Tetrahydronaphthalene derivates, process for preparing them and their use as antiinflammatory agents

Abstract

The invention relates to multiply substituted tetrahydronaphthalene derivatives of the formula (Ia) to processes for preparing them and to their use as antiinflammatory agents.

1 .- 18 . (canceled) 
     
     
         19 . A method of treating an inflammatory disease wherein the disease is a lung disorder, a rheumatic/autoimmune disorder, a dermatological disorder, a degenerative joint disorder, vascular inflammation, graft-versus-host disease, a severe state of shock, emesis, or inflammation-related pain, comprising administering to a subject in need thereof at least one compound of the formula (Ia): 
       
         
           
           
               
               
           
         
       
       wherein
 the compounds of the 1-amino-1,2,3,4-tetrahydronaphthalen-2-ol parent structure are present in the 1α,2α,4β stereoisomer configuration and the compounds of the 5,6,7,8-tetrahydronaphthalen-1,6-diol parent structure are present in the 5α,6α,8β stereoisomer configuration; 
 the radicals R 1 , R 2  and R 3  independently of one another are selected from —OH, —O—CH 3 , Cl, F, or H; 
 the radical R 4  is selected from:
 2-methylquinolin-5-yl, 
 2-methylquinazolin-5-yl, 
 2-ethylquinazolin-5-yl, 
 7-fluoro-2-methylquinazolin-5-yl, 
 8-fluoro-2-methylquinazolin-5-yl, 
 7,8-difluoro-2-methylquinazolin-5-yl, 
 quinolin-2(1H)-on-5-yl, 
 8-fluoroquinolin-2(1H)-on-5-yl, 
 isochromen-1-on-5-yl, 
 2-methylphthalazin-1-on-5-yl, or 
 isoquinolin-2(1H)-on-5-yl; 
 
 the radical R 5  is —CF 3 ; and 
 the radical R 6  is selected from —CH 3 , —CH 2 —CH 3 , —(CH 2 ) 2 —CH 3 , or —CH═CH 2 ; 
 or a stereoisomer thereof or a salt thereof with a physiologically tolerated anion. 
 
     
     
         20 . A method of treating an inflammatory disease wherein the disease is a lung disorder, a rheumatic/autoimmune disorder, a dermatological disorder, a degenerative joint disorder, vascular inflammation, graft-versus-host disease, a severe state of shock, emesis, or inflammation-related pain, comprising administering to a subject in need thereof at least one compound of the formula (Ia): 
       
         
           
           
               
               
           
         
       
       wherein
 the compounds with the 1-amino-1,2,3,4-tetrahydronaphthalen-2-ol parent structure have an absolute configuration of (1S, 2R, 4R) or (1S, 2R, 4S), and 
 the compounds with the 5,6,7,8-tetrahydronaphthalen-1,6-diol parent structure have an absolute configuration of (5S, 6R, 8R) or (5S, 6R, 8S), 
 the radicals R 1 , R 2  and R 3  independently of one another are selected from —OH, —O—CH 3 , Cl, F, or H; 
 the radical R 4  is selected from:
 2-methylquinolin-5-yl, 
 2-methylquinazolin-5-yl, 
 2-ethylquinazolin-5-yl, 
 7-fluoro-2-methylquinazolin-5-yl, 
 8-fluoro-2-methylquinazolin-5-yl, 
 7,8-difluoro-2-methylquinazolin-5-yl, 
 quinolin-2(1H)-on-5-yl, 
 8-fluoroquinolin-2(1H)-on-5-yl, 
 isochromen-1-on-5-yl, 
 2-methylphthalazin-1-on-5-yl, or 
 isoquinolin-2(1H)-on-5-yl; 
 
 the radical R 5  is —CF 3 ; and 
 the radical R 6  is selected from —CH 3 , —CH 2 —CH 3 , —(CH 2 ) 2 —CH 3 , or —CH═CH 2 ; 
 or a stereoisomer thereof or a salt thereof with a physiologically tolerated anion. 
 
