Hiv integrase inhibitors

Abstract

Compounds of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: wherein m, n, X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are defined herein. The compounds are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

1 . A compound of Formula I, or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is N(R K ); 
 R K  is:
 (1) H, 
 (2) C 1-6  alkyl, 
 (3) C 1-6  alkyl substituted with T, wherein T is CO 2 R A , CN, SO 2 R A , N(R D )R E , C(O)N(R D )R E , N(R A )—C(O)C(O)—N(R D )R E , N(R A )—C(O)R B , N(R A )—SO 2 R B , N(R A )—SO 2 N(R D )R E , or N(R A )—CO 2 R B , 
 (4) C 1-6  haloalkyl, 
 (5) C(O)R A , 
 (6) C(O)—C 1-6  haloalkyl, 
 (7) CO 2 R A , 
 (8) C(O)—U, 
 (9) C(O)—C 1-6  alkylene-U, 
 (10) C(O)N(R D )R E , 
 (11) C(O)—C 1-6  alkylene-N(R D )R E , 
 (12) C(O)C(O)—U, 
 (13) C(O)C(O)—C 1-6  alkylene-U, 
 (14) C(O)C(O)—N(R D )R E , 
 (15) C(O)C(O)—C 1-6  alkylene-N(R D )R E , 
 (16) SO 2 R A , 
 (17) SO 2 —U, 
 (18) SO 2 —C 1-6  alkylene-U, 
 (19) SO 2 N(R D )R E , 
 (20) CycB, 
 (21) C 1-6  alkyl substituted with U, or 
 (22) C 1-6  alkyl substituted with C(O)N(R A )—C 1-6  alkylene-U,
 wherein U is CycB, AryB, or HetB; 
 
 
 m and n are each 1; 
 R1 is:
 (1) H, 
 (2) C 1-6  alkyl, 
 (3) C 1-6  haloalkyl, 
 (4) C 1-6  alkyl substituted with V, wherein V is OH, O—C 1-6  alkyl, O—C 1-6  haloalkyl, SR A , S(O)R A , SO 2 R A , N(R D )R E , C(O)N(R D )R E , N(R A )—C(O)C(O)—N(R D )R E , N(R A )—C(O)R E , N(R A )—SO 2 R B , N(R A )—C 1-6  alkylene-SO 2 R B , N(R A )C(O)—C 1-6  alkylene-SO 2 R B , N(R A )—SO 2 N(R D )R E , N(R A )—CO 2 R B , or N(R A )—C(O)N(R D )R E , 
 (5) C 1-6  alkyl substituted with W, wherein W is CycA, AryA, HetA, O—C 1-6  alkylene-CycA, O—C 1-6  alkylene-AryA, O—C 1-6  alkylene-HetA, S(O) j —C 1-6  alkylene-CycA, S(O) j —C 1-6  alkylene-AryA, S(O) j —C 1-6  alkylene-HetA, N(R A )—C(O)-AryA, or N(R A )—C(O)-HetA, 
 (6) N(R A )—SO 2 R B , 
 (7) N(R A )—SO 2 N(R D )R E , 
 (8) N(R A )—CO 2 R B , 
 (9) N(R D )R E , 
 (10) N(R C )R A , 
 (11) N(R A )—C(O)R B , 
 (12) N(R C )—C(O)R A , 
 (13) S(O) j R F , 
 (14) OR F , 
 (16) CycA, 
 (17) AryA, 
 (18) HetA, 
 (19) N(R A )—C(O)-CycA, 
 (20) N(R A )—C(O)-AryA, 
 (21) N(R A )—C(O)-HetA, 
 (22) N(R A )—C(O)—N(R D )R E , 
 (23) N(R C )—C(O)-CycA, 
 (24) N(R C )—C(O)-AryA, 
 (25) N(R C )—C(O)-HetA, 
 (26) N(R C )—C(O)—N(R D )R E , 
 (27) N(R A )—C(O)C(O)-CycA, 
 (28) N(R A )—C(O)C(O)-AryA, 
 (29) N(R A )—C(O)C(O)-HetA, 
 (30) N(R A )—C(O)C(O)—N(R D )R E , 
 (31) N(R C )—C(O)C(O)-CycA, 
 (32) N(R C )—C(O)C(O)-AryA, 
 (33) N(R C )—C(O)C(O)-HetA, or 
 (34) N(R C )—C(O)C(O)—N(R D )R E ; 
 
 each j is independently an integer equal to zero, 1, or 2; 
 R 2  is H or C 1-6  alkyl; or alternatively R 1  and R 2  together with the ring carbon atom to which they are both attached form (i) a 3- to 7-membered saturated carbocyclic ring or (ii) a 4- to 7-membered saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, where independently each N is optionally substituted with C 1-6  alkyl and each S is optionally oxidized to S(O) or S(O) 2 ; 
 each R 3  is independently H or C 1-6  alkyl, and each R 4  is independently H or C 1-6  alkyl; or alternatively R 3  and R 4  attached to the same carbon atom together form oxo or thioxo; 
 each R 5  is independently H or C 1-6  alkyl, and each R 6  is independently H or C 1-6  alkyl; or alternatively R 5  and R 6  attached to the same carbon atom together form oxo or thioxo; 
 R 7  is H or C 1-6  alkyl; 
 R 8  is H or C 1-6  alkyl; or alternatively R 7  and R 8  together form oxo or thioxo; 
 R 9  is H or C 1-6  alkyl; 
 R 10  is C 1-6  alkyl substituted with CycC, AryC or HetC; 
 each R A  is independently H or C 1-6  alkyl; 
 each R B  is independently H or C 1-6  alkyl; 
 R C  is C 1-6  alkyl substituted with CycA, AryA, or HetA; or alternatively, when R 1  includes the N(R C ) moiety, R C  and R K  together with (i) the N atom to which R K  is attached, (ii) the N atom to which R C , is attached, (iii) the ring carbon to which R 1  is attached, and (iv) the 1 ring carbon atom between X and the ring carbon to which R 1  is attached, join to form a fused 5- to 7-membered diazacycloalkyl ring, wherein the portion of the fused ring obtained from R C  and R K  is a 1- to 4-membered methylene chain optionally substituted with oxo or C 1-6  alkyl; 
 each R D  and R E  are each independently H or C 1-6  alkyl, or together with the nitrogen to which they are both attached form a 4- to 7-membered saturated heterocyclic ring optionally containing a heteroatom in addition to the nitrogen attached to R D  and R E  selected from N, O, and S, where the S is optionally oxidized to S(O) or S(O) 2 , and wherein the saturated heterocyclic ring is optionally substituted with 1 or 2 substituents each of which is independently C 1-6  alkyl or S(O) 2 —C 1-6  alkyl; 
 R F  is C 1-6  alkyl, or alternatively, when R 1  is SR F  or OR F , R F  and R K  together with (i) the N atom to which R K  is attached, (ii) the S or O atom to which R F  is attached, (iii) the ring carbon to which R 1  is attached, and (iv) the 1 ring carbon atom between X and the ring carbon to which R 1  is attached, join to form a fused 5- to 7-membered oxyazacycloalkyl or thioazacycloalkyl ring, wherein the portion of the fused ring obtained from R F  and R K  is a 1- to 4-membered methylene chain; 
 each CycA is independently C 3-8  cycloalkyl which is optionally substituted with a total of from 1 to 6 substituents, wherein:
 from zero to 6 substituents are each independently:
 (1) halogen, 
 (2) CN 
 (3) C 1-6  alkyl, 
 (4) OH, 
 (5) O—C 1-6  alkyl, 
 (6) C 1-6  haloalkyl, or 
 (7) O—C 1-6  haloalkyl, and 
 
 (ii) from zero to 2 substituents are each independently:
 (1) CycD, 
 (2) AryD, 
 (3) HetD, or 
 (4) C 1-6  alkyl substituted with CycD, AryD, or HetD; 
 
 
 CycB and CycC each independently have the same definition as CycA; 
 each AryA is independently aryl which is optionally substituted with a total of from 1 to 5 substituents, wherein:
 (i) from zero to 5 substituents are each independently:
 (1) C 1-6  alkyl, 
 (2) C 1-6  alkyl substituted with OH, O—C 1-6  alkyl, O—C 1-6  haloalkyl, CN, NO 2 , 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 , S(O) 2 R A , S(O) 2 N(R A )R B , N(R A )C(O)R B , N(R A )CO 2 R B , N(R A )S(O) 2 R B , N(R A )S(O) 2 N(R A )R B , OC(O)N(R A )R B , N(R A )C(O)N(R A )R B , or N(R A )C(O)C(O)N(R A )R B , 
 (3) O—C 1-6  alkyl, 
 (4) C 1-6  haloalkyl, 
 (5) O—C 1-6  haloalkyl, 
 (6) OH, 
 (7) halogen, 
 (8) CN, 
 (9) NO 2 , 
 (10) N(R A )R B , 
 (11) C(O)N(R A )R B , 
 (12) C(O)R A , 
 (13) C(O)—C 1-6  haloalkyl, 
 (14) C(O)OR A , 
 (15) OC(O)N(R A )R B , 
 (16) SR A , 
 (17) S(O)R A , 
 (18) S(O) 2 R A , 
 (19) S(O) 2 N(R A )R B , 
 (20) N(R A )S(O) 2 R B , 
 (21) N(R A )S(O) 2 N(R A )R B , 
 (22) N(R A )C(O)R B , 
 (23) N(R A )C(O)N(R A )R B , 
 (24) N(R A )C(O)—C(O)N(R A )R B , or 
 (25) N(R A )CO 2 R B , and 
 
