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Synthesis of novel antagonists of leukotriene B4

✍ Scribed by Joel Morris; Donn G. Wishka

Publisher: Elsevier Science
Year: 1988
Tongue: French
Weight: 250 KB
Volume: 29
Category: Article
ISSN: 0040-4039
DOI: 10.1016/s0040-4039(00)80037-4

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✦ Synopsis

As part of a program to tdentlfy a stable LTB4 antagontst, several novel compounds contarnmg a 2,6-drsubstrtuted pyrrdlne ring In place of carbons 7-9 of the natural ercosanord were synthesized utrlrzrng a Pd-Cu cross coupling reaction Leukotrrene B4,5S,12R-6,14-~1~-8,1O-trans-e1cosatetraeno1c acid (LTB4). IS believed to be a potent mediator of Immediate hypersensmvrty reactions and lnflammatron 1 It stimulates aggregatron and degranulatlon of human neutrophlls, promotes chemotaxls and chemokrnesls of leukocytes, and IS a medtator of lysosomal enzyme release and superoxide generation 2 LTB4 also constructs respiratory smooth muscle v/a an Indirect mechanism involving stimulation of the release of cyclooxygenase products 3 Receptors for leukotrlene Bq have been characterized In human neutrophrls and HL-60 cells 4 Given Its srgnrflcant brologlcal actrvrty It IS possrble that a receptor level antagonist of leukotrlene B4

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