Back to results
US 7,253,319 B2Granted
Disubstituted chalcone oximes having RARγ retinoid receptor antagonist activity
AssigneeAllergan, Inc.
InventorsKwok Yin Tsang, Santosh Sinha, Xiaoxia Liu, Smita Bhat, Roshantha A. Chandraratna
Life of this patent
Estimating the term…
Abstract
Compounds of the formula where the variables have the values described in the specification are antagonists of RARγ retinoid receptors.
Claims18
A compound of the formula
- wherein R is selected from the groups consisting of the radicals defined by formulas (a) through (d)
- where the dashed line in a ring represents a bond, or absence of a bond with the proviso that one and only one dashed line in the ring represents a bond;
- a * denotes a ring carbon to which the chalcone oxime group is attached;
- X is (R5)r-substituted alkenyl of 1–6 carbons and 1 or 2 double bonds, (R5)r-substituted alkynyl of 1–6 carbons and 1 or 2 triple bonds, (R5)r-phenyl, (R5)r-naphthyl, (R5)r-heteroaryl where the heteroaryl group has 1 to 3 heteroatoms selected from the group consisting of O, S and N;
- Y is a phenyl or naphthyl group, or heteroaryl selected from a group consisting of pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, imidazolyl and pyrrazolyl, said phenyl and heteroaryl groups being optionally substituted with one or two R4 groups;
- m is an integer having the values 0 to 5;
- n is an integer having the values 0 to 3;
- p is an integer having the values 0 to 2;
- r is an integer having the values 0 to 5;
- R1 is independently alkyl of 1 to 6 carbons, F, Cl, Br or I;
- R2 is independently alkyl of 1 to 6 carbons, F, Cl, Br, I, OH, SH, alkoxy having 1 to 6 carbons, alkylthio having 1 to 6 carbons, NH2, C1-6alkylamino or di(C1-6alkyl)amino;
- R3 is H or alkyl of 1 to 10 carbons;
- R4 is independently halogen, alkyl of 1 to 10 carbons, fluoro substituted alkyl of 1 to 6 carbons, alkoxy of 1 to 10 carbons, or alkylthio of 1 to 10 carbons;
- R5 is independently alkyl of 1 to 6 carbons, F, Cl, Br, I, OH, SH, alkoxy having 1 to 6 carbons, alkylthio having 1 to 6 carbons, NH2, C1-6alkylamino or di(C1-6alkyl)amino;
- A is (CH2)q where q is 0–5, lower branched chain alkyl having 3–6 carbons, cycloalkyl having 3–6 carbons, alkenyl having 2–6 carbons and 1 or 2 double bonds, alkynyl having 2–6 carbons and 1 or 2 triple bonds;
- B is COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10, —CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, —COR7, CR7(OR12)2, CR7OR13O, or tri-lower alkylsilyl, where R7 is an alkyl group of 1 to 6 carbons, cycloalkyl of 3 to 5 carbons, or alkenyl group containing 2 to 5 carbons, R8 is an alkyl group of 1 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, CH2OCH3 or CH2OCH2OOC1-6alkyl, or R8 is phenyl or C1-6 alkylphenyl, R9 and R10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5–10 carbons, or phenyl or C1-6alkylphenyl, R11 is alkyl of 1 to 6 carbons, phenyl or C1-6alkylphenyl, R12 is alkyl of 1 to 6 carbons, and R13 is divalent alkyl radical of 2–5 carbons, or a pharmaceutically acceptable salt of said compound.
13 more elements
A compound of the formula
- wherein R1 is alkyl of 1 to 6 carbons;
- R2 is independently alkyl of 1 to 6 carbons, F, Cl, Br, I, OH, SH, alkoxy having 1 to 6 carbons, alkylthio having 1 to 6 carbons, NH2, C1-6alkylamino or di(C1-6alkyl)amino;
- R4 is independently halogen, alkyl of 1 to 10 carbons, fluoro substituted alkyl of 1 to 6 carbons, alkoxy of 1 to 10 carbons, or alkylthio of 1 to 10 carbons;
- R5 is independently alkyl of 1 to 6 carbons, F, Cl, Br, I, OH, SH, alkoxy having 1 to 6 carbons, alkylthio having 1 to 6 carbons, NH2, C1-6alkylamino or di(C1-6alkyl)amino;
- n is an integer having the values 0 to 3;
- r is an integer having the values 0 to 5;
- A is (CH2)q where q is 0–5, lower branched chain alkyl having 3–6 carbons, cycloalkyl having 3–6 carbons, alkenyl having 2–6 carbons and 1 or 2 double bonds, alkynyl having 2–6 carbons and 1 or 2 triple bonds;
- B is COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10, —CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, —COR7, CR7(OR12)2, CR7OR13O, or tri-lower alkylsilyl, where R7 is an alkyl group of 1 to 6 carbons, cycloalkyl of 3 to 5 carbons, or alkenyl group containing 2 to 5 carbons, R8 is an alkyl group of 1 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, CH2OCH3 or CH2OCH2OOC1-6alkyl, or R8 is phenyl or C1-6 alkylphenyl, R9 and R10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5–10 carbons, or phenyl or C1-6alkylphenyl, R11 is alkyl of 1 to 6 carbons, phenyl or
- C1-6alkylphenyl, R12 is alkyl of 1 to 6 carbons, and R13 is divalent alkyl radical of 2–5 carbons, or a pharmaceutically acceptable salt of said compound.
6 more elements
A compound of the formula
- wherein R1 is alkyl of 1 to 6 carbons;
- R2 is independently alkyl of 1 to 6 carbons, F, Cl, Br, I, OH, SH, alkoxy having 1 to 6 carbons, alkylthio having 1 to 6 carbons, NH2, C1-6alkylamino or di(C1-6alkyl)amino;
- R4 is independently halogen, alkyl of 1 to 10 carbons, fluoro substituted alkyl of 1 to 6 carbons, alkoxy of 1 to 10 carbons, or alkylthio of 1 to 10 carbons;
- R5 is independently alkyl of 1 to 6 carbons, F, Cl, Br, I, OH, SH, alkoxy having 1 to 6 carbons, alkylthio having 1 to 6 carbons, NH2, C1-6alkylamino or di(C1-6alkyl)amino;
- n is an integer having the values 0 to 3;
- r is an integer having the values 0 to 5;
- A is (CH2)q where q is 0–5, lower branched chain alkyl having 3–6 carbons, cycloalkyl having 3–6 carbons, alkenyl having 2–6 carbons and 1 or 2 double bonds, alkynyl having 2–6 carbons and 1 or 2 triple bonds;
- B is COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10, —CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, —COR7, CR7(OR12)2, CR7OR13O, or tri-lower alkylsilyl, where R7 is an alkyl group of 1 to 6 carbons, cycloalkyl of 3 to 5 carbons, or alkenyl group containing 2 to 5 carbons, R8 is an alkyl group of 1 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, CH2OCH3 or CH2OCH2OOC1-6alkyl, or R8 is phenyl or C1-6 alkylphenyl, R9 and R10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5–10 carbons, or phenyl or C1-6alkylphenyl, R11 is alkyl of 1 to 6 carbons, phenyl or
- C1-6alkylphenyl, R12 is alkyl of 1 to 6 carbons, and R13 is divalent alkyl radical of 2–5 carbons, or a pharmaceutically acceptable salt of said compound.
6 more elements
Dependencies are inferred from the claim text.