 (ii) from zero to 2 substituents are each independently:
 (1) CycD, 
 (2) AryD, 
 (3) HetD, or 
 (4) C 1-6  alkyl substituted with CycD, AryD, or HetD; 
 
 
 AryB and AryC each independently have the same definition as AryA; 
 each HetA is independently a heteroaryl which is optionally substituted with a total of from 1 to 5 substituents, wherein:
 (i) from zero to 5 substituents are each independently:
 (1) C 1-6  alkyl, 
 (2) C 1-6  alkyl substituted with OH, O—C 1-6  alkyl, O—C 1-6  haloalkyl, CN, NO 2 , 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 , S(O) 2 R A , S(O) 2 N(R A )R B , N(R A )C(O)R B , N(R A )CO 2 R B , N(R A )S(O) 2 R B , N(R A )S(O) 2 N(R A )R B , OC(O)N(R A )R B , N(R A )C(O)N(R A )R B , or N(R A )C(O)C(O)N(R A )R B , 
 (3) O—C 1-6  alkyl, 
 (4) C 1-6  haloalkyl. 
 (5) O—C 1-6  haloalkyl, 
 (6) OH, 
 (7) oxo, 
 (8) halogen, 
 (9) CN, 
 (10) NO 2 , 
 (11) N(R A )R B , 
 (12) C(O)N(R A )R B , 
 (13) C(O)R A , 
 (14) C(O)—C 1-6  haloalkyl, 
 (15) C(O)OR A , 
 (16) OC(O)N(R A )R B , 
 (17) SR A , 
 (18) S(O)R A , 
 (19) S(O) 2 R A , 
 (20) S(O) 2 N(R A )R B , 
 (21) N(R A )S(O) 2 R B , 
 (22) N(R A )S(O) 2 N(R A )R B , 
 (23) N(R A )C(O)R B , 
 (24) N(R A )C(O)N(R A )R B , 
 (25) N(R A )C(O)—C(O)N(R A )R B , or 
 (26) N(R A )CO 2 R B , and 
 
 (ii) from zero to 2 substituents are each independently:
 (1) CycD, 
 (2) AryD, 
 (3) HetD, or 
 (4) C 1-6  alkyl substituted with CycD, AryD, or HetD; 
 
 
 HetB and HetC each independently have the same definition as HetA; 
 each CycD is independently a C 3-8  cycloalkyl which is optionally substituted with from 1 to 4 substituents each of which is independently halogen, C 1-6  alkyl, OH, O—C 1-6  alkyl, or C 1-6  haloalkyl; 
 each AryD is independently phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted with from 1 to 5 substituents each of which is independently any one of the substituents (1) to (25) as set forth above in part (i) of the definition of AryA; 
 each HetD is independently a 5- or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from N, O and S, wherein the heteroaromatic ring is optionally substituted with from 1 to 4 substituents each of which is independently halogen, C 1-6  alkyl, C 1-6  haloalkyl, O—C 1-6  alkyl, O—C 1-6  haloalkyl, or hydroxy; 
 each aryl is independently (i) phenyl, (ii) a 9- or 10-membered bicyclic, fused carbocyclic ring system in which at least one ring is aromatic, or (iii) an 11- to 14-membered tricyclic, fused carbocyclic ring system in which at least one ring is aromatic; 
 each heteroaryl is independently (i) a 5- or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from N, O and S, wherein each N is optionally in the form of an oxide, or (ii) a 9- or 10-membered bicyclic, fused ring system containing from 1 to 4 heteroatoms independently selected from N, O and S, wherein either one or both of the rings contain one or more of the heteroatoms, at least one ring is aromatic, each N is optionally in the form of an oxide, and each S in a ring which is not aromatic is optionally S(O) or S(O) 2 ; 
 and provided that:
 when R K  is:
 (1) H, 
 (2) C 1-6  alkyl, 
 (3) C 1-6  alkyl substituted with T, wherein T is CO 2 R A , CN, SO 2 R A , N(R D )R E , C(O)N(R D )R E , or N(R A )—C(O)R B , 
 (4) C 1-6  haloalkyl, 
 (5) C(O)R A , 
 (6) C(O)—C 1-6  haloalkyl, 
 (8) C(O)—U and U is AryB or HetB, 
 (9) C(O)—C 1-6  alkylene-U 
 (10) C(O)N(R D )R E , 
 (11) C(O)—C 1-6  alkylene-N(R D )R E , 
 (14) C(O)C(O)—N(R D )R E  (except when R D  and R E  together with the N to which they are both attached form a saturated heterocyclic ring), 
 (16) SO 2 R A , or 
 (18) SO 2 —C 1-6  alkylene-U; 
 
