Pharmaceutical gallium compositions and methods
AssigneeGenta Incorporated
InventorThomas N. Julian
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Abstract
Novel pharmaceutical gallium compositions, including gallium complexes having increased oral bioavailability relative to uncomplexed gallium salts are disclosed. Such compositions are useful in the treatment of conditions and diseases in which inhibition of abnormally increased calcium resorption is desired, including cancer, hypercalcemia, osteoporosis, osteopenia and Paget's disease. Methods for preparation and treatment are also provided.
Claims11
A method for treating cancer comprising administering to a patient in need of such treatment a therapeutically effective amount of gallium and a compound represented by structural formula I:
- 2-OH—Ar—CR1—NR2—R3—COOH I
- wherein 2-OH—Ar is an optionally substituted 2-hydroxyaryl;
- R1 is —OH or ═O;
- R2 is hydrogen, hydroxyl or an optionally substituted C1-C4 alkyl, C1-C4 alkoxy, or C2-C4 alkenyl;
- and
- R3 is an optionally substituted aryl, heteroaryl, cycloalkyl, heterocyclyl, C1-C24 alkyl, C2-C20 alkenyl, C2-C20 alkynl, C1-C10 alkylaryl, C1-C10 arylalkyl, C2-C10 alkenylaryl, C2-C10 arylalkenyl, C2-C10 alkynylaryl or C2-C10 arylalkynyl, which optionally is interrupted by O, N, S or any combination thereof,
- and at least one pharmaceutically acceptable excipient,
- wherein a complex of gallium and the compound is prepared prior to administration of the complex to the patient.
A pharmaceutical composition for treatment of cancer in a patient in need of such treatment comprising, in solid form for oral administration, a therapeutically effective amount of gallium, a compound represented by structural formula I:
- 2-OH—Ar—CR1—NR2—R3—COOH I
- wherein 2-OH—Ar is an optionally substituted 2-hydroxyaryl;
- R1 is —OH or ═O;
- R2 is hydrogen, hydroxyl or an optionally substituted C1-C4 alkyl, C1-C4 alkoxy, or C2-C4 alkenyl;
- and
- R3 is an optionally substituted aryl, heteroaryl, cycloalkyl, heterocyclyl, C1-C24 alkyl, C2-C20 alkenyl, C2-C20 alkynl, C1-C10 alkylaryl, C1-C10 arylalkyl, C2-C10 alkenylaryl, C2-C10 arylalkenyl, C2-C10 alkynylaryl or C2-C10 arylalkynyl, which optionally is interrupted by O, N, S or any combination thereof,
- means to inhibit, under the acidic conditions of the stomach, dissociation of a complex formed by the gallium and the compound,
- and at least one pharmaceutically acceptable excipient.
Dependencies are inferred from the claim text.