Non-nucleoside reverse transcriptase inhibitors

1. A compound, or a pharmaceutically acceptable salt or prodrug thereof, wherein the compound is a compound of Formula III:

R 1 is AryA which is phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted with from 1 to 3 substituents each of which is independently halogen, CN, NO 2 , C 1-4 alkyl, C 1-4 haloalkyl, C 2-4 alkenyl, C 2-4 alkenyl substituted with CN, OH, O—C 1-4 alkyl, O—C 1-4 haloalkyl, N(R A )R B , C(O)N(R A )R B , C(O)R A , CO 2 R A , SR A , S(O)R A , SO 2 R A , SO 2 N(R A )R B , or SO 2 N(R A )C(O)R B ;

R 2B and R 2C are each independently:

(1) H,

(2) C 1-4 alkyl,

(3) CF 3 ,

(4) CH 2 CF 3 ,

(5) CH 2 OH,

(6) CH 2 O—C 1-4 alkyl,

(7) CH 2 CN,

(8) CH 2 N(R A )R B ,

(9) CH 2 C(O)N(R A )R B ,

(10) CH 2 C(O)R A ,

(11) CH 2 CO 2 R A ,

(12) CH 2 S(O) 2 R A ,

(13) O—C 1-4 alkyl,

(14) OCF 3 ,

(15) Cl,

(16) Br,

(17) F,

(18) CN,

(19) NO 2 ,

(20) N(R A )R B ,

(21) C(O)N(R A )R B ,

(22) C(O)R A ,

(23) C(O)—C 1-4 fluoroalkyl,

(24) C(O)OR A ,

(25) S(O) 2 R A ,

(38) cyclopropyl, or

(39) O-cyclopropyl;

V is H, CH 3 , C(O)CH 3 , C(O)OCH 3 , or S(O) 2 CH 3 ;

R F is H, C 1-4 alkyl, Br, Cl, F, or CN;

L is a single bond that attaches the ring nitrogen directly to M, CH 2 , or CH(CH 3 );

M is CH 2 or CH(CH 3 );

Z is G 1 or G 2 ;

G 1 is:

G 2 is:

and provided that when Z is G 2 , then L is CH 2 or CH(CH 3 ), and M is CH 2 or CH(CH 3 );

R 4 and R 5 are each independently:

(1) H,

(2) C 1-4 alkyl,

(3) CF 3 ,

(4) CH 2 CF 3 ,

(5) CH 2 OH,

(6) CH 2 O—C 1-4 alkyl,

(7) CH 2 CN,

(8) CH 2 N(R A )R B ,

(9) CH 2 C(O)N(R A )R B ,

(10) CH 2 C(O)R A ,

(11) CH 2 CO 2 R A ,

(12) CH 2 S(O) 2 R A ,

(13) O—C 1-4 alkyl,

(14) OCF 3 ,

(15) Cl,

(16) Br,

(17) F,

(18) CN,

(19) NO 2 ,

(20) N(R A )R B ,

(21) C(O)N(R A )R B ,

(22) C(O)R A ,

(23) C(O)—C 1-4 fluoroalkyl,

(24) C(O)OR A ,

(25) S(O) 2 R A ,

(38) cyclopropyl,

(39) O-cyclopropyl,

(40) OH, or

(41) imidazolyl;

each T 1 is independently H, C 1-4 alkyl, C(O)R A , C(O)O R A , C(O)N(R A )R B , or S(O) 2 R A ;

R6 is:

(1) H,

(2) C 1-4 alkyl,

(3) OH,

(4) O—C 1-4 alkyl,

(5) NH 2 ,

(6) N(H)—C 1-4 alkyl,

(7) N(—C 1-4 alkyl) 2 , or

(8) a saturated heterocyclic ring selected from the group consisting of 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, 1-azepanyl, 4-morpholinyl, and 4-thiomorpholinyl wherein the S in the ring is optionally S(O) or S(O) 2 , wherein the heterocyclic ring is optionally substituted with 1 or 2 substituents each of which is independently C 1-4 alkyl, C(O)—C 1-4 alkyl, C(O)O—C 1-4 alkyl C(O)NH 2 , C(O)NH(—C 1-4 alkyl), C(O)N(—C 1-4 alkyl) 2 , or S(O) 2 -C 1-4 alkyl;

R 7 is H or C 1-4 alkyl;

each R A is independently H or C 1-4 alkyl; and

each R B is independently H or C 1-4 alkyl.

2. The compound of Formula III according to claim 1 , or a pharmaceutically acceptable salt or prodrug thereof, wherein:

R 1 is AryA which is:

 wherein K 1 and K 2 are each independently Br, Cl, or CN;

R 2B is H, CH 3 , CF 3 , Cl, Br, F, or CN;

R 2C is H, CH 3 , CF 3 , Cl, Br, F, or CN;

R F is H;

L is a bond or CH 2 ;

M is CH 2 ;

Z is

 and

R 4 is H or NH 2 .

3. The compound of Formula III according to claim 2 , or a pharmaceutically acceptable salt or prodrug thereof, wherein:

R 1 is AryA which is selected from the group consisting of 3-chloro-5-cyanophenyl, 3-bromo-5-chlorophenyl, 3,5-dicyanophenyl, and 3,5-dichlorophenyl;

R 2B is H, CH 3 , CF 3 , or Cl;

R 2C is H, CH 3 , or Cl; and

L is a bond.

4. A compound of Formula III according to claim 2 , or a pharmaceutically acceptable salt or prodrug thereof, wherein R 1 is 3-chloro-5-cyanophenyl.

