Tricyclic compounds useful as HIV reverse transcriptase inhibitors

Abstract

The present invention relates to tricyclic compounds of formula (I): or stereoisomeric forms, stereoisomeric mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same, and methods of using the same for treating viral infection or as an assay standard or reagent.

What is claimed is:  
     
         1 . A compound of formula (I):  
       
         
           
           
               
               
           
         
       
       or a stereoisomeric form or mixture of stereoisomeric forms or a pharmaceutically acceptable salt form thereof, wherein: 
 n is selected from 0, 1, 2 and 3;  
 A is a ring selected from the group:  
                     
 wherein a ring nitrogen in ring A may optionally be in an N-oxide form;  
 said ring A being substituted with 0-3 B, said substituent B being independently selected from the group C 1-4  alkyl, —OH, C 1-4  alkoxy, —S—C 1-4  alkyl, OCF 3 , CF 3 , F, Cl, Br, I, —NO 2 , —CN, and —NR 5 R 5a ;  
 W is N or CR 3 ;  
 X is N or CR 3a ;  
 Y is N or CR 3b ;  
 Z is N or CR 3c ;  
 provided that if two of W, X, Y, and Z are N, then the remaining are other than N;  
 R 1  is selected from the group C 1-3  alkyl substituted with 0-7 halogen, and cyclopropyl substituted with 0-5 halogen;  
 R 2  is selected from the group —R 2c , —OH, —CN, —OR 2c , —OCHR 2a R 2b , —OCH 2 CHR 2a R 2b , —O(CH 2 ) 2 CHR 2a R 2b , —OCHR 2a C(R 2a )═C(R 2b ) 2 , —OCHR 2a C(R 2a )═C(R 2b ) 2 , —OCHR 2a C≡C—R 2b , —SR 2c , SCHR 2a R 2b , —SCH 2 CHR 2a R 2b , —S(CH 2 ) 2 CHR 2a R 2b , —SCHR 2a C(R 2a )═C(R 2b ) 2 , —SCHR 2a C(R 2a )═(R 2b ) 2 , —SCHR 2a C≡C—R 2b , —NR 2a R 2c , —NHCHR 2a R 2b , —NHCH 2 CHR 2a R 2b , —NH(CH 2 ) 2 CHR 2a R 2b , —NHCHR 2a C(R 2a )═C(R 2b ) 2 , —NHCHR 2a C(R 2a )═(R 2b ) 2 , and —NHCHR 2a C≡C—R 2b ;  
 R 2a  is selected from the group H, CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , and CH 2 CH 2 CH 3 ;  
 R 2b  is H or R 2c ;  
 R 2c  is selected from the group methyl substituted with 0-3 R 3f , C 1-6  alkyl substituted with 0-3 R 4 , C 2-5  alkenyl substituted with 0-2 R 4 , C 2-5  alkynyl substituted with 0-1 R 4 , C 3-6  cycloalkyl substituted with 0-2 R 3d , phenyl substituted with 0-2 R 3d , and 3-6 membered heterocyclic system containing 1-3 heteroatoms selected from the group O, N, and S, substituted with 0-2 R 3d ;  
 alternatively, the group —NR 2a R 2c  represents a 4-7 membered cyclic amine, wherein 0-1 carbon atoms are replaced by O or NR 5 ;  
 R 3  is selected from the group H, C 1-4  alkyl, —OH, C 1-4  alkoxy, OCF 3 , F, Cl, Br, I, —NR 5 R 5a , —NO 2 , —CN, —C(O)R 6 , —NHC(O)R 7 , —NHC(O)NR 5 R 5a , —NHSO 2 R 10 , —SO 2 NR 5 R 5a , and a 5-6 membered heteroaromatic ring containing 1-4 heteroatoms selected from the group O, N, and S;  
 R 3a  is selected from the group H, C 1-4  alkyl, —OH, C 1-4  alkoxy, OCF 3 , F, Cl, Br, I, —NR 5 R 5a , —NO 2 , —CN, —C(O)R 6 , —NHC(O)R 7 , —NHC(O)NR 5 R 5a , —NHSO 2 R 10 , —SO 2 NR 5 R 5a , and a 5-6 membered heteroaromatic ring containing 1-4 heteroatoms selected from the group O, N, and S;  
