- CRTH2 ANTAGONISTS
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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.
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Page/Page column 14
(2008/12/06)
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- IMDOLIZINE DERIVATIVES AS LIGANDS OF THE CRTH2 RECEPTOR
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Compounds of formula (I) are CRTH2 antagonists, useful in the treatment of, for example, asthma, chronic obstructive pulmonary disease, rhinitis, allergic airway syndrome, and allergic rhinobronchitis. Formula (I) wherein R1, R2. R3 and R4 each independently are hydrogen, C1-C6alkyl, fully or partially fluorinated C1-C6alkyl, 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 C1-C6alkyl, aryl, heteroaryl; R10 is independently hydrogen, C1-C6alkyl, aryl, or heteroaryl; R11 is hydrogen, C1-C6alkyl, fully or partially fluorinated C1-C6alkyl or a group -SO2R10 ; n is 0, 1 or 2; R5 is C1-C6alkyl, fully or partially fluorinated C1-C6alkyl, C1-C6alkenyl, C1-C6alkynyl, optionally substituted aryl, or optionally substituted heteroaryl; R6 is hydrogen, C1-C6alkyl or fully or partially fluorinated C1-C6alkyl ; R7 and R8 are independently hydrogen or C1-C6alkyl, or R7 and R8 together with the atom to which they are attached form a cycloalkyl group; and X is -CHR6-, -S(O)n-, -C(O)-, -NR6SO2- or -SO2NR6- wherein n is 0, 1 or 2.
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Page/Page column 60
(2008/06/13)
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