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US 6,555,690 B2Granted
Alkyl or aryl substituted dihydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
AssigneeAllergan, Inc.
InventorsAlan T. Johnson, Min Teng, Vidyasagar Vuligonda, Richard L. Beard, Samuel J. Gillett, Tien T. Duong, Roshantha A. Chandraratna
Life of this patent
Estimating the term…
Abstract
Compounds of the formula where the symbols have the meaning described in the application, have retinoid-like or retinoid antagonist-like biological activity.
Claims12
A compound of the formula
- wherein X1 is (C(R1)2)n where R1 is independently H or alkyl of 1 to 6 carbons, and n is an integer between 0 and 2;
- Z is —CO—CR1═CR1—;
- R2 is hydrogen, lower alkyl of 1 to 6 carbons, F, Cl, Br, I, CF3, fluoro substituted alkyl of 1 to 6 carbons, OH, SH, alkoxy of 1 to 6 carbons, or alkylthio of 1 to 6 carbons;
- R3 is hydrogen, lower alkyl of 1 to 6 carbons or F;
- m is an integer having the value of 0-3;
- o is an integer having the value of 0-3;
- Y is heteroaryl selected from a group consisting of pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, imidazolyl and pyrrazolyl, said heteroaryl groups being optionally substituted with one or two R2 groups;
- 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 bond;
- B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10, —CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, —COR7, CR7(OR12)2, CR7OR13O, or Si(C1-6alkyl)3, where R7 is an alkyl, cycloalkyl or alkenyl group containing 1 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, or R8 is phenyl or lower 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 lower alkylphenyl, R11 is lower alkyl, phenyl or lower alkylphenyl, R12 is lower alkyl, and R13 is divalent alkyl radical of 2-5 carbons;, and
- R14 is (R15)r-substituted alkyl of 1-6 carbons, (R15)r-substituted alkenyl of 1-6 carbons and 1 or 2 double bonds, (R15)r-substituted alkynyl of 1-6 carbons and 1 or 2 triple bonds, (R15)r-phenyl, (R15)-naphthyl, (R15)r-heteroaryl where the heteroaryl group has 1 to 3 heteroatoms selected from the group consisting of O, S and N, or R14 is (CH2)pCO2H or (CH2)pCO2R8 where p is integer between 0 to 10, r is an integer having the values of 0-5, and
- R15 is independently H, F, Cl, Br, I, NO2, N(R8)2, N(R8)COR8. NR8CON(R8)2, OH, OCOR8, OR8, CN, COOH, COOR8 an alkyl group having 1 to 10 carbons, fluoro substituted alkyl group having 1 to 10 carbons, an alkenyl group having 1 to 10 carbons and 1 to 3 double bonds, alkynyl group having 1 to 10 carbons and 1 to 3 triple bonds, or a trialkylsilyl or trialkylsilyloxy group where the alkyl groups independently have 1 to 6 carbons.
8 more elements
(twice amended) A compound of the formula
- where R1 is independently H or alkyl of 1 to 6 carbons;
- Z is —CO—CR1═CR1—;
- R2 is hydrogen, lower alkyl of 1 to 6 carbons;
- R3 is hydrogen, lower alkyl of 1 to 6 carbons or F;
- m is an integer having the value of 0-3;
- o is an integer having the value of 0-4;
- Y is pyridyl or thienyl;
- 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 hydrogen, COOH or a pharmaceutically acceptable salt thereof COOR8, CONR9R10, —CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, —COR7, CR7(OR12)2, CR7OR13O, or Si(C1-6alkyl)3, where R7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R8 is an alkyl group of 1 to 10 carbons or (trimethylsilyl)alkyl where the alkyl group has 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R8 is phenyl or lower 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 lower alkylphenyl, R11 is lower alkyl, phenyl or lower alkylphenyl, R12 is lower alkyl, and R13 is divalent alkyl radical of 2-5 carbons, and
- R14 is alkyl of 1-6 carbons, CH2COOH, CH2COOR8 or (R15)r-heteroaryl where the heteroaryl group has 1 to 3 heteroatoms selected from the group consisting of O, S and N, r is an integer having the values of 0-5, and
- R15 is independently H, F, Cl, Br, I, NO2, N(R8)2, OH, OCOR8, OR8, CN, COOH, COOR8, an alkyl group having 1 to 10 carbons, or fluoro substituted alkyl group having 1 to 10 carbons.
8 more elements
Dependencies are inferred from the claim text.