 then R 1  is:
 (4) C 1-6  alkyl substituted with V, wherein V is S(O)R A , N(R A )—C(O)C(O)—N(R D )R E , N(R A )—SO 2 R B , N(R A )—C 1-6  alkylene-SO 2 R B , N(R A )C(O)—C 1-6  alkylene-SO 2 R B , N(R A )—SO 2 N(R D )R E , N(R A )—CO 2 R B , or N(R A )—C(O)N(R D )R E  when N(R A )—C(O)N(R D )R E  is other than NH—C(O)NH 2 , 
 (5) C 1-6  alkyl substituted with W, wherein W is O—C 1-6  alkylene-CycA, O—C 1-6  alkylene-AryA, O—C 1-6  alkylene-HetA, S(O) j —C 1-6  alkylene-CycA, S(O) j —C 1-6  alkylene-AryA, S(O) j —C 1-6  alkylene-HetA, N(R A )—C(O)-AryA, or N(R A )—C(O)-HetA, 
 (7) N(R A )—SO 2 N(R D )R E  when R D  and R E  together with the N to which they are both attached form an optionally substituted saturated heterocyclic ring, 
 (10) N(R C )R A  when R C  and R K  are involved in the formation of an optionally substituted fused diazacycloalkyl ring, 
 (12) N(R C )—C(O)R A  when R C  and R K  are involved in the formation of an optionally substituted fused diazacycloalkyl ring, 
 (13) S(O) j R F  when R F  and R K  are involved in the formation of a fused thioazacycloalkyl ring, 
 (14) OR F  when R F  and R K  are involved in the formation of a fused oxyazacycloalkyl ring, 
 (16) CycA, 
 (21) N(R A )—C(O)-HetA, 
 (22) N(R A )—C(O)—N(R D )R E  when R D  and R E  together with the N to which they are both attached form an optionally substituted saturated heterocyclic ring, 
 (23) N(R C )—C(O)-CycA when R C  and R K  are involved in the formation of an optionally substituted fused diazacycloalkyl ring, 
 (24) N(R C )—C(O)-AryA when R C  and R K  are involved in the formation of an optionally substituted fused diazacycloalkyl ring, 
 (25) N(R C )—C(O)-HetA, 
 (26) N(R C )—C(O)—N(R D )R E  when (i) R D  and R E  together with the N to which they are both attached form a optionally substituted saturated heterocyclic ring or (ii) R C  and R K  are involved in the formation of an optionally substituted fused diazacycloalkyl ring), 
 (27) N(R A )—C(O)C(O)-CycA, 
 (28) N(R A )—C(O)C(O)-AryA, 
 (29) N(R A )—C(O)C(O)-HetA, 
 (30) N(R A )—C(O)C(O)—N(R D )R E , 
 (31) N(R C )—C(O)C(O)-CycA, 
 (32) N(R C )—C(O)C(O)-AryA, 
 (33) N(R C )—C(O)C(O)-HetA, or 
 (34) N(R C )—C(O)C(O)—N(R D )R E . 
 
 
 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 R 9  is H; and   R 10  is:
 (1) CH 2 -phenyl or CH 2 -HetC, wherein the phenyl is optionally substituted with a total of from 1 to 3 substituents, wherein (i) from zero to 3 substituents are each independently bromo, chloro, fluoro, C 1-4  alkyl, CF 3 , C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2 , S—C 1-4  alkyl, SO 2 —C 1-4  alkyl, or SO 2 N(C 1-4  alkyl) 2 , and (ii) from zero to 1 substituent is a heteroaromatic selected from the group consisting of imidazolyl, triazolyl, oxadiazolyl, pyrrolyl, and pyrazolyl, wherein the heteroaomatic ring is optionally substituted with 1 or 2 substituents each of which is independently Cl, Br, F, C 1-4  alkyl, CF 3 , O—C 1-4  alkyl, OCF 3 , or OH, 
 (2) CH 2 -HetC, wherein HetC is a heteroaryl which is (i) a 5- or 6-membered heteroaromatic ring containing a total of from 1 to 4 heteroatoms independently selected from 1 to 4 N atoms, zero to 1 O atom, and zero to 1 S atom, or (ii) a 9 or 10-membered bicyclic, fused ring system in which one ring is a benzene ring and the other ring is a 5- or 6-membered heteroaromatic ring containing from 1 to 3 heteroatoms independently selected from zero to 3 N atoms, zero to 1 O atom, and zero to 1 S atom, wherein the heteroaryl is optionally substituted with from 1 to 3 substituents each of which is independently Cl, Br, F, or C 1-4  alkyl. 
   
