Patent ID: 6258603
Filing Date: 2001-07-10
Classification: C07C,C07D,C12Q

Abstract:
In a method to modulate exogenous gene expression comprising contacting an ecdysone receptor complex comprising:a) a DNA binding domain;b) a ligand binding domain;c) a transactivation domain; andd) a ligand;with a DNA construct comprising:a) the exogenous gene; andb) a response element;wherein:a) the exogenous gene is under the control of the response element; andb) binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene;the improvement comprising:selecting the ligand from a compound of the formula: ##STR4##wherein:E is a (C.sub.4 -C.sub.6)alkyl containing a tertiary carbon or a cyano(C.sub.3 -C.sub.5)alkyl containing a tertiary carbon;R.sup.1 is H, Me, Et, i-Pr, F, formyl, CF.sub.3, CHF.sub.2, CHCl.sub.2, CH.sub.2 F, CH.sub.2 Cl, CH.sub.2 OH, CH.sub.2 OMe, CH.sub.2 CN, CN, C.ident.CH, 1-propynyl, 2-propynyl, vinyl, OH, OMe, OEt, cyclopropyl, CF.sub.2 CF.sub.3, CH.dbd.CHCN, allyl, azido, SCN, or SCHF.sub.2 ;R.sup.2 is H, Me, Et, n-Pr, i-Pr, formyl, CF.sub.3, CHF.sub.2, CHCl.sub.2, CH.sub.2 F, CH.sub.2 Cl, CH.sub.2 OH, CH.sub.2 OMe, CH.sub.2 CN, CN, C.ident.CH, 1-propynyl, 2-propynyl, vinyl, Ac, F, Cl, OH, OMe, OEt, O-n-Pr, OAc, NMe.sub.2, NEt.sub.2, SMe, SEt, SOCF.sub.3, OCF.sub.2 CF.sub.2 H, COEt, cyclopropyl, CF.sub.2 CF.sub.3, CH.dbd.CHCN, allyl, azido, OCF.sub.3, OCHF.sub.2, O-i-Pr, SCN, SCHF.sub.2, SOMe, NH--CN, or joined with R.sup.3 and the phenyl carbons to which R.sup.2 and R.sup.3 are attached to form an ethylenedioxy, a dihydrofuryl ring with the oxygen adjacent to a phenyl carbon, or a dihydropyryl ring with the oxygen adjacent to a phenyl carbon;R.sup.3 is H, Et, or joined with R.sup.2 and the phenyl carbons to which R.sup.2 and R.sup.3 are attached to form an ethylenedioxy, a dihydrofuryl ring with the oxygen adjacent to a phenyl carbon, or a dihydropyryl ring with the oxygen adjacent to a phenyl carbon;R.sup.4, R.sup.5, and R.sup.6 are independently H, Me, Et, F, Cl, Br, formyl, CF.sub.3, CHF.sub.2, CHCl.sub.2, CH.sub.2 F, CH.sub.2 Cl, CH.sub.2 OH, CN, C.ident.CH, 1-propynyl, 2-propynyl, vinyl, OMe, OEt, SMe, or SEt;provided that:a) when R.sup.1 is Me and R.sup.2 is OMe;then R.sup.3 is H; and the combination R.sup.4, R.sup.5, and R.sup.6 is 3,5-di-Me, 3,5-di-OMe-4-Me, 3,5-di-Cl, or 3,5-di-F;b) when R.sup.1 is Me and R.sup.2 is OEt;then R.sup.3 is H and the combination R.sup.4, R.sup.5, and R.sup.6 is 3,5-di-Me, 3,5-di-OMe-4-Me, 3,5-di-Cl, 3,5-di-F, 2,4- or 2,5-di-F, 2,4- or 2,5-di-Cl;c) when R.sup.1 is Et and R.sup.2 is OMe or OEt;then R.sup.3 is H and the combination R.sup.4, R.sup.5, and R.sup.6 is:i) 3,5-di-OMe-4-Me, 3,5-di-Cl, 3,5-di-F, 2,4- or 2,5-di-F, 2,4- or 2,5-di-Cl, 3-OMe, 2-Cl-5-Me, 2-Br-5-Me, 2-Cl, 2-Br, or 3-Me; orii) R.sup.6 is H, R.sup.4 is Me, and R.sup.5 is Et, F, Cl, Br, formyl, CF.sub.3, CHF.sub.2, CHCl.sub.2, CH.sub.2 F, CH.sub.2 Cl, CH.sub.2 OH, CN, C.ident.CH, 1-propynyl, 2-propynyl, vinyl, OMe, OEt, SMe, or SEt;d) when R.sup.1 is i-Pr;then R.sup.2 is OMe, or OEt; R.sup.3 is H; and the combination R.sup.4, R.sup.5, and R.sup.6 is 3,5-di-Me;e) when R.sup.3 is Et;then R.sup.2 is H, R.sup.1 is F or Cl, and the combination R.sup.4, R.sup.5, and R.sup.6 is 3,5-di-Me;f) when R.sup.2 and R.sup.3, together with the phenyl carbons to which they are attached, form an ethylenedioxy ring;then R.sup.1 is Me or Et and the combination R.sup.4, R.sup.5, and R.sup.6 is 3,5-di-Me;g) when R.sup.2 and R.sup.3, together with the phenyl carbons to which they are attached, form a dihydrofuryl or dihydropyryl ring;then R.sup.1 is Et and the combination R.sup.4, R.sup.5, and R.sup.6 is 3,5-di-Me;h) when R.sup.1 is formyl, CF.sub.3, CHF.sub.2, CHCl.sub.2, CH.sub.2 F, CH.sub.2 Cl, CH.sub.2 OH, CH.sub.2 OMe, CH.sub.2 CN, CN, C.ident.CH, 1-propynyl, 2-propynyl, vinyl, OH, cyclopropyl, CF.sub.2 CF.sub.3, CH.dbd.CHCN, allyl, azido, SCN, or SCHF.sub.2 ;then R.sup.2 is OMe or OEt, R.sup.3 is H, and the combination R.sup.4, R.sup.5, and R.sup.6 is 3,5-di-Me; andi) when R.sup.2 is Me, Et, n-Pr, i-Pr, formyl, CF.sub.3, CHF.sub.2, CHCl.sub.2, CH.sub.2 F, CH.sub.2 Cl, CH.sub.2 OH, CH.sub.2 OMe, CH.sub.2 CN, CN, C.ident.CH, 1-propynyl, 2-propynyl, vinyl, Ac, F, Cl, OH, O-n-Pr, OAc, NMe.sub.2, NEt.sub.2, SMe, SEt, SOCF.sub.3, OCF.sub.2 CF.sub.2 H, COEt, cyclopropyl, CF.sub.2 CF.sub.3, CH.dbd.CHCN, allyl, azido, OCF.sub.3, OCHF.sub.2, O-i-Pr, SCN, SCHF.sub.2, SOMe, or NH--CN;then R.sup.1 is Et, R.sup.3 is H, and the combination R.sup.4, R.sup.5, and R.sup.6 is 3,5-di-Me.