 alternatively, R 3  and R 3a  together form —OCH 2 O—;  
 R 3b  is selected from the group H, C 1-4  alkyl, —OH, C 1-4  alkoxy, OCF 3 , F, Cl, Br, I, —NR 5 R 5a , —NO 2 , —CN, —C(O)R 6 , —NHC(O)R 7 , —NHC(O)NR 5 R 5a , —NHSO 2 R 10 , and —SO 2 NR 5 R 5a ;  
 alternatively, R 3a  and R 3b  together form —OCH 2 O—;  
 R 3c  is selected from the group H, C 1-4  alkyl, —OH, C 1-4  alkoxy, OCF 3 , F, Cl, Br, I, —NR 5 R 5a , —NO 2 , —CN, —C(O)R 6 , —NHC(O)R 7 , —NHC(O)NR 5 R 5a , —NHSO 2 R 10 , and —SO 2 NR 5 R 5a ;  
 alternatively, R 3b  and R 3c  together form —OCH 2 O—;  
 R 3d , at each occurrence, is independently selected from the group H, C 1-4  alkyl, —OH, C 1-4  alkoxy, OCF 3 , F, Cl, Br, I, —NR 5 R 5a , —NO 2 , —CN, —C(O)R 6 , —NHC(O)R 7 , —NHC(O)NR 5 R 5a , —NHSO 2 R 10 , and —SO 2 NR 5 R 5a ;  
 R 3e , at each occurrence, is independently selected from the group H, C 1-4  alkyl, —OH, C 1-4  alkoxy, OCF 3 , F, Cl, Br, I, —NR 5 R 5a , —NO 2 , —CN, —C(O)R 6 , —NHC(O)R 7 , —NHC(O)NR 5 R 5a , —NHSO 2 R 10 , and —SO 2 NR 5 R 5a ;  
 R 3f , is selected from the group group H, F, Cl, Br, I, —OH, —O—R 11 , —O—C 3-10  carbocycle substituted with 0-2 R 3e , —O(CO)—R 13 , —OS(O) 2 C 1-4  alkyl, —NR 12 R 12a , —C(O)R 13 , —NHC(O)R 13 , —NHSO 2 R 10 , and —SO 2 NR 12 R 12a ;  
 R 4  is selected from the group H, F, Cl, Br, I, —OH, —O—R 11 , —O—C 3-10  carbocycle substituted with 0-2 R 3e , —OS(O) 2 C 1-4  alkyl, —NR 12 R 12a , C 1-6  alkyl substituted with 0-2 R 3e , C 3-10  carbocycle substituted with 0-2 R 3e , phenyl substituted with 0-5 R 3e , and a 5-10 membered heterocyclic system containing 1-3 heteroatoms selected from the group O, N, and S, substituted with 0-2 R 3e ;  
 R 5  and R 5a  are independently selected from the group H and C 1-4  alkyl;  
 alternatively, R 5  and R 5a , together with the nitrogen to which they are attached, combine to form a 5-6 membered ring containing 0-1 O or N atoms;  
 R 6  is selected from the group H, OH, C 1-4  alkyl, C 1-4  alkoxy, and NR 5 R 5a ;  
 R 7  is selected from the group H, C 1-3  alkyl and C 1-3  alkoxy;  
 R 8  is selected from the group H, (C 1-6  alkyl)carbonyl, C 1-6  alkoxyalkyl, (C 1-4  alkoxy)carbonyl, C 6-10  aryloxyalkyl, (C 6-10  aryl)oxycarbonyl, (C 6-10  aryl)methylcarbonyl, (C 1-4  alkyl)carbonyloxy(C 1-4  alkoxy)carbonyl, C 6-10  arylcarbonyloxy(C 1-4  alkoxy)carbonyl, C 1-6  alkylaminocarbonyl, phenylaminocarbonyl, phenyl(C 1-4  alkoxy)carbonyl, and (C 1-6  alkyl substitued with NR 5 R 5a )carbonyl; and  
 R 10  is selected from the group C 1-4  alkyl and phenyl;  
 R 11  is selected from C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  alkyl substituted with C 3-6 cycloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl;  
 R 12  and R 12a  are independently selected from H, C 1-6  alkyl, and C 3-6  cycloalkyl;  
 alternatively, R 12  and R 12a  can join to form 4-7 membered ring; and  
 R 13  is selected from the group H, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  alkoxy, C 2-6  alkenyl, C 2-6  alkynyl, —O—C 2-6  alkenyl, —O—C 2-6  alkynyl, NR 12 R 12a , C 3-6  carbocycle, and —O—C 3-6  carbocycle.  
 
