Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof

Abstract

A compound of Formula (IA) or Formula (IB) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

1 . A compound of Formula (IA):  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is an aryl or heteroaryl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 1  is independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1 -C 5  alkoxy, C 2 -C 5  alkenyloxy, C 2 -C 5  alkynyloxy, aryloxy, acyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, C 1 -C 5  dialkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, C 1 -C 5  dialkylaminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, aminosulfonyl, C 1 -C 5  alkylaminosulfonyl, C 1 -C 5  dialkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, nitro, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl or aryl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
 wherein each substituent group of R 1  is optionally independently substituted with one to three substituent groups selected from C 1 -C 3  alkyl, C 1 -C 3  alkoxy, halogen, hydroxy, oxo, cyano or amino;  
 
 R 2  and R 3  are each independently hydrogen or C 1 -C 5  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a C 3 -C 8  spiro cycloalkyl ring;  
 R 4  is C 1 -C 5  alkyl, C 2 -C 5  alkenyl, or C 2 -C 5  alkynyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 4  is independently C 1 -C 3  alkyl, hydroxy, halogen, amino, or oxo; and  
 
 R 5  is a heteroaryl group optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1 -C 5  alkoxy, C 2 -C 5  alkenyloxy, C 2 -C 5  alkynyloxy, aryloxy, acyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, C 1 -C 5  dialkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, C 1 -C 5  dialkylaminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, aminosulfonyl, C 1 -C 5  alkylaminosulfonyl, C 1 -C 5  dialkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, nitro, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, 
 wherein each substituent group of R 5  is optionally independently substituted with one to three substituent groups selected from C 1 -C 3  alkyl, C 1 -C 3  alkoxy, halogen, hydroxy, oxo, cyano, amino, or trifluoromethyl,  
 
 
 R 6  and R 7  are each independently hydrogen, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 1-8  alkoxy, C 2-8  alkenyloxy, C 2-8  alkynyloxy, hydroxy, carbocyclyl, heterocyclyl, aryl, aryloxy, acyl, heteroaryl, carbocycle-C 1 -C 8  alkyl, aryl-C 1 -C 8  alkyl, aryl-C 1 -C 8  haloalkyl, heterocyclyl-C 1 -C 8  alkyl, heteroaryl-C 1 -C 8  alkyl, carbocycle-C 2 -C 8  alkenyl, aryl-C 2 -C 8  alkenyl, heterocyclyl-C 2 -C 8  alkenyl, heteroaryl-C 2 -C 8  alkenyl, or C 1 -C 5  atkylthio wherein the sulfur atom is oxidized to a sulfoxide or sulfone, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 6  and R 7  are independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, phenyl, C 1 -C 5  alkoxy, phenoxy, C 1 -C 5  alkanoyl, aroyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, C 1 -C 5  dialkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, C 1 -C 5  dialkylaminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, aminosulfonyl, C 1 -C 5  alkylaminosulfonyl, C 1 -C 5  dialkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, oxo, trifluoromethyl, trifluoromethoxy, nitro; or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
 or a tautomer, prodrug, solvate, or salt thereof.  
 
 
   
   
       2 . The compound of Formula (IA) according to  claim 1 , wherein: 
 R 1  is phenyl, naphthyl, indanyl, indenyl, dihydrobenzofuranyl, benzofuranyl, chromanyl, dihydroindolyl, indolyl, dihydrobenzothienyl, benzothienyl, benzodioxolanyl, dihydrobenzoxazolyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzimidazolyl, quinolinyl, isoquinolinyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, or pyrazinyl each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 1  is independently C 1 -C 3  alkyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, C 1 -C 3  alkoxy, C 2 -C 3  alkenyloxy, C 1 -C 3  alkanoyl, C 1 -C 3  alkoxycarbonyl, C 1 -C 3  alkanoyloxy, halogen, hydroxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, nitro, or C 1 -C 3  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
 wherein each substituent group of R 1  is independently optionally substituted with a substituent group selected from methyl, methoxy, halogen, hydroxy, oxo, cyano, or amino;  
   R 2  and R 3  are each independently hydrogen or C 1 -C 3  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a C 3 -C 6  spiro cycloalkyl ring;    R 4  is C 1 -C 3  alkyl or C 2 -C 3  alkenyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 4  is independently methyl, hydroxy, fluoro, chloro, bromo, or oxo; and  
   R 5  is an imidazolyl, pyridinyl, indolyl, azaindolyl, diazaindolyl, benzofuranyl, furanopyridinyl, furanopyrimidinyl, benzothienyl, thienopyridinyl, thienopyrimidinyl, benzoxazolyl, oxazolopyridinyl, benzothiazolyl, thiazolopyridinyl, benzimidazolyl, imidazolopyridinyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently C 1 -C 3  alkyl, C 2 -C 3  alkenyl, phenyl, C 1 -C 3  alkoxy, methoxycarbonyl, aminocarbonyl, C 1 -C 3  alkylaminocarbonyl, C 1 -C 3  dialkylaminocarbonyl, heterocyclylcarbonyl, hydroxy, fluoro, chloro, bromo, cyano, trifluoromethyl, or C 1 -C 3  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, 
 wherein each substituent group of R 5  is optionally independently substituted with a substituent group selected from methyl, methoxy, hydroxy, fluoro, chloro, bromo, oxo, or trifluoromethyl,  
 
   R 6  and R 7  are each independently hydrogen, C 1-5  alkyl, C 1-5  alkoxy, C 2-5  alkenyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, benzyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, phenethyl, phenoxy, hydroxy or C 1 -C 5  alkylthio wherein the sulfur atom is oxidized to a sulfoxide or sulfone, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 6  and R 7  are independently methyl, methoxy, hydroxy, halogen, cyano, oxo or trifluoromethyl;  
 or a tautomer, prodrug, solvate, or salt thereof.  
   
   
   
       3 . The compound of Formula (IA) according to  claim 1 , wherein: 
 R 1  is thienyl, phenyl, naphthyl, pyridinyl, chromanyl, dihydrobenzofuranyl, or benzofuranyl, each optionally independently substituted with one or two substituent groups, 
 wherein each substituent group of R 1  is independently methyl, ethyl, methoxy, ethoxy, fluoro, chloro, bromo, hydroxy, trifluoromethyl, trifluoromethoxy, oxo or cyano;  
   R 2  and R 3  are each independently C 1 -C 3  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a spiro cyclopropyl or cyclobutyl ring;    R 4  is C 1 -C 3  alkyl; and    R 5  is a pyridinyl, indolyl, azaindolyl, benzofuranyl, furanopyridinyl, benzothienyl, thienopyridinyl, benzoxazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, phenyl, methoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, morpholinylcarbonyl, methoxy, hydroxy, fluoro, chloro, bromo, cyano, or trifluoromethyl,  
   R 6  and R 7  are each independently hydrogen, C 1-5  alkyl, benzyl, hydroxy or C 1 -C 5  alkylthio wherein the sulfur atom is oxidized to a sulfoxide or sulfone, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 6  and R 7  are independently methyl or oxo;  
 or a tautomer, prodrug, solvate, or salt thereof.  
   
   
   
       4 . The compound of Formula (IA) according to  claim 1 , wherein: 
 R 1  is phenyl, dihydrobenzofuranyl, benzofuranyl or pyridinyl substituted with one or two substituent groups, 
 wherein each substituent group of R 1  is independently methyl, methoxy, fluoro, chloro, bromo, trifuoromethyl, trifluoromethoxy, cyano or hydroxy;  
   R 2  and R 3  are each independently C 1 -C 3  alkyl;    R 4  is CH 2 ; and    R 5  is a pyridinyl, indolyl, azaindolyl, benzimidazolyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, fluoro, chloro, cyano or trifluoromethyl,  
   R 6  and R 7  are each independently hydrogen, methyl, ethyl, propyl, butyl, isobutyl, acetyl, formyl, methylsulfonyl or hydroxy,    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       5 . The compound of Formula (IA) according to  claim 1 , wherein: 
 R 1  is a pyridinyl, is a phenyl substituted with a fluoro, is a phenyl substituted with a methoxy group and a fluoro, is a phenyl substituted with a hydroxy group and a fluoro, is a benzofuranyl group, is a dihydrobenzofuranyl group or is a dihydrobenzofuranyl group substituted with a cyano group,    R 2  and R 3  are each independently methyl;    R 4  is CH 2 ; and    R 5  is a quinolinyl, azaindolyl, pyridinyl, benzimidazolyl or indolyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, fluoro, chloro, trifluoromethyl or cyano,  
   R 6  and R 7  are each independently hydrogen, methyl, ethyl, propyl, butyl, isobutyl, acetyl, formyl, methylsulfonyl or hydroxy,    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       6 . The compound of Formula (IA) according to  claim 11 , wherein: 
 R 1  is an aryl or heteroaryl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 1  is independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, aryl, C 1 -C 5  alkoxy, C 2 -C 5  alkenyloxy, C 2 -C 5  alkynyloxy, aryloxy, acyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, di-C 1 -C 5 alkyl-aminocarbonyl, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, di-C 1 -C 5 alkylaminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, C 1 -C 5  alkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, nitro, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl or aryl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
 wherein each substituent group of R 1  is independently optionally substituted with one to three substituent groups selected from C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halogen, hydroxy, oxo, cyano or amino;  
   R 2  and R 3  are each independently hydrogen or C 1 -C 5  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a C 3 -C 8  spiro cycloalkyl ring;    R 4  is C 1 -C 5  alkyl, C 2 -C 5  alkenyl, or C 2 -C 5  alkynyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 4  is independently C 1 -C 3  alkyl, hydroxy, halogen, or oxo;  
   R 5  is a heteroaryl group optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1 -C 5  alkoxy, C 2 -C 5  alkenyloxy, C 2 -C 5  alkynyloxy, aryloxy, acyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, di-C 1 -C 5 alkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, di-C 1 -C 5 alkylaminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, C 1 -C 5  alkylaminosulfonyl, di-C 1 -C 5  alkyl-aminosulfonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, nitro, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, 
 wherein each substituent group of R 5  is optionally independently substituted with one to three substituent groups selected from C 1 -C 3  alkyl, C 1 -C 3  alkoxy, halogen, hydroxy, oxo, cyano, amino, or trifluoromethyl; and  
 
   R 6  and R 7  are hydrogen;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       7 . The compound of Formula (IA) according to  claim 1 , wherein: 
 R 1  is phenyl, naphthyl, indanyl, indenyl, dihydrobenzofuranyl, dihydroindolyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, thienyl, furanyl, pyrrolyl, pyridinyl, pyrazinyl, pyrimidinyl, indolyl, benzofuranyl or benzothienyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 1  is independently C 1 -C 3  alkyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, C 1 -C 3  alkoxy, C 2 -C 3  alkenyloxy, C 1 -C 3  alkanoyl, C 1 -C 3  alkoxycarbonyl, C 1 -C 3  alkanoyloxy, halogen, hydroxy, carboxy, cyano, trifluoromethyl, nitro, or C 1 -C 3  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
 wherein each substituent group of R 1  is independently optionally substituted with a substituent group selected from methyl, methoxy, halogen, hydroxy, oxo, cyano, or amino;  
   R 2  and R 3  are each independently hydrogen or C 1 -C 3  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a C 3 -C 6  spiro cycloalkyl ring;    R 4  is C 1 -C 3  alkyl or C 2 -C 3  alkenyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 4  is independently methyl, hydroxy, fluoro, chloro, bromo, or oxo;  
   R 5  is a pyridyl, indolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently C 1 -C 3  alkyl, C 2 -C 3  alkenyl, phenyl, C 1 -C 3  alkoxy, fluoro, chloro, bromo, cyano, trifluoromethyl, or C 1 -C 3  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, 
 wherein each substituent group of R 5  is optionally independently substituted with a substituent group selected from methyl, methoxy, fluoro, chloro, bromo, or trifluoromethyl, and  
 
