Abca1 elevating compounds

Abstract

The present invention provides compounds useful for increasing cellular ATP binding cassette transporter ABCA1 production in mammals, and to methods of using such compounds in the treatment of coronary artery diseases, dyslipidiemias and metabolic syndrome. The invention also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.

1 . A compound having the structure of Formula I: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 1  and R 2  are independently optionally substituted lower alkyl, optionally substituted aryl, optionally substituted alkenyl, optionally substituted heteroaryl, or optionally substituted heterocyclyl; or 
 R 1  and R 2  when taken together with the carbon atom to which they are attached represent a 5 or 6 membered carbocyclic or heterocyclic ring; 
 R 3 , R 4  and R 5  are independently hydrogen, hydroxyl, optionally substituted lower alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted lower alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, cyano, halo, —SO 2 —NR 9 R 10 , or —C(O)R 11 , in which R 9  and R 10  are independently hydrogen, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, or may joint to form a 5 or 6 membered optionally substituted heterocyclic ring, and R 11  is —OH or optionally substituted lower alkoxy; 
 R 6  is hydrogen, optionally substituted lower alkyl, optionally substituted cycloalkyl, —C(O)R 12 , or —S(O) 2 R 13 , in which R 12  is optionally substituted lower alkyl, lower alkoxy or —NR 14 R 15 , in which R 13 , R 14 , and R 15  are independently hydrogen, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl, or R 14  and R 15  may join to form a 5 or 6 membered optionally substituted heterocyclic ring; 
 R 7  is hydrogen, hydroxyl, optionally substituted lower alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, or —NR 14 R 15 ; and 
 R 8  is hydrogen, cyano, optionally substituted lower alkyl, optionally substituted heterocyclyl, optionally substituted phenyl, —C(O)R 11 , —C(O)R 14 , —SR 13 , —OR 13 , —NR 9 S(S) 2 R 10 , —NR 14 C(O)NR 14 R 15 , —C(O)NR 14 R 15 , —CH 2 C(O)R 11 , —S(O) 2 R 13 , —B(OH) 2 , —C(CF 3 ) 2 OH, —CH 2 P(O)(R 11 ) 2 , halo, —NHC(O)R, —N[(CH 2 ) 2 ] 2 SO 2 , or —S(O) 2 NR 9 R 10 ; or 
 R 7  and R 8  may join together to form an optionally substituted 5 or 6 membered heterocyclic or heteroaryl ring; 
 R 20  is hydrogen, cyano, hydroxyl, halo, optionally substituted lower alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —NR 14 R 15 , —C(O)R 1 , —C(O)R 14 , —SR 14 , —OR 14 , —C(S)R 11 , C(S)R 14 , —NR 9 S(O) 2 R 10 , —NR 14 C(O)NR 14 R 14 , —C(O)NR 15 R 14 , —C(S)NR 15 R 14 R 15 , —CH 2 C(O)R 1 , —S(O) 2 R 13 , B(OH) 2 , —C(CF 3 ) 2 OH, —CH 2 P(O)(R 11 ) 2 , —NHC(O)CH 3 , —N[(CH 2 ) 2 ] 2 SO 2 , or —S(O) 2  NR 9 R 10 ; 
 A and D are independently 5 or 6 membered monocyclic heterocyclic, monocyclic heteroaryl, or monocyclic aryl rings; and 
 X is oxygen, sulfur, —S(O)—, —S(O) 2 — or —NR 16 —, in which R 16  is hydrogen, optionally substituted lower alkyl, optionally substituted aryl, —C(O)R 12 , or —S(O) 2 R 13 . 
 
   
   
       2 . The compound of  claim 1 , wherein A and D are both phenyl. 
   
   
       3 . The compound of  claim 2 , wherein X is oxygen. 
   
   
       4 . The compound of  claim 3 , wherein R 1  and R 2  are both independently optionally substituted lower alkyl. 
   
   
       5 . The compound of  claim 4 , wherein R 5 , R 7 , and R 8  are hydrogen. 
   
   
       6 . The compound of  claim 5 , wherein R 6  is hydrogen. 
   
   
       7 . The compound of  claim 6 , wherein R 4  is hydrogen. 
   
   
       8 . The compound of  claim 7 , wherein R 20  is hydrogen. 
   
   
       9 . The compound of  claim 8 , selected from the group consisting of: 
     4,7,7-trimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline; 
     (12aS)-4,7,7-trimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline; 
     (6aS,12aR)-4-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline; 
     (12aS,6aS)-4-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline; and 
     (12aS,6aR)-1-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline. 
   
   
       10 . The compound of  claim 7 , wherein R 20  is optionally substituted lower alkyl. 
   