     
     
         21 . A method according to  claim 19 , which excludes administering a compound wherein, simultaneously, R 1 , R 2  and R 3  provide 6-fluoro and 5-OH substitution on the ring, R 4  is 2-methylquinolin-5-yl, and R 6  is —CH 2 —CH 3 . 
     
     
         22 . A method according to  claim 19 , wherein, in the compound of formula (Ia), at least one of R 1 , R 2  and R 3  is fluoro. 
     
     
         23 . A method according to  claim 19 , wherein, in the compound of formula (Ia), R 4  is 7-fluoro-2-methylquinazolin-5-yl. 
     
     
         24 . A method according to  claim 19 , wherein, in the compound of formula (Ia), R 1 , R 2  and R 3  provide 6-fluoro and 5-OH substitution on the ring. 
     
     
         25 . A method of treating an inflammatory disease wherein the disease is a lung disorder, a rheumatic/autoimmune disorder, a dermatological disorder, a degenerative joint disorder, vascular inflammation, graft-versus-host disease, a severe state of shock, emesis, or inflammation-related pain, comprising administering to a subject in need thereof at least one compound from the following compounds:
 (5α,6α,8β)-2-fluoro-8-methyl-5-[(2-methylquinoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (+)-(5α,6α,8β)-2-fluoro-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (−)-(5α,6α,8β)-2-fluoro-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5α,6α,8β)-2-fluoro-5-[(8-fluoro-2-methylquinazoline-5-yl)amino]8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5α,6α,8β)-5-[(7,8-difluoro-2-methylquinazoline-5-yl)amino]-2-fluoro-8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5α,6α,8β)-2-fluoro-8-methyl-5-[-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[(5α,6α,8β)-1,6-dihydroxy-2-fluoro-8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-5-yl]amino}quinolin-2(1H)-one;   8-fluoro-5-{[(1α,2α,4β)-6-fluoro-2-hydroxy-5-methoxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-quinolin-2(1H)-one;   (+)-5-{[(1α,2α,4β)-6-fluoro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoroquinolin-2(1H)-one;   (−)-5-{[(1α,2α,4β)-6-fluoro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoroquinolin-2(1H)-one;   5-{[(1α,2α,4β)-6-fluoro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-2-methylphthalazin-1-one;   (5α,6α,8β)-3-chloro-2-fluoro-8-methyl-5-[(2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5α,6α,8β)-3-chloro-2-fluoro-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-1-methoxy-8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-6-ol;   (5α,6α,8β)-3-chloro-2-fluoro-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5α,6α,8β)-3-chloro-2-fluoro-5-[(8-fluoro-2-methylquinazoline-5-yl)amino]-1-methoxy-8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-6-ol;   (5α,6α,8β)-3-chloro-2-fluoro-5-[(8-fluoro-2-methylquinazoline-5-yl)amino]-8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5α,6α,8β)-3-chloro-5-[(7,8-difluoro-2-methylquinazoline-5-yl)amino]-2-fluoro-8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5α,6α,8β)-3-chloro-2-fluoro-8-methyl-5-[-2-methylquinoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (+)-5-{[(1α,2α,4β)-7-chloro-2,5-dihydroxy-6-fluoro-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]-amino}-quinolin-2(1H)-one;   (−)-5-{[(1α,2α,4β)-7-chloro-2,5-dihydroxy-6-fluoro-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]-amino}-quinolin-2(1H)-one;   5-{[(1α,2α,4β)-7-chloro-2,5-dihydroxy-6-fluoro-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]-amino}-8-fluoroquinolin-2(1H)-one;   (5α,6α,8β)-8-methyl-5-[-2-methylquinoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5α,6α,8β)-8-ethyl-5-[2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (+)-(5α,6α,8β)-8-ethyl-2-fluoro-5-[(2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (−)-(5α,6α,8β)-8-ethyl-2-fluoro-5-[(2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5S,6R,8R)-8-ethyl-2-fluoro-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalen-1,6-diol;   (+)-(5α,6α,8β)-8-ethyl-2-fluoro-5-[(8-fluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (−)-(5α,6α,8β)-8-ethyl-2-fluoro-5-[(8-fluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5α,6α,8β)-5-[(7,8-difluoro-2-methylquinazoline-5-yl)amino]-8-ethyl-2-fluoro-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[1a,2a,4b)-4-ethyl-6-fluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-quinoline-2(1H)-one;   5-{[(1α,2α,4β)-4-ethyl-6-fluoro-2-hydroxy-5-methoxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoroquinolin-2(1H)-one;   (+)-5-{[(1α,2α,4β)-4-ethyl-6-fluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoroquinolin-2(1H)-one;   (−)-5-{[(1α,2α,4β)-4-ethyl-6-fluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoroquinolin-2(1H)-one;   5-{[(1α,2α,4β)-4-ethyl-6-fluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-2-methylphthalazin-1-one;   5-{[(1α,2α,4β)-4-ethyl-6-fluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-isoquinoline-(2H)-one;   5-{[(1α,2α,4β)-4-ethyl-6-fluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}isochromen-1-one;   (5α,6α,8β)-5-[(2-ethylquinazoline-5-yl)amino]-2-fluoro-8-propyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5S,6R,8R)-8-ethyl-2,3-difluoro-5-[(2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (+)-(5α,6α,8β)-8-ethyl-2,3-difluoro-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (−)-(5α,6α,8β)-8-ethyl-2,3-difluoro-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5S,6R,8R)-8-ethyl-2,3-difluoro-5-[(8-fluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5S,6R,8R)-8-ethyl-2,3-difluoro-5-[(7,8-difluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (+)-5-{[(1a,2a,4b)-4-ethyl-6,7-difluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}quinolin-2(1H)-one;   (−)-5-{[(1α,2α,4β)-4-ethyl-6,7-difluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}quinoline-2(1H)-one;   (5α,6α,8β)-8-ethyl-2,3-difluoro-5-[(2-methylquinoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[(1α,2α,4β)-4-ethyl-6,7-difluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}phthalazin-1-one;   (5α,6α,8β)-2-fluoro-5-[(2-methylquinazoline-5-yl)amino]-8-prop-1-yl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5α,6α,8β)-2-fluoro-5-[(7-fluoro-2-methylquinazolin-5-yl)amino]-8-prop-1-yl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[(1α,2α,4β)-4-ethyl-6,7-difluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}quinoline-2(1H)-one;   5-{[(1α,2α,4β)-4-ethyl-6,7-difluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}isoquinoline-1(2H)-one;   5-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   5-{[(1S,2R,4R)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   5-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4R)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-2H-quinolin-1-one;   5-{[(1S,2R,4R)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-2H-quinolin-1-one;   5-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-isochromen-1-one;   5-{[(1S,2R,4R)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-isochromen-1-one;   4-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1,3-dihydroindol-2-one;   4-{[(1S,2R,4R)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1,3-dihydroindol-2-one;   5-{[(1S,2R,4S)-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   5-{[(1a,2a,4b)-6-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   5-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4R)-6-chloro-4-ethyl-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-2H-quinolin-1-one;   5-{[(1S,2R,4R)-6-chloro-4-ethyl-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-2H-quinolin-1-one;   5-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-isochromen-1-one;   5-{[(1S,2R,4R)-6-chloro-4-ethyl-2,5-dihydroxy-4-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-isochromen-1-one;   4-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1,3-dihydroindol-2-one;   4-{[(1S,2R,4R)-6-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1,3-dihydroindol-2-one;   5-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4R)-6-chloro-4-ethyl-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4S)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4R)-6-chloro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   (5α,6α,8β)-2-chloro-8-ethyl-5-[(indazol-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   