5. A compound selected from the group consisting of:

3-chloro-5-({5-chloro-3-fluoro-6-[(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)amino]pyridin-2-yl}oxy)benzonitrile (1-7);

3-[(6-{[(6-amino-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl]amino}-5-chloro-3-fluoropyridin-2-yl)oxy]-5-chlorobenzonitrile(2-7);

3-chloro-5-({3-chloro-2-oxo-6-[2-(1H-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl}oxy)benzonitrile (3-8);

3-chloro-5-({2-oxo-6-[2-(1H-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl}oxy)benzonitrile (3-9);

3-({6-[2-(6-amino-1H-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-3-chloro-2-oxo-1,2-dihydropyridin-4-yl}oxy)-5-chlorobenzonitrile (4-4);

3-chloro-5-({3,5-dichloro-2-oxo-6-[2-(1H-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl}oxy)benzonitrile (5-6);

ethyl 3-chloro-5-({3,5-dichloro-2-oxo-6-[2-(1H-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-1,2-dihydropyridin-4-yl}oxy)benzoate (5-7);

3-chloro-5-({5-chloro-2-[2-(1H-pyrazolo[3,4-b]pyridin-3-yl)ethyl]pyridin-4-yl}oxy)benzonitrile (6-5);

3-chloro-5-{[3,5-dichloro-2-methyl-6-(1H-pyrazolo[3,4-b]pyridin-3-ylmethoxy)pyridin-4-yl]oxy}benzonitrile (7-1);

3-chloro-5-({3-chloro-2-oxo-6-[(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)amino]-1,2-dihydropyridin-4-yl} oxy)benzonitrile (8-5);

3-chloro-5-({3-chloro-2-oxo-6-[(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)methyl]-1,2-dihydropyridin-4-yl}oxy)benzonitrile(9-8);

3-chloro-5-({3-chloro-2,5-difluoro-6-[(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)amino]pyridin-4-yl}oxy)benzonitrile (10-4);

3-chloro-5-{[4-methyl-2-oxo-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile (11-7);

3-chloro-5-({4-methyl-2-oxo-1-[2-(1H-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-1,2-dihydropyridin-3-yl}oxy)benzonitrile (12-7);

3-chloro-5-{[2-oxo-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile (13-2);

N-(2-chlorobenzyl)-2-[3-(3-chloro-5-cyanophenoxy)-2-oxo-4-(trifluoromethyl)pyridin-1(2H)-yl]-N-methylacetamide (14);

N-[4-(aminosulfonyl)-2-chlorophenyl]-2-[3-(3-chloro-5-cyanophenoxy)-2-oxo-4-(trifluoromethyl)pyridin-1(2H)-yl]acetamide (15);

N-[4-(aminosulfonyl)-2-chlorophenyl]-2-[3-(3-bromo-5-chlorophenoxy)-2-oxo-4-(trifluoromethyl)pyridin-1(2H)-yl]acetamide (16);

3-{[1-[(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]oxy}-5-chlorobenzonitrile (17-2);

5-{ [2-oxo-1-(1H-pyrazolo[3,4-b]pyridine-3-ylmethyl)-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]oxy}isophthalonitrile (18-4);

3-(3,5-dichlorophenoxy)-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-4-(trifluoromethyppyridin-2(1H)-one (19-4);

1-[(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-3-(3,5-dichlorophenoxy)-4-(trifluoromethyl)pyridin-2(1H)-one (20-3);

3-chloro-5-{[4-chloro-2-oxo-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile (21-8);

3-({1-[(6-amino-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl]-4-chloro-2-oxo-1,2-dihydropyridin-3-yl}oxy)-5-chlorobenzonitrile trifluoroacetate (22);

3-chloro-5-{[4,5-dichloro-2-oxo-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile (23-2);

3-chloro-5-{[3-chloro-2-oxo-6-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1,2-dihydropyridin-4-yl]oxy}benzonitrile (24-7);

3-chloro-5-({3-chloro-6-[hydroxy(1H-pyrazolo[3,4-b]pyridin-3-yl)methyl]-2-oxo-1,2-dihydropyridin-4-yl}oxy)benzonitrile (25);

and pharmaceutically acceptable salts thereof.

6. A compound according to claim 5 selected from the group consisting of:

3-chloro-5-{[4-methyl-2-oxo-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile (11-7);

3-chloro-5-({4-methyl-2-oxo-1-[2-(1H-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-1,2-dihydropyridin-3-yl}oxy)benzonitrile (12-7);

3-chloro-5-{[2-oxo-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile (13-2);

3-{[1-[(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]oxy}-5-chlorobenzonitrile (17-2);

5-{[2-oxo-1-(1H-pyrazolo[3,4-b]pyridine-3-ylmethyl)-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]oxy}isophthalonitrile (18-4);

3-(3,5-dichlorophenoxy)-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-4-(trifluoromethyppyridin-2(1H)-one (19-4);

1-[(6-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-3-(3,5-dichlorophenoxy)-4-(trifluoromethyl)pyridin-2(1H)-one (20-3);

3-chloro-5-{[4-chloro-2-oxo-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile (21-8);

3-({1-[(6-amino-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl]-4-chloro-2-oxo-1,2-dihydropyridin-3-yl}oxy)-5-chlorobenzonitrile trifluoroacetate (22);

3-chloro-5-{[4,5-dichloro-2-oxo-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile (23-2);

and pharmaceutically acceptable salts thereof.