[Design and synthesis of cholecystokinin-4 dipeptide analogues with anxiolytic and anxiogenic activities].
A new series of dipeptide analogues of the general formula Ph(CH2)nCO-NH(CH2)mCO-Trp-NH2 (n = 1, 3-5; m = 1-3) was designed based on the structure of the endogenous tetrapeptide cholecystokinin-4 (CCK-4) and the topochemical Shemyakin-Ovchinnikov-Ivanov principle. The L-tryptophan derivatives exhibited anxiolytic properties and the D-tryptophan derivatives, anxiogenic properties. The dipeptide Ph(CH2)5CO-Gly-L-Trp-NH2 (GB-115) with the activity in rats of 0.05-0.2 mg/kg after oral and intraperitoneal administration was chosen for further studies as a promising anxiolytic agent.
Gudasheva
T A
TA
Kir'ianova
E P
EP
Kolik
L G
LG
Konstantinopol'skiĭ
M A
MA
Seredenin
S B
SB
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D015195:Drug Design; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013758:Tetragastrin / Q000737:chemistry*
D014151:Anti-Anxiety Agents; D004151:Dipeptides; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin