Synthesis and gastrointestinal pharmacology of some 15- and 16- modified (+/-)-11-deoxyprostaglandins.
The synthesis and gastrointestinal pharmacology of some 11-deoxyprostaglandin E1 analogues are described with results analysed for selectivity from side effects. 11-Deoxygenation reduced potency relative to PGE2 but, as has been reported for natural PGs, 15- or 16-methyl analogues were more potent than the unsubstituted parent compound in the order 16-methyl greater than 15-methyl greater than 16,16-dimethyl. The results suggest that a complex interaction between C-15 and C-16 in methyl analogues affects their profile of activity, but that none of the modifications studied conferred a substantial potency or selectivity advantage over PGE2.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003248:Constipation / Q000139:chemically induced; D004064:Digestive System / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D005750:Gastric Juice / Q000378:metabolism; D007213:Indomethacin / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010418:Pentagastrin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy
D011459:Prostaglandins E, Synthetic; D009020:Morphine; D010418:Pentagastrin; D007213:Indomethacin