Racemic and optically active esters of trans-apovincaminic acid functioning as medicaments

• Main Authors: INCZE MARIA, ZAJERNE BALAZS MARIA, FARKAS JENONE MARIA, VEDRES ANDRAS, PELLIONISZNE PAROCZAI MARGIT, GERE ANIKO, LAPIS ERZSEBET, KARPATI EGON, DEUTSCHNE JUHASZ IDA, SARKADI ADAM, AUTH FERENC, SZEKERES ANDRAS, SZANTAY CSABA, KREIDL JANOS, FARKAS SANDOR, KISS BELA, CZIBULA LASZLO, MOLDVAI ISTVAN
• Format: Patent
• Language: Czech; English
• Published: 17.07.2002
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Racemick , nebo opticky aktivn estery trans-apovinkaminov kyseliny obecn ho vzorce I, v n m R znamen vod k nebo skupinu a, kde Z znamen nasycenou nebo nenasycenou alkylovou skupinu C.sub.1-4.n. s p° m²m nebo rozv tven²m °et zcem, p° padn substituovan² C.sub.6-10.n.aryl, C.sub.6-12.n.arylC.sub.1-4.n.alkyl, heteroaryl, nebo 14-eburnameninylovou skupinu; a n je cel slo 2, 3 nebo 4; kde heteroaryl znamen pyrrolylovou, furylovou, thienylovou, pyridylovou, pyranylovou, pyrazolylovou, imidazolylovou, pyrimidinylovou nebo morfolinylovou skupinu; a kde substituenty v² e zm n n²ch arylov²ch, aralkylov²ch a heteroarylov²ch skupin mohou b²t vybr ny z halogenu, alkylov skupiny C.sub.1-4 .n.a alkoxylov skupiny C.sub.1-4.n., hydroxylov , nitro-, amino-, kyan-, nebo trifluormethylov skupiny; stejn jako jejich terapeuticky pou iteln soli. Farmaceutick kompozice obsahuj c tyto estery, zp sob p° pravy v² e uveden²ch ester a kompozic a jejich pou it . Estery vzorce I vykazuj zvl tn antioxida n , antiischemick a antiamnezick · inky a jsou pou iteln pro inhibici peroxidace lipid a pro ochranu proti ischemii a amn zii a pro jejich l bu, a pro l en r zn²ch neurodegenerativn ch chorob jako je Alzheimerova choroba.\ In the present invention there are disclosed trans-apovincaminic acid racemic and optically active esters of the general formula I, in which R represents hydrogen or the group a, wherein Z represents a saturated or unsaturated alkyl group containing 1 to 4 carbon atoms with either straight or branched chain, an optionally substituted aryl having 6 to 10 carbon atoms, arylalkyl containing 6 to 12 carbon atoms in the aryl moiety and 1 to 4 carbon atoms in the alkyl moiety, heteroaryl, or 14-eburnameninyl group; and n is an integer 2, 3 or 4; wherein the heteroaryl represents a pyrrolyl, furyl, thienyl, pyridyl, pyranyl, pyrazolyl, imidazolyl, pyrimidinyl or morpholinyl group; and wherein the substituents of the above indicated aryl, aralkyl and heteroaryl groups can be selected from a group comprising halogen, alkyl group having 1 to 4 carbon atoms and alkoxyl group containing 1 to 4 carbon atoms, hydroxyl, nitro, amino, cyan, or trifluoromethyl group; as well as their therapeutically acceptable salts. The present invention relates also to a pharmaceutical composition containing these esters, further to process for preparing the aforementioned esters and compositions as well as their use. The esters of the general formula I exhibit special anti-oxidative, anti-ischemic and anti-amnesic activity and they can be therefore used for inhibition of lipid peroxidation and for protection against ischemia and amnesia and for treating thereof, as well as for treating various neurodegenerative diseases such as Alzheimer?s disease.