Back to results
US 10,537,552 B2Granted
Substituted 5-hydroxyoxindoles and their use as analgesics and fever reducers
AssigneeCarafe Drug Innovation, LLC
InventorsJohn R. Carson, Robert B. Raffa, Kenneth G. Carson
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds and compositions which are useful in methods for modulating pain and fevers in a subject. These compounds are of the structure of formula (I), wherein Rx-R4, X, Y, and Z are defined herein, or a pharmaceutically acceptable salt, solvate, or prodrug thereof to the subject. In one embodiment, the compound is 5-hydroxy-7-methyloxindole.
Claims22
A method for treating pain or fever, comprising administering a compound of formula (I) to a subject, wherein said compound is:
- wherein:
- R1 and R2 are, independently, H, optionally substituted C1 to C6 alkyl, optionally substituted C3 to C8 cycloalkyl, optionally substituted C3 to C8 oxycycloalkyl, optionally substituted C1 to C6 hydroxyalkyl, NH2, optionally substituted C1 to C6 alkylamino, optionally substituted C1 to C6 dialkylamino, OH, optionally substituted C1 to C6 alkoxy, optionally substituted C1 to C6 alkylcarboxy, optionally substituted C1 to C3 alkylidenecarboxy, optionally substituted C1 to C6 carbalkoxy, optionally substituted C1 to C6 alkylcarboxamido, N-(optionally substituted C1 to C6 alkyl)carboxamido, N,N-di(optionally substituted C1 to C6 alkyl)carboxamido, or optionally substituted C1 to C6 acyl;
- or
- R1 and R2 are joined to form a 3 to 7 membered ring;
- R3 is H, optionally substituted C1 to C6 alkyl, optionally substituted C1 to C6 acyl, N,N-(di-optionally substituted C1 to C6 alkyl)aminoacyl), optionally substituted C1 to C6 carbalkoxy, optionally substituted C1 to C3 phosphatoalkylenyl, or optionally substituted C1 to C3 acyloxyalkylenyl;
- R4 is H, optionally substituted C1 to C6 alkyl, optionally substituted C1 to C6 acyl, N,N-(di-optionally substituted C1 to C6 alkyl)aminoacyl, N-(optionally substituted C1 to C6 alkyl)aminoacyl, C1 to C6 optionally substituted carbalkoxy, optionally substituted C1 to C3 phosphatoalkylenyl, amino(C3 to C8 optionally substituted cycloalkyl)acyl, or optionally substituted C1 to C3 acyloxyalkylenyl;
- X, Y and Z are, independently, H, deuterium, optionally substituted C1 to C6 alkyl, optionally substituted C3 to C8 cycloalkyl, optionally substituted C1 to C6 hydroxyalkyl, optionally substituted C1 to C6 acyl, CN, halogen, C1 to C3 polyfluoroalkyl, NO2, NH2, optionally substituted C1 to C6 alkylamino, optionally substituted C1 to C6 dialkylamino, formyl, optionally substituted C1 to C6 carboxy, optionally substituted C1 to C6 carbalkoxy, OH, optionally substituted C1 to C6 alkoxy, or optionally substituted C1 to C6 thioalkoxy;
- or
- any two of X, Y, and Z are joined to form a 3 to 7 membered ring;
- wherein R1-R3, X, Y, and Z are not all H;
- or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
8 more elements
A composition comprising:
- (a) one or more pharmaceutically acceptable excipient;
- and
- (b) about 1000 mg or less of a compound of the structure of formula (I):
- wherein:
- R1 and R2 are, independently, H, optionally substituted C1 to C6 alkyl, optionally substituted C3 to C8 cycloalkyl, optionally substituted C3 to C8 oxycycloalkyl, optionally substituted C1 to C6 hydroxyalkyl, NH2, optionally substituted C1 to C6 alkylamino, optionally substituted C1 to C6 dialkylamino, OH, optionally substituted C1 to C6 alkoxy, optionally substituted C1 to C6 alkylcarboxy, optionally substituted C1 to C3 alkylidenecarboxy, optionally substituted C1 to C6 carbalkoxy, optionally substituted C1 to C6 alkylcarboxamido, N-(optionally substituted C1 to C6 alkyl)carboxamido, N,N-di(optionally substituted C1 to C6 alkyl)carboxamido, or optionally substituted C1 to C6 acyl;
- or
- R1 and R2 are joined to form a 3 to 7 membered ring;
