Substituted imidazole derivatives having agonist-like activity at alpha 2B or 2B/2C adrenergic receptors

摘要

A compound having selective agonist activity at the a2B or a2B/a2C adrenergic receptor subtype (s) as compared to the 2A adrenergic receptor subtype represented by the formula (I) wherein: the dotted lines represent optional double bonds; R is H or lower alkyl; X is S or C(H)R1, wherein R1 is H or lower alkyl or R1 is absent when X is S or when the bond between X and the five membered ring of formula(a) is a double bond; Y is O, N, S, (CR1x)y, wherein y is an integer of from 1 to 3, -CH=CH- or -Y1CH2-, wherein Y1 is O, N or S; x is an integer of 1 or 2, wherein x is 1 when R2, R3 or R4 is bound to an unsaturated carbon atom and x is 2 when R2, R3 or R4 is bonded to a saturated carbon atom; W is H, lower alkyl, halogen, hydroxy or lower alkoxy, or, when attached to a saturated carbon atom, R2 may be oxo; R3 and R4 are, each independently, H, lower alkyl, bromine hydroxy, lower alkoxy, or phenyl or, together, are -(C(R2)x)z-; Y1- (C(R2)x)z'-; -Y1(C(R2)x)yY1-; -(C(R2)x)-Y1(C(R2)x)-; - (C(R2)x)-Y1-(C(R2)x)-(C(R2)x)- and -Y1-(C(R2)x)-Y1-(C(R2)x)- wherein z is an integer of from 3 to 5, z' is an integer of from 2 to 4 and x and y are as defined above, and further either end of each of these divalent moieties may attach at either R3 or R4 to form the condensed ring structure (shown herein) and the ring thus formed may be totally unsaturated, partially unsaturated, or totally saturated provided that a ring carbon has no more than 4 valences, nitrogen no more than three and O and S have no more than two, and including pharmaceutically acceptable salts thereof. These compounds are useful for treating muscle spasticity including hyperactive micturition, diarrhea, diuresis, withdrawal syndromes, pain including neuropathic pain, neurodegenerative diseases, memory and cognition deficits, psychoses including manic disorders and anxiety, hypertension, cardiac ischemia, congestive heart failure, and nasal congestion without sedating or cardiovascular side effects.