A pharmaceutical composition comprising as active principle at least one among the 3-aza-bicyclo[3.2.1]octane derivatives of general formula (I), or their dimers of general formula (II) and (III), or mixtures thereof
- wherein:
- R1 and R′1, equal or different between each other, are selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, cycloalkyl, aryl, heterocycle, arylC1-8alkyl;
- heterocycleC1-8alkyl, RR′N—C1-8alkyl, RR′N-aryl, FmocNR′-aryl, BocNR′-aryl, CBzNR′-aryl, RO-aryl, R(O)C-aryl, RO(O)C-aryl, RR′N(O)C-aryl;
- FmocNR′—C1-8alkyl, BocNR′—C1-8alkyl, CbzNR′—C1-8alkyl, FmocNR′—C1-8aryl, BocNR′—C1-8aryl and CbzNR′—C1-8 aryl,
- R2 and R′2, equal or different between each other, are selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, cycloalkyl, aryl, arylC1-8alkyl, heterocycleC1-8alkyl, aminoC1-8alkyl, aminoaryl, C1-8alkyloxyaryl, hydroxyaryl, hydroxyC1-8alkyl, carboxyC1-8alkyl, methyloxycarbonylC1-8alkyl, carboxyaryl, carboalkyloxyaryl, alkylcarbamoylaryl and -(side chains of amino acids), or
- R1 and R2, taken together, and R1′ and R2′, taken together, are C1-4alkyl, C2-4 alkenyl, cycloalkyl or benzofused cycloalkyl, to form a bridge of 3, 4, 5, 6 terms,
- R3 and R3′ are selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, cycloalkyl, aryl, arylC1-8alkyl, heterocycleC1-8alkyl, RR′NC1-8alkyl, RR′Naryl, RO—C1-8alkyl, RO(O)C—C1-8alkyl, R(O)C—C1-8alkyl, RC(O)O—C1-8alkyl, RC(O)N(R)C1-8alkyl, RO-aryl, RO(O)C-aryl, R(O)C-aryl RC(O)O-aryl, RC(O)N(R)aryl, —CH(amino acid side-chain)CO2R, —CH(amino acid side-chain)C(O)NR, —CH(CO2R)— amino acid side-chain, CH(CONRR′)— amino acid side-chain, Fmoc, Boc and Cbz,
- R4, R′4 R5, and R′5, equal or different amongst each other, are selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkinyl, cycloalkyl, aryl, heterocycle, arylC1-8alkyl and heterocycleC1-8alkyl,
- R6 is selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, cycloalkyl, aryl, arylC1-8alkyl, heterocycle, heterocycleC1-8alkyl;
- —C(O)R, —C(O)OR, —C(O)NRR′, CH2OR, CH2NRR′, —C(O)NH—CH(amino acid side-chain)C(O)OR, CH2NR-Fmoc, CH2NR-Boc and CH2NR-CBz,
- R and R′, equal or different between each other, are selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, cycloalkyl, aryl, heterocycle, arylC1-8alkyl;
- heterocycleC1-8alkyl;
- protecting group, —C(O)CH-(amino acid side-chain)-NHT, —NH—CH(amino acid side-chain)COOT and —CH(amino acid side-chain)COOT,
- where T is selected from between H and C1-8alkyl;
- X and X′, equal or different between each other, are selected from between O and S, when a is a double bond, or
- X and X′ are both H, when a is a single bond,
- Y and Z, equal or different from each other, are selected from the group consisting of O, S, SO, SO2 and N—R, wherein R is as above defined;
- Q is selected from the group consisting of C═O, CH2, CO—NH—CH (amino acid side-chain)-CO, CONR(CH2)nCO, CONR—C2-8alkenyl-CO C(O)O(CH2)nCO, CH2OC(O)(CH2)nCO, and CH2NRC(O)(CH2)nCO, wherein n is comprised between 2 and 6, and R is as above defined,
- Q′ is selected from the group consisting of C(O)OCH2, C(O)NRCH2, CH2OC(O), CH2NRC(O), CONR(CH2)nNRCO, CONR—C2-8alkenyl-NRCO, C(O)O(CH2)nNRCO, CONR(CH2)nOC(O), CH2OC(O)(CH2)nOC(O)CH2, CH2NRC(O)(CH2)nNRC(O)CH2, CH2OC(O)(CH2)nNRC(O)CH2, CH2NRC(O)(CH2)nOC(O)CH2, CH2NR(CH2)nNRCH2, CH2O(CH2)nOCH2, CH2O(CH2)nNRCH2, and CH2NR(CH2)nOCH2, wherein n is comprised between 2 and 6, and R is as above defined, and where the groups alkyl, alkenyl, alkynyl, cycloalkyl, aryl and the heterocyclic groups above reported, are possibly substituted.