| 摘要 |
<p>Polyaza compounds (I) and their isomers, enantiomers and/or diastereomers and salts, are new. Polyaza compounds (I) of formula (IIa), (IIb) and (VIa) or linear polyaza compounds (Vb) of formula (R 5-CH(X 5)-N(CHX 4R 4)-CH(K 16)-CH(K 15)-N(CH(R 3)(X 3))-CH(K 14)-CH(K 13)-N(CHX 2R 2)-CH(R 1)-X 1), and their isomers, enantiomers and/or diastereomers and salts of (VIa) and (VIb), are new. R 1-R 5COOH, P(O)(OH) 2or R 6-P(O)-OH, preferably COOH; R 6H or 1-3C alkyl; X 1-X 5L-Y 1; L : 1-3C alkyl, preferably (CH 2) n; n : 1-3; Y 1-CONH 2, CO-NR 7R 8or NR 7-CO-R 8; R 7, R 7H or 1-6C (hydroxy)alkyl, preferably -CH 2-CH 2-OH, CHOH-CH 2OH, -CH-(CH 2OH) 2, -(CH 2) m-(CHOH) p-CH 2OH or -C(CH 2OH) 3; m : 1-3; p : 1-4; D, E, F 1CH or N; either K 1-K 20H, -(CH 2) j-CH 3or -(CH 2) i-OH, preferably H; or K 3K 5, K 4K 5, K 3K 6, K 4K 6, K 7K 9, K 7K 10, K 8K 9, K 8K 10, K 13K 14, K 15K 16, K 17K 18, K 19K 203-6C ring; j : 0-3; and i : 1-3. Provided that the sum of m and p is 2-5. Independent claims are included for: (1) a multimer, preferably dimer or trimer, of (II) or (VI); (2) vectorized compound comprising (II) or (VI) coupled to a biovector by an intermediate optionally of a bridging group; (3) a complex compound or multimer or a vectorized compound having a metal ion (M); (4) lipidic pharmaceutical composition comprising the compound, multimer, vectorized product or complex bound to a lipidic nanoparticule; (5) diagnostic composition for magnetic resonance imaging comprising the compound, multimer, vectorized product or complex; and (6) preparation of the metal complex of (IIa) comprising reacting an ester compound of formula (R aOOC-CHQ-(CH 2) n-COOR a) with a fused macrocycle of formula (IV) to obtain a hexaacid of formula (V), optionally hydrolyzing or hydrogenating the ester groups of (V) to obtain the hexaacid of formula (Va), reacting a salt or an oxide of the metal to be complexed with (Va), to obtain the complex or its base salts and reacting amino alcohol groups of formula NHR 7R 8with the complex, in the presence of a carboxylic acid group activating agent to obtain the triamide of formula (IIa). M : metal ion of atomic number 21-29, 42-44 or 58-70, preferably Gd, Mn or Fe, or radionuclide e.g. 99>Tc, 117>Sn, 111>In, 97>Ru, 67>Ga, 68>Ga, 89>Zr, 177>Lu, 47>Sc, 105>Rh, 188>Re, 60>Cu, 62>Cu, 64>Cu, 67>Cu, 90>Y, 159>Gd, 149>Pr or 166>Ho; X 1-X 3-(CH 2) n-CO-NR 7R 8; n : 1-3; Q = halo (preferably Br), 1-3C alkyl sulfonate, tosylate or triflate; and R aH, 1-3C alkyl or benzyl. [Image] [Image].</p> |