   R 6  and R 7  are hydrogen;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       8 . The compound of Formula (IA) according to  claim 1 , wherein: 
 R 1  is phenyl, pyridinyl, dihydrobenzofuranyl, or benzofuranyl, each optionally independently substituted with one or two substituent groups, 
 wherein each substituent group of R 1  is independently methyl, ethyl, methoxy, ethoxy, fluoro, chloro, bromo, hydroxy, or cyano;  
   R 2  and R 3  are each independently C 1 -C 3  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a spiro cyclopropyl or cyclobutyl ring;    R 4  is C 1 -C 3  alkyl;    R 5  is a pyridyl, indolyl, benzofuranyl, benzoxazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, phenyl, fluoro, chloro, cyano, or trifluoromethyl; and  
   R 6  and R 7  are hydrogen;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       9 . The compound of Formula (IA) according to  claim 1 , wherein: 
 R 1  is phenyl substituted with one or two substituent groups, 
 wherein each substituent group of R 1  is independently methoxy, fluoro, chloro, bromo or hydroxy;  
   R 2  and R 3  are each independently C 1 -C 3  alkyl;    R 4  is CH 2 ;    R 5  is a pyridyl, indolyl, benzimidazolyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, fluoro, chloro, or trifluoromethyl, and  
   R 6  and R 7  are hydrogen;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       10 . The compound of Formula (IA) according to  claim 1 , wherein: 
 R 1  is phenyl substituted with a methoxy group and a fluoro, or is a phenyl substituted with a hydroxy group and a fluoro,    R 2  and R 3  are each independently methyl;    R 4  is CH 2 ;    R 5  is a pyridyl or indolyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, fluoro or chloro; and  
   R 6  and R 7  are hydrogen;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       11 . A compound according to  claim 1  selected from: 
 3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-pyridin-2-ylmethyl-1-trifluoromethyl-butylamine;    3-(5-Fluoro-2-methoxy-phenyl)-1-(1H-indol-2-ylmethyl)-3-methyl-1-trifluoromethyl-butylamine;    1-(2,6-Dichloro-pyridin-4-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    1-(4,6-Dimethyl-pyridin-2-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    1-(2-Chloro-pyridin-4-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(5-Fluoro-2-methyl-phenyl)-3-methyl-1-(3-methyl-1H-indol-2-ylmethyl)-1-trifluoromethyl-butylamine;    3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-(3-methyl-1H-indol-2-ylmethyl)-1-trifluoromethyl-butylamine;    1-(6-Fluoro-1H-indol-2-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(4-Fluoro-phenyl)-3-methyl-1-(3-methyl-1H-indol-2-ylmethyl)-1-trifluoromethyl-butylamine;    3-Benzofuran-7-yl-1-(2,6-dichloro-pyridin-4-ylmethyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(2,3-Dihydro-benzofuran-7-yl)-1-(6-fluoro-1H-indol-2-ylmethyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butylamine;    1-(2-Chloro-quinolin-4-ylmethyl)-3-(5-fluoro-2-methyl-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(4-Fluoro-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butylamine;    7-[3-Amino-3-(1H-benzoimidazol-2-ylmethyl)-4,4,4-trifluoro-1,1-dimethyl-butyl]-2,3-dihydro-benzofuran-5-carbonitrile;    1-(6-Fluoro-1H-benzoimidazol-2-ylmethyl)-3-(5-fluoro-2-methyl-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    2-[3-Amino-3-(1H-benzoimidazol-2-ylmethyl)-4,4,4-trifluoro-1,1-dimethyl-butyl]4-fluoro-phenol;    1-(1H-Benzoimidazol-2-ylmethyl)-3-(4-fluoro-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    1-(1H-Indol-2-ylmethyl)-3-methyl-3-pyridin-3-yl-1-trifluoromethyl-butylamine;    1-(1H-Benzoimidazol-2-ylmethyl)-3-methyl-3-pyridin-4-yl-1-trifluoromethyl-butylamine;    3-Methyl-1-(3-methyl-1H-indol-2-ylmethyl)-3-pyridin-3-yl-1-trifluoromethyl-butylamine;    1-(6-Fluoro-1H-indol-2-ylmethyl)-3-methyl-3-pyridin-3-yl-1-trifluoromethyl-butylamine;    3-(2,3-Dihydro-benzofuran-7-yl)-1-(1H-indol-2-ylmethyl)-3-methyl-1-trifluoromethyl-butylamine;    [3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butyl]-methyl-amine;    Ethyl-[3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butyl]-amine;    [3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butyl]-propyl-amine;    [3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butyl]-isobutyl-amine;    Butyl-[3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butyl]-amine;    [3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butyl]-dimethyl-amine;    N-[3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butyl]-acetamide;    N-[3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butyl]-formamide;    N-[3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butyl]-methanesulfonamide;    1-(2,6-Dimethyl-pyridin-4-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)-1-trifluoromethyl-butylamine;    2-[2-Amino-4-(5-fluoro-2-methoxy-phenyl)-4-methyl-2-trifluoromethyl-pentyl]-4-methyl-1H-indole-6-carbonitrile;    N-[3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butyl]-hydroxylamine; and    2-(3-Amino-4,4,4-trifluoro-1,1-dimethyl-3-quinolin-4-ylmethyl-butyl)-4-fluoro-phenol;    or the tautomers, prodrugs, solvates, or salts thereof.    
   
   
       12 . A compound according to  claim 1 , selected from: 
 3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-pyridin-2-ylmethyl-1-trifluoromethyl-butylamine;    3-(5-Fluoro-2-methoxy-phenyl)-1-(1H-indol-2-ylmethyl)-3-methyl-1-trifluoromethyl-butylamine;    1-(2,6-Dichloro-pyridin-4-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    1-(4,6-Dimethyl-pyridin-2-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    1-(2-Chloro-pyridin-4-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(5-Fluoro-2-methyl-phenyl)-3-methyl-1-(3-methyl-1H-indol-2-ylmethyl)-1-trifluoromethyl-butylamine;    3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-(3-methyl-1H-indol-2-ylmethyl)-1-trifluoromethyl-butylamine;    1-(6-Fluoro-1H-indol-2-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(4-Fluoro-phenyl)-3-methyl-1-(3-methyl-1H-indol-2-ylmethyl)-1-trifluoromethyl-butylamine;    3-Benzofuran-7-yl-1-(2,6-dichloro-pyridin-4-ylmethyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(2,3-Dihydro-benzofuran-7-yl)-1-(6-fluoro-1H-indol-2-ylmethyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butylamine;    1-(2-Chloro-quinolin-4-ylmethyl)-3-(5-fluoro-2-methyl-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    3-(4-Fluoro-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butylamine;    7-[3-Amino-3-(1H-benzoimidazol-2-ylmethyl)-4,4,4-trifluoro-1,1-dimethyl-butyl]-2,3-dihydro-benzofuran-5-carbonitrile;    1-(6-Fluoro-1H-benzoimidazol-2-ylmethyl)-3-(5-fluoro-2-methyl-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    2-[3-Amino-3-(1H-benzoimidazol-2-ylmethyl)-4,4,4-trifluoro-1,1-dimethyl-butyl]-4-fluoro-phenol;    1-(1H-Benzoimidazol-2-ylmethyl)-3-(4-fluoro-phenyl)-3-methyl-1-trifluoromethyl-butylamine;    1-(1H-Indol-2-ylmethyl)-3-methyl-3-pyridin-3-yl-1-trifluoromethyl-butylamine;    1-(1H-Benzoimidazol-2-ylmethyl)-3-methyl-3-pyridin-4-yl-1-trifluoromethyl-butylamine;    3-Methyl-1-(3-methyl-1H-indol-2-ylmethyl)-3-pyridin-3-yl-1-trifluoromethyl-butylamine;    1-(6-Fluoro-1H-indol-2-ylmethyl)-3-methyl-3-pyridin-3-yl-1-trifluoromethyl-butylamine;    3-(2,3-Dihydro-benzofuran-7-yl)-1-(1H-indol-2-ylmethyl)-3-methyl-1-trifluoromethyl-butylamine;    or the tautomers, prodrugs, solvates, or salts thereof.    
   
