Azaprostaglandin analogues. Synthesis and biological properties of 11-azaprostaglandin derivatives.

New nitrogen analogues of prostaglandins (11, 11a, 12, and 12a) have been synthesized starting from a 4,5-disubstituted 2-pyrrolidinone nucleus (5 and 5a) containing one side chain and a suitable functionality for elaborating the second one. These analogues had no better activity than natural prostaglandins in vitro [guinea pig ileum and trachea, rat stomach fundus strip, uterus and portal vein, ADP-induced guinea pig platelet-rich plasma (PRP) aggregation]. They similarly lacked any interesting activity in vivo [anesthetized rat blood pressure, stress, and acetylsalycilic acid (ASA) induced gastric lesions in rat].

dl-9a-Deoxy-9a-methylene-PGI2 (a stable prostacyclin derivative): preliminary pharmacological data.

Carboprostacyclin (dl-9a-deoxy-9a-methylene-PGI2), a new stable PGI2-analogue, has been studied in vitro and in vivo. This analogue relaxes bovine coronary artery (potency ratio to PGI2 = 0.17), inhibits human PRP aggregation induced by ADP (IC50 = 12.

A new selective antagonist of prostaglandins: 20-methyl-13,14-didehydro-PGF2 alpha.

20-methyl-13,14-didehydro-PGF2 alpha has been assayed for antagonistic activity against PGF2 alpha and PGE2 on different smooth msucle preparations in vitro. This compound may be considered a selective and probably a competitive antagonist of PGF2 alpha on rat uterus in vitro.

Inhibition of harmaline induced tremors by 16 (S)-16-methyl PGE2 in different mammalian species: a correlation with central cyclic nucleotides and prostaglandins.

Harmaline, an alcaloid of Paganum Armala, induces tremors of central origin and increases cerebellar cGMP without affecting cortical and cerebellar prostaglandin levels. 16(S)-16-methyl PGE2 protects the animals against the seizures induced by the alcaloid and prevents the concomitant rise in cerebellar cGMP. Experiment performed in cats and limited to pharmacological observations, confirmed that, the PGE2 derivative, is a powerful antitremorogenic agent at doses that are devoid of appreciable side effects.