N-(Acyloxyalkyl) pyridinium salts as soluble prodrugs of a potent platelet activating factor antagonist

SK Davidsen, JB Summers, DH Albert…

Index: Davidsen, Steven K.; Summers, James B.; Albert, Daniel H.; Holms, James H.; Heyman, H. Robin; et al. Journal of Medicinal Chemistry, 1994 , vol. 37, # 26 p. 4423 - 4429

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Citation Number: 64

Abstract

Pyrrolothiazole 4 is a potent antagonist of platelet activating factor-mediated effects in a variety of in vitro and in vivo assays. Despite its positive activity in models of inflammation and septic shock, 4 lacks the aqueous solubility necessary for intravenous administration. This deficit was overcome by conversion of 4 to water-soluble pyridinium prodrugs. A two- step procedure was used to prepare a series of N-(acyloxyalky1) pyridinium salts, all of ...