     
     
         5 . A compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 R K  is:
 (1) H, 
 2) C 1-4  alkyl, 
 (3) C 1-4  alkyl substituted with T, wherein T is CO 2 R A , CN, N(R D )R E , or C(O)N(R D )R E , 
 (4) C(O)R A , 
 (5) C(O)—C 1-4  fluoroalkyl. 
 (6) CO 2 R A , 
 (7) SO 2 R A , 
 8) SO 2 -AryB, 
 (9) SO 2 N(R D )R E , 
 (10) C(O)N(R D )R E , 
 (11) C(O)C(O)—N(R D )R E , 
 (12) C(O)—C 1-4  alkylene-N(R D )R E , 
 (13) CycB, 
 (14) C 1-4  alkyl substituted with U, wherein U is CycB, AryB, or HetB, or 
 (15) C 1-4  alkyl substituted with C(O)N(R A )—C 1-4  alkylene-HetB; 
   R1 is:
 (1) H, 
 (2) C 1-4  alkyl, 
 (3) C 1-4  alkyl substituted with V, wherein V is OH, O—C 1-4  alkyl, SR A , S(O)R A , SO 2 R A , N(R D )R E , C(O)N(R D )R E , N(R A )—C(O)C(O)—N(R D )R E , N(R A )—C(O)R B, N(R A )—SO 2 R B , N(R A )—C 1-4  alkylene-SO 2 R B , N(R A )C(O)—C 1-4  alkylene-SO 2 R B , N(R A )—SO 2 N(R D )R E , or N(R A )—CO 2 R B , 
 (4) C 1-4  alkyl substituted with W, wherein W is CycA, AryA, HetA, O—C 1-4  alkylene-AryA, O—C 1-4  alkylene-HetA, or N(R A )—C(O)-HetA, 
 (5) N(R A )—SO 2 R B , 
 (6) N(R A )—SO 2 N(R D )R E , 
 (7) N(R A )—CO 2 R B , 
 (8) N(R D )R E , 
 (9) N(R C )R A , 
 (10) N(R A )—C(O)R B , 
 (11) N(R C )—C(O)R A , 
 (12) SR F , S(O)R F , or S(O) 2 R F , 
 (13) N(R A )—C(O)-HetA, 
 (14) N(R C )—C(O)—N(R D )R E , or 
 (15) N(R A )—C(O)C(O)—N(R D )R E , or 
 (16) N(R C )—C(O)C(O)—N(R D )R E ; 
   R 2  is H or C 1-4  alkyl; or alternatively R 1  and R 2  together with the ring carbon atom to which they are both attached form (i) a 3- to 6-membered saturated carbocyclic ring or (ii) a 6-membered saturated heterocyclic ring containing I heteroatom selected from N, O and S, where the N is optionally substituted with C 1-4  alkyl and the S is optionally oxidized to S(O) or S(O) 2 ;   each R 3  is independently H or C 1-4  alkyl, and each R 4  is independently H or C 1-4  alkyl; or alternatively R 3  and R 4  attached to the same carbon atom together form oxo;   each R 5  is independently H or C 1-4  alkyl, and each R 6  is independently H or C 1-4  alkyl; or alternatively R 5  and R 6  attached to the same carbon atom together form oxo;   R 7  is H or C 1-4  alkyl:   R 8  is H or C 1-4  alkyl: or alternatively R 7  and R 8  together form oxo;   R 9  is H or C 1-4  alkyl;   R 10  is C 1-4  alkyl substituted with CyeC, AryC or HetC;   each R A  is independently H or C 1-4  alkyl:   each R B  is independently H or C 1-4  alkyl;   R C  is C 1-4  alkyl substituted with CycA, AryA, or HetA; or alternatively, when X is N(R K ) and R 1  includes the N(R C ) moiety, R C  and R K  together with (i) the N atom to which R K  is attached, (ii) the N atom to which R C  is attached, (iii) the ring carbon to which R 1  is attached, and (iv) the 1 ring carbon atom