     
     
         2 . A compound of  claim 1  or pharmaceutically acceptable salt forms thereof, wherein: 
 R 2  is selected from the group —R 2c , —OH, —CN, —OR 2c , —OCHR 2a R 2b , —OCH 2 CHR 2a R 2b , —O(CH 2 ) 2 CHR 2a R 2b , —OCHR 2a CH═CHR 2b , —OCHR 2a CH═CHR 2c , —OCHR 2a C≡CR 2b , —NR 2a R 2c , —SR 2c , —SCHR 2a R 2b , —SCH 2 CHR 2a R 2b , —SCHR 2a CH═CHR 2b , —SCHR 2a CH═CHR 2c , and —SCHR 2a C≡CR 2b ;  
 R 2a  is selected from the group H, CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , and CH 2 CH 2 CH 3 ;  
 R 2b  is H or R 2c ;  
 R 2c  is selected from the group methyl substituted with 0-3 R 3f , C 1-5  alkyl substituted with 0-3 R 4 , C 2-5  alkenyl substituted with 0-2 R 4 , C 2-5  alkynyl substituted with 0-1 R 4 , C 3-6  cycloalkyl substituted with 0-2 R 3d , and phenyl substituted with 0-2 R 3d ;  
 R 3  and R 3a , at each occurrence, are independently selected from the group H, C 1-4  alkyl, OH, C 1-4  alkoxy, F, Cl, Br, I, NR 5 R 5a , NO 2 , —CN, C(O)R 6 , NHC(O)R 7 , NHC(O)NR 5 R 5a , and a 5-6 membered heteroaromatic ring containing 1-4 heteroatoms selected from the group O, N, and S;  
 alternatively, R 3  and R 3a  together form —OCH 2 O—;  
 R 3b  and R 3c , at each occurrence, are independently selected from the group H, C 1-4  alkyl, OH, C 1-4  alkoxy, F, Cl, Br, I, NR 5 R 5a , NO 2 , —CN, C(O)R 6 , NHC(O)R 7 , and NHC(O)NR 5 R 5a ;  
 alternatively, R 3a  and R 3b  together form —OCH 2 O—;  
 R 4  is selected from the group H, Cl, F, —OH, —O—C 1-6  alkyl, —O—C 3-5  carbocycle substituted with 0-2 R 3e , —OS(O) 2 C 1-4  alkyl, —NR 12 R 12a , C 1-4  alkyl substituted with 0-2 R 3e , C 3-5  carbocycle substituted with 0-2 R 3e , phenyl substituted with 0-5 R 3e , and a 5-6 membered heterocyclic system containing 1-3 heteroatoms selected from the group O, N, and S, substituted with 0-2 R 3e ;  
 R 5  and R 5a  are independently selected from the group H, CH 3  and C 2 H 5 ;  
 R 6  is selected from the group H, OH, CH 3 , C 2 H 5 , OCH 3 , OC 2 H 5 , and NR 5 R 5a ; and  
 R 7  is selected from the group CH 3 , C 2 H 5 , CH(CH 3 ) 2 , OCH 3 , OC 2 H 5 , and OCH(CH 3 ) 2 .  
 
     
     
