AZA-AND POLYAZA-NAPHTHALENYL CARBOXAMIDES USEFUL AS HIV INTEGRASE INHIBITORS

Abstract: Aza- and polyaza-naphthalenyl carboxamide derivatives including certain quinoline carboxamide and naphthyridine carboxamide derivatives are described as inhibitors of HIV integrase and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating, or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

Description: AZA-AND POLYAZA-NAPHTHALENYL CARBOXAMIDES USEFUL AS HIV INTEGRASE INHIBITORS FIELD OF THE INVENTION The present invention is directed to aza-and polyaza-naphthalenyl carboxamides and pharmaceutically acceptable salts thereof, wherein the carboxamido nitrogen is part of a heterocyclic ring system. The present invention is also directed to the synthesis of the compounds and salts thereof and their use as inhibitors of the HIV integrase enzyme. The compounds of the present invention include 7-carboxamido-8-hydroxy-1, 6-naphthyridines, quinolines, and quinoxalines in which the carboxamido nitrogen is part of a saturated or unsaturated heterocyclic ring which is optionally fused to a phenyl ring or a second heterocyclic ring. The compounds and pharmaceutically acceptable salts thereof of the present invention are useful for preventing or treating infection by HIV and for treating AIDS. References are made throughout this application to various published documents in order to more fully describe the state of the art to which this invention pertains. The disclosures of these references are hereby incorporated by reference in their entireties. BACKGROUND OF THE INVENTION A retrovirus designated human immunodeficiency virus (HIV) is the etiological agent of the complex disease that includes progressive destruction of the immune system (acquired immune deficiency syndrome; AIDS) and degeneration of the central and peripheral nervous system. This virus was previously known as LAV, HTLV-III, or ARV. A common feature of retrovirus replication is the insertion by virally-encoded integrase of proviral DNA into the host cell genome, a required step in HIV replication in human T-lymphoid and monocytoid cells. Integration is believed to be mediated by integrase in three steps: assembly of a stable nucleoprotein complex with viral DNA sequences; cleavage of two nucleotides from the 3'termini of the linear proviral DNA; covalent joining of the recessed 3'OH termini of the proviral DNA at a staggered cut made at the host target site. The fourth step in the process, repair synthesis of the resultant gap, may be accomplished by cellular enzymes. Nucleotide sequencing of HIV shows the presence of a pol gene in one open reading frame [Ratner, L. et al., Nature, 313,277 (1985)]. Amino acid sequence homology provides evidence that the pol sequence encodes reverse transcriptase, integrase and an HIV protease [Toh, H. et al., EMBO J. 4,1267 (1985); Power, M. D. et al., Science, 231,1567 (1986); Pearl, L. H. et al., Nature, 329,351 (1987)]. All three enzymes have been shown to be essential for the replication of HIV. It is known that some antiviral compounds which act as inhibitors of HIV replication are effective agents in the treatment of AIDS and similar diseases, including reverse transcriptase inhibitors such as azidothymidine (AZT) and efavirenz and protease inhbitors such as indinavir and nelfinavir. The compounds of this invention are inhibitors of HIV integrase and inhibitors of HIV replication. The following references are of interest as background: Chemical Abstracts No. 33-2525 discloses the preparation of 5-chloro 8-hydroxy-1, 6-naphthyridine-7-carboxylic acid amide from the corresponding methyl ester. Derwent Abstract No. 97-048296 is an abstract of Japanse Published Application No. 08301849. The abstract discloses certain heterocyclic carboxamide derivatives. The derivatives are said to be useful as tachykinin receptor inhibitors. N (3,5-bis (trifluoromethyl) benzyl-1, 2-dihydro-N, 2-dimethyl-l-oxo-4-pyrrolidino-3- isoquinoline carboxamide is specifically disclosed. WO 98/13350 discloses certain quinoline derivatives which inhibit vascular endothelial growth factor. The reference also discloses certain 1,8naphthryidine derivatives; i. e., Examples 53 and 54 respectively describe preparations of 2-acetamido-5-(2-fluoro-5-hydroxy-4-methylanilino)-1, 8-naphthyridine and 2-amino-5- (2-fluoro-5-hydroxy-4-methylanilino)-1, 8-naphthyridine. WO 99/32450 discloses 4-hydroxyquinoline-2-carboxamide derivatives which are proposed for use in treating herpes virus infections. WO 98/11073 discloses 8-hydroxyquinoline-7carboxamides which are proposed for use in treating herpes virus infections. SUMMARY OF THE INVENTION The present invention is directed to novel aza-and polyazanaphthalenyl carboxamides, in which the carboxamido nitrogen is part of a heterocyclic ring system. These compounds are useful in the inhibition of HIV integrase, the prevention of infection by HIV, the treatment of infection by HIV and in the prevention, treatment, and delay in the onset of AIDS and/or ARC, either as compounds, pharmaceutically acceptable salts or hydrates (when appropriate), pharmaceutical composition ingredients, whether or not in combination with other HtV/AIDS antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. More particularly, the present invention includes a compound of Formula (I) : EMI3.1 wherein A is a 5-or 6-membered saturated or unsaturated heterocyclic ring which contains from 1 to 4 nitrogen atoms one of which is directly attached to the exocyclic carbonyl moiety, zero to 2 heteroatoms selected from oxygen and sulfur, and a balance of carbon atoms; wherein the heterocyclic ring is optionally fused to a phenyl ring or to a second 5-or 6-membered heterocyclic ring which is saturated or unsaturated and which contains from 1 to 4 nitrogen atoms, zero to 2 heteroatoms selected from oxygen and sulfur, and a balance of carbon atoms, wherein the second heterocyclic ring is optionally fused to a phenyl ring; A is substituted by Rl, R2, R3, and R4; XisNorC-Q1 ; Y is N or C-Q2, provided that X and Y are not both N; ZlisNorC-Q3 ; Z2 is N or C-Q4 ; Z3 is N or CH; each of Q1, Q2, Q3, and Q4 is independently (1)-H, (2)-C1-6 alkyl, (3) -C1-6 haloalkyl, (4) -O-C1-6 alkyl, (5) -O-C1-6 haloalkyl, (6) halo, (7)-CN, (8)-Ci-6 alkyl-ORa, (9)-Cp-6 alkyl-C (=O) Ra, (10) -C0-6 alkyl-C02Ra, (11) -C0-6 alkyl-SRa, (12)-N (Ra) 2, (13) -C1-6 alkyl-N (Ra) 2, (14) -C0-6 alkyl-C (=O) N (Ra) 2, (15) -C0-6 alkyl-G-C1-6 alkyl-C(=O) N (Ra) 2, wherein G is O, S, N (Ra), or N(SO2Ra), (16)-N (Ra)-C (Ra) =O, (17)-C1 alkyl-N (Ra)-C (Ra) =O, (18)-C (=O)-N (Ra) -C1-6 alkyl-[C(=O)]0-1-N(Ra)2, (19)-C (=O)-N (Ra)-C1-6 alkyl substituted with 1 or 2-ORa, (20) -C0-6 alkyl-SO2Ra, (21) -C0-6 alkyl-N (Ra) SO2Ra, (22)-C2-6 alkenyl, (23)-C2-6 alkenyl-C (=O)-N (Ra) 2, (24)-C2-5 alkynyl, (25)-C2-5 alkynyl-CH2N (Ra) 2, (26) -C2-5 alkynyl-CH2ORa, (27)-C2-5 alkynyl-CH2S (O) n-Ra, or EMI5.1 (30)-C (=NRa)-N (Ra) 2, (31)-N (Ra)-C1-6 alkyl-S (O) nRa, (32)-N (Ra)-C1-6 alkyl-ORa, (33)-N (Ra)-C1-6 alkyl-N (Ra) 2, (34) -N(Ra)-C1-6 alkyl-N(Ra)-C(Ra)=O, (35)-N (Ra)-C0-6 alkyl-[C(=O)]1-2N(Ra)2, (36)-N (Ra)-C1-6 alkyl-CO2Ra, (37)-N (Ra) C (=O) N (Ra)-C1-6 alkyl-C(=O) N (Ra) 2, (38)-N (Ra) C (=O)-C1-6 alkyl-N (Ra) 2, (39)-N (Ra)-S02-N (Ra) 2, (40)-Rk, (41) -C1-6 alkyl substituted with Rk, (42)-C1-6 haloalkyl substituted with Rk, (43)-C2-5 alkenyl-Rk, (44) -C2-5 alkynyl-Rk, (45)-Cp-6 alkyl-O-Rk, (46) -C0-6 alkyl-O-C1-6 alkyl-Rk, (47)-Cp-6 alkyl-S (O) n-Rk, (48)-Cp-6 alkyl-S (O) n-C1-6 alkyl-Rk, (49)-0-Cl-6 alkyl-ORk, (50) -O-C1-6 alkyl-O-C1-6 alkyl-Rk, (51) -O-C1-6 alkyl-S (O) nRk, (52) -C0-6 alkyl-N (Rc)-Rk, (53) -C0-6 alkyl-N (Rc)-C1-6 alkyl substituted with one or two Rk groups, (54) -C0-6 alkyl-N (RC) -Cl-6 alkyl-ORk, (55) -C0-6 alkyl-C (=O)-Rk, (56) -C0-6 alkyl-C (=O) N (Ra)-Rk, (57)-CO-6 alkyl-N (Ra) C (=O)-Rk, (58) -C0-6 alkyl-C (=O) N (Ra)-C1-6 alkyl-Rk, or (59) -C0-6 alkyl-N (Ra)-C0-6 alkyl-S (O) nRk; each of R1