The pharmacologic activity of leukotriene B< (LTB<) continues to generate intense research interest. LTB4 is known to stimulate degranulation, aggregation, chemotaxis, and chemokinesis of polymorphonuclear leukocytes, as well as promote superoxide generation.1 The proinflammatory effects of this eicosanoid mediator may play a role in the pathogenesis of several inflammatory diseases such as asthma,2 inflammatory bowel disease,3 psoriasis,4 and gout.1*'5 We recently disclosed the acetophenone/ xanthone LTB4 receptor antagonist LY282210 (compound 4, Chart I),6 which evolved from two separate series of compounds represented by LY255283 (1, acetophenone class)7 and LY223982/LY210073 (2/3, benzophenone/

A hypothetical model for receptor binding of leukotriene D4 (LTD4) was deduced from conformational analysis of LTD4 and from the structure-activity relationships (SAR) of known LTD4 receptor antagonists. A new structural series of LTD4 receptor antagonists exemplified by 5-[4-(4-phenylbutoxy)phenyl]-2-[4-(tetrazol-5-yl)butyl]-2H-t etrazole was designed in which a phenyltetrazole moiety was incorporated as a receptor binding equivalent of the triene unit of LTD4. A number of these phenyltetrazoles were prepared and found to possess LTD4 receptor antagonist activity. The structure-activity relationship (SAR) of this series is described.