PROCEDE DE PREPARATION DE NOUVEAUX COMPOSES CYTOSTATIQUES ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT

• Main Author: L. DANCSI, T. KEVE, G. FEKETE, E. DEZSERI, S. GOROG, T. ACS, C. SZANTAY, L. SZABO, K. HONTY, S. ECKHARDT, I. HINDI, S. KERPEL-FRONIUS, Z. RELLE NEE SOMFAI ET J. SUGAR
• Format: Patent
• Language: French
• Published: 23.04.1982
• 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

The invention relates to novel cytostatic compounds of the general formula I in which R represents ss-hydroxyl and R represents alpha -ethyl or R represents hydrogen and R represents ss-ethyl ( alpha and ss designate the spatial position), R'' denotes a straight-chain alkyl group having 1 or 3-10 carbon atoms, a branched alkyl group having 3-10 carbon atoms, where the carbon atom bonded to the -N-CH2-O- group is a primary or secondary carbon atom, or an arylalkyl group containing 1-3 carbon atoms in the alkyl moiety, and R represents a methoxy group, and R represents an acetyl group. The novel compounds have strong cytostatic properties and are less toxic by more than an order of magnitude than known compounds of similar structure and type of action. The compounds are prepared according to the invention by reacting a compound of the general formula II in which the meaning of R , R , R and R is the same as above, with a large excess of an alcohol of the general formula III in which the meaning of R'' is the same as above with the difference here that the carbon atom connecting to the OH group can only be primary or secondary, in the presence of chromium trioxide, a suitable organic solvent, acetic anhydride and an acid at temperatures between -60 and -30 DEG C, then adjusting the pH of the reaction mixture to 8-10, isolating the product and, if desired, purifying it. PROCEDE DE PREPARATION DE NOUVEAUX COMPOSES CYTOSTATIQUES ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT.COMPOSES DE FORMULE I:(CF DESSIN DANS BOPI)OU R DESIGNE B-HYDROXYLE ET R DESIGNE A-ETHYLE;OU R DESIGNE HYDROGENE ET R DESIGNE B-ETHYLE;R DESIGNE UN ETHYLE OU UN ALKYLE A CHAINE DROITE OU RAMIFIEE EN C-C;R METHOXY;R ACETYLE.CES COMPOSES SONT PREPARES PAR REACTION D'UN COMPOSE DE DEPART CORRESPONDANT DANS LEQUEL L'ATOME D'AZOTE EN POSITION 1 EST SUBSTITUE PAR UN GROUPE -CH, AVEC UN GRAND EXCES D'ALCOOL DE FORMULE R-OH III OU R A LA SIGNIFICATION CI-DESSUS INDIQUEE, EN PRESENCE DE DIOXYDE DE CHROME, D'UN SOLVANT ORGANIQUE, D'ANHYDRIDE ACETIQUE ET D'UN ACIDE A UNE TEMPERATURE DE -60 A 30C, A UN PH DE 8-10.LES COMPOSES PRECITES ONT UNE FORTE ACTIVITE CYTOSTATIQUE.