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US 6,452,032 B1Granted
Organosilyl compounds having nuclear hormone receptor modulating activity
AssigneeAllergan Sales, Inc.
InventorsRichard L. Beard, Michael E. Garst, Roshantha A. Chandraratna
Life of this patent
Estimating the term…
Abstract
Silicone-containing organic compounds useful as modulators of mammalian nuclear hormone receptors, particularly the retinoid receptors and the farnesoid receptors.
Claims34
A compound selected from the group consisting of Formulas 1, 2, 3 and
- wherein the dashed line represents a bond or absence of a bond;
- X is S, O, NR′ where R′ is H or alkyl of 1 to 6 carbons, or
- X is (C(R1)2)n where R1 is H or alkyl of 1 to 6 carbons, and n is an integer
- having the value of 0 or 1;
- 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 12 carbons, or alkylthio of 1 to 12 carbons, benzyloxy or C1-C12 alkylbenzyloxy;
- 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 when the dashed line represents absence of a bond, and 0-3 when the dashed line represents a bond;
- R3′ is hydrogen, lower alkyl of 1 to 6 carbons, F or (R15)r-phenyl, (R15)r-naphthyl, 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;
- R4 is alkyl of 1 to 8 carbons or phenyl;
- 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 R2 groups;
- R15 is independently H, F, Cl, Br, I, NO2, N(R8)2, NH(R8), COR8, NR8CON(R8)2, OH, OCOR8, OR8, CN, 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;
- 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, NO2, P(O)(OH)2, P(O)(OH)OR8, P(O)(OR8)2, SO2OH, SO2(OR8), COOR8, CONR9R10, —CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, —COR7, CR7(OR12)2, CR7OR13O, or tri-lower alklsilyl, 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, or a pharmaceutically acceptable salt of said compound.
11 more elements
A compound of the formula
- where R2 is H or methyl, R4 is lower alkyl of 1 to 8 carbons, Y is phenyl or thienyl and B is CH2OH, or COOR8 where R8 is H or ethyl.
A compound of the formula
- where R2 is H or methyl, R4 is lower alkyl of 1 to 8 carbons and B is CH2OH, or COOR8 where R8 is H or ethyl.
A compound of the formula
- wherein R2 is H or lower alkyl, R4 is lower alkyl of 1 to 8 carbons and B is CH2OH or COOR8 where R8 is H or ethyl.
Dependencies are inferred from the claim text.