   
       13 . A pharmaceutical composition comprising an effective amount of a compound according to  claim 1 , or a tautomer, prodrug, solvate, or salt thereof, and a pharmaceutically acceptable excipient or carrier.  
   
   
       14 . A method of modulating the glucocorticoid receptor function in a patient, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to  claim 1 , or a tautomer, prodrug, solvate, or salt thereof.  
   
   
       15 . A method of treating a disease-state or condition mediated by the glucocorticoid receptor function in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to  claim 1 , or a tautomer, prodrug, solvate, or salt thereof.  
   
   
       16 . A method of treating a disease-state or condition selected from: type II diabetes, obesity, cardiovascular diseases, hypertension, arteriosclerosis, neurological diseases, adrenal and pituitary tumors, and glaucoma, in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to  claim 1 , or a tautomer, prodrug, solvate, or salt thereof.  
   
   
       17 . A method of treating a disease characterized by inflammatory, allergic, or proliferative processes, in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to  claim 1 , or a tautomer, prodrug, solvate, or salt thereof.  
   
   
       18 . The method according to  claim 17 , wherein the disease is selected from: (i) lung diseases; (ii) rheumatic diseases or autoimmune diseases or joint diseases; (iii) allergic diseases; (iv) vasculitis diseases; (v) dermatological diseases; (vi) renal diseases; (vii) hepatic diseases; (viii) gastrointestinal diseases; (ix) proctological diseases; (x) eye diseases; (xi) diseases of the ear, nose, and throat (ENT) area; (xii) neurological diseases; (xiii) blood diseases; (xiv) tumor diseases; (xv) endocrine diseases; (xvi) organ and tissue transplantations and graft-versus-host diseases; (xvii) severe states of shock; (xviii) substitution therapy; and (xix) pain of inflammatory genesis.  
   
   
       19 . The method according to  claim 17 , wherein the disease is selected from: type I diabetes, osteoarthritis, Guillain-Barre syndrome, restenosis following percutaneous transluminal coronary angioplasty, Alzheimer disease, acute and chronic pain, atherosclerosis, reperfusion injury, bone resorption diseases, congestive heart failure, myocardial infarction, thermal injury, multiple organ injury secondary to trauma, acute purulent meningitis, necrotizing enterocolitis, and syndromes associated with hemodialysis, leukopheresis, and granulocyte transfusion.  
   
   
       20 . A method of treating a disease-state or condition mediated by the glucocorticoid receptor function in a patient in need of such treatment, the method comprising sequentially or simultaneously administering to the patient: (a) an effective amount of a pharmaceutically acceptable compound according to  claim 1 , or a tautomer, prodrug, solvate, or salt thereof; and (b) a pharmaceutically acceptable glucocorticoid.  
   
   
       21 . A kit for the in vitro diagnostic determination of the glucocorticoid receptor function in a sample, comprising: 
 (a) a diagnostically effective amount of a compound according to  claim 1  or a tautomer, prodrug, solvate, or salt thereof; and    (b) instructions for use of the diagnostic kit.    
   
   
       22 . A method of making a compound of Formula (IA) according to  claim 1  wherein R 6  and R 7  are both hydrogen:  
     
       
         
         
             
             
         
       
     
     where R 1 , R 2 , R 3 , R 4 , and R 5  are as defined in  claim 1 , the method comprising: 
 reacting a compound of Formula (V) with an organometallic reagent R 5 R 4 M where M is Li or MgX and X is Cl, Br, or I, in a suitable solvent to form the compound of Formula (IA):  
                     
 where R is alkyl and R 1 , R 2 , R 3 , R 4 , and R 5  are as defined in  claim 1 .  
 
   
   
       23 . A method of making a compound of Formula (IA) according to  claim 1  wherein R 6  and R 7  are both hydrogen:  
     
       
         
         
             
             
         
       
     
     where R 1 , R 2 , R 3 , R 4 , and R 5  are as defined in  claim 1 , the method comprising: 
 (a) reacting an ester of Formula (II) with a suitable reducing agent in a suitable solvent to form a diol of Formula (III)  
                     
 (b) reacting the diol of Formula (III) under suitable oxidative cleavage conditions to form a ketone of Formula (IV)  
                     
 (c) reacting the ketone of Formula (IV) with a suitable Lewis acid and an alkylsulfinamide of formula RS(O)NH 2  where R is alkyl to form the compound of Formula (V)  
                     
 (d) reacting a compound of Formula (V) with an organometallic reagent R 5 R 4 M where M is Li or MgX and X is Cl, Br, or I, in a suitable solvent to form the compound of Formula (IA):  
                     
 (a′) reacting the trifluoroacetamide of Formula (XII) with a vinyl magnesium bromide bearing R 2  and R 3  of the formula R 2 R 3 CH═CHMgBr in a suitable solvent to provide the trifluoromethylenone of Formula (XIII)  
                     
 (b′) reacting the trifluoromethylenone of Formula (XIII) with a suitable organocopper reagent generated from an organometallic reagent R 1 M where M is Li or MgX and a copper salt CuX, where X is Cl, Br or I, in a suitable solvent to form the ketone of Formula (IV)  
                     
 and performing steps (c) and (d) as set forth above to form the compound of Formula (IA);  
 where R is alkyl and R 1 , R 2 , R 3 , R 4 , and R 5  are as defined in  claim 1 .  
 
   
   
       24 . A compound of Formula (IB):  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is an aryl or heteroaryl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 1  is independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1 -C 5  alkoxy, C 2 -C 5  alkenyloxy, C 2 -C 5  alkynyloxy, aryloxy, acyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, C 1 -C 5  dialkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, C 1 -C 5  dialkylaminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, aminosulfonyl, C 1 -C 5  alkylaminosulfonyl, C 1 -C 5  dialkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, nitro, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl or aryl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
 wherein each substituent group of R 1  is independently optionally substituted with one to three substituent groups selected from C 1 -C 3  alkyl, C 1 -C 3  alkoxy, halogen, hydroxy, oxo, cyano or amino.  
 