between X and the ring carbon to which R 1  is attached, join to form a fused 5- or 6-membered diazacycloalkyl ring; wherein the portion of the fused ring obtained from R C  and R K  is a 1- to 3-membered methylene chain optionally substituted with oxo or C 1-4  alkyl;   each R D  and R E  are independently H or C 1-4  alkyl, or together with the nitrogen to which they are both attached form a 5- or 6-membered saturated heterocyclic ring optionally containing a heteroatom in addition to the nitrogen attached to R C  and R D  selected from N, O, and S, where the S is optionally oxidized to S(O) or S(O) 2 , and wherein the saturated heterocyclic ring is optionally substituted with 1 or 2 substituents each of which is independently C 1-4  alkyl or S(O) 2 —C 1-4  alkyl;   R F  is C 1-4  alkyl, or alternatively, when X is N(R K ) and R 1  is SR F , R F  and R K  together with (i) the N atom to which R K  is attached, (ii) the S atom to which R F  is attached, (iii) the ring carbon to which R 1  is attached, and (iv) the 1 ring carbon atom between X and the ring carbon to which R 1  is attached, join to form a fused 5- or 6-membered thioazacycloalkyl ring, wherein the portion of the fused ring obtained from R F  and R K  is a 1- to 3-membered methylene chain;   each CycA is independently a C 3-6  cycloalkyl which is optionally substituted with 1 or 2 substituents each of which is independently C 1-4  alkyl, OH, or O—C 1-4  alkyl;   CycB is a C 3-6  cycloalkyl which is optionally substituted with 1 or 2 substituents each of which is independently C 1-4  alkyl, OH, or O—C 1-4  alkyl;   CycC is a C 3-6  cycloalkyl which is optionally substituted with 1 or 2 substituents each of which is independently C 1-4  alkyl, OH, or O—C 1-4  alkyl;   each AryA is independently phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted with from 1 to 3 substituents each of which is independently:
 (1) C 1-4  alkyl, which is optionally substituted with OH, O—C 1-4  alkyl, O—C 1-4  haloalkyl, CN, 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 , or SO 2 N(R A )R B , 
 (2) O—C 1-4  alkyl, 
 (3) C 1-4  haloalkyl, 
 (4) O—C 1-4  haloalkyl, 
 (5) OH, 
 (6) halogen, 
 (7) CN, 
 (8) NO 2 , 
 (9) N(R A )R B , 
 10) C(O)N(R A )R B , 
 (11) C(O)R A , 
 (12) C(O)—C 1-4  haloalkyl, 
 (13) CO 2 R A , 
 (14) SR A , 
 (15) S(O)R A , 
 (16) SO 2 R A , or 
 (17) SO 2 N(R A )R B , 
   AryB independently has the same definition as AryA;   AryC is phenyl or naphthyl, wherein the phenyl or naphthyl is:
 (i) optionally substituted with from 1 to 3 substituents each of which is independently any one of the substituents (1) to (17) as set forth above in the definition of AryA, and 
 (ii) optionally substituted with:
 (1) AryD, 
 (2) HetD, 
 (3) CycD, or 
 (4) C 1-4  alkyl substituted with CycD, AryD or HetD; 
 
