl ; R 7 and R 8 are independently hydrogen or C 1 C 6 alkyl, or R 7 and R 8 together with the atom to which they are attached form a cycloalkyl group; and X is -CHR 6 -, -S(O) n -, -NR 6 SO 2 - or -SO 2 NR 6 - 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：式（I）其中R 1，R 2，R SUB > 3和R 4各自独立地是氢，C 1 -C 6烷基，完全或部分氟化的C 1 C 6烷基，卤素，-S（O）n R 10，-SO 2 N， N（R 10）2，-N（R 10）2 - ， - C（O）N（R 10） R 10，-NR 10 C（O）R 9，-CO 2， R 10，-C（O）R 9，-NO 2，-CN或-OR 11， SUB>; 其中每个R 9独立地是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C 1 -C 6 烷基或基团-SO 2 R 9; n为0,1或2; R 5是C 1 -C 6烷基，完全或部分氟化的C 1 -C 6烷基，C 1 -C 6烷基，C 1 -C 6烷基， 1个C 6链烯基，C 1 -C 6炔基，任选取代的芳基或任选取代的杂芳基; R 6是氢，C 1 -C 6烷基或完全或部分氟化的C 1 -C 6 烷基; R 7和R 8独立地是氢或C 1 -C 6烷基，或R 7， / SUB和R 8与它们所连接的原子一起形成环烷基; 并且X是-CHR 6 - ， - S（O）n - ， - NR 6 SO 2 - 或-SO 2 NR 6 - ，其中n为0,1或2。

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