 R 2  and R 3  are each independently hydrogen or C 1 -C 5  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a C 3 -C 8  spiro cycloalkyl ring;  
 R 4  is C 1 -C 5  alkyl, C 2 -C 5  alkenyl, or C 2 -C 5  alkynyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 4  is independently C 1 -C 3  alkyl, hydroxy, halogen, amino, or oxo;  
 
 R 5  is a heteroaryl group optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1 -C 5  alkoxy, C 2 -C 5  alkenyloxy, C 2 -C 5  alkynyloxy, aryloxy, acyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, C 1 -C 5  dialkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, C 1 -C 5  dialkylaminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, aminosulfonyl, C 1 -C 5  alkylaminosulfonyl, C 1 -C 5  dialkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, nitro, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, 
 wherein each substituent group of R 5  is optionally independently substituted with one to three substituent groups selected from C 1 -C 3  alkyl, C 1 -C 3  alkoxy, halogen, hydroxy, oxo, cyano, amino, or trifluoromethyl;  
 
 
 R 6  and R 7  are each independently hydrogen, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 1-8  alkoxy, C 2-8  alkenyloxy, C 2-8  alkynyloxy, hydroxy, carbocyclyl, heterocyclyl, aryl, aryloxy, acyl, heteroaryl, carbocycle-C 1 -C 8  alkyl, aryl-C 1 -C 8  alkyl, aryl-C 1 -C 8  haloalkyl, heterocyclyl-C 1 -C 8  alkyl, heteroaryl-C 1 -C 8  alkyl, carbocycle-C 2 -C 8  alkenyl, aryl-C 2 -C 8  alkenyl, heterocyclyl-C 2 -C 8  alkenyl, heteroaryl-C 2 -C 8  alkenyl, or C 1 -C 5  alkylthio wherein the sulfur atom is oxidized to a sulfoxide or sulfone, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 6  and R 7  are independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, phenyl, C 1 -C 5  alkoxy, phenoxy, C 1 -C 5  alkanoyl, aroyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, C 1 -C 5  dialkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, C 1 -C 5  dialkylaminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, aminosulfonyl, C 1 -C 5  alkylaminosulfonyl, C 1 -C 5  dialkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, oxo, trifluoromethyl, trifluoromethoxy, nitro; or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
 
 R 8  is C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, carbocycle, heterocyclyl, aryl, heteroaryl, carbocycle-C 1 -C 8  alkyl, aryl-C 1 -C 8  alkyl, aryl-C 1 -C 8  haloalkyl, heterocyclyl-C 1 -C 8  alkyl, heteroaryl-C 1 -C 8  alkyl, carbocycle-C 2 -C 8  alkenyl, aryl-C 2 -C 8  alkenyl, heterocyclyl-C 2 -C 8  alkenyl, or heteroaryl-C 2 -C 8  alkenyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 8  is independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, phenyl, C 1 -C 5  alkoxy, phenoxy, C 1 -C 5  alkanoyl, aroyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, C 1 -C 5  dialkylaminocarbonyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, C 1 -C 5  dialkylaminocarbonyl, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, aminosulfonyl, C 1 -C 5  alkylaminosulfonyl, C 1 -C 5  dialkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, oxo, trifluoromethyl, nitro; or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
 
 wherein R 8  cannot be trifluoromethyl;  
 or a tautomer, prodrug, solvate, or salt thereof.  
 
   
   
       25 . A compound of Formula (IB) according to  claim 24 , wherein: 
 R 1  is phenyl, naphthyl, indanyl, indenyl, dihydrobenzofuranyl, benzofuranyl, chromanyl, dihydroindolyl, indolyl, dihydrobenzothienyl, benzothienyl, benzodioxolanyl, dihydrobenzoxazolyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzimidazolyl, dihydroquinolinyl, quinolinyl, dihydroisoquinolinyl, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, furanyl, thienyl, pyrrolyl, pyridinyl, pyrazinyl, or pyrimidinyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 1  is independently C 1 -C 3  alkyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, C 1 -C 3  alkoxy, C 2 -C 3  alkenyloxy, C 1 -C 3  alkanoyl, C 1 -C 3  alkoxycarbonyl, C 1 -C 3  alkanoyloxy, halogen, hydroxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, nitro, or C 1 -C 3  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
 wherein each substituent group of R 1  is optionally independently substituted with a substituent group selected from methyl, methoxy, halogen, hydroxy, oxo, cyano, or amino;  
   R 2  and R 3  are each independently hydrogen or C 1 -C 3  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a C 3 -C 6  spiro cycloalkyl ring;    R 4  is C 1 -C 3  alkyl or C 2 -C 3  alkenyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 4  is independently methyl, hydroxy, fluoro, chloro, bromo, or oxo;  
   R 5  is an imidazolyl, pyridinyl, indolyl, azaindolyl, diazaindolyl, benzofuranyl, furanopyridinyl, furanopyrimidinyl, benzothienyl, thienopyridinyl, thienopyrimidinyl, benzoxazolyl, oxazolopyridinyl, benzothiazolyl, thiazolopyridinyl, benzimidazolyl, imidazolopyridinyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently C 1 -C 3  alkyl, C 2 -C 3  alkenyl, phenyl, C 1 -C 3  alkoxy, methoxycarbonyl, aminocarbonyl, C 1 -C 3  alkylaminocarbonyl, C 1 -C 3  dialkylaminocarbonyl, heterocyclylcarbonyl, hydroxy, fluoro, chloro, bromo, cyano, trifluoromethyl, or C 1 -C 3  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, 
 wherein each substituent group of R 5  is optionally independently substituted with a substituent group selected from methyl, methoxy, hydroxy, fluoro, chloro, bromo, oxo or trifluoromethyl,  
 