   each HetA is independently a 5- or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from zero to 4 N atoms, zero or 1 O atom, and zero or 1 S atom, wherein each N is optionally in the form of an oxide, and wherein the heteroaromatic ring is optionally substituted with from 1 to 3 substituents each of which is independently halogen, C 1-4  alkyl, or OH;   HetB is a 5- or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from zero to 4 N atoms, zero or 1 O atom, and zero or 1 S atom, wherein the heteroaromatic ring is optionally substituted with from 1 to 3 substituents each of which is independently halogen, C 1-4  alkyl, or OH;   HetC is a 5- or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from zero to 4 N atoms, zero or 1 O atom, and zero or 1 S atom, wherein each N is optionally in the form of an oxide, and wherein the heteroaromatic ring is:
 (i) optionally substituted with from 1 to 3 substituents each of which is independently halogen, C 1-4  alkyl, or OH; and 
 (ii) optionally substituted with AryD, HetD, CycD, or C 1-4  alkyl substituted with AryD, HetD or CycD; 
   each CycD is independently a C 3-6  cycloalkyl which is optionally substituted with 1 or 2 substituents each of which is independently C 1-4  alkyl, OH, or O—C 1-4  alkyl;   each AryD is independently phenyl or naphthyl, wherein the phenyl or naphthyl is optionally substituted with from 1 to 3 substituents each of which is independently any one of the substituents (1) to (17) as set forth above in the definition of AryA; and   each HetD is independently a 5- or 6-membered heteroaromatic ring containing from to 4 heteroatoms independently selected from zero to 4 N atoms, zero or 1 O atom, and zero or 1 S atom, wherein the heteroaromatic ring is optionally substituted with from 1 to 3 substituents each of which is independently halogen, C 1-4  alkyl, or OH;   and provided that:
 when R K  is:
 (1) H, 
 (2) C 1-4  alkyl, 
 (3) C 1-4  alkyl substituted with T, wherein T is CO 2 R A , CN, N(R D )R E , or C(O)N(R D )R E , 
 (4) C(O)R A , 
 (5) C(O)—C 1-4  fluoroalkyl. 
 (7) SO 2 R A , 
 (10) C(O)N(R D )R E , 
 (11) C(O)C(O)—N(R D )R E  (except when R D  and R E  together with the N to which they are both attached form a saturated heterocyclic ring), or 
 (12) C(O)—C 1-4  alkylene-N(R D )R E , 
 then R 1  is: 
 (3) C 1-4  alkyl substituted with V, wherein V is S(O)R A , N(R A )—C(O)C(O)—N(R D )R E , N(R A )—SO 2 R B , N(R A )—C 1-4  alkylene-SO 2 R B , N(R A )C(O)—C 1-4  alkylene-SO 2 R B , N(R A )—SO 2 N(R D )R E , or N(R A )—CO 2 R B , 
 (4) C 1-4  alkyl substituted with W, wherein W is O—C 1-4  alkylene-AryA, O—C 1-4  alkylene-HctA, or N(R A )—C(±)-HetA, 
 (6) N(R A )—SO 2 N(R D )R E  when R D  and R E  together with the N to which they are both attached form an optionally substituted saturated heterocyclic ring, 
 (9) N(R C )R A  when R C  and R K  are involved in the formation of an optionally substituted fused diazacycloalkyl ring, 
 (11) N(R C )—C(O)R A  when R C  and R K  are involved in the formation of an optionally substituted fused diazacycloalkyl ring, 
 (12) SR F , S(O)R F , or S(O) 2 R F  when R F  and R K  are involved in the formation of a fused thioazacycloalkyl ring, 
 (13) N(R A )—C(O)-HetA, 
 (14) N(R C )—C(O)—N(R D )R E  when (i) R D  and R E  together with the N to which they are both attached form a optionally substituted saturated heterocyclic ring or (ii) R C  and R K  are involved in the formation of an optionally substituted fused diazacycloalkyl ring), 
 (15) N(R A )—C(O)C(O)—N(R D )R E , or 
 (16) N(R C )—C(O)C(O)—N(R D )R E . 
 
