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Synthesis and enantioselectivity of the enantiomers of PG 9 and SM 21 , new potent analgesic and cognition‐enhancing drugs
Author(s) -
Romanelli M. Novella,
Bartolini Alessandro,
Bertucci Carlo,
Dei Silvia,
Ghelardini Carla,
Giovannini M. Grazia,
Gualtieri Fulvio,
Pepeu Giancarlo,
Scapecchi Serena,
Teodori Elisabetta
Publication year - 1996
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1996)8:3<225::aid-chir1>3.0.co;2-g
Subject(s) - chemistry , enantiomer , analgesic , enantioselective synthesis , pharmacology , cognition , chirality (physics) , stereochemistry , combinatorial chemistry , catalysis , organic chemistry , psychology , neuroscience , medicine , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
The enantiomers of two α‐tropanyl esters, SM 21 (1) and PG 9 (2), derived from (+)‐R‐hyoscyamine, that act by increasing the central cholinergic tone, were obtained by esterification after resolution of the corresponding racemic acids [(−)‐S‐1, (−)‐R‐2 and (+)‐S‐2] and by stereospecific synthesis [(+)‐R‐1]. Their analgesic and cognition‐enhancing activities were tested in mice and their ACh‐releasing properties determined on rat parietal cortex. These compounds show enantioselectivity in analgesic and cognition‐enhancing tests on mice, the eutomers being the isomers which possess the same spatial arrangement of the groups on the chiral atom as (+)‐R hyoscyamine [(+)‐R‐SM 21 , (+)‐S‐PG 9 ]. The ACh‐releasing effect of the enantiomers of SM 21 in rats is in agreement with the results in mice, while PG 9 enantiomers do not show any appreciable enantioselectivity in this test. On the basis of the different effects of the 5‐HT 4 antagonist SDZ 205557 on analgesia induced by the enantiomers of 1 and 2 and by (+)‐R‐hyoscyamine and the α‐tropanyl ester of 2‐phenylpropionic acid 3, a mechanism of action is proposed for this class of compounds. © 1996 Wiley‐Liss, Inc.