   R 6  and R 7  are each independently hydrogen, C 1-5  alkyl, C 1-5  alkoxy, C 2-5  alkenyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, benzyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, phenethyl, phenoxy, hydroxy or C 1 -C 5  alkylthio wherein the sulfur atom is oxidized to a sulfoxide or sulfone, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 6  and R 7  are independently methyl, methoxy, halogen, hydroxy, cyano, oxo or trifluoromethyl;  
   R 8  is C 1-5  alkyl, C 2-5  alkenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, benzyl, cyclopentylethyl, cyclohexylethyl, phenethyl, or phenyl-difluoromethyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 8  is independently methyl, methoxy, hydroxy, halogen, cyano, or trifluoromethyl;  
   wherein R 8  cannot be trifluoromethyl;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       26 . A compound of Formula (IB) according to  claim 24 , wherein: 
 R 1  is phenyl, thienyl, naphthyl, chromanyl, pyridinyl, dihydrobenzofuranyl, or benzofuranyl, each optionally independently substituted with one or two substituent groups, 
 wherein each substituent group of R 1  is independently methyl, ethyl, methoxy, ethoxy, trifluoromethyl, trifluoromethoxy, fluoro, chloro, bromo, hydroxy, oxo or cyano;  
   R 2  and R 3  are each independently C 1 -C 3  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a spiro cyclopropyl or cyclobutyl ring;    R 4  is C 1 -C 3  alkyl;    R 5  is a pyridinyl, indolyl, azaindolyl, benzofuranyl, furanopyridinyl, benzothienyl, thienopyridinyl, benzoxazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, phenyl, methoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, morpholinylcarbonyl, methoxy, hydroxy, fluoro, chloro, bromo, cyano, or trifluoromethyl,  
   R 6  and R 7  are each independently hydrogen, C 1-5  alkyl, benzyl, hydroxy or C 1 -C 5  alkylthio wherein the sulfur atom is oxidized to a sulfoxide or sulfone, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 6  and R 7  are independently methyl, or oxo; and  
   R 8  is C 1-5  alkyl, cyclopropyl, cyclopentylmethyl, cyclohexylmethyl or benzyl,    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       27 . A compound of Formula (IB) according to  claim 24 , wherein: 
 R 1  is phenyl, dihydrobenzofuranyl, benzofuranyl or pyridinyl substituted with one or two substituent groups, 
 wherein each substituent group of R 1  is independently methyl, methoxy, fluoro, chloro, bromo, trifuoromethyl, trifluoromethoxy, cyano or hydroxy;  
   R 2  and R 3  are each independently C 1 -C 3  alkyl;    R 4  is CH 2 ;    R 5  is a pyridinyl, indolyl, azaindolyl, benzimidazolyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, fluoro, chloro, cyano or trifluoromethyl,  
   R 6  and R 7  are each independently hydrogen, methyl, ethyl, propyl, butyl, isobutyl, acetyl, formyl, methylsulfonyl or hydroxy, and    R 8  is methyl, ethyl, n-propyl, i-propyl, cyclopropyl, cyclopentylmethyl or cyclohexylmethyl;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       28 . A compound of Formula (IB) according to  claim 24 , wherein: 
 R 1  is phenyl substituted with a methoxy group and a fluoro, or is a phenyl substituted with a hydroxy group and a fluoro;    R 2  and R 3  are each independently methyl;    R 4  is CH 2 ;    R 5  is a quinolinyl, azaindolyl, pyridinyl or indolyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, fluoro, chloro, trifluoromethyl or cyano;  
   R 6  and R 7  are each independently hydrogen, methyl or isobutyl; and    R 8  is methyl, cyclopropyl, or cyclohexylmethyl;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       29 . A compound of Formula (IB) according to  claim 24 , wherein: 
 R 1  is an aryl or heteroaryl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 1  is independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, aryl, C 1 -C 5  alkoxy, C 2 -C 5  alkenyloxy, C 2 -C 5  alkynyloxy, aryloxy, acyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, di-C 1 -C 5 alkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, di-C 1 -C 5 alkylaminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, C 1 -C 5  alkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, nitro, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl or aryl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
 wherein each substituent group of R 1  is independently optionally substituted with one to three substituent groups selected from C 1 -C 3 alkyl, C 1 -C 3 alkoxy, halogen, hydroxy, oxo, cyano or amino.  
   R 2  and R 3  are each independently hydrogen or C 1 -C 5  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a C 3 -C 8  spiro cycloalkyl ring;    R 4  is C 1 -C 5  alkyl, C 2 -C 5  alkenyl, or C 2 -C 5  alkynyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 4  is independently C 1 -C 3  alkyl, hydroxy, halogen, or oxo;  
   R 5  is a heteroaryl group optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1 -C 5  alkoxy, C 2 -C 5  alkenyloxy, C 2 -C 5  alkynyloxy, aryloxy, acyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5  alkanoyloxy, aminocarbonyl, C 1 -C 5  alkylaminocarbonyl, di-C 1 -C 5 alkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5  alkylaminocarbonyloxy, di-C 1 -C 5  alkyl-aminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, C 1 -C 5  alkylaminosulfonyl, di-C 1 -C 5  alkyl-aminosulfonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, nitro, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, 
 wherein each substituent group of R 5  is optionally independently substituted with one to three substituent groups selected from C 1 -C 3  alkyl, C 1 -C 3  alkoxy, halogen, hydroxy, oxo, cyano, amino, or trifluoromethyl;  
 
   R 6  and R 7  are each hydrogen; and    R 8  is C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, carbocycle, heterocyclyl, aryl, heteroaryl, carbocycle-C 1 -C 8  alkyl, aryl-C 1 -C 8  alkyl, aryl-C 1 -C 8  haloalkyl, heterocyclyl-C 1 -C 8  alkyl, heteroaryl-C 1 -C 8  alkyl, carbocycle-C 2 -C 8  alkenyl, aryl-C 2 -C 8  alkenyl, heterocyclyl-C 2 -C 8  alkenyl, or heteroaryl-C 2 -C 8  alkenyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 8  is independently C 1 -C 5  alkyl, C 2 -C 5  alkenyl, C 2 -C 5  alkynyl, C 3 -C 8  cycloalkyl, phenyl, C 1 -C 5  alkoxy, phenoxy, C 1 -C 5  alkanoyl, aroyl, C 1 -C 5  alkoxycarbonyl, C 1 -C 5 alkanoyloxy, aminocarbonyl, C 1 -C 5 alkylaminocarbonyl, di-C 1 -C 5 alkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5 alkylaminocarbonyloxy, di-C 1 -C 5 alkylaminocarbonyloxy, C 1 -C 5  alkanoylamino, C 1 -C 5  alkoxycarbonylamino, C 1 -C 5  alkylsulfonylamino, C 1 -C 5  alkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, or nitro; or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C 1 -C 5  alkyl; or ureido wherein either nitrogen atom is optionally independently substituted with C 1 -C 5  alkyl; or C 1 -C 5  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
   wherein R 8  cannot be trifluoromethyl;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       30 . A compound of Formula (IB) according to  claim 24 , wherein: 
 R 1  is phenyl, naphthyl, indanyl, indenyl, dihydrobenzofuranyl, dihydroindolyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, thienyl, furanyl, pyrrolyl, pyridinyl, pyrazinyl, pyrimidinyl, indolyl, benzofuranyl or benzothienyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 1  is independently C 1 -C 3  alkyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, C 1 -C 3  alkoxy, C 2 -C 3  alkenyloxy, C 2 -C 3  alkynyloxy, C 1 -C 3  alkanoyl, C 1 -C 3  alkoxycarbonyl, C 1 -C 3  alkanoyloxy, halogen, hydroxy, carboxy, cyano, trifluoromethyl, nitro, or C 1 -C 3  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;  
   R 2  and R 3  are each independently hydrogen or C 1 -C 3  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a C 3 -C 6  spiro cycloalkyl ring;    R 4  is C 1 -C 3  alkyl or C 2 -C 3  alkenyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 4  is independently methyl, hydroxy, fluoro, chloro, bromo, or oxo;  
   R 5  is a pyridyl, indolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently C 1 -C 3  alkyl, C 2 -C 3  alkenyl, phenyl, C 1 -C 3  alkoxy, fluoro, chloro, bromo, cyano, trifluoromethyl, or C 1 -C 3  alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, 
 wherein each substituent group of R 5  is optionally independently substituted with a substituent group selected from methyl, methoxy, fluoro, chloro, bromo, or trifluoromethyl;  
 
