Synthesis and inhibitory activity on carbonic anhydrase of some new sulpiride analogues studied by means of a new method.

The pharmacological activity of several new sulpiride analogues was studied by means of a new approach, based on a potentiometric technique with a pCO2 sensor, capable of detecting carbonic anhydrase inhibition at equilibrium conditions. This procedure gives results stated as percent of inhibition of enzymatic activity (IP, inhibitory power). To prove the reliability of the proposed approach and to study structure-activity relationships, several new molecules were synthesized and tested in comparison with the two sulpiride enantiomers. A possible inhibition mechanism is discussed in terms of experimental evidence obtained from the interactions between the molecular structures of the new synthesized compounds and carbonic anhydrase.

Constituents of Shashen (Adenophora axilliflora).

From the ethyl acetate extract of the Chinese drug "Shashen", the root of Adenophora axilliflora Borb., three triterpenoids, cycloartenol acetate ( 1), lupenone ( 2) and beta-sitosterol ( 3), two triterpenoid derivatives, beta- D-glucopyranosyl-(1-->3)-beta-sitosterol ( 7) and its 6- O-palmitoyl ester ( 6), along with two coumarins, (+)-praeruptorin A ( 4) and 3'-angeloyl-4'-isovaleryl-(3' S, 4' S) CIS-khellactone ( 5) have been isolated. A detailed (1)H-NMR analysis of compounds 6, 7 and their acetates is reported. The structure of the partial hydrolysis product of 5 is revised on the basis of spectroscopic evidences and mechanistic considerations.

Stereochemistry of viminol, a novel central analgesic.

The synthesis of the stereoisomers of the centrally acting analgesic 1-[1-(2-chlorobenzyl)-pyrrol-2-yl]-2-di-sec.-butylamino-ethanol (viminol) is described. Their absolute configuration has been shown by comparing the circular dichroism (CD) curves with those of some phenyl analogs: for one of the viminol stereoisomers the postulated configurational assignment has been recently confirmed by an X-ray analysis. The pharmacological properties shared by the viminol stereoisomers are also described. The R,R configuration of the sec.-butyl groups and the S configuration of the hydroxy group appear to be essential for the agonistic effects: analgesia, tolerance and physical dependence in rodents. The S,R,R configurated viminol does not substitute, however, for morphine in monkeys, using the single dose suppression test. S,S or R,S(S,R) configurations of the sec.-butyl groups are associated with antagonistic properties. The binding capacity of the viminol stereoisomers to the opiate receptors and their influence on the acetylcholine release from the intestinal cholinergic terminals electrically stimulated are also described.