         3 . A compound of  claim 2 , wherein: 
 ring A is selected from                          R 1  is selected from the group CF 3 , C 2 F 5 , CHF 2 , CF 2 CH 3  and cyclopropyl;    R 2  is selected from the group —R 2c , —OH, —CN, —OR 2c , —OCHR 2a R 2b , —OCH 2 CHR 2a R 2b , —OCHR 2a CH═CHR 2b , —OCHR 2a CH═CHR 2c , —OCHR 2a C≡CR 2b , and —NR 2a R 2c ;    R 2a  is selected from the group H, CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , and CH 2 CH 2 CH 3 ;    R 2b  is H or R 2c ;    R 2c  is selected from the group methyl substituted with 0-3 R 3f , C 1-3  alkyl substituted with 0-3 R 4 , C 2-3  alkenyl substituted with 0-2 R 4 , C 2-3  alkynyl substituted with 0-1 R 4 , and C 3-6  cycloalkyl substituted with 0-2 R 3d ;    R 3 , R 3a , R 3b , and R 3c , at each occurrence, are independently selected from the group H, C 1-3  alkyl, OH, C 1-3  alkoxy, F, Cl, Br, I, NR 5 R 5a , NO 2 , —CN, C(O)R 6 , NHC(O)R 7 , and NHC(O)NR 5 R 5a ;    alternatively, R 3  and R 3a  together form —OCH 2 O—;    R 3e , at each occurrence, is independently selected from the group H, C 1-4  alkyl, —OH, C 1-4  alkoxy, OCF 3 , F, Cl, —NR 5 R 5a , —C(O)R 6 , and —SO 2 NR 5 R 5a ;    R 3f  is selected from the group group H, F, Cl, Br, —OH, —O—R 11 , —O-cyclopropyl substituted with 0-2 R 3e , —O-cyclobutyl substituted with 0-2 R 3e , —O-phenyl substituted with 0-2 R 3e , —O(CO)—R 13 , —OS(O) 2 C 1-4  alkyl, —NR 12 R 12a , —C(O)R 13 , —NHC(O)R 13 , —NHSO 2 R 10 , and —SO 2 NR 12 R 12a ;    R 4  is selected from the group H, Cl, F, —OH, —O—C 1-6  alkyl, —O—C 3-10  carbocycle substituted with 0-2 R 3e , —OS(O) 2 C 1-4  alkyl, —NR 12 R 12a  C 1-4  alkyl substituted with 0-1 R 3e , C 3-5  carbocycle substituted with 0-2    R 3e , phenyl substituted with 0-2 R 3e , and a 5-6 membered heterocyclic system containing 1-3 heteroatoms selected from the group O, N, and S, substituted with 0-1 R 3e ;    R 5  and R 5a  are independently selected from the group H, CH 3  and C 2 H 5 ;    R 6  is selected from the group H, OH, CH 3 , C 2 H 5 , OCH 3 , OC 2 H 5 , and NR 5 R 5a ; and    R 7  is selected from the group CH 3 , C 2 H 5 , OCH 3 , and OC 2 H 5 ;    R 11  is selected from methyl, ethyl, propyl, i-propyl, butyl, pentyl, hexyl, CF 3 , CH 2 CF 3 , CH 2 CH 2 CF 3 , —CH 2 -cyclopropyl, and cyclopropyl;    R 12  and R 12a  are independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, pentyl, and cyclopropyl;    R 13  is selected from the group H, methyl, ethyl, propyl, i-propyl, butyl, pentyl, hexyl, C 1-6  haloalkyl, methoxy, ethoxy, propoxy, i-propoxy, butoxy, NR 12 R 12a , cyclopropyl, cyclobutyl, cyclopropoxy, and cyclobutoxy.    
     
     
         4 . A compound of  claim 3 , or a pharmaceutically acceptable salt form thereof, wherein: 
 R 1  is CF 3 , CF 2 CH 3 , or CHF 2 ;    R 2  is selected from the group —R 2c , —OH, —CN, —OCH 2 R 2b , —OCH 2 CH 2 R 2b , —OCH 2 CH═CHR 2b , —OCH 2 C≡CR 2b , and —NR 2a R 2c ;    R 2b  is H or R 2c ;    R 2c  is selected from the group methyl substituted with 0-3 R 3f , C 1-3  alkyl substituted with 0-3 R 4 , C 2-3  alkenyl substituted with 1 R 4 , and C 2-3  alkynyl substituted with 1 R 4 ;    R 3 , R 3a , R 3b , and R 3c , at each occurrence, are independently selected from the group H, C 1-3  alkyl, OH, C 1-3  alkoxy, F, Cl, NR 5 R 5a , NO 2 , —CN, C(O)R 6 , NHC(O)R 7 , and NHC(O)NR 5 R 5a ;    alternatively, R 3  and R 3a  together form —OCH 2 O—;    R 3e , at each occurrence, is independently selected from the group CH 3 , —OH, OCH 3 , OCF 3 , F, Cl, and —NR 5 R 5a ;    R 3f , is selected from the group group H, F, Cl, —OH, —O—R 11 , —O(CO)—R 13 , —OS(O) 2 C 1-4  alkyl, —NR 12 R 12a , and —NHC(O)NR 12 R 12a ;    R 4  is selected from the group H, Cl, F, CH 3 , CH 2 CH 3 , cyclopropyl substituted with 0-1 R 3e , 1-methyl-cyclopropyl substituted with 0-1 R 3e , cyclobutyl substituted with 0-1 R 3e , phenyl substituted with 0-2 R 3e , and a 5-6 membered heterocyclic system containing 1-3 heteroatoms selected from the group O, N, and S, substituted with 0-1 R 3e , wherein the heterocyclic system is selected from the group 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, 2-imidazolyl, morpholinyl, piperidinyl, pyrrolidinyl, and piperazinyl;    R 5  and R 5a  are independently selected from the group H, CH 3  and C 2 H 5 ;    R 6  is selected from the group H, OH, CH 3 , C 2 H 5 , OCH 3 , OC 2 H 5 , and NR 5 R 5a ; and    R 7  is selected from the group CH 3 , C 2 H 5 , OCH 3 , and OC 2 H 5 .    
     
