Tricyclic-2-pyridone compounds useful as HIV reverse transcriptase inhibitors

• US 20040023955A1
• Filed: 06/10/2003
• Published: 02/05/2004
• Est. Priority Date: 07/20/2000
• Status: Active Grant

• Current Assignee: Anthony J. Cocuzza, Argyrios Arvanitis, Haisheng Wang, James D. Rodgers, Mona Patel
• Original Assignee: Anthony J. Cocuzza, Argyrios Arvanitis, Haisheng Wang, James D. Rodgers, Mona Patel
• Inventors: Wang, Haisheng, Rodgers, James D., Patel, Mona, Cocuzza, Anthony J., Arvanitis, Argyrios
• Granted Patent: US 6,969,721 B2
• Time in Patent Office: Days
• US Class Current: 514/228.5
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The present invention relates to tricyclic 2-pyridone 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.

Claims

1. A compound of formula (I):

2. A compound of claim 1 or pharmaceutically acceptable salt forms thereof, wherein:

R² is selected from the group methyl substituted with 0-3 R^3f, C_1-5 alkyl substituted with 0-2 R⁴, C_2-5 alkenyl substituted with 0-2 R⁴, C_2-5 alkynyl substituted with 0-1 R⁴, C_3-6 cycloalkyl substituted with 0-2 R^3d, and 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, wherein the heterocyclic system is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, 2-imidazolyl, pyrazolyl, triazolyl, 1,3-dioxolanyl, and 1,3-dioxanyl;

R³ 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, NR⁵R^5a, NO₂, —

CN, C(O)R⁶, NHC(O)R⁷, NHC(O)NR⁵R^5a, and a 5-6 membered heteroaromatic ring containing 1-4 heteroatoms selected from the group O, N, and S;

alternatively, R³ and R^3a together form —

OCH₂O—

;

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, NR⁵R^5a, NO₂, —

CN, C(O)R⁶, NHC(O)R⁷, and NHC (O)NR⁵R^5a;

alternatively, R^3a and R^3b together form —

OCH₂O—

;

R⁴ is selected from the group H, Cl, F, C_1-4 alkyl substituted with 0-2 R^3e, C_3-6 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;

R⁵ and R^5a are independently selected from the group H, CH₃ and C₂H₅;

R⁶ is selected from the group H, OH, CH₃, C₂H₅, OCH₃, OC₂H₅, and NR⁵R^5a; and

R⁷ is selected from the group CH₃, C₂H₅, CH(CH₃)₂, OCH₃, OC₂H₅, and OCH(CH₃)₂.

3. A compound of claim 2, wherein:

P is O;

Ring A is;

R^b, at each occurrence, is selected from H, F, Cl, and Br, C_1-4 alkyl, CN, C_1-4 alkyl-NH-, NH₂;

R^c is selected from H and methyl;

W is CR³;

X is CR^3a;

Y is CR^3b;

Z is CR^3c;

R² is selected from the group methyl substituted with 0-3 R^3f, C_1-3 alkyl substituted with 0-2 R⁴, C_2-3 alkenyl substituted with 0-2 R⁴, C_2-3 alkynyl substituted with 0-1 R⁴, and C_3-6 cycloalkyl substituted with 0-2 R^3d;

R³, 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, NR⁵R^5a, NO₂, —

CN, C(O)R⁶, NHC(O)R⁷, and NHC(O) NR⁵R^5a;

alternatively, R³ and R^3a together form —

OCH₂O—

;

R^3e, at each occurrence, is independently selected from the group H, C_1-4 alkyl, —

OH, C_1-4 alkoxy, OCF₃, F, Cl, —

NR⁵R^5a, —

C(O)R⁶, and —

SO₂NR⁵R^5a;

R^3f, at each occurrence, is independently selected from the group H, F, Cl, Br, I, C_1-4 alkyl, CN, —

OH, —

O—

R¹¹, —

O(CO)—

R¹³, —

SR¹¹, —

S(O)R¹¹, —

S(O)₂R¹¹, and —

NR¹²R^12a;

R⁴ is selected from the group H, Cl, F, 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, wherein the heterocyclic system is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-oxazolyl, 2-thiazolyl, 4-isoxazolyl, 2-imidazolyl, pyrazolyl, triazolyl, 1,3-dioxolanyl, and 1,3-dioxanyl;

R⁵ and R^5a are independently selected from the group H, CH₃ and C₂H₅;

R⁶ is selected from the group H, OH, CH₃, C₂H₅, OCH₃, OC₂H₅, and NR⁵R^5a;

R⁷ is selected from the group CH₃, C₂H₅, OCH₃, and OC₂H₅;

R⁸ is H;

R⁹ is H, methyl, ethyl, propyl, and i-propyl;

R¹¹ is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, and C_3-6 carbocycle substituted with 0-2 R^3e wherein the C_3-6 carbocycle is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and phenyl; and

R¹² and R^12a are independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, and C_3-6 carbocycle substituted with 0-2 R^3e wherein the C_3-6 carbocycle is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and phenyl.

