Patent ID: 6702705
Filing Date: 2004-03-09
Classification: C07C,C07D,C07F,C07H,C07K,C12N,C12Q,G01N

Abstract:
A catalytic antibody raised to a hapten of formula IGâ€”Fâ€”(CH2)nâ€”Eâ€”Dâ€”Bâ€”Aâ€”Xâ€ƒâ€ƒ(I) wherein:X is (a) a nucleoside analog joined at the 5â€² and/or 3â€² position of the aldose ring wherein the hydroxyl groups on the sugar moiety of the nucleoside analog are unsubstituted, independently substituted with acyl, phosphate and all radicals, or replaced with H, halogen or azide, and wherein the O of the nucleoside by which it is attached can be replaced by S, NH, or CH2, (b) QP(O)(NH2)NR1R2, wherein Q is O or CH2, or Q can be omitted, and R1 and R2 are the same or different but both cannot be H and each is haloalkyl, alkyl, alkyl with heteroatoms, cycloalkyl, phenyl, substituted phenyl, alkylphosphonate, alkylsulfonate, alkylcarboxylate, alkylammonium or alkene, or R1 and R2 are connected to each other in a ring structure such as morpholino or piperidine, (c) melphalan joined to the remainder of the compound at a primary amino group, or melphalan joined to the remainder of the compound at a primary amino group wherein the primary amino group can be replaced by CH2 or S; or (d) daunomycin or other drug joined to the remainder of the compound at a hydroxy, amino or thio group which can be replaced by CH2, S, or O; A, which may be omitted, is ethylene or any isomer of propenyl; B, which may be omitted, is O, S, CH2, or NR3, wherein R3 is H, alkyl, alkyl with heteroatoms, cycloalkyl, phenyl, substituted phenyl, alkylphosphonate, alkylsulfonate, alkylcarboxylate, alkylammonium or alkene; D, which may be omitted, is (a) C&boxH;O, (b) C&boxH;NR4 or R5R6Nâ€”C&boxH;NR4, wherein R4 is H, alkyl, alkyl with heteroatoms, cycloalkyl, phenyl, substituted phenyl, alkylphosphonate, alkylsulfonate, alkylcarboxylate, alkylammonium or alkene, R4 and R5 or R5 and R6 can be connected to each other in a ring structure such as morpholino or piperidine, or R5 and R6 can be haloalkyl, alkyl, alkyl with heteroatoms, cycloalkyl, phenyl, substituted phenyl, alkylphosphonate, alkylsulfonate, alkylcarboxylate, alkylammonium or alkene, (c) SO or CHOH with any stereochemistry, (d) SO2, or (e) P(T)(TR7) wherein T is O, N, S or CH2 and R7 is H, alkyl, alkyl with heteroatoms, cycloalkyl, phenyl, substituted phenyl, alkylphosphonate, alkylsulfonate, alkylcarboxylate, alkylammonium or a alkene and is unattached or attached to E at R8, R11 or R13; E, which may be omitted, is the radical â€ƒor R12R13C wherein R8-13 are the same or different and are H or alkyl with 1-10 carbon atoms, phenyl, substituted phenyl, alkene with 1-10 carbon atoms, hydroxyalkyl, alkoxy, aminoalkyl, alkylthio, thioalkyl, amino, aklylamino, alkylphosphonate, alkylsulfonate, alkylcarboxylate, alkylammonium, carboxylate, sulfate, phosphate, or hydroxyl, and wherein R12 and R13 are the same or different and are O substituted with alkyl, alkyl with heteroatoms, cycloalkyl, phenyl, substituted phenyl, alkylphosphonate, alkylsulfonate, alkylcarboxylate, alkylammonium or alkene, or R8-13 are connected to each other in a ring structure such as a five-membered or six-membered acetal ring where the diol is derived from a sugar, cycloalkyl or phenyl moiety, and is unattached or attached to the radical D at R7 through R8 or R11 or R13; n is an integer from 0 to 3; F, which may be omitted, is an oxygen, carbonyloxy, or oxycarbonyl radical; and G, which may be omitted, is (a) H or alkyl with 1-10 carbon atoms, alkoxy with 1-10 carbon atoms, phenyl, substituted phenyl, alkene with 1-10 carbon atoms, hydroxyalkyl, aminoalkyl, thioalkyl, amino, alkylamino, alkylphosphonate, alkylsulfonate, alkylcarboxylate, alkylammonium, carboxylate, sulfate, phosphate, or hydroxyl, or â€ƒwherein Y is C&boxH;O, SO2, CHOH or SO with any stereochemistry, Z is O, N, CH with any stereochemistry, or S, and R14, R15, R16, R17 or R18 is the site of attachment to the remainder of the compound, provided that where R14 is the site of attachment, then R15, R16, R17, and R18 are the same or different and are hydrogen, alkyl with 1-10 carbon atoms, alkenyl with 1-10 carbon atoms, phenyl, substituted phenyl, carboxylalky with 1-10 carbon atoms which is unsubstituted or substituted by a heterocyclic ring or phenyl ring, said rings being unsubstituted or substituted, alkoxy with 1-10 carbon atoms, alkylamino with 1-10 carbon atoms, aminoalkyl with 1-10 carbon atoms, acyloxy with 1-10 carbon atoms which is unsubstituted or substituted by a heterocyclic ring or a phenyl ring, said rings being unsubstituted or substituted, or acylamino with 1-10 carbon atoms which is unsubstituted or substituted by a heterocyclic ring or a phenyl ring, said rings being unsubstituted or substituted, and further provided that where one of R15, R16, R17, or R18 is the site of attachment, then R14 and the remainder of R15, R16, R17, and R18 are the same or different and are as defined for R15-R18 above when R14 is the site of attachment and R14 is either SO3H or SO4H, said catalytic antibody being capable of catalytically enhancing the rate of cleavage of a drug X or Bâ€”Aâ€”X, wherein B, A, and X are defined as above, from a residue of a prodrug of formula I, wherein said catalytic antibody exhibits catalytic activity which corresponds to activities exhibited by an enzyme selected from the group consisting of an esterase, an amidase, an acetal hydrolase and a glycosidase.