| abstract |
Compounds of the formula <IMAGE> I wherein X is O or CH2; Y is O, -CH2-CH2-, -CH=CH-, -C 3BOND C-, or -OCH2C6H4-; Z is -CH2-CH2-, -CH=CH- or -C 3BOND C-; f, h, k, m and t, independently, are 0 or 1; n is an integer from 1 to 12; R1 is hydrogen, lower alkyl, lower alkenyl, cycloalkyl, or aralkyl; and A is B or -O-B, wherein B is a mono-, di- or tricyclic aromatic or heteroaromatic moiety substituted by the group -COR2, -(O)t-(W)s-COR2 or -(CH=CH)pCOR2 and which may also contain up to 4 additional substituents selected, independently, from the group consisting of halogen, cyano, lower alkyl, lower alkoxy, sulfonamido, alkanoyl, aroyl, -(Q)k-(W)s'-E or -(Q)k-(W)s''-C6H4-(W)s'''-E, provided that no more than one of said substituents is -(Q)k-(W)s'-E or -(Q)k-(W)s''-C6H4-(W)s'''-E, and wherein E is COR2 or R2, W is -CR3R4-, Q is O or carbonyl, p is an integer from 1 to 2, s and s', independently, are an integer from 1-12, s'' and s''', independently, are an integer from 0 to 12, C6H4 is a 1,2-, 1,3-, or 1,4-phenylene moiety, and R2 is hydroxy, lower alkoxy or NR3R4, wherein R3 and R4, each occurence, independently, are hydrogen or lower alkyl, their geometric and optical isomers and, when R2 is hydroxy, pharmaceutically acceptable salts thereof with bases. The compounds of formula I are potent leukotriene B4 antagonists and are therefore useful in the treatment of inflammatory diseases, such as psoriasis, inflammatory bowel disease, asthma, allergy, arthritis, dermatitis, gout, pulmonary disease, ischemia/reperfusion injury, and trauma induced inflammation, such as spinal cord injury. |