     
         5 . A compound of  claim 1 , or a pharmaceutically acceptable salt form thereof, wherein: 
 n is 0 or 1;    ring A is optionally in an N-oxide form;    R 1  is CF 3 , CHF 2 , or CF 2 CH 3 ;    R 2  is selected from the group —R 2c , —OR 2c , —OH, —CN, —OCH 2 R 2b , —OCH 2 CH 2 R 2b , —OCH 2 C═C—R 2b , —OCH 2 C≡C—R 2b , —NR 2a R 2c , —SR 2c , —SCH 2 R 2b , —SCH 2 CH 2 R 2b , —SCH 2 CH═CHR 2b , and —SCH 2 C≡CR 2b ;    R 2b  is H or R 2c ;    R 2c  is selected from the group methyl substituted with 0-2 R 3f , ethyl substituted with 0-3 R 4 , propyl substituted with 0-2 R 4 , ethenyl substituted with 0-2 R 4 , 1-propenyl substituted with 0-2 R 4 , 2-propenyl substituted with 0-2 R 4 , ethynyl substituted with 0-2 R 4 , 1-propynyl substituted with 0-2 R 4 , 2-propynyl substituted with 0-2 R 4 , and cyclopropyl substituted with 0-1 R 3d ;    R 3e , at each occurrence, is independently selected from the group CH 3 , —OH, OCH 3 , OCF 3 , F, Cl, and —NR 5 R 5a ;    R 3f , is selected from the group group H, F, Cl, —OH, —O—R 11 , —O(CO)—R 13 , —OS(O) 2 C 1-4  alkyl, —NR 12 R 12a , and —NHC(O)NR 12 R 12a ;    R 4  is selected from the group H, Cl, F, CH 3 , CH 2 CH 3 , cyclopropyl substituted with 0-1 R 3e , 1-methyl-cyclopropyl substituted with 0-1 R 3e , cyclobutyl substituted with 0-1 R 3e , phenyl substituted with 0-2 R 3e , and a 5-6 membered heterocyclic system containing 1-3 heteroatoms selected from the group O, N, and S, substituted with 0-1 R 3e , wherein the heterocyclic system is selected from the group 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, 2-imidazolyl, morpholinyl, piperidinyl, pyrrolidinyl, and piperazinyl;    R 5  and R 5a  are independently selected from the group H, CH 3  and C 2 H 5 ;    R 6  is selected from the group H, OH, CH 3 , C 2 H 5 , OCH 3 , OC 2 H 5 , and NR 5 R 5a ;    R 7  is selected from the group CH 3 , C 2 H 5 , OCH 3 , and OC 2 H 5 ; R 8  is H.    
     
     
         6 . A compound of  claim 4 , or a pharmaceutically acceptable salt form thereof, wherein: 
 n is selected from 0 or 1;    A is selected from                          B is selected from methyl, ethyl, propyl, —OH, Cl, Br, —S—CH 3 ;    W is CR 3 ;    X is CR 3a ;    Y is CR 3a ;    Z is N or CR 3a ;    R 1  is selected from CF 3 , CHF 2 , and CF 2 CH 3 ;    R 2  is selected from —R 2c , —OH, —CN, —OR 2c , —OCH 2 C═C—R 2b , —OCH 2 C≡C—R 2b , and —NR 2a R 2c ;    R 2a  is H;    R 2b  is H;    R 2c  is selected from the group methyl substituted with 0-3 R 3f , ethyl substituted with 0-3 R 4 , propyl substituted with 0-3 R 4 , i-propyl substituted with 0-3 R 4 , butyl substituted with 0-3 R 4 , 1-propenyl substituted with 0-2 R 4 , 2-propenyl substituted with 0-2 R 4 , 1-propynyl substituted with 0-2 R 4 , 2-propynyl substituted with 0-2 R 4 ;    R 3  is H;    R 3a  is H, F, Cl, or Br;    R 3b  is H;    R 3c  is H;    R 3e , at each occurrence, is independently selected from the group H, methyl, and ethyl, —OH, C 1-4  alkoxy, OCF 3 , F, Cl, Br, I, —NR 5 R 5a , —NO 2 , —CN, —C(O)R 6 , —NHC(O)R 7 , —NHC(O)NR 5 R 5a , —NHSO 2 R 10 , and —SO 2 NR 5 R 5a ;    R 3f  is selected from H, F, Cl, OH, —OR 11 , —OSO 2 methyl, —NR 12 R 12a , and —NHC(O)NR 5 R 5a ;    R 4  is selected from H, F, —OH, —O-i-propyl, —OS(O) 2 CH 3 , cyclopropyl substituted with 0-1 R 3e , cyclobutyl substituted with 0-1 R 3e , phenyl, N-morpholinyl, 2-pyridyl, 3-pyridyl, 4-pyridiyl, N2-methyl-N1-piperidinyl, N-piperidinyl, N-pyrrolidinyl, and N-piperazinyl;    R 8  is H;    R 11  is selected from H, methyl, ethyl, propyl, i-propyl, CH 2 cyclopropyl, and cyclopropyl; and    R 12  and R 12a  are independently selected from H, methyl, ethyl, propyl, i-propyl, and cyclopropyl.    
     