4. A compound of claim 3, or a pharmaceutically acceptable salt form thereof, wherein:

R² is selected from the group methyl substituted with 0-3 R^3f, C_1-3 alkyl substituted with 1 R⁴, C_2-3 alkenyl substituted with 1 R⁴, and C_2-3 alkynyl substituted with 1 R⁴;

R³, 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, NR⁵R^5a, NO₂, —

CN, C(O)R⁶, NHC(O)R⁷, and NHC(O)NR⁵R^5a;

alternatively, R³ and R^3a together form —

OCH₂O—

;

R^3e, at each occurrence, is independently selected from the group CH₃, —

OH, OCH₃, OCF₃, F, Cl, and —

NR⁵R^5a;

R^3f, at each occurrence, is independently selected from the group H, F, Cl, Br, I, C_1-4 alkyl, —

OH, CN, —

O—

R¹¹, —

O(CO)—

R¹³, and —

NR¹²R^12a, —

SR¹¹, —

S(O)R¹¹, —

S(O)₂R¹¹, and —

OS(O)₂methyl;

R⁴ is selected from the group H, Cl, F, CH₃, CH₂CH₃, 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-imidazolyl, pyrazolyl, triazolyl, 1,3-dioxolanyl, and 1,3-dioxanyl;

R⁵ and R^5a are independently selected from the group H, CH₃ and C₂H₅;

R⁶ is selected from the group H, OH, CH₃, C₂H₅, OCH₃, OC₂H₅, and NR⁵R^5a;

R⁷ is selected from the group CH₃, C₂H₅, OCH₃, and OC₂H₅; and

R⁹ is selected from H and methyl.

5. A compound of claim 4, or a pharmaceutically acceptable salt form thereof, wherein:

R² is selected from the group methyl substituted with 0-2 R^3f, methyl substituted with 0-2 R⁴, ethyl substituted with 0-2 R⁴, propyl substituted with 0-2 R⁴, ethenyl substituted with 0-2 R⁴, 1-propenyl substituted with 0-2 R⁴, 2-propenyl substituted with 0-2 R⁴, ethynyl substituted with 0-2 R⁴, 1-propynyl substituted with 0-2 R⁴, 2-propynyl substituted with 0-2 R⁴, and cyclopropyl substituted with 0-1 R^3d;

R^3e, at each occurrence, is independently selected from the group CH₃, —

OH, OCH₃, OCF₃, F, Cl, and —

NR⁵R^5a;

R⁴ is selected from the group H, Cl, F, CH₃, CH₂CH₃, 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-imidazolyl, pyrazolyl, triazolyl, 1,3-dioxolanyl, and 1,3-dioxanyl;

R⁵ and R^5a are independently selected from the group H, CH₃ and C₂H₅;

R⁶ is selected from the group H, OH, CH₃, C₂H₅, OCH₃, OC₂H₅, and NR⁵R^5a;

R⁷ is selected from the group CH₃, C₂H₅, OCH₃, and OC₂H₅;

R⁸ is H.

6. A compound of claim 5, or a pharmaceutically acceptable salt form thereof, wherein:

R¹ is selected from methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, CF₃, CF₂CH₃, CN, and hydroxymethyl;

R² is selected from the group methyl substituted with 0-2 R^3f, methyl substituted with 0-2 R⁴, ethyl substituted with 0-2 R⁴, propyl substituted with 0-1 R⁴, ethenyl substituted with 0-2 R⁴, 1-propenyl substituted with 0-2 R⁴, 2-propenyl substituted with 0-2 R⁴, ethynyl substituted with 0-2 R⁴, 1-propynyl substituted with 0-2 R⁴;

R³, R^3b, and R^3c are H;

R^3e is CH₃;

R^3f, at each occurrence, is independently selected from the group H, F, Cl, Br, I, C_1-4 alkyl, CN, —

OH, —

O—

R¹¹, —

SR¹¹, —

S(O)R¹¹, —

S(O)₂R¹¹, and —

NR¹²R^12a;

R⁴ is selected from the group H, cyclopropyl substituted with 0-1 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-imidazolyl, pyrazolyl, triazolyl, 1,3-dioxolanyl, and 1,3-dioxanyl;

R¹² and R^12a are independently selected from H, methyl, ethyl, propyl, and i-propyl, and C_3-6 carbocycle substituted with 0-2 R^3e wherein the C_3-6 carbocycle is selected from cyclopropyl.