- R3 is H, optionally substituted C1 to C6 alkyl, optionally substituted C1 to C6 acyl, N,N-(di-optionally substituted C1 to C6 alkyl)aminoacyl), optionally substituted C1 to C6 carbalkoxy, optionally substituted C1 to C3 phosphatoalkylenyl, or optionally substituted C1 to C3 acyloxyalkylenyl;
- R4 is H, optionally substituted C1 to C6 alkyl, optionally substituted C1 to C6 acyl, N,N-(di-optionally substituted C1 to C6 alkyl)aminoacyl, N-(optionally substituted C1 to C6 alkyl)aminoacyl, C1 to C6 optionally substituted carbalkoxy, optionally substituted C1 to C3 phosphatoalkylenyl, amino(C3 to C8 optionally substituted cycloalkyl)acyl, or optionally substituted C1 to C3 acyloxyalkylenyl;
- X, Y and Z are, independently, H, optionally substituted C1 to C6 alkyl, optionally substituted C3 to C8 cycloalkyl, optionally substituted C1 to C6 hydroxyalkyl, optionally substituted C1 to C6 acyl, CN, halogen, C1 to C3 polyfluoroalkyl, NO2, NH2, optionally substituted C1 to C6 alkylamino, optionally substituted C1 to C6 dialkylamino, formyl, optionally substituted C1 to C6 carboxy, optionally substituted C1 to C6 carbalkoxy, OH, optionally substituted C1 to C6 alkoxy, or optionally substituted C1 to C6 thioalkoxy;
- or
- any two of X, Y, and Z are joined to form a 3 to 7 membered ring;
- wherein R1-R3, X, Y, and Z are not all H;
- or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
11 more elements
A kit comprising:
- (a) about 1000 mg or less of a compound of the structure of formula (I):
- wherein:
- R1 and R2 are, independently, H, optionally substituted C1 to C6 alkyl, optionally substituted C3 to C8 cycloalkyl, optionally substituted C3 to C8 oxycycloalkyl, optionally substituted C1 to C6 hydroxyalkyl, NH2, optionally substituted C1 to C6 alkylamino, optionally substituted C1 to C6 dialkylamino, OH, optionally substituted C1 to C6 alkoxy, optionally substituted C1 to C6 alkylcarboxy, optionally substituted C1 to C3 alkylidenecarboxy, optionally substituted C1 to C6 carbalkoxy, optionally substituted C1 to C6 alkylcarboxamido, N-(optionally substituted C1 to C6 alkyl)carboxamido, N,N-di(optionally substituted C1 to C6 alkyl)carboxamido, or optionally substituted C1 to C6 acyl;
- or
- R1 and R2 are joined to form a 3 to 7 membered ring;
- R3 is H, optionally substituted C1 to C6 alkyl, optionally substituted C1 to C6 acyl, N,N-(di-optionally substituted C1 to C6 alkyl)aminoacyl), optionally substituted C1 to C6 carbalkoxy, optionally substituted C1 to C3 phosphatoalkylenyl, or optionally substituted C1 to C3 acyloxyalkylenyl;
- R4 is H, optionally substituted C1 to C6 alkyl, optionally substituted C1 to C6 acyl, N,N-(di-optionally substituted C1 to C6 alkyl)aminoacyl, N-(optionally substituted C1 to C6 alkyl)aminoacyl, C1 to C6 optionally substituted carbalkoxy, optionally substituted C1 to C3 phosphatoalkylenyl, amino(C3 to C8 optionally substituted cycloalkyl)acyl, or optionally substituted C1 to C3 acyloxyalkylenyl;
- X, Y and Z are, independently, H, optionally substituted C1 to C6 alkyl, optionally substituted C3 to C8 cycloalkyl, optionally substituted C1 to C6 hydroxyalkyl, optionally substituted C1 to C6 acyl, CN, halogen, C1 to C3 polyfluoroalkyl, NO2, NH2, optionally substituted C1 to C6 alkylamino, optionally substituted C1 to C6 dialkylamino, formyl, optionally substituted C1 to C6 carboxy, optionally substituted C1 to C6 carbalkoxy, OH, optionally substituted C1 to C6 alkoxy, or optionally substituted C1 to C6 thioalkoxy;
- or
- any two of X, Y, and Z are joined to form a 3 to 7 membered ring;
- wherein R1-R3, X, Y, and Z are not all H;
- or a pharmaceutically acceptable salt, solvate, or prodrug thereof;
- and
- (b) instructions for administering said compound to a subject.
11 more elements
Dependencies are inferred from the claim text.