Antitumor compounds Activated by PAF comprising an amino Group and a cytotoxic cyclic Group and its Synthesis method

摘要

A formula compound (I) EMI file = "00034117 =" U1 "id =" 1 "IMF = JPEG or a pharmaceutically acceptable salt, wherein R1 represents an amino acrylic acid or an oligoformaldehyde group, and its amino terminal function can be determined as a terminal protection group, The terms carbamate and oligopropionic acid describe a fixed radical, an amino acid or an oligomer composed of up to 12 amino acids, which is directly proportional to the heterocyclic nitrogen atom through the Amida link; RA and Rb form a heterocyclic cyclic cyclic cyclic cyclic ring together with the adjacent N-C group. 3 to 8 members, saturated or unsaturated,optionally substituted and optionally fused with benzo or cyclohexane, in which one or two CH2 groups can also be replaced by NH, O or S, R4 represents H, C1-C6 alkyl, C3-C8 cycloalkyl, aryl or heteroaryl; and Cyt 'represents the residue of a cytotoxic or cytostatic compound; selected from the group consisting of: Anthracycline derivatives such as doxorubicin, methotrexate analogs such as methotrexate, pritrexima, trimetrexate, or DDMP, melphalan, cisplatin analogs such as cisplatin, JM216, JM335, bis (platinum) or carboplatin, purine analogs and pyrimidines such as citarbin, gemcitabine, azacitidine. 6-thioguanine,flurdarabine or 2-deoxycoformycin, and analogues of other chemotherapeutic agents such as 9-aminocamptothecin, D, L-aminoglutethimide, trimethoprim, pyrimethamine, mitomycin C, mitoxantrone, cyclophosphamamide, 5-fluorouracil, extramustine, podofilotoxin provided N2-ocetil-L-homoarginyl-L-tyrosyl-L-glutaminyl-L-seril-N- [2,3,6-trideoxy-1-O - [(1S, 3S) -1 are excluded , 2,3,4,6,11-hexohydro-3,5,12-trihydroxy-3- (hydroxyacetyl) -10-methoxy-6,11-dioxo-1-naphthacenyl] -. Alpha.-L-lixo- hexopyrans-3-yl] -L-prolinamide; and N2-acetyl-L-homoarginyl-L-tyrosyl-L-glutaminyl-L-seril-L-seril-N- [2,3,6-trideoxy-1-O - [(1S, 3S) -1.2 , 3,4,6,11-hexahydro-3,5,12-trihidroxi-3- (hidroxiacetil) -10-metoxi-6 11-dioxo-1-naftacenil - alfa -L-lixo-hexopiranos- 3-il -L-prolinamida