   
     
     
         6 . A compound according to  claim 5 , or a pharmaceutically acceptable salt thereof, which is a compound of formula: 
       
         
           
           
               
               
           
         
       
     
     
         7 . (canceled) 
     
     
         8 . A compound according to  claim 6 , or a pharmaceutically acceptable salt thereof, which is a compound of Formula V, wherein
 R 1  is N(R A )—C(O)C(O)—N(R D )R E  or N(R C )—C(O)C(O)—N(R D )R E ; and   R 2  is H.   
     
     
         9 . A compound, or a pharmaceutically acceptable salt thereof, which is a compound selected from the group consisting of:
 (+) N-[2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-8-(2-phenylethyl)-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl]-N,N′,N′-trimethylethanediamide;   (−) N-[2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-8-(2-phenylethyl)-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl]-N,N′,N′-trimethylethanediamide;   N-(8-[(dimethylamino)(oxo)acetyl]-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-(cyclohexylmethyl)-N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N′,N′-dimethylethanediamide;   N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N-benzyl-N′,N′-dimethylethanediamide;   N-(8-benzyl-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-[2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-(methylsulfonyl)-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl]-N,N′,N′-trimethylethanediamide;   (+)N-(2-{[(3-chloro-4-fluorobenzyl)amino]carbonyl}-8-cyclopropyl-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−)N-(2-{[(3-chloro-4-fluorobenzyl)amino]carhonyl}-8-cyclopropyl-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-8-cyclopropyl-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-8-cyclopropyl-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(8-(cyclopropylmethyl)-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′, trimethylethanediamide;   (−) N-(8-(cyclopropylmethyl)-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′, trimethylethanediamide;   (+) N-(8-cyclopentyl-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide:   (−) N-(8-cyclopentyl-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N-isobutyl-N′,N′-dimethylethanediamide;   (+) N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-8-isopropyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-8-isopropyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-(4-fluorobenzyl)-3-hydroxy-8-methyl-10-{methyl[morpholin-4-yl(oxo)acetyl]amino}-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-2-carboxamide;   (+) N-(8-(cyclopropyl methyl)-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(8-(cyclopropylmethyl)-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(8-cyclopropyl-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(8-cyclopropyl-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-(2-{[(3-chloro-4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(8-ethyl-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(8-ethyl-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-ethyl-N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N′,N′-dimethylethanediamide;   (+) N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-isopropyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-isopropyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-(8-acetyl-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-(4-fluorobenzyl)-3-hydroxy-8-methyl-10-{methyl[oxo(pyrrolidin-1-yl)acetyl]amino}-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-2-carboxamide;   10-[acetyl(cyclohexylmethyl)amino]-N-(4-fluorobenzyl)-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   10-[acetyl(benzyl)amino]-N-(4-fluorobenzyl)-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   8-acetyl-10-[benzyl(methyl)amino]-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   (+) N-(2-{[(3-chlorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(3-chlorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide:   (−) N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(8-ethyl-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(8-ethyl-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-ethyl-N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N′,N′-dimethylethanediamide;   (−) N-(4-fluorobenzyl)-3-hydroxy-8-methyl-10-{methyl[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino}-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-2-carboxamide;   (+) N-(4-fluorobenzyl)-3-hydroxy-8-methyl-10-{methyl[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino}-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-2-carboxamide;   10-[[(dimethylamino)sulfonyl](methyl)amino]-N-(4-fluorobenzyl)-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   (+)N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(2-([(4-fluoro-3-methylbenzyl)amino]carbonyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   11-[(dimethylamino)(oxo)acetyl]-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-6,7,9,10,11,12-hexahydro-4H-8,12-methanopyrimido[1,2-a][1,4,7]triazonine-2-carboxamide;   10-[benzyl(methyl)amino]-N-(4-fluorobenzyl)-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-2-carboxamide;   N′-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N-dimethylethanediamide;   10-[acetyl(isobutyl)amino]-N-(4-fluorobenzyl)-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   10-[(cyclohexylmethyl)amino]-N-(4-fluorobenzyl)-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   N-(4-fluorobenzyl)-3-hydroxy-8-methyl-10-[methyl(methylsulfonyl)amino]-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   10-(benzylamino)-N-(4-fluorobenzyl)-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   N-(4-fluorobenzyl)-3-hydroxy-8-methyl-10-[(methylsulfonyl)amino]-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   methyl (2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)methylcarbamate;   8-[(dimethylamino)(oxo)acetyl]-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   8-benzyl-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   N-(4-fluorobenzyl)-3-hydroxy-10-(isobutylamino)-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   10-[acetyl(methyl)amino]-N-(4-fluorobenzyl)-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   N-(4-fluorobenzyl)-3-hydroxy-8-(methylsulfonyl)-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   10-(acetylamino)-N-(4-fluorobenzyl)-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide; and   8-acetyl-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide.   
     
     
         10 . A compound according to  claim 9 , or a pharmaceutically acceptable salt thereof, which is a compound selected from the group consisting of:
 (−) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-8-cyclopropyl-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(8-(cyclopropylmethyl)-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(8-(cyclopropylmethyl)-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(8-cyclopentyl-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N-isobutyl-N′,N′-dimethylethanediamide;   (−) N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-8-isopropyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-(4-fluorobenzyl)-3-hydroxy-8-methyl-10-{methyl[morpholin-4-yl(oxo)acetyl]amino}-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-2-carboxamide;   (+) N-(8-(cyclopropylmethyl)-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(8-(cyclopropylmethyl)-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(8-cyclopropyl-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(8-cyclopropyl-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d]) [1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-(2-{[(3-chloro-4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]-diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(8-ethyl-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(8-ethyl-2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-ethyl-N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-dimethylethanediamide (HCl salt);   (+) N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-isopropyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido 1,2-[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-isopropyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(2-{[(3-chlorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(3-chlorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′N′-trimethylethanediamide;   (+) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(3-chloro-4-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(8-ethyl-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(8-ethyl-2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   N-ethyl-N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-dimethylethanediamide;   (+)N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (−) N-(2-{[(4-fluorobenzyl)amino]carbonyl}-3-hydroxy-8-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide;   (+) N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide; and   (−) N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide.   
     
     
         11 . A pharmaceutical composition comprising an effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         12 . A method for the inhibition of HIV integrase in a subject in need thereof which comprises administering to the subject an effective amount of the compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         13 . A method for the treatment or prophylaxis of infection by HIV or for the treatment, prophylaxis, or delay in the onset of AIDS in a subject in need thereof, which comprises administering to the subject an effective amount of the compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled)