| 摘要 |
Immunoglobulin conjugates are formed by reaction of an antineoplastic indole-dihydroindole vinca alkaloid containing a hydrazide group attached at C-3 or C-4 with an oxidized IgG antibody having unusually high carbohydrate content, and are of the formula <CHEM> wherein R<2> is H, CH3 or CHO; when R<4> and R<5> are taken singly, R<5> is H, and one of R<3> and R<4> is ethyl and the other is H or OH; when R<4> and R<5> are taken together with the carbons to which they are attached, they form an oxirane ring in which case R<3> is ethyl; R is NHN=, <CHEM> O(C1-3 alkyl), NH2, NH(C1-3 alkyl), NH-CH2CH2-Y, 1-pyrrolidinyl or 1-piperidinyl, wherein n is 2-4 and Y is Cl, OCH3 or SCH3; R<1> is H, (C1-3 alkyl)-CO, chloro-substituted (C1-3 alkyl)-CO or R<6> wherein R<6> is COXCONHN= wherein X is C1-4 straight chain alkylene, C2-8 branched chain alkylene, C2-4 alkenylene, C3-4 alkenylene, C3-6 cycloalkylene, phenylene, hydroxy-substituted C1-4 alkylene, or a direct bond, provided that either R is NHN= or R<1> is R<6>, but R cannot be NHN= when R<1> is R<6> and R<1> cannot be R<6> when R is NHN=; m is an integer from about 5 to about 35; Ab is an antibody of the IgG class, containing from about 6% to about 18% of carbohydrate. |