6-{[(1α,2α,4β)-6-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-4-methylbenzo[d][1,2]oxazin-1-one;   5-{[(1α,2α,4β)-7-isopropyl-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   (5α,6α,8β)-8-ethyl-3-isopropyl-5-[2-methylquinazoline-5-ylamino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[(1α,2α,4β)-7-isopropyl-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-2H-quinolin-1-one;   4-{[(1α,2α,4β)-7-isopropyl-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1,3-dihydroindol-2-one;   5-{[(1α,2α,4β)-7-isopropyl-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-isochromen-1-one;   5-{[(1α,2α,4β)-7-isopropyl-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1α,2α,4β)-7-isopropyl-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1α,2α,4β)-7-chloro-2,5-dihydroxy-4-ethyl-6-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   5-{[(1α,2α,4β)-7-chloro-2,5-dihydroxy-6-methyl-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-2H-quinolin-1-one;   4-{[(1α,2α,4β)-7-chloro-2,5-dihydroxy-6-methyl-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1,3-dihydroindol-2-one;   5-{[(1α,2α,4β)-7-chloro-2,5-dihydroxy-4-ethyl-6-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4R)-7-chloro-2,5-dihydroxy-4-ethyl-6-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   (5α,6α,8β)-3-chloro-8-ethyl-2-methyl-5-[2-methylquinazoline-5-ylamino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[(1S,2R,4S)-7-chloro-2,5-dihydroxy-4-ethyl-6-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   5-{[(1a,2a,4b)-7-chloro-2,5-dihydroxy-4-ethyl-6-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4R)-7-chloro-2,5-dihydroxy-4-ethyl-6-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   (5S,6R,8R)-8-ethyl-2,3-difluoro-5-[(2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[1S,2R,4R)-4-ethyl-7-fluoro-2,5-dihydroxy-6-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}quinolin-2(1H)-one;   5-{[1S,2R,4R)-4-ethyl-7-fluoro-2,5-dihydroxy-6-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoroquinolin-2(1H)-one;   5-{[1S,2R,4R)-4-ethyl-7-fluoro-2,5-dihydroxy-6-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoroquinolin-2(1H)-one;   5-{[1S,2R,4R)-4-ethyl-7-fluoro-2,5-dihydroxy-6-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}isoquinolin-1(2H)-one;   (5S,6R,8R)-8-ethyl-3-fluoro-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-2-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5S,6R,8R)-8-ethyl-3-fluoro-5-[(8-fluoro-2-methylquinazoline-5-yl)amino]-2-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[1S,2R,4S)-4,6-diethyl-7-fluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}quinolin-2(1H)-one;   5-{[1S,2R,4R)-4,6-diethyl-7-fluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}quinolin-2(1H)-one;   5-{[1S,2R,4S)-4,6-diethyl-7-fluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoroquinolin-2(1H)-one;   5-{[1S,2R,4R)-4,6-diethyl-7-fluoro-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoroquinolin-2(1H)-one;   5-{[1S,2R,4S)-4,6-diethyl-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   5-{[1S,2R,4R)-4,6-diethyl-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   5-{[(1S,2R,4S)-4,6-diethyl-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4R)-4,6-diethyl-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   (5S,6R,8S)-2,8-diethyl-5-[2-methylquinazoline-5-ylamino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[(1α,2α,4β)-7-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   5-{[(1α,2α,4β)-7-chloro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4R)-6-chloro-4-ethyl-2,5-dihydroxy-7-fluoro-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}quinolin-2(1H)-one;   5-{[(1S,2R,4R)-6-chloro-4-ethyl-2,5-dihydroxy-7-fluoro-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoroquinolin-2(1H)-one;   5-{[(1S,2R,4R)-6-chloro-4-ethyl-2,5-dihydroxy-7-fluoro-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoroquinolin-2(1H)-one;   (5S,6R,8R)-2-chloro-8-ethyl-3-fluoro-5-[(2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5S,6R,8R)-2-chloro-8-ethyl-3-fluoro-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[(1α,2α,4β)-7-fluoro-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   