Patent ID: 7375093
Filing Date: 2008-05-20
Classification: A61P,C07C,C07D,C07F,C07K,C12Q

Abstract:
1. A method of modulating the expression of a target gene in a host cell, wherein the host cell includes a first gene expression cassette comprising a first polynucleotide encoding a first polypeptide comprising: (i) a transactivation domain; (ii) a DNA-binding domain; and (iii) a Group H nuclear receptor ligand binding domain; a second gene expression cassette comprising: (i) a response element capable of binding to said DNA binding domain; (ii) a promoter that is activated by the transactivation domain; and (iii) said target gene; the method comprising contacting said host cell with a compound of formula: wherein Q 1 is selected from the group consisting of O and S; R 1 is i. (C ii. unsubstituted or substituted phenyl, 1-naphthyl, 2-naphthyl, phenyl(C ii unsubstituted or substituted phenyl, phenyl(C wherein in said substituted phenyl, 1-naphthyl, 2-naphthyl, phenyl(C 1 -C 3 )alkyl, phenyl(C 2 -C 3 )alkenyl, naphthyl(C 1 -C 3 )alkyl, phenoxy(C 1 -C 3 )alkyl, phenylamino, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, thiophenyl, benzothiophenyl, benzofuranyl, isoxazolyl, imidazolyl or other heterocyclyl, two adjacent substituted positions may be joined together with the atoms to which they are attached to form an unsubstituted or substituted, unsaturated, partially unsaturated, or saturated 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring wherein: the heterocyclic ring contains from one to three heteroatoms selected from N, O, or S; and one to four substituents are independently selected from the group consisting of cyano, nitro, halo, aminocarbonyl, aminothiocarbonyl, carboxy, formyl, hydroxy, amino, carbamoyl, (C 1 -C 3 )alkyl, (C 1 -C 3 )haloalkyl, (C 1 -C 3 )alkoxy, (C 1 -C 3 )haloalkoxy, (C 1 -C 3 )alkythio, (C 1 -C 3 )haloalkylthio, (C 1 -C 3 )alkylsulfonyl, (C 1 -C 3 )alkylamino, di(C 1 -C 3 ) alkylamino, (C 1 -C 2 )alkoxy(C 1 -C 2 )alkyl, (C 1 -C 2 )alkylthio(C 1 -C 2 )alkyl, (C 1 -C 2 ) alkylsulfonyl(C 1 -C 2 )alkyl, (C 1 -C 2 )alkylamino(C 1 -C 2 )alkyl, di(C 1 -C 2 )alkylamino(C 1 -C 2 ) alkyl, (C 1 -C 3 )alkylcarbonyl, 1-C 3 )alkoxycarbonyl, (C 1 -C 3 )alkylaminocarbonyl, di(C 1 -C 3 )alkylaminocarbonyl, cyano(C 1 -C 3 )alkyl, oxo, and methoxyimino; R 2 and R 3 are independently selected from: (a) cyano, aminocarbonyl, carboxy, (C (b) unsubstituted or substituted phenyl, phenyl(C wherein R 2 and R 3 may be joined together with the carbon to which they are attached to form an unsubstituted or substituted, partially unsaturated or saturated 3-, 4-, 5-, 6-, 7- or 8-membered carbocyclic or heterocyclic ring wherein the heterocyclic ring contains from one to three heteroatoms selected from 0, N, or S; and one to four substituents are independently selected from the group consisting of cyano, nitro, halo, aminocarbonyl, aminothiocarbonyl, carboxy, formyl, hydroxy, amino, carbamoyl, (C 1 -C 3 )alkyl, (C 1 -C 3 )haloalkyl, (C 1 -C 3 )alkoxy, (C 1 -C 3 )haloalkoxy, (C 1 -C 3 )alkythio, (C 1 -C 3 )haloalkylthio, (C 1 -C 3 )alkylsulfonyl, 1-C 3 )alkylamino, di(C 1 -C 3 )alkylamino, (C 1 -C 2 )alkoxy(C 1 -C 2 )alkyl, (C 1 -C 2 )alkylthio(C 1 -C 2 )alkyl, (C 1 -C 2 )alkylsulfonyl(C 1 -C 2 )alkyl, (C 1 -C 2 )alkylamino(C 1 -C 2 ) alkyl, di(C 1 -C 2 )alkylamino(C 1 -C 2 )alkyl, (C 1 -C 3 )alkylcarbonyl, (C 1 -C 4 ) alkoxycarbonyl, (C 1 -C 4 )alkoxycarbonyl(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxycarbonylcarbonyl, (C 1 -C 3 )alkylaminocarbonyl, di(C 1 -C 3 )alkylaminocarbonyl, cyano(C 1 -C 3 )alkyl, oxo, methoxyimino, and spiro-(C 1 -C 4 )alkadioxy; and R 4 is selected from: (a) (C (b) unsubstituted or substituted phenyl, 1-naphthyl, 2-naphthyl, phenyl(C wherein in said substituted phenyl, 1-naphthyl, 2-naphthyl, phenyl(C 1 -C 3 )alkyl, phenyl(C 2 -C 3 )alkenyl, naphthyl(C 1 -C 3 )alkyl, phenoxy(C 1 -C 3 )alkyl, phenylamino, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, thiophenyl, benzothiophenyl, benzofuranyl, isoxazolyl, imidazolyl or other heterocyclyl, two adjacent substituted positions on R 4 may be joined together with the atoms to which they are attached to form an unsubstituted or substituted, unsaturated, partially unsaturated, or saturated 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring wherein the heterocyclic ring contains from one to three heteroatoms selected from N, O, or S; and one to four substituents are independently selected from the group consisting of cyano, nitro, halo, aminocarbonyl, aminothiocarbonyl, carboxy, formyl, hydroxy, amino, carbamoyl, (C 1 -C 3 )alkyl, (C 1 -C 3 )haloalkyl, (C 1 -C 3 )alkoxy, (C 1 -C 3 )haloalkoxy, (C 1 -C 3 )alkythio, (C 1 -C 3 )haloalkylthio, (C 1 -C 3 )alkylsulfonyl, (C 1 -C 3 )alkylamino, di(C 1 -C 3 )alkylamino, (C 1 -C 2 )alkoxy(C 1 -C 2 )alkyl, (C 1 -C 2 )alkylthio(C 1 -C 2 )alkyl, (C 1 -C 2 )alkylsulfonyl(C 1 -C 2 )alkyl, (C 1 -C 2 )alkylamino(C 1 -C 2 ) alkyl, di(C 1 -C 2 )alkylamino(C 1 -C 2 )alkyl, (C 1 -C 3 )alkylcarbonyl, (C 1 -C 3 )alkoxycarbonyl, (C 1 -C 3 )alkylaminocarbonyl, di(C 1 -C 3 )alkylaminocarbonyl, cyano (C 1 -C 3 )alkyl, oxo, and methoxyimino.