Synthesis and platelet aggregation inhibiting activity of prostaglandin D analogues.
Several prostaglandin D (PGD) analogues have been synthesized, incorporating the following variations: (a) varying degrees of side-chain unsaturation, (b) C-9 hydroxy removed or in the unnatural 9 beta configuration, (c) metabolically stabilized analogues (e.g., 15-methyl, 16,16-dimethyl, 17-phenyl, etc.), and (d) delta 12 isomers resulting from decomposition of PGD2. With regard to their ability to inhibit adenosine diphosphate (ADP) induced human platelet aggregation: (a) PGD3 greater than or equal to PGD2 greater than PGD1 greater than 13,14-dihydro-PGD1, (b) the 9 beta- and 9-deoxy-PGD2 analogues are more potent than PGD2, (c) metabolically stabilized analogues with bulky substituents at or near C-15 have substantially reduced antiaggregatory activity relative to PGD2 and (d) the delta 12 isomers of PGD2 are much less active than PGD2.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003106:Colon / Q000187:drug effects; D006224:Cricetinae; D003967:Diarrhea / Q000139:chemically induced; D005298:Fertility / Q000187:drug effects; D005849:Gerbillinae; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D011457:Prostaglandins D / Q000138:chemical synthesis / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D011457:Prostaglandins D; D011465:Prostaglandins, Synthetic