Ginkgolide analogs

One goal of SAR studies is to put forward a pharmacophore model that can elucidate the activities of synthesized derivatives, as well as predict the activity of novel derivatives. A three-dimensional quantitative SAR study was attempted for ginkgolides and the PAF receptor, using comparative molecular field analysis and 25 ginkgolide analogs, mainly those synthesized by Corey et al. " In agreement with the SAR studies just described, this pharmacophore model predicted that substituents in the lO-OH position of GB would improve activity. 

In the initial description of the ability of ginkgolides to inhibit the PAF receptor, it was shown that GB was the most potent ginkgolide with an IC50 of 1.88 pM, GA was slightly less potent, and GC was a weak antagonist (Table 7-1). A few years later, methoxy and ethoxy analogs of GA, GB, and GC were prepared, in which the alkyl groups were introduced at C-1 or C-10 by reaction with diazoaUcane to yield... 

Corey, E. J. Gavai, A. V. Simple analogs of ginkgolide-B which are highly-active antagonists of platelet activating factor. Tetrahedron Lett., 1989, 30 6959-6962. 

In their role as enantioselective catalysts for the reduction of prochiral ketones, chiral oxazaborolidines have been used for the preparation of prostaglandins, PAF antagonists, a key intermediate of ginkgolide B, bilobalide, a key intermediate of forskolin, (/ )- and (S)-fluoxetine, (R)- and (S)-isopreterenol, vitamin D analogs, the carbonic anhydrase inhibitor the dopamine D1 agonist A-77636, ... 

Synthesis and antagonistic activities towards platelet activating factor receptor (PAFR) and glycine receptor (GlyR) of ginkgolide derivatives and analogs 13CJ01263. 

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