HETEROCYCLIC COMPOUNDS WHICH INHIBIT LEUKOCYTE ADHESION MEDIATED BY .ALPHA.4 INTEGRINS

摘要

Disclosed are compounds which bind a4 integrins, preferably VLA-4.Certain of these compounds also inhibit leukocfyte adhesion and, inparticular, leukocyte adhesion mediated by a4 integrins, preferably VLA-4.Such compounds are useful in the treatment of inflammatory diseases in amammalian patient, e.g., human, such as asthma, Alzheimer's disease,atherosclerosis, AIDS, dementia, diabetes, inflammatory bowel disease,rheumatoid arthritis, tissue transplantation, tumor metastasis andmyocardial ischemia. The compounds can also be administered for thetreatment of inflammatory brain diseases such as multiple sclerosis. Onesuch compound is(see formula I)wherein each X is independently fluoro, chloro or bromo;p is an integer from 0 to 3;R1 and R3 together with the nitrogen atom to which they are boundform an azetidinyl, pyrrolidinyl, pyrrolyl, 2,5-dihydopyrrol-1-yl,piperidinyl,or 1,2,3,6-tetrahydro-pyridin-1-yl;R2 is selected from the group consisting of lower alkyl, loweralkenyl, and lower alkylenecycloalkyl;and pharmaceutically acceptable salts thereof.