     
         7 . A compound of  claim 1 , or a pharmaceutically acceptable salt form thereof, wherein the compound is of formula (Ic):  
       
         
           
           
               
               
           
         
       
     
     
         8 . A compound of  claim 1 , or a pharmaceutically acceptable salt form thereof, wherein the compound is of formula (Id):  
       
         
           
           
               
               
           
         
       
     
     
         9 . A compound of  claim 1 , or a pharmaceutically acceptable salt form thereof or an N-oxide form thereof, wherein the compound of formula (I) is selected from: 
 7-Chloro-5-(cyclopropylmethoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(benzyloxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(cyclobutylmethoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(ethoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(hydroxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(n-propoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(i-propoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(butyl)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(methoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5(S)-(cyclopropylmethoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5(R)-(cyclopropylmethoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(2-cyclopropylethyl)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(2,2,2-trifluoroethoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(propargoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(ethyl)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(cyclopropylmethoxy)-2-methyl-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(n-butyl)-2-methyl-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(2-cyclopropylethyl)-2-methyl-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine, 
 7-Chloro-5-(cyclopropylmethoxy)-5,10-dihydro-2-(methylthio)-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,  
   7-Chloro-5-(i-butoxy)-5,10-dihydro-2-(methylthio)-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(benzyloxy)-5,10-dihydro-2-(methylthio)-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(2-pyridylmethoxy)-5,10-dihydro-2-(methylthio)-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(cyclopropylmethoxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(cyclopropylamino)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(i-propylamino)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(N,N-dimethylaminoethoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(N-morpholinylethylamino)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-((1-methylcyclopropyl)methoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(3,3,3-trifluoroprop-1-oxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(cyclopropylmethylamino)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(methylamino)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(ethylamino)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    (S)-7-Chloro-5-(cyclopropylethyl)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    (R)-7-Chloro-5-(cyclopropylethyl)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Fluoro-5-(cyclopropylmethoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Fluoro-5-(cyclopropylethoxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Fluoro-5-(allyloxy)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(phenylamino)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(cyclopropylmethoxy)-2-methyl-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(n-butyl)-2-methyl-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(cyclopropylethyl)-2-methyl-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine,    7-Chloro-5-(cyclobutylmethoxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(methoxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    (S)-7-Chloro-5-(cyclopropylmethoxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    (R)-7-Chloro-5-(cyclopropylmethoxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(N-piperidinylethoxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(N-pyrrolidinylethoxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-((4-methylpiperazin-1-yl)prop-1-oxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(prop-1-oxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(N,N-dimethylaminoprop-1-yl)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(benzyloxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(3-pyridinylmethyl)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(allyloxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline,    7-Chloro-5-(propargoxy)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline, and    7-Chloro-5-(N,N-dimethylaminoethyl)-5,10-dihydro-5-(trifluoromethyl)pyrimido[4,5-b]quinoline;    7-Chloro-5-cyclopropylmethoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    5-Allyloxy-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    7-Fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine-5-carbonitrile;    7-Fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-ol;    5-Cyclopropylmethoxy-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Chloro-5-prop-2-ynyloxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Chloro-5-(1-methyl-cyclopropylmethoxy)-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Chloro-5-(2-cyclopropyl-ethoxy)-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (7-Chloro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-yl)-isopropyl-amine;    (7-Chloro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-yl)-cyclobutylmethylamine;    7-Chloro-5-(2-cyclopropyl-ethyl)-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    5-Cyclobutylmethoxy-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (7-Fluoro-1-oxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-yl)-isopropyl-amine;    5-Cyclobutylmethoxy-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-2-ol;    7-Chloro-5-(pyridin-2-ylmethoxy)-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    5-Butyl-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    7-Chloro-1-oxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-ol;    7-Chloro-5-cyclopropylmethoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Chloro-5-pyridin-2-ylmethyl-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Fluoro-5-pyridin-2-ylmethyl-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    