Compounds having CRTH2 antagonist activity

摘要

Compounds of general formula (II);
wherein
W is chloro or fluoro;R1 is phenyl optionally substituted with one or more substituents, selected from halo, —CN, —C1-C6 alkyl, —SOR3, —SO2R3, —SO2N(R2)2, —N(R2)2, —NR2C(O)R3, —CO2R2, —CONR2R3, —NO2, —OR2, —SR2, —O(CH2)pOR2, or —O(CH2)pO(CH2)qOR2 wherein
each R2 is independently hydrogen, —C1-C6 alkyl, —C3-C8 cycloalkyl, aryl or heteroaryl;each R3 is independently, —C1-C6 alkyl, —C3-C8 cycloalkyl, aryl or heteroaryl;p and q are each independently an integer from 1 to 3; andR4 is hydrogen, C1-C6 alkyl, C1-C6 alkyl substituted with aryl, aryl, (CH2)mOC(═O)C1-C6alkyl, ((CH2)mO)nCH2CH2X, (CH2)mN(R5)2 or CH((CH2)mO(C═O)R6)2;
m is 1 or 2;n is 1-4;X is OR5 or N(R5)2;R5 is hydrogen or methyl; andR6 is C1-C18 alkyl;and their pharmaceutically acceptable salts, hydrates, solvates, complexes or prodrugs are useful in orally administrable compositions for the treatment of allergic diseases such as asthma, allergic rhinitis and atopic dermatitis.

主权项

1. A method for the treatment of a disease or condition mediated by PGD2 or other agonist at the CRTH2 receptor comprising administering to a patient in need of such treatment a suitable amount of a compound of formula (II):wherein
W is chloro or fluoro; Rl is phenyl, optionally substituted with one or more substituents, selected from halo, —CN, —C1-C6 alkyl, —SOR3, —SO2R3, —SO2N(R2)2, —N(R2)2, —NR2C(O)R3, —CO2R2, —CONR2R3, —NO2, —OR2, —SR2, —O(CH2)pOR2, or —O(CH2)pO(CH2)qOR2 wherein each R2 is independently hydrogen, —C1-C6 alkyl, —C3-C8 cycloalkyl, aryl, or heteroaryl; each R3 is independently, —C1-C6 alkyl, —C3-C8 cycloalkyl, aryl, or heteroaryl; and p and q are each independently an integer from 1 to 3; and R4 is hydrogen, C1-C6 alkyl, C1-C6 alkyl substituted with aryl, aryl, (CH2)mOC(═O)C1-C6alkyl, ((CH2)mO)nCH2CH2X, (CH2)mN(R5)2, or CH((CH2)mO(C═O)R6)2;
M is 1 or 2;n is 1-4;X is OR5 or N(R5)2;R5 is hydrogen or methyl; andR6 is C1-C18 alkyl; or a pharmaceutically acceptable salt, hydrate, solvate, complex, or prodrug thereof;wherein the disease or condition mediated by PGD2 or other agonist at the CRTH2 receptor is selected from the group consisting of an infection due to rhinovirus, coronavirus, respiratory syncytial virus, influenza, or adenovirus; contact hypersensitivity; contact dermatitis; male-pattern baldness; eosinophilic bronchitis; eosinophilic oesophagitis; and gastroesophageal reflux disease (GERD).