Prostaglandin E antagonist activity of 11,15-bisdeoxy prostaglandin E1 and congeners

PINANE THROMBOXANE A2 ANALOGUES ARE NON‐SELECTIVE PROSTANOID ANTAGONISTS IN RAT AND HUMAN STOMACH MUSCLE

“…Nicolaou et al (1979) found that epi-PTxA2 was less potent than PTxA2 as an antagonist of platelet aggregation. We obtained a similar potency relationship in rat stomach but, unlike PTxA2, the epicompound had the advantage of not causing contraction, perhaps due to the unnatural 15-hydroxy configuration (Fried, Santhanakrishnan, Himizu, Lin, Ford, Rubin & Grigas, 1969;Tolman, Partridge & Barris, 1977;Birnbaum & Tolman, 1979). Since the block of contractions to PGI2 in rat stomach by both pinane isomers was substantial, and evidence with the prostaglandin antagonist SC-19220 suggests that PGI2 and PGH2 analogues act at different receptors in rat fundus , neither PTxA2 nor epi-PTxA2 are selective thromboxane antagonists.…”

Prostaglandins and congeners. 21. Synthesis of some cyclohexyl analogs (11.alpha.-homoprostaglandins)

“…The more polar component (0.10 g), 9-oxo-l la, 15-dihydroxylla-homo-13-trans-prostenoic acid (30), was obtained as white crystals, mp 77-81 °C, after recrystallization from ethyl acetatepetroleum ether; NMR (acetone-dg) 5.50 (2, m, 13-H and 14-H), 4.37 9-Oxo-15-epi"-hydroxy-lla-homo-10,13-trans-prostadienoic Acid (29) and 9-Oxo-l la,15-epi-dihydroxy-l la-homo-13-trans-prostenoic Acid (31). From 0.83 g of 27 was obtained 523 mg of 29 and 84 mg of 31 after hydrolysis and chromatography as above.…”

Synthesis and prostaglandin-like activity of 2-(trans-3-hydroxy-1-octenyl)-3-indoleheptanoic acid

“…After drying, the solvent was removed in vacuo and the residue chromatographed on a silica gel column. Elution with Et20-hexane (4:6) gave 2 g of 6: mp 53-54 °C (41%); IR (Nujol) 3370,1725,1680 cm'1; NMR (CDC13) 3.67 (s, 3 H, -COOCH3), 3.90 (s, 3 H, -COOCH3), 9.15 ppm (s, 1 , NH).…”

“…The mixture was left at room temperature for 2 h and then extracted with Et20. The organic extracts, after washing with saturated brine, were dried (MgS04) and evaporated in vacuo to give 0.9 g of 10 (76.9%): IR (Nujol) 3500-3300,1730 cm"1; NMR (CDClg) 3.67 (s, 3 H, -COOCHg), 4.75 (s, 2 H, -CH2OH), 9.00 ppm (s, 1 , NH).…”

“…The log dose-response curve for PGE4 was linear for both the smooth muscles in the tested concentration range. According to Tolman et al,9 antagonist activity of compound 1 was determined by comparing the magnitude of rat fundus strip contractions induced by 11.3 X 10-9 mol/L of PGE!, in the presence and in the absence of different concentrations of the indole analogue (2.15-21,5 X -6 mol/L). The approximate IC^w as obtained from the concentration-response curve of analogue 1 as an inhibitor of PGErinduced rat fundus strip contractions in four separate preparations.…”