   
       11 . The compound of  claim 10 , selected from the group consisting of: 
     2-(2-bromo-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     2-((6aS,12aR)-2-bromo-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     2-((12aS,6aS)-2-bromo-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     1,1,1,3,3,3-hexafluoro-2-(2-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))propan-2-ol 
     1,1,1,3,3,3-hexafluoro-2-(4-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))propan-2-ol 
     2-[7,7-dimethyl-2-(trifluoromethoxy)(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl)]-1,1,1,3,3,3-hexafluoropropan-2-ol 
     2-[(12aS,6aS)-7,7-dimethyl-2-(trifluoromethoxy)(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl)]-1,1,1,3,3,3-hexafluoropropan-2-ol 
     3-methylbut-2-enyl 7,7-dimethyl-9-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-3-carboxylate 
     3-methylbut-2-enyl 7,7-dimethyl-9-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-2-carboxylate 
     7,7-dimethyl-9-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-3-carboxylic acid 
     1,1,1,3,3,3-hexafluoro-2-(4,7,7-trimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))propan-2-ol 
     2-(4-ethoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     1,1,1,3,3,3-hexafluoro-2-(1-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))propan-2-ol 
     2-[7,7-dimethyl-4-(3-methylbut-2-enyloxy)(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl)]-1,1,1,3,3,3-hexafluoropropan-2-ol 
     2-(4-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl)acetic acid 
     1,1,1,3,3,3-hexafluoro-2-(4-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))propan-2-ol 
     2-((6aR)-4-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     4-ethoxy-7,7-dimethyl-9-(trifluoromethyl)-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline 
     1-(4-ethoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl)ethan-1-one 
     1-(1-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl)ethan-1-one 
     1-methoxy-7,7-dimethyl-9-(trifluoromethyl)-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline 
     (6aS,12aR)-4-methoxy-7,7-dimethyl-9-(methylethyl)-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline 
     (12aS,6aS)-4-methoxy-7,7-dimethyl-9-(methylethyl)-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline 
     1,1,1,3,3,3-hexafluoro-2-(4-fluoro-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))propan-2-ol 
     (12aS,6aR)-1-methoxy-7,7-dimethyl-9-(methylethyl)-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline 
     2-((6aS,12aR)-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     4-methoxy-7,7-dimethyl-9-(1,2,3,4-tetraazol-5-ylmethyl)-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline 
     diethyl (6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)methylphosphonate; 
   
   
       12 . The compound of  claim 7 , wherein R 20  is halogen, acyl, alkoxy, or cyano. 
   
   
       13 . The compound of  claim 12 , selected from the group consisting of: 
     (6aS,12aR)-9-fluoro-4-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline; 
     ((6aS,12aR)-4-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yloxy))trifluoromethane; 
     (12aS,6aR)-9-fluoro-1-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline; 
     (12aS,6aR)-9-ethoxy-1-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline; 
     (12aS,6aR)-1-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-9-carboxylic acid; 
     ((12aS,6aR)-1-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yloxy))trifluoromethane; 
     {[(4-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))methyl]sulfonyl}methylamine; 
     methylethyl 3-(4-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl)benzoate; and 
     (12aS,6aR)-1-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-10-carbonitrile. 
   
   
       14 . The compound of  claim 7 , wherein R 20  is —C(O)NR 14 R 15 . 
   
   
       15 . The compound of  claim 14 , selected from the group consisting of: 
     2-bromo-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-9-carboxamide 
     4-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-9-carboxamide 
     4,7,7-trimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-9-carboxamide 
     4-ethoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-9-carboxamide 
     1-methoxy-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-9-carboxamide 
     4-fluoro-7,7-dimethyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-9-carboxamide 
     (6aR,12aS)-6a,7,12,12a-tetrahydro-N-(2-hydroxyethyl)-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline-9-carboxamide; 
     ((6aR,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(morpholino)methanone; 
     ((6aS,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(morpholino)methanone; 
     ((6aR,12aS)-6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(1,1-dione-1,4-thiazaperhydroin-yl)methanone; 
     (6aR,12aS)-6a,7,12,12a-tetrahydro-1-methoxy-N,N,7,7-tetramethyl-6H-chromeno[4,3-b]quinoline-9-carboxamide; 
     ((6aR,12aS)-6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(4-tert-butyl-carboxylate-piperazin-1-yl)methanone; 
     ((6aR,12aS)-6a,7,12,12a-tetrahydro-1-fluoro-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(4-tert-butyl-carboxylate-piperazin-1-yl)methanone; 
     ((6aR,12aS)-6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(piperazin-1-yl)methanone; 
     ((6aS,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(1,1-dione-1,4-thiazaperhydroin-yl)methanone; 
     ((6aR,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(1,1-dione-1,4-thiazaperhydroin-yl)methanone; 
     ((6aR,12aS)-1-fluoro-6a,7,12,12a-tetrahydro-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(piperazin-1-yl)methanone; 
     ((6aR,12aS)-1-methoxy-6a,7,12,12a-tetrahydro-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(4-ethanesulfonylpiperazin-1-yl)methanone; 
     ((6aS,12aS)-4-methoxy-6a,7,12,12a-tetrahydro-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(4-ethanesulfonylpiperazin-1-yl)methanone; 
     ((6aR,12aS)-4-methoxy-6a,7,12,12a-tetrahydro-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(4-ethanesulfonylpiperazin-1-yl)methanone; and 
     ((6aS,12aS)-4-fluoro-6a,7,12,12a-tetrahydro-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)(4-ethanesulfonylpiperazin-1-yl)methanone. 
   
