Conjugated nitro alkene anticancer agents based on isoprenoid metabolism
AssigneeArizona Biomedical Research Commission
InventorsSeth D. Rose, Karl J. Okolotowicz, Rosemarie F. Hartman, Jason Houtchens
Life of this patent
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Abstract
Conjugated nitro alkene compounds hamper or prevent proliferation of cancer cells in cell culture and in cancer patients, which can result in a decrease in tumor size and/or disappearance of the cancer. The compounds may act by interference with cancer cell biochemistry, in which isoprenoid groups such as farnesyl and geranylgeranyl become bonded to various oncogenic proteins such as Ras, RhoA, RhoB, or some other growth-related cellular protein(s).
Claims20
A method for the treatment of cancer in a patient, the method comprising administering an effective amount of a compound of Formula (I)
- or pharmaceutically acceptable salt thereof, wherein:
- G1 is selected from the group consisting of alkyl, haloalkyl, alkoxy, alkylthio and the sulfoxide and sulfone derivatives thereof, alkenyl, cycloalkyl, cycloalkoxy, aryl, aralkyl, aryloxy, heterocyclo, optionally substituted heterocyclo, alkynyl, alkanoyl, aroyl, aminocarbonyl, aminoalkanoyl, optionally substituted aminoalkanoyl, alkoxycarbonyl, alkylcarbonyloxy, alkoxyalkanoyl, alkanoylamido, a polypeptide, and combinations thereof;
- G2 and G3 are independently a hydrogen atom or a substituent selected from the group consisting of alkyl, haloalkyl, alkoxy, alkylthio and the sulfoxide and sulfone derivatives thereof, alkenyl, cycloalkyl, cycloalkoxy, aryl, aralkyl, aryloxy, heterocyclo, optionally substituted heterocyclo, alkoxyalkyl, alkynyl, alkanoyl, aroyl, aminocarbonyl, aminoalkanoyl, optionally substituted aminoalkanoyl, carbocycloalkyl, optionally substituted carbocycloalkyl, heteroaryl, optionally substituted heteroaryl, halo, (heterocyclo)alkyl, (heteroaryl)alkyl, alkoxycarbonyl, alkylcarbonyloxy, alkoxyalkanoyl, alkanoylamido, a polypeptide, and combinations thereof;
- or
- G1, G2, or G3 is a peptidomimetic group selected from the group consisting of
- and L is selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, and aralkyl, with the provisos that (i) when L is a bond, G1 is not aryl and (ii) G2 and G3 are not both hydrogen.
A method for the treatment of cancer in a patient, the method comprising administering an effective amount of a compound of Formula (I)
- or a pharmaceutically acceptable salt thereof, wherein:
- A is hydrogen,
- wherein m is from 0 to 10;
- B is hydrogen or methyl;
- G2 is hydrogen, methyl, or a peptidomimetic group selected from the group consisting of
- and n is 0, 1, or 2.
A method for the treatment of cancer in a patient, the method comprising administering an effective amount of a compound of Formula (I)
- or a pharmaceutically acceptable salt, ester, or prodrug thereof, wherein:
- A is hydrogen, methyl,
- wherein m is from 0 to 10;
- B is hydrogen;
- G2 is hydrogen, methyl, or a peptidomimetic group selected from the group consisting of
- and n is 0, 1, or 2.
A method for the treatment of cancer in a patient, the method comprising administering an effective amount of a compound of Formula (I)
- or a pharmaceutically acceptable salt thereof, wherein:
- A is hydrogen, methyl,
- wherein m is from 0 to 10;
- B is hydrogen or methyl;
- G2 is methyl or a peptidomimetic group selected from the group consisting of
- and n is 0, 1, or 2.
A method for the treatment of cancer in a patient, the method comprising administering an effective amount of a compound of Formula
- or a pharmaceutically acceptable salt thereof, wherein:
- G1 is
- wherein m is from 0 to 10;
- G2 is hydrogen, methyl, or a peptidomimetic group selected from the group consisting of
- and G3 is methyl, phenyl,
A method for the treatment of cancer in a patient, the method comprising administering an effective amount of a compound of Formula (I)
- or pharmaceutically acceptable salt thereof, wherein:
- G1 is selected from the group consisting of alkyl, haloalkyl, alkoxy, alkylthio and the sulfoxide and sulfone derivatives thereof, alkenyl, cycloalkyl, cycloalkoxy, aryl, aralkyl, aryloxy, alkynyl, alkanoyl, aroyl, aminocarbonyl, aminoalkanoyl, optionally substituted aminoalkanoyl, alkoxycarbonyl, alkylcarbonyloxy, alkoxyalkanoyl, alkanoylamido, a polypeptide, and combinations thereof;
- G2 and G3 are independently a hydrogen atom or a substituent selected from the group consisting of alkyl, haloalkyl, alkoxy, alkylthio and the sulfoxide and sulfone derivatives thereof, alkenyl, cycloalkyl, cycloalkoxy, aryl, aralkyl, aryloxy, heterocyclo, optionally substituted heterocyclo, alkoxyalkyl, alkynyl, alkanoyl, aroyl, aminocarbonyl, aminoalkanoyl, optionally substituted aminoalkanoyl, carbocycloalkyl, optionally substituted carbocycloalkyl, heteroaryl, optionally substituted heteroaryl, halo, (heterocyclo)alkyl, (heteroaryl)alkyl, alkoxycarbonyl, alkylcarbonyloxy, alkoxyalkanoyl, alkanoylamido, a polypeptide, and combinations thereof;
- or
- G1, G2, or G3 is a peptidomimetic group selected from the group consisting of
- and L is selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, and aralkyl, with the provisos that (i) when L is a bond, G1 is not aryl and (ii) G2 and G3 are not both hydrogen.
Dependencies are inferred from the claim text.