Water-soluble SHPs as novel alkylating agents
AssigneeVion Pharmaceuticals, Inc.
InventorsXu Lin, Terrence W. Doyle, Ivan King
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds according to the structure (I): Where R is —CH3 or —CH2CH2Cl; R′ is C1-C7 alkyl or —CH2CH2Cl; R2 or R4 is OPO3H2, NO2, OCO(Glu-OH), NHCO(Glu-OH), NHR7 and unassigned groups of R2, R3, R4, R5 and R6 are, independently H, F, Cl, Br, I, OH, OPO3H2, OCH3, CF3, OCF3, NO2, CN, SO2CH3, SO2CF3, COCH3, COOCH3, SCH3, SF5, NH2, NHR7, N(CH3)2, OPO3H2, or a C1-C7 alkyl group with the proviso that when any two of unassigned groups of R2, R3, R4, R5 or R6 are other than H, the other two of unassigned groups of R2, R3, R4, R5 or R6 are H. R7 is H or polyglutamyl as described. Phosphoric acid and glutamic acid can be a free acid or pharmaceutically acceptable salt thereof.
Claims73
A compound or its pharmaceutically acceptable salt of the structure:
- Where
- R is —CH3 or —CH2CH2Cl;
- R′ is C1-C7 alkyl or —CH2CH2Cl;
- one of R2 or R4, but not both, is selected from OPO3H2, NO2, OCO(Glu), NHCO(Glu) and NHR7 and the other of R2 or R4 which is unassigned, and R3, R5 and R6, are, independently selected from H, F, Cl, Br, I, OH, OPO3H2, OCH3, CF3, OCF3, NO2, CN, SO2CH3, SO2CF3, COCH3, COOCH3, SCH3, SF5, NHR8, N(R9)2 and C1-C7 alkyl,
- with the proviso that at least two of R2, R3, R4, R5 and R6 are H;
- R7 is H, glutamyl or a polyglutamic acid polypeptide residue —OCH(NHR7a)CH2CH2CO2H where R7a is glutamyl or a polyglutamic acid polypeptide residue having from 1 to 50 peptide linkages;
- R8 is H or C1-C7 alkyl;
- and
- R9 is CH3 or CH2CH3.
A pharmaceutical composition comprising an effective amount for treating a tumor of a compound or its pharmaceutically acceptable salt according to the structure:
- Where
- R is —CH3 or —CH2CH2Cl;
- R′ is C1-C7 alkyl or —CH2CH2Cl;
- one of R2 or R4, but not both, is selected from OPO3H2, NO2, OCO(Glu), NHCO(Glu) and NHR7 and the other of R2 or R4 which is unassigned, and R3, R5 and R6, are, independently selected from H, F, Cl, Br, I, OH, OPO3H2, OCH3, CF3, OCF3, NO2, CN, SO2CH3, SO2CF3, COCH3, COOCH3, SCH3, SF5, NHR8, N(R9)2 and C1-C7 alkyl, with the proviso that at least two of R2, R3, R4, R5 and R6 are H;
- R7 is H, glutamyl or a polyglutamic acid polypeptide residue (—COCH(NHR7a)CH2CH2CO2H where R7a is glutamyl or a polyglutamic acid polypeptide residue having from 1 to 50 peptide linkages;
- R8 is H or C1-C7 alkyl;
- and
- R9 is CH3 or CH2CH3;
- optionally, in combination with a pharmaceutically acceptable additive, carrier, or excipient.
A method of treating a tumor in a patient in need of therapy comprising administering to said patient an effective amount of a compound or its pharmaceutically acceptable salt according to the structure:
- Where
- R is —CH3 or —CH2CH2Cl;
- R′ is C1-C7 alkyl or —CH2CH2Cl;
- one of R2 or R4, but not both, is selected from OPO3H2, NO2, OCO(Glu), NHCO(Glu) and NHR7 and the other of R2 or R4 which is unassigned, and R3, R5 and R6, are, independently selected from H, F, Cl, Br, I, OH, OPO3H2, OCH3, CF3, OCF3, NO2, CN, SO2CH3, SO2CF3, COCH3, COOCH3, SCH3, SF5, NHR9, N(R9)2 and C1-C7 alkyl, with the proviso that at least two of R2, R3, R4, R5 and R6 are H;
- R7 is H, glutamyl or a polyglutamic acid polypeptide residue —COCH(NHR7a)CH2CH2CO2H where R7a is glutamyl or a polyglutamic acid polypeptide residue having from 1 to 50 peptide linkages;
- R8 is H or C1-C7 alkyl;
- and
- R9 is CH3 or CH2CH3;
- optionally, in combination with a pharmaceutically acceptable additive, carrier, or excipient.
Dependencies are inferred from the claim text.