7. A compound of claim 6, 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 of formula (I) is selected from:

7-fluoro-2-methyl-5-[(6-methyl-2-pyridinyl)methyl]-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H) -one;

5-(2-cyclopropylethynyl)-7-fluoro-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-propyl-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-butyl-7-fluoro-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(4-fluorophenylmethyl) -5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(2-pyridylmethyl)-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(isopropyl)-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(3-pyridylmethyl)-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(4-pyridylmethyl)-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(3-propynyl)-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(2-pyridylethynyl)-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(2-(2-pyridyl)ethyl)-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

3-chloro-7-fluoro-5-propyl-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(3-propenyl)-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-cyclopropylethyl)-7-fluoro-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(ethynyl)-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-fluoro-5-(2-ethoxyethyl)-5-(trifluoromethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-Butyl-7-chloro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(2-pyridylmethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(2-cyclopropylethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-cyclopropylethynyl-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(N-cyclopropylaminomethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-hydroxymethy 1-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-3-methyl-5- (2-pyridylmethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(2-cyclopropylethyl)-3-methyl-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(n-propoxymethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(i-propoxymethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(2-methoxyethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(i-propylaminomethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(N-methyl-N-i-propylaminomethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(cyclopropylaminomethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(n-propylaminomethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(cyclobutylaminomethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(i-butylaminomethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(i-propoxymethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Cyano-5-(n-butyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Cyano-5-(i-propoxymethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(cyclopropylsulfanylmethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(cyclopropanesulfinylmethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(t-butylsulfinylmethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(methylsulfanylmethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(ethylsulfanylmethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(i-propylsulfanylmethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Fluoro-5-(i-propylsulfanylmethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(t-butylsulfanylmethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(cyclopropylmethoxymethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(cyclobutoxymethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(Cyclobutoxymethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(Cyclopropylmethoxymethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-3-methyl-5-(i-propoxymethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-3-methyl-5-(n-butyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Cyano-3-methyl-5-(n-butyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-2-methyl-5-(i-propoxymethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

3,7-Dichloro-5-(n-butyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

4,7-Dichloro-5-(n-butyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(ethoxyethyl)-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(n-butyl)-5-methyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(i-propoxymethyl)-5-methyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(n-butyl)-5-cyano-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(n-butyl)-5-(hydroxymethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(n-butyl)-5-difluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(i-propoxymethyl)-5-difluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(n-Butyl)-5-(1,1-difluoroethyl)-7-Fluoro-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(n-butyl)-5-(1,1-difluoroethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Cyano-5-(n-butyl)-5-(1,1-difluoroethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

7-Chloro-5-(ethoxymethyl)-5-(1,1-difluoroethyl)-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(allyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-methyl-1-propenyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(1-propynyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(cyanomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(ethylamino)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(dimethylamino)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(methylamino)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-ethoxyethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(i-propylamino)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(diethylamino)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(cyclopropylamino)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(pentyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(i-butyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(vinyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(imidazolylethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(pyrazolylethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(1,2,4-triazolylethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(i-propylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(i-propoxymethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(methylethylamino)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(i-propylethylamino)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(pyrrolidinyl)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(methoxy)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(i-propoxymethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(3-pentanylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(dimethoxymethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(i-butylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(cyclopropylmethylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(allylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-((R)-sec-butylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-((S)-sec-butylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(diethoxymethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

3-chloro-5-(propyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(butyl)-7-fluoro-2-methyl-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(i-propoxy)ethyl)-7-fluoro-2-methyl-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(i-propylaminomethyl)-7-fluoro-2-methyl-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(i-propoxymethyl)-7-fluoro-2-methyl-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-ethoxyethyl)-7-fluoro-2-methyl-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(sec-butylaminomethyl)-7-fluoro-2-methyl-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H) -one;

5-(cyclopentylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(cyclobutylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(dimethylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(pyrrolidinylmethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(cyclopropylaminomethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(dimethoxy)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(diethoxy)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one;

5-(2-(1,3-dioxolanyl)methyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one; and

5-(2-(methoxy)ethyl)-7-fluoro-5-trifluoromethyl-5,10-dihydrobenzo [b]-1,7-naphthyridin-1(2H)-one.

10. A method for treating HIV infection which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound according to one of claim 1 or pharmaceutically acceptable salt form thereof.

11. 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 according to one of claim 1;

and,

(b) at least one compound selected from the group consisting of HIV reverse transcriptase inhibitors, HIV protease inhibitors, fusion inhibitors, and CCR-5 inhibitors.

12. A method of claim 11, 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 AG1549 (S1153), TMC-120, TMC-125, Calanolide A, and PMPA, 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, ABT-378, DMP-450, AG-1776, VX-175, MK-944, and VX-478, the CCR-5 inhibitor is selected from TAK-779 (Takeda), SC-351125 (SCH-C, Schering) and SCH-D (Schering), and the fusion inhibitor is selected from T-20 and T1249.

13. A method of claim 12, 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.

14. A method of claim 13, wherein the reverse transcriptase inhibitor is AZT.

15. A method of claim 13, wherein the protease inhibitor is indinavir.

16. A pharmaceutical kit useful for the treatment of HIV infection, which comprises a therapeutically effective amount of:

(a) a compound according to one 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.

17. A compound according to one of claim 1 for use in therapy.

18. The use of a compound according to one of claim 1 for the manufacture of a medicament for the treatment of HIV infection.

9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to one of claim or pharmaceutically acceptable salt form thereof.

19. A compound of formula (I):

20. A compound of formula (I):