title: Synthesis and evaluation of 2'-hydroxyethyl trans-apovincaminate derivatives as antioxidant and cognitive enhancer agents.
abstract: A series of trans-2'-hydroxyethyl and 2'-acyloxyethyl apovincaminates 4b- f and 7b- f has been synthesized and evaluated for their antioxidant and antiamnesic effects. The new esters were prepared from 4a and 7a ethyl esters or from the corresponding carboxylic acid sodium salt. For starting materials 11a, b, a new stereoselective trans-reduction was elaborated. From the combined results of the data obtained from in vitro and in vivo tests and examination of the metabolism, (3 R,16 S)-2'-hydroxyethyl apovincaminate ( 7b, RGH-10885) was identified as the most promising compound, owing to its potent neuroprotective and antiamnesic activities. The in vivo effectiveness of selected compounds on the cognitive functions was studied in a one-trial passive avoidance task and a water-labyrinth test.
authors.affiliation: Gedeon Richter Ltd, Budapest, Hungary. a.nemes@richter.hu
authors.forename: András
authors.initials: A
authors.lastname: Nemes
authors.forename: László
authors.initials: L
authors.lastname: Czibula
authors.forename: Csaba
authors.initials: C
authors.lastname: Szántay
authors.forename: Anikó
authors.initials: A
authors.lastname: Gere
authors.forename: Béla
authors.initials: B
authors.lastname: Kiss
authors.forename: Judit
authors.initials: J
authors.lastname: Laszy
authors.forename: István
authors.initials: I
authors.lastname: Gyertyán
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szombathelyi
authors.forename: Csaba
authors.initials: C
authors.lastname: Szántay
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000187:drug effects; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014748:Vinca Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C528499:2'-hydroxyethyl apovincaminate; D000975:Antioxidants; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D014748:Vinca Alkaloids