   R 6  and R 7  are each hydrogen; and    R 8  is C 1-5  alkyl, C 2-5  alkenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, benzyl, cyclopentylethyl, cyclohexylethyl, phenethyl, or phenyl-difluoromethyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 8  is independently methyl, methoxy, hydroxy, halogen, cyano, or trifluoromethyl;  
   wherein R 8  cannot be trifluoromethyl;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       31 . A compound of Formula (IB) according to  claim 24 , wherein: 
 R 1  is phenyl, pyridinyl, dihydrobenzofuranyl, or benzofuranyl, each optionally independently substituted with one or two substituent groups, 
 wherein each substituent group of R 1  is independently methyl, ethyl, methoxy, ethoxy, fluoro, chloro, bromo, hydroxy, or cyano;  
   R 2  and R 3  are each independently C 1 -C 3  alkyl, or R 2  and R 3  together with the carbon atom they are commonly attached to form a spiro cyclopropyl or cyclobutyl ring;    R 4  is C 1 -C 3  alkyl;    R 5  is a pyridyl, indolyl, benzofuranyl, benzoxazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, phenyl, fluoro, chloro, cyano, or trifluoromethyl;  
   R 6  and R 7  are each hydrogen; and    R 8  is C 1-5  alkyl, cyclopropyl, cyclopentylmethyl, cyclohexylmethyl or benzyl,    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       32 . A compound of Formula (IB) according to  claim 24 , wherein: 
 R 1  is phenyl substituted with one or two substituent groups, 
 wherein each substituent group of R 1  is independently methoxy, fluoro, chloro, bromo or hydroxy;  
   R 2  and R 3  are each independently C 1 -C 3  alkyl;    R 4  is CH 2 ;    R 5  is a pyridyl, indolyl, benzimidazolyl, quinolinyl, or isoquinolinyl group, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, fluoro, chloro, or trifluoromethyl;  
   R 6  and R 7  are each hydrogen; and    R 8  is methyl, ethyl, n-propyl, i-propyl, cyclopentylmethyl or cyclohexylmethyl;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       33 . A compound of Formula (IB) according to  claim 24 , wherein: 
 R 1  is phenyl substituted with a methoxy group and a fluoro, or is a phenyl substituted with a hydroxy group and a fluoro;    R 2  and R 3  are each independently methyl;    R 4  is CH 2 ;    R 5  is a pyridyl or indolyl, each optionally independently substituted with one to three substituent groups, 
 wherein each substituent group of R 5  is independently methyl, fluoro or chloro;  
   R 6  and R 7  are each hydrogen; and    R 8  is methyl or cyclohexylmethyl;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       34 . A compound according to  claim 24  selected from: 
 1-(2,6-Dichloro-pyridin-4-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-1,3-dimethyl-butylamine;    1-Ethyl-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-butylamine;    1-Cyclohexylmethyl-3-(5-fluoro-2-methoxy-phenyl)-1-(1H-indol-2-ylmethyl)-3-methyl-butylamine;    1-(2-Chloro-quinolin-4-ylmethyl)-1-cyclopentyl-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-butylamine;    1-(2-Chloro-pyridin-4-ylmethyl)-1-cyclopentylmethyl-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-butylamine;    3-(5-Fluoro-2-methoxy-phenyl)-1,3-dimethyl-1-quinolin-4-ylmethyl-butylamine;    1-Cyclopropyl-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-butylamine;    3-(5-Fluoro-2-methoxy-phenyl)-1,3-dimethyl-1-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)-butylamine;    1-Cyclopropyl-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)-butylamine;    2-[3-Amino-1,1,3-trimethyl-4-(1H-pyrrolo[2,3-c]pyridin-2-yl)-butyl]-4-fluoro-phenol;    2-[2-Amino-4-(5-fluoro-2-methoxy-phenyl)-2,4-dimethyl-pentyl]-4-methyl-1H-indole-6-carbonitrile;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       35 . A compound according to  claim 24  selected from: 
 1-(2,6-Dichloro-pyridin-4-ylmethyl)-3-(5-fluoro-2-methoxy-phenyl)-1,3-dimethyl-butylamine;    1-Ethyl-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-butylamine;    1-Cyclohexylmethyl-3-(5-fluoro-2-methoxy-phenyl)-1-(1H-indol-2-ylmethyl)-3-methyl-butylamine;    1-(2-Chloro-quinolin-4-ylmethyl)-1-cyclopentyl-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-butylamine;    1-(2-Chloro-pyridin-4-ylmethyl)-1-cyclopentylmethyl-3-(5-fluoro-2-methoxy-phenyl)-3-methyl-butylamine;    or a tautomer, prodrug, solvate, or salt thereof.    
   
   
       36 . A pharmaceutical composition comprising an effective amount of a compound according to  claim 24 , or a tautomer, prodrug, solvate, or salt thereof, and a pharmaceutically acceptable excipient or carrier.  
   
   
       37 . A method of modulating the glucocorticoid receptor function in a patient, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to  claim 24 , or a tautomer, prodrug, solvate, or salt thereof.  
   
   
       38 . A method of treating a disease-state or condition mediated by the glucocorticoid receptor function in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to  claim 24 , or a tautomer, prodrug, solvate, or salt thereof.  
   
