Conjugates of disorazoles and their derivatives with cell binding molecules, new disorazol derivatives, preparation processes and uses thereof

摘要

A compound of formula (I) or (IV) C1 -B1 -A-B2-C2 (I), C1 - B1 -A (IV), in which for (I) and (IV): A is a disorazol moiety according to formula (III) ** Formula ** in which: Rio, Rjo, Rkp, Rmp, R28, R30, R31, R32, R33, R34, R35, R36, R38, R40, R41, R42, R43 , R44 are hydrogen; Rlp, Rnp together form a double bond or are independently selected from the group consisting of "hydrogen, alkoxy"; R27, R29 together form a double bond or an epoxide (oxirane); R37, R39 together form a double bond or an epoxide (oxirane); R25, R26 are independently selected from each other from the group consisting of: "alkyl" which is optionally substituted on the alkyl group with 1, 2 or 3 substituents independently selected from each other from the group consisting of "alkyl, cycloalkyl, cycloalkyl- alkyl, aryl, heteroaryl, aryl-alkyl, heteroaryl-alkyl, heterocyclyl, heterocyclyl-alkyl, alkylsulfonyl, arylsulfonyl, aryl-alkylsulfonyl, -F, -Cl, -Br, -I, -N3, = O, = S, = S (O) 2, hydroxyl, acetyl, carboxyl, carboxylester, amide, carbonate, carbamate, alpha-amino acid residues, beta-amino acid residues, alkoxy, amino, hydroxylamino, mono-alkylamino, di- alkylamino, hydrazinyl, cyano, cyano-alkyl, sulfhydryl, disulfidylalkyl and / or alkyl sulfidyl "; B1 and / or B2 are independently selected from each other from the group consisting of "dicarbonic acid moiety linker, succinyl, glutaryl"; C1 and / or C2 are independently selected from each other from the group consisting of "LHRH, [D-Lys6] - LHRH, somatostatin, somatostatin analogs, human serum albumin (HSA)"; o is 1 or 2; p is 1 or 2; wherein the term "alkyl" includes saturated, partially unsaturated or unsaturated acyclic hydrocarbons having C1-C12 carbon atoms, which may be straight chain or branched and may contain one or more double bonds and / or one or more triple bonds ; wherein the term "alkoxy" refers to radicals in which a group "alkyl", "cycloalkyl", "cycloalkylalkyl", "aryl", "aryl-alkyl", "heteroaryl", "heteroaryl-alkyl", "heterocyclyl "and / or" heterocyclyl-alkyl "is attached through an oxygen atom (group -O-).