5-{[(5S,6R,8R)-8-ethyl-3-fluoro-1,6-dihydroxy-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-5-yl]amino}-8-fluoroquinolin-2(1H)-one;   5-{[(1α,2α,4β)-7-fluoro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   5-{[(1α,2α,4β)-7-fluoro-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1α,2α,4β)-7-bromo-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   5-{[(1S,2R,4R)-7-bromo-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   5-{[(1α,2α,4β)-7-bromo-2,5-dihydroxy-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1α,2α,4β)-6-fluoro-2,7-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   (5α,6α,8β)-8-ethyl-1,6-dihydroxy-5-(2-oxo-1,2-dihydroquinoline-5-ylamino)-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile;   (5α,6α,8β)-8-ethyl-1,6-dihydroxy-5-(8-fluoro-2-oxo-1,2-dihydroquinoline-5-ylamino)-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile;   (5α,6α,8β)-8-ethyl-1,6-dihydroxy-5-[(1-oxo-1,2-dihydroisoquinoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile;   (5α,6α,8β)-1,6-dihydroxy-8-methyl-5-[(2-oxo-2,3-dihydro-1H-indol-4-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile;   (5α,6α,8β)-5-[(8-fluoro-2-oxo-1,2-dihydroquinoline-5-yl)amino]-1,6-dihydroxy-8-methyl-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile;   5-{[(5S,6R,8R)-8-ethyl-1,6-dihydroxy-3-fluoro-5-[(2-oxo-1,2-dihydroquinoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile;   (5α,6α,8β)-8-ethyl-1,6-dihydroxy-3-fluoro-5-[(8-fluoro-2-oxo-1,2-dihydroquinoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile;   5-{[(1S,2R,4S)-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4R)-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4S)-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1S,2R,4R)-2,5-dihydroxy-4-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1α,2α,4β)-4-ethyl-2,5-dihydroxy-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-6-fluoro-1H-quinolin-2-one;   5-{[(1α,2α,4β)-4-ethyl-6-fluoro-2,5-dihydroxy-7-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinoline-2-one;   5-{[(1α,2α,4β)-4-ethyl-6-fluoro-2,5-dihydroxy-7-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-7-fluoro-1H-quinoline-2-one;   5-{[(1α,2α,4β)-4-ethyl-6-fluoro-2,5-dihydroxy-7-methyl-2-(trifluoroomethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1α,2α,4β)-4-ethyl-6-fluoro-2,5-dihydroxy-7-methyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-2H-quinolin-1-one;   (5α,6α,8β)-8-ethyl-2-fluoro-3-methyl-5-[2-methylquinazoline-5-ylamino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5S,6R,8R)-8-ethyl-2,3-difluoro-5-[(2-methyl-1-oxyquinoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   5-{[(1α,2α,4β)-2,5-dihydroxy-6,7-dimethyl-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-1H-quinolin-2-one;   5-{[(1α,2α,4β)-2,5-dihydroxy-6,7-dimethyl-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-8-fluoro-1H-quinolin-2-one;   5-{[(1α,2α,4β)-2,5-dihydroxy-6,7-dimethyl-4-ethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1-yl]amino}-2H-quinolin-1-one;   5-{[(5S,6R,8R)-2-chloro-8-ethyl-1,6-dihydroxy-3-fluoro-2-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-5-yl]amino}quinolin-2(1H)-one;   5-{[(5S,6R,8R)-3-chloro-8-ethyl-1,6-dihydroxy-2-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-5-yl]amino}-7-fluoroquinolin-2(1H)-one   (5S,6R,8R)-2,3-dichloro-8-ethyl-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   (5S,6R,8R)-2-chloro-8-ethyl-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol;   or   (5S,6R,8R)-3-chloro-8-ethyl-5-[(7-fluoro-2-methylquinazoline-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol.   
     
     
         26 . The method of  claim 19 , wherein the method is for treating a lung disorder, a rheumatic/autoimmune disorder, or a dermatological disorder. 
     
     
         27 . The method of  claim 20 , wherein the method is for treating a lung disorder, a rheumatic/autoimmune disorder, or a dermatological disorder. 
     
     
         28 . The method of  claim 25 , wherein the method is for treating a lung disorder, a rheumatic/autoimmune disorder, or a dermatological disorder.