5-Cyclopropylmethoxy-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Chloro-5-pyridin-2-ylmethyl-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    3,7-Dichloro-5-cyclopropylmethoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    3,7-Dichloro-5-cyclopropylmethoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    3,7-Dichloro-5-pentyl-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    5-(2-Cyclopropyl-ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    5-(2-Cyclopropyl-ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    3,7-Dichloro-5-cyclopropylmethoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    5-(2-Cyclopropyl-ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    3-Chloro-5-cyclopropylmethoxy-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    3-Chloro-5-cyclopropylmethoxy-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Chloro-5-isobutoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    5-Butyl-7-chloro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (S) 3-Chloro-5-cyclopropylmethoxy-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (7-Chloro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-yl)-methanol;    7-Fluoro-5-isobutoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Fluoro-5-isopropoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    Methanesulfonic acid 7-chloro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-ylmethyl ester;    7-Chloro-5-isopropoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (7-Fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-yl)-acetonitrile;    7-Fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine-5-carbaldehyde;    3-Bromo-5-cyclopropylmethoxy-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    5-Butyl-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    5-Diisopropoxymethyl-7-fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    7-Fluoro-5-isopropoxymethyl-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Chloro-5-isobutyl-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Chloro-5-propoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (S) 7-Fluoro-5-isobutoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (R) 7-Fluoro-5-isobutoxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (7-Chloro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-yl)-acetaldehyde;    7-Chloro-5-(2,2-diisopropoxy-ethyl)-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    7-Chloro-5-(2-isopropoxy-ethyl)-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    2-(7-Chloro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-yl)-ethanol;    7-Chloro-5-(2-isopropoxy-ethyl)-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (R) 7-Fluoro-5-(2-isopropoxy-ethyl)-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (7-Fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-yl)-acetic acid tert-butyl ester;    (7-Fluoro-1-oxy-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-yl)-acetic acid tert-butyl ester;    (7-Fluoro-5-trifluoromethyl-5,10-dihydro-benzo[b][1,8]naphthyridin-5-yl)-acetic acid;    7-Chloro-5-cyclopropylmethoxy-2-methylsulfanyl-5-trifluoromethyl-5,10-dihydro-pyrimido[4,5-b]quinoline;    7-Chloro-5-isobutoxy-2-methylsulfanyl-5-trifluoromethyl-5,10-dihydro-pyrimido[4,5-b]quinoline;    5-Benzyloxy-7-chloro-2-methylsulfanyl-5-trifluoromethyl-5,10-dihydro-pyrimido[4,5-b]quinoline;    7-Chloro-2-methylsulfanyl-5-(pyridin-2-ylmethoxy)-5-trifluoromethyl-5,10-dihydro-pyrimido[4,5-b]quinoline;    7-Chloro-5-cyclopropylmethoxy-5-trifluoromethyl-5,10-dihydro-pyrimido[4,5-b]quinoline 1-oxide;    7-Chloro-5-cyclopropylmethoxy-5-(1,1-difluoro-ethyl)-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    5-Cyclopropylmethoxy-5-(1,1-difluoro-ethyl)-7-fluoro-5,10-dihydro-benzo[b][1,8]naphthyridine;    5-Cyclopropylmethoxy-5-(1,1-difluoro-ethyl)-7-fluoro-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-Chloro-5-(1,1-difluoro-ethyl)-5-isobutoxy-5,10-dihydro-benzo[b][1,8]naphthyridine;    7-Chloro-5-(1,1-difluoro-ethyl)-5-isobutoxy-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (R) 7-Chloro-5-cyclopropylmethoxy-5-(1,1-difluoro-ethyl)-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    (S) 7-Chloro-5-cyclopropylmethoxy-5-(1,1-difluoro-ethyl)-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    3-Chloro-10-cyclopropylmethoxy-10-trifluoromethyl-9,10-dihydro-1,8,9-triaza-anthracene;    3-Chloro-10-cyclopropylmethoxy-10-trifluoromethyl-9,10-dihydro-1,8,9-triaza-anthracene 8-oxide;    3,6-Dichloro-10-cyclopropylmethoxy-10-trifluoromethyl-9,10-dihydro-1,8,9-triaza-anthracene;    3-Chloro-10-isobutoxy-10-trifluoromethyl-9,10-dihydro-1,8,9-triaza-anthracene;    3-Chloro-10-isobutoxy-10-trifluoromethyl-9,10-dihydro-1,8,9-triaza-anthracene 8-oxide;    7-Chloro-5-difluoromethyl-5-isopropoxymethyl-5,10-dihydro-benzo[b][1,8]naphthyridine;    7-Chloro-5-difluoromethyl-5-isopropoxymethyl-5,10-dihydro-benzo[b][1,8]naphthyridine 1-oxide;    7-chloro-1,5-dihydro-5-(N-ethylaminomethyl)-5-(trifluoromethyl)benzo[b][1,8]napthyridine;    7-chloro-5,10-dihydro-5-(N-isopropylaminomethyl)-5-(trifluoromethyl)benzo[b][1,8]napthyridine;    7-chloro-5,10-dihydro-5-(N-isopropyl-N-ethylaminomethyl)-5-(trifluoromethyl)benzo[b][1,8]napthyridine;    7-chloro-5-(N,N-diethylaminomethyl)-5,10-dihydro-5-(trifluoromethyl)benzo[b][1,8]napthyridine;    5-(acetamidomethyl)-7-chloro-5,10-dihydro-5-(trifluoromethyl)[b][1,8]napthyridine;    5,10-dihydro-7-fluoro-5-(N-methylsulfonylmethyl)-5-(trifluoromethyl)[b][1,8]napthyridine;    5,10-dihydro-7-fluoro-5-(isopropylamidomethyl)-5-(trifluoromethyl)[b][1,8]napthyridine;    5,10-dihydro-7-fluoro-5-(isopropylguanadinomethyl)-5-(trifluormethyl)[b][1,8]napthyridine;    1,5-dihydro-7-fluoro-5-(N-isopropylmethyl)-5-(trifluoromethyl)[b][1,8]napthyridine-1-(N-oxide);    5-(N,N-diethylaminomethyl)-5,10-dihydro-7-fluoro-5-(trifluoromethyl)[b][1,8]napthyridine-1-(N-oxide);    5,10-dihydro-5-(N,N-dimethylaminomethyl)-7-fluoro-5-(trifluoromethyl)[b][1,8]napthyridine-1-(N-oxide);    7-chloro-5,10-dihydro-5-(N-isopropylaminomethyl)-5-(trifluoromethyl)[b][1,8]napthyridine-1-(N-oxide);    7-chloro-5-(N,N-diethylaminomethyl)-5,10-dihydro-5-(trifluoromethyl)[b][1,8]napthyridine-1-(N-oxide); and    7-chloro-5,10-dihydro-5-(N,N-dimethylaminomethyl)-5-(trifluoromethyl)[b][1,8]napthyridine-1-(N-oxide.    
     
