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US 10,294,271 B1Granted
Compound, composition, and method for detecting caspase activity and/or apoptosis
AssigneeVanderbilt University
InventorsH. Charles Manning, Matthew R. Hight
Life of this patent
Estimating the term…
Abstract
Molecular probe suitable for quantification of caspase activity in vivo using positron emission tomography (PET). Embodiments of the present invention can detect apoptosis in tumors and as a novel, potentially translatable biomarker for predicting response to personalized medicine.
Claims14
A method of imaging a molecular event in a sample, comprising:
- (a) administering to said sample a probe having an affinity for a target, the probe comprising a compound of the following:
- wherein:
- R1 is selected from
- (i) alkyl-halogen, CO-alkyl-halogen, CO-phenyl, CO-alkyl-phenyl, CO-pyridinyl, wherein alkyl is optionally substituted with one or more R7, and phenyl or pyridinyl is optionally halogen-substituted;
- X is iodine or fluorine;
- R3 is halogen;
- R5 is selected from alkyl, alkoxy;
- R7 is selected from hydrogen, C1-6 alkyl, C3-10 cycloalkyl, aryl, benzyl, heteroaryl, halogen, CN, CF3, CONR5R5, S(O)0-2NR5R5, CSNH2;
- X1 is selected from alkyl, alkoxy, R5—C3-8 membered ring containing C, O, S and/or N, optionally substituted with one or more R7;
- and
- X2 is H;
- X3 is independently C, CR7, N, NR7;
- and pharmaceutically acceptable salts thereof;
- and
- (b) detecting a signal from said probe.
12 more elements
A compound of the following formula:
- wherein:
- R1 is selected from
- (i) alkyl-halogen, CO-alkyl-halogen, CO-phenyl, CO-alkyl-phenyl, CO-pyridinyl, wherein alkyl is optionally substituted with one or more R7, and phenyl or pyridinyl is optionally halogen-substituted;
- X is iodine or fluorine;
- R3 is halogen;
- R5 is selected from alkyl, alkoxy;
- R7 is selected from hydrogen, C1-6 alkyl, C3-10 cycloalkyl, aryl, benzyl, heteroaryl, halogen, CN, CF3, CONR5R5, S(O)0-2NR5R5, CSNH2;
- X1 is selected from alkyl, alkoxy, R5—C3-8 membered ring containing C, O, S and/or N, optionally substituted with one or more R7;
- and
- X2 is H;
- X3 is independently C, CR7, N, NR7;
- and pharmaceutically acceptable salts thereof.
9 more elements
A method of quantifying the progression of a disease state in a subject, comprising:
- (a) administering to a first sample of the subject a probe having an affinity for a target, the probe comprising a compound of the following:
- wherein:
- R1 is selected from
- (i) alkyl-halogen, CO-alkyl-halogen, CO-phenyl, CO-alkyl-phenyl, CO-pyridinyl, wherein alkyl is optionally substituted with one or more R7, and phenyl or pyridinyl is optionally halogen-substituted;
- X is iodine or fluorine;
- R3 is halogen;
- R5 is selected from alkyl, alkoxy;
- R7 is selected from hydrogen, C1-6 alkyl, C3-10 cycloalkyl, aryl, benzyl, heteroaryl, halogen, CN, CF3, CONR5R5, S(O)0-2NR5R5, CSNH2;
- X1 is selected from alkyl, alkoxy, R5-C3-8 membered ring containing C, O, S and/or N, optionally substituted with one or more R7;
- and
- X2 is H;
- X3 is independently C, CR7, N, NR7;
- and pharmaceutically acceptable salts thereof;
- (b) detecting a signal from said probe;
- (c) after a period of time from step (b), administering to a second sample of the subject a probe having an affinity for a target, the probe comprising a compound of the following:
- wherein:
- R1 is selected from
- (i) alkyl-halogen, CO-alkyl-halogen, CO-phenyl, CO-alkyl-phenyl, CO-pyridinyl, wherein alkyl is optionally substituted with one or more R7, and phenyl or pyridinyl is optionally halogen-substituted;
- X is iodine or fluorine;
- R3 is halogen;
- R5 is selected from alkyl, alkoxy;
- R7 is selected from hydrogen, C1-6 alkyl, C3-10 cycloalkyl, aryl, benzyl, heteroaryl, halogen, CN, CF3, CONR5R5, S(O)0-2NR5R5, CSNH2;
- X1 is selected from alkyl, alkoxy, R5-C3-8 membered ring containing C, O, S and/or N, optionally substituted with one or more R7;
- and
- X2 is H;
- X3 is independently C, CR7, N, NR7;
- and
- pharmaceutically acceptable salts thereof;
- (d) detecting a second signal;
- and
- (e) comparing the first signal with the second signal to determine the progress of a disease state.
28 more elements
A method of determining the presence of a disease state, comprising:
- (a) administering to a first sample of the subject a probe having an affinity for a target, the probe comprising a compound of the following:
- wherein:
- R1 is selected from
- (i) alkyl-halogen, CO-alkyl-halogen, CO-phenyl, CO-alkyl-phenyl, CO-pyridinyl, wherein alkyl is optionally substituted with one or more R7, and phenyl or pyridinyl is optionally halogen-substituted;
- X is iodine or fluorine;
- R3 is halogen;
- R5 is selected from alkyl, alkoxy;
- R7 is selected from hydrogen, C1-6 alkyl, C3-10 cycloalkyl, aryl, benzyl, heteroaryl, halogen, CN, CF3, CONR5R5, S(O)0-2NR5R5, CSNH2;
- X1 is selected from alkyl, alkoxy, R5-C3-8 membered ring containing C, O, S and/or N, optionally substituted with one or more R7;
- and
- X2 is H;
- X3 is independently C, CR7, N, NR7;
- and pharmaceutically acceptable salts thereof;
- (b) detecting a signal from said probe.
11 more elements
Dependencies are inferred from the claim text.