   
       16 . The compound of  claim 7 , wherein R 20  is optionally substituted heteroaryl. 
   
   
       17 . The compound of  claim 7 , wherein R 20  is optionally substituted heterocycle. 
   
   
       18 . The compound of  claim 7 , wherein R 20  is aryl. 
   
   
       19 . The compound of  claim 7 , wherein R 20  is —SR 14 , —SR 15 , —S(O) 2 R 13 , —C(S)R 14 —C(S)NR 14 R 15 . 
   
   
       20 . The compound of  claim 4 , wherein R 4 , R 5 , R 6 , R 7 , and R 8  are hydrogen. 
   
   
       21 . The compound of  claim 20 , selected from the group consisting of: 
     1,1,1,3,3,3-hexafluoro-2-(1-methoxy-7-phenyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))propan-2-ol 
     4-{[(12aS,7R,6aR)-1-methoxy-7-methyl-7-(4-methylpent-3-enyl)-7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl]methyl}-1,4-thiazaperhydroine-1,1-dione 
     methyl (12aS,7R,6aR)-1-methoxy-7-methyl-7-(4-methylpent-3-enyl)-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-9-carboxylate 
     (12aS,7R,6aR)-1-methoxy-7-methyl-7-(4-methylpent-3-enyl)-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline-9-carbonitrile 
     ((7S,12aS,6aR)-1-methoxy-7-phenyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-N,N-dimethylcarboxamide 
     (7S,12aS,6aR)-1-methoxy-9-morpholin-4-yl-7-phenyl-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline 
     (12aS,7R,6aR)-1-methoxy-7-methyl-7-(4-methylpent-3-enyl)-9-(1,3-oxazol-5-yl)-7,12,12a,6a-tetrahydrochromano[4,3-b]quinoline 
   
   
       22 . The compound of  claim 4 , wherein R 1  and R 2  are optionally substituted lower alkyl and R 5 , R 6 , R 7 , and R 8  are hydrogen. 
   
   
       23 . The compound of  claim 22 , selected from the group consisting of: 
     diethyl ((6aS,12aS)-2-bromo-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)methylphosphonate; 
     diethyl ((6aR,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-2-(1H-pyrazol-4-yl)-6H-chromeno[4,3-b]quinolin-9-yl)methylphosphonate; and 
     2-((6aS,12aR)-1-bromo-4-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     2-((6aS,12aR)-2-bromo-4-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     2-((12aR,6aR)-2-bromo-4-methoxy-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     2-(2,4-difluoro-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     2-(2,4-dichloro-7,7-dimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     2-(2-chloro-4,7,7-trimethyl(7,12,12a,6a-tetrahydrochromano[4,3-b]quinolin-9-yl))-1,1,1,3,3,3-hexafluoropropan-2-ol 
     diethyl ((6aR,12aS)-2-bromo-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)methylphosphonate; 
     diethyl ((6aS,12aS)-2-bromo-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)methylphosphonate; 
     diethyl ((6aR,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-2-(1H-pyrazol-4-yl)-6H-chromeno[4,3-b]quinolin-9-yl)methylphosphonate; 
     (6aR,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-2-(1H-pyrazol-4-yl)-6H-chromeno[4,3-b]quinoline-9-carbonitrile; 
     (6aR,12aS)-methyl 2-bromo-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline-9-carboxylate; 
     (6aS,12aS)-methyl 2-bromo-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline-9-carboxylate; 
     (6aR,12aS)-methyl 6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-2-(1H-pyrazol-4-yl)-6H-chromeno[4,3-b]quinoline-9-carboxylate; 
     (6aR,12aS)-methyl 6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-2-(3,5-dimethylisoxazol-4-yl)-6H-chromeno[4,3-b]quinoline-9-carboxylate; and 
     (6aR,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-2-(1H-pyrazol-4-yl)-6H-chromeno[4,3-b]quinoline-9-carbonitrile. 
     (6aS,12aS)-2-bromo-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-9-(1H-tetrazol-5-yl)-6H-chromeno[4,3-b]quinoline; 
     1-((6aS,12aS)-6a,7,12,12a-tetrahydro-2-iodo-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)-5-methyl-1H-pyrazole-4-carboxylic acid; and 
     1-((6aR,12aS)-6a,7,12,12a-tetrahydro-2-iodo-4-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-9-yl)-5-methyl-1H-pyrazole-4-carboxylic acid. 
     (6aR,12aS)-2-bromo-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-9-(1H-tetrazol-5-yl)-6H-chromeno[4,3-b]quinoline; 
     (6aR,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-2-(3,5-dimethylisoxazol-4-yl)-9-(oxazol-5-yl)-6H-chromeno[4,3-b]quinoline. 
     (6aR,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-9-(oxazol-5-yl)-2-(1H-pyrazol-4-yl)-6H-chromeno[4,3-b]quinoline; 
     (6aS,12aS)-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-9-(oxazol-5-yl)-2-(1H-pyrazol-4-yl)-6H-chromeno[4,3-b]quinoline; 
     (6aR,12aS)-2-bromo-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-9-(oxazol-5-yl)-6H-chromeno[4,3-b]quinoline; and 
     (6aS,12aS)-2-bromo-6a,7,12,12a-tetrahydro-4-methoxy-7,7-dimethyl-9-(oxazol-5-yl)-6H-chromeno[4,3-b]quinoline. 
   
