Preparation of indolylacetic acid derivs. as CRTH2 antagonists for the treatment of allergic diseases and other disorders.

Abstract

Compds. of general formula I (wherein W is chloro or fluoro; Z is a -SO2YR1 group wherein R1 is C3-C8 heterocyclyl, aryl or heteroaryl any of which may optionally be substituted and Y is a straight or branched C1-C4 alkylene) and their pharmaceutically acceptable salts, hydrates, solvates, complexes or prodrugs are useful in orally administrable compns. for the treatment of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and other diseases mediated by PGD2 or other agonists acting at the CRTH2 receptor. Synthetic procedures for prepg. I are exemplified and claimed. Example compd. II was prepd. in a multistep synthesis that involved reaction 4-(benzylsulfonyl)benzaldehyde and 2-(5-fluoro-2-methyl-1H-indol-1-yl)acetic acid Et ester followed by sapon. of the resulting intermediate. II had a Ki of 1 nM in a radioligand binding assay that measured CRTH2 antagonist activity. [on SciFinder(R)]