   
       39 . A method of treating a disease-state or condition selected from: type II diabetes, obesity, cardiovascular diseases, hypertension, arteriosclerosis, neurological diseases, adrenal and pituitary tumors, and glaucoma, in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to  claim 24 , or a tautomer, prodrug, solvate, or salt thereof.  
   
   
       40 . A method of treating a disease characterized by inflammatory, allergic, or proliferative processes, in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to  claim 24 , or a tautomer, prodrug, solvate, or salt thereof.  
   
   
       41 . The method according to  claim 40 , wherein the disease is selected from: (i) lung diseases; (ii) rheumatic diseases or autoimmune diseases or joint diseases; (iii) allergic diseases; (iv) vasculitis diseases; (v) dermatological diseases; (vi) renal diseases; (vii) hepatic diseases; (viii) gastrointestinal diseases; (ix) proctological diseases; (x) eye diseases; (xi) diseases of the ear, nose, and throat (ENT) area; (xii) neurological diseases; (xiii) blood diseases; (xiv) tumor diseases; (xv) endocrine diseases; (xvi) organ and tissue transplantations and graft-versus-host diseases; (xvii) severe states of shock; (xviii) substitution therapy; and (xix) pain of inflammatory genesis.  
   
   
       42 . The method according to  claim 40 , wherein the disease is selected from: type I diabetes, osteoarthritis, Guillain-Barre syndrome, restenosis following percutaneous transluminal coronary angioplasty, Alzheimer disease, acute and chronic pain, atherosclerosis, reperfusion injury, bone resorption diseases, congestive heart failure, myocardial infarction, thermal injury, multiple organ injury secondary to trauma, acute purulent meningitis, necrotizing enterocolitis, and syndromes associated with hemodialysis, leukopheresis, and granulocyte transfusion.  
   
   
       43 . A method of treating a disease-state or condition mediated by the glucocorticoid receptor function in a patient in need of such treatment, the method comprising sequentially or simultaneously administering to the patient: (a) an effective amount of a pharmaceutically acceptable compound according to  claim 24 , or a tautomer, prodrug, solvate, or salt thereof; and (b) a pharmaceutically acceptable glucocorticoid.  
   
   
       44 . A kit for the in vitro diagnostic determination of the glucocorticoid receptor function in a sample, comprising: 
 (a) a diagnostically effective amount of a compound according to  claim 24  or a tautomer, prodrug, solvate, or salt thereof; and    (b) instructions for use of the diagnostic kit.    
   
   
       45 . A method of making a compound of Formula (IB) according to  claim 24  wherein R 6  and R 7  are both hydrogen:  
     
       
         
         
             
             
         
       
     
     where R 1  is an optionally substituted 2-alkoxyphenyl group and R 2 , R 3 , R 4 , R 5 , and R 8  are as defined in  claim 24 , the method comprising: reacting a compound of Formula (XIX) wherein each R is alkyl with a suitable organometallic reagent R 5 R 4 M where M is Li or MgX and X is Cl, Br, or I, in a suitable solvent to form the compound of Formula (IB)  
     
       
         
         
             
             
         
       
     
   
   
       46 . A method of making a compound of Formula (IB) according to  claim 24  wherein R 6  and R 7  are both hydrogen:  
     
       
         
         
             
             
         
       
     
     where R 1  is an optionally substituted 2-alkoxyphenyl group and R 2 , R 4 , R 5 , and R 8  are as defined in  claim 24 , the method comprising: 
 (a) reacting an optionally substituted phenol of Formula (XIV) with an acryloyl chloride of Formula (XV) in the presence of a suitable base, followed by cyclization of the intermediate ester by treatment with a suitable Lewis acid to form a lactone of Formula (XVI)  
                     
 (b) reacting the lactone of Formula (XVI) with a suitable amine HNR″R′″, followed by treatment of the intermediate phenol with an alkyl halide RX, where R is alkyl and X is halogen, in the presence of a suitable base to form an amide of Formula (XVII)  
                     
 (c) reacting the amide of Formula (XVII) with a suitable organometallic reagent R 8 M, where M is Li or MgX and X is Cl, Br, or I, in a suitable solvent to form a ketone of Formula (XVIII)  
                     
 (d) reacting the compound of Formula (XVIII) with an alkylsulfinamide RS(O)NH 2  wherein R is alkyl, and a suitable Lewis acid to produce the compound of Formula (XIX)  
                     
 (e) reacting a compound of Formula (XIX) wherein each R is alkyl with a suitable organometallic reagent R 5 R 4 M where M is Li or MgX and X is Cl, Br, or I, in a suitable solvent to form the compound of Formula (IB)  
                     
 
   
   
       47 . A method of making a compound of Formula (IB) according to  claim 24  wherein R 6  and R 7  are both hydrogen:  
     
       
         
         
             
             
         
       
     
     where R 1 , R 2 , R 3 , R 4 , R 5  and R 8  are as defined in  claim 24 , the method comprising: 
 reacting a compound of Formula (XXIV) with an organometallic reagent R 5 R 4 M where M is Li or MgX and X is Cl, Br, or I, in a suitable solvent to form the compound of Formula (IB):  
                     
 where R is alkyl and R 1 , R 2 , R 3 , R 4 , R 5  and R 8  are as defined in  claim 24 .  
 
   
   
       48 . A method of making a compound of Formula (IB) according to  claim 24  wherein R 6  and R 7  are both hydrogen:  
     
       
         
         
             
             
         
       
     
     where R 1 , R 2 , R 3 , R 4 , R 5  and R 8  are as defined in  claim 24 , the method comprising: 
 (a′) reacting an amide of Formula (XXI) with a vinyl magnesium bromide bearing R 2  and R 3  of the formula R 2 R 3 CH═CHMgBr in a suitable solvent to provide an enone of Formula (XXII)  
                     
 (b′) reacting the enone of Formula (XXII) with a suitable organocopper reagent generated from an organometallic reagent R 1 M, where M is Li or MgX, and a copper salt CuX, where X is Cl, Br or I, in a suitable solvent to form a ketone of Formula (XXIII)  
                     
 (c′) reacting the compound of Formula (XXIII) with a suitable Lewis acid and an alkylsulfinamide of formula RS(O)NH 2  where R is alkyl to form the compound of Formula (XXIV)  
                     
 (d′) reacting a compound of Formula (XXIV) with an organometallic reagent R 5 R 4 M where M is Li or MgX and X is Cl, Br, or I, in a suitable solvent to form the compound of Formula (IB):  
                     
 where R is alkyl and R 1 , R 2 , R 3 , R 4 , R 5  and R 8  are as defined in  claim 24.