     
         10 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of  claim 1  or pharmaceutically acceptable salt form thereof.  
     
     
         11 . A method for treating HIV infection which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of  claim 1  or pharmaceutically acceptable salt form thereof.  
     
     
         12 . A method of treating HIV infection which comprises administering, in combination, to a host in need thereof a therapeutically effective amount of: 
 (a) a compound of  claim 1;  and,    (b) at least one compound selected from the group consisting of HIV reverse transcriptase inhibitors and HIV protease inhibitors.    
     
     
         13 . A method of  claim 12 , wherein the reverse transcriptase inhibitor is selected from the group AZT, ddC, ddI, d4T, 3TC, delavirdine, efavirenz, nevirapine, Ro 18,893, trovirdine, MKC-442, HBY 097, HBY1293, GW867, ACT, UC-781, UC-782, RD4-2025, MEN 10979 and AG1549 (S1153), and the protease inhibitor is selected from the group saquinavir, ritonavir, indinavir, amprenavir, nelfinavir, palinavir, BMS-232623, GS3333, KNI-413, KNI-272, LG-71350, CGP-61755, PD 173606, PD 177298, PD 178390, PD 178392, U-140690, and ABT-378.  
     
     
         14 . A method of  claim 13 , wherein the reverse transcriptase inhibitor is selected from the group AZT, efavirenz, and 3TC and the protease inhibitor is selected from the group saquinavir, ritonavir, nelfinavir, and indinavir.  
     
     
         15 . A method of  claim 14 , wherein the reverse transcriptase inhibitor is AZT.  
     
     
         16 . A method of  claim 14 , wherein the protease inhibitor is indinavir.  
     
     
         17 . A pharmaceutical kit useful for the treatment of HIV infection, which comprises a therapeutically effective amount of: 
 (a) a compound of  claim 1;  and,    (b) at least one compound selected from the group consisting of HIV reverse transcriptase inhibitors and HIV protease inhibitors, in one or more sterile containers.