Heteroaryl-hexanoic acid amide derivatives, their preparation and their use as selective inhibitors of MIP-1-alpha binding to its CCRI receptor

摘要

Compounds of formula (I) wherein R1 is optionally substituted (C2-C9)heteroaryl; R2 is optionally substituted phenyl-(CH2)m-, naphthyl-(CH2)m-, (C3-C10)cycloalkyl-(CH2)m-, (C1-C6)alkyl or (C2-C9)heteroaryl-(CH2)m-, m is an integer from zero to four; R3 is hydrogen, or optionally substituted (C1-C10)alkyl, (C3-C10)cycloalkyl-(CH2)n-, (C2-C9)heterocycloalkyl-(CH2)n-, (C2-C9)heteroaryl-(CH2)n- or aryl-(CH2)n-, n is an integer from zero to six; or R3 and the carbon to which it is attached form an optionally substituted and/or fused five to seven membered carbocyclic ring; R4 is hydrogen, (C1-C6)alkyl, hydroxy, (C1-C6)alkoxy, hydroxy (C1-C6)alkyl, (C1-C6)alkoxyCO, (C3-C10)cycloalkyl-(CH2)p-, or optionally substituted (C2-C9)heterocycloalkyl-(CH2)p-, (C2-C9)heteroaryl-(CH2)p-, phenyl-(CH2)p- or naphthyl-(CH2)p-, p is an integer from zero to four; or R4 and R5 together with the nitrogen atom to which they are attached form an optionally substituted (C2-C9)heterocycloalkyl group; R5 is hydrogen, (C1-C6)alkyl or amino. The present compounds are potent and selective inhibitors of MIP-1-alpha. binding to its receptor CCR1, and are thus useful to treat inflammation and other immune disorders.