ANTI-INFLAMMATORY PIPERAZINYL-BENZYL-TETRAZOLE DERIVATIVES AND INTERMEDIATES THEREOF

This invention relates to tetrazoles and their pharmaceutically acceptable salts which are selective agonists for the delta opioid receptor, particularly useful in the treatment of inflammatory diseases such as arthritis, psoriasis, asthma, inflammatory bowel disease, disorders or respiratory function, gastrointestinal disorders such as functional bowel disease and functional GI disorders, of formula (I)wherein R1 is H, C2-C6 alkanoyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (C3-C7 cycloalkyl)-(C1-C4 alkyl), (C1-C4 alkoxy)-(C1-C4 alkyl), carboxy-(C1-C4 alkyl), aryl-(C1-C4 alkyl) or heteroaryl-(C1-C4 alkyl); R2 and R3 are each independently H or C1-C4 alkyl; R4 is selected from (i) H, (ii) a group of the formula R6-(CH2)m-Z-(CH2)n-, where m is 0, 1, 2 or 3, n is 1, 2 or 3, Z is a direct link or O, and R6 is -CO2H or -CO2(C1-C4 alkyl), and (iii) a group of formula (a)where R7 is H or C1-C4 alkyl; and R5 is hydroxy, C1-C4 alkoxy or -NHSO2(C1-C4 alkyl); with the proviso that when Z is O, m is 1, 2 or 3 and n is 2 or 3.