Portal de Periódicos da CAPES

Chapter 9: Prostaglandin Structure-Activity Relationships

1976; Elsevier BV; Linguagem: Inglês

10.1016/s0065-7743(08)61392-5

1557-8437

Thomas Schaaf,

Sesquiterpenes and Asteraceae Studies

Extensive pharmacological evaluation of unique natural products like extremely potent C20 fatty acids has, however, uncovered a broad spectrum of activities, both in animals and man. Despite the demonstration of potent pharmacological activity, the original optimistic predictions of clinical utility for the natural prostaglandins have not been realized. The lack of selectivity and oral efficacy, chemical instability, and short duration of action of the natural materials have limited their commercial use to prostaglandin F2α, (dinoprost tromethamine) as an abortifacient and prostaglandin E2 (dinoprostone) both as an abortifacient and inducer of labor. Conclusions concerning prostaglandin analog activity must be accepted with caution unless data for several biological assays is presented because inactivity in one assay may be merely a reflection of selectivity. This chapter summarizes a number of useful prostaglandin structure–activity relationships (SAR), derived over the past decade. As the activity of the natural prostaglandins differs widely with changes in number, type, and stereochemistry of oxygenated substituents, it seems reasonable that cyclopentane ring analogs would exhibit different pharmacological profiles. The interesting concept of substituting a heteroatom for a ring carbon (and its pendant oxygen function) has been investigated with the synthesis of 8-aza, 9-thia, 10-oxa, 11-oxa, 11-thia, and 9, 11-dioxa analogs. Animal studies with many of the modified prostaglandins suggest that some may be superior to the natural materials. However, with the exception of the 15- and ldmethylated prostaglandins little has been reported concerning the therapeutic effects of prostaglandin analogs in man.