Omega-[(omega-arylalkyl)thienyl]alkanoic acids: from specific LTA4 hydrolase inhibitors to LTB4 receptor antagonists.

A series of omega-[(omega-arylalkyl)thienyl]alkanoic acid isomers was prepared and a structure-activity relationship was investigated. These compounds have displayed either LTA4 hydrolase inhibition activities or LTB4 receptor binding activities, or both, depending on the relative orientation of the two side chains on the thiophene ring. Whereas the 2,5-isomers specifically exhibited LTA4 hydrolase inhibition, 3,5-isomers displayed both activities.

Omega-[(omega-arylalkyl)aryl]alkanoic acids: a new class of specific LTA4 hydrolase inhibitors.

The synthesis and structure-activity profile of a new class of potent and specific LTA4 hydrolase inhibitors are described. Many compounds of this series of omega-[5-(omega-arylalkyl)-2-thienyl]- and omega-[4-(omega-arylalkyl)phenyl]alkanoic acids were found to be potent in vitro inhibitors of the LTB4 production by porcine leukocytes with IC50 ranging from 1 to 10 microM. The side-chain lengths were critical for an optimal activity.