Neocarzinostatin derivatives and method of producing the same

Details Neocarzinostatin derivatives and method of producing the same Neocarzinostatin derivatives and method of producing the same

C - Chemistry, Metallurgy

07

K

530/13

C07K 17/08 (2006.01) C07K 14/00 (2006.01)

Patent

CA 1240315

Abstract of the Disclosure Novel neocarzinostatin derivatives having excellent anticancer activity, which have the following formula (A) (SMA)-(NCS)-(SMA) (A) wherein (NCS) represents divalent neocarzinostatin residue in which one hydrogen atom is removed from each of the primary amino group in alanine residue at the N-terminal of neocarzinostatin and that in lysine residue at 20th position from the N-terminal and (SMA) represents monovalent partially half-esterified styrene- maleic acid copolymeric residue having a weight-average molecular weight of 800~2,500 and consisting of structural units of (a) styrene residue Image (b) half-esterified maleic acid residue Image wherein R is an alcohol residue wherein hydroxyl group is removed from an alkanol having 1-4 carbon atoms, ethylene glycol monoalkyl ether in which the alkyl - 54 - group has 1-2 carbon atoms or glycerine dialkyl ether wherein the alkyl group has 1-2 carbon atoms; (c) maleic acid residue Image ; and (d) a residue having the following formula in which a hydroxyl group of one carboxyl group in maleic acid residue is removed and linked to be bonded to the neocarzinostatin residue Image wherein the linkage of carbon atom in carbonyl group bonds to the neocarzinostatin residue. Said neo- carzinostatin derivative is prepared by reacting neocarzinostatin in an aqueous medium with a large molar excess of powdery partially half-esterified styrene-maleic anhydride copolymer consisting of structural units of styrene residue Image half-esterified maleic acid residue Image - 55 -

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