Heterocyclic prostaglandin analogues. Part 2. Hydantoins and other imidazole analogues

Abstract

The stable hydantoin prostaglandin analogues (2b) and (3b) have been synthesised as racemic compounds. The less polar diastereoisomer of (2b) is a potent inhibitor of platelet aggregation in human platelet-rich plasma and its cyclohexyl analogue (22, R = CsHI1) has ca. 14 times the potency of prostaglandin E, in this test coupled with selectivity of biological action. Other structural modifications such as introduction of a 15-methyl group and insertion of the rn-phenylene or rn-oxaphenylene moieties into the acid side-chain of (2b) led to a reduction in anti-aggregatory potency. Synthesis of the imidazole (41 ) is described.

Triphenylphosphine-Mediated Chemoselective Synthesis of Functionalized Spiro-Imidazol-4-Ones

“…A number of imidazol-4-one derivatives display a wide range of biological properties, including anticonvulsant, 1 antidepressent, 2 antiinflammatory, 3 antiviral, 4 antitumor, 5 and platelet-inhibitory activities, 6 and are a conspicuous structural feature of several inhibitors of aldose reductase. 7 As part of our study on the development of new routes to heterocyclic and carbocyclic systems, 8−12 we now report on the chemoselective synthesis of functionalized spiro-imidazol-4-ones 4.…”

Modification of Biomaterials to Improve Blood Compatibility

“…We shall see later that as far as platelet adhesion is concerned, the compounds [14,15,16] confer a significant degree of passivity on polymer surfaces to which they are attached.…”

“…We have employed the potent synthetic prostaglandin analogue BW 245C [1] first synthesized by Caldwell, Harris, Stepney and Whittaker (16). This compound, unlike PGI 2 , is stable in solution at physiological temperatures and pH.…”

“…glucamine, by reacting these compounds with [13]. Poly(ethylene glycol) (pEG) may also be converted to a polymerizable vinyl monomer [16] by reaction with [13]. We have coupled this monomer to Biomer by free-radical polymerization, using the halogen-functionalized form of Biomer, as indicated in Scheme 2.…”

“…acrylamide, N-vinylpyrrolidone. Copolymers have also been synthesized by copolymerization of heparin and PEG macromers [20,16] with methyl methacrylate in ethylene glycol solution.…”