   
       24 . The compound of  claim 4 , wherein R 1  and R 2  are optionally substituted lower alkyl and R 4 , R, R 7 , R 8 , and R 20  are hydrogen. 
   
   
       25 . The compound of  claim 24 , selected from the group consisting of: 
     2-((6aR,12aS)-6a,7-dihydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-12(12aH)-yl)acetic acid; 
     (6aR,12aS)-6a,7,12,12a-tetrahydro-12-isopropyl-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline; 
     2-((6aS,12aS)-6a,7-dihydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-12(12aH)-yl)acetic acid; 
     ethyl 2-((6aS,12aS)-6a,7-dihydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-12(12aH)-yl)acetate; 
     ethyl 2-((6aR,12aS)-6a,7-dihydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-12(12aH)-yl)acetate;
 (6aS,12aS)-12-ethyl-6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline; 
 
     (6aR,12aS)-12-cyclohexyl-6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline; and 
     (6aS,12aS)-12-cyclohexyl-6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline 
     methyl 3-((6aS,12aR)-6a,7-dihydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-12(12aH)-yl)propanoate; 
     methyl 3-((6aR,12aR)-6a,7-dihydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinolin-12(12aH)-yl)propanoate; 
     (6aR,12aS)-12-propyl-6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline; 
     (6aS,12aS)-12-propyl-6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline; 
     (6aR,12aS)-12-butyl-6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline; and 
     (6aS,12aS)-12-butyl-6a,7,12,12a-tetrahydro-1-methoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline. 
   
   
       26 . The compound of  claim 4 , wherein R 1  and R 2  are optionally substituted lower alkyl and R 4 , R 5 , R 7 , and R 8  are hydrogen. 
   
   
       27 . The compound of  claim 26 , selected from the group consisting of: 
     (6aS,12aS)-6a,7,12,12a-tetrahydro-1,9-dimethoxy-7,7,12-trimethyl-6H-chromeno[4,3-b]quinoline; and 
     (6aR,12aS)-12-benzyl-6a,7,12,12a-tetrahydro-1,9-dimethoxy-7,7-dimethyl-6H-chromeno[4,3-b]quinoline; 
     (6aR,12aS)-methyl 6a,7,12,12a-tetrahydro-1-methoxy-7,7,12-trimethyl-6H-chromeno[4,3-b]quinoline-9-carboxylate; 
   
   
       28 . The compound of  claim 1 , wherein the 12a,6a ring juncture is cis. 
   
   
       29 . The compound of  claim 1 , wherein the 12a,6a ring juncture is trans. 
   
   
       30 . The compound of  claim 1 , wherein the 12a,6a ring juncture provides a single enantiomer 
   
   
       31 . A method of treating a disease state or condition in a mammal that is alleviable by treatment with an agent capable of increasing ABCA-1 expression, comprising administering to a mammal in need thereof a therapeutically effective dose of a compound of  claim 1 . 
   
   
       32 . The method of  claim 35 , wherein the disease state or condition is coronary artery disease or atherosclerosis. 
   
   
       33 . A method for elevating serum levels of HDL cholesterol in a mammal, comprising administering to a mammal in need thereof a therapeutically effective dose of a compound of  claim 1 . 
   
   
       34 . A method for promoting cholesterol efflux from cells in a mammal, comprising administering to a mammal in need thereof a therapeutically effective dose of a compound of  claim 1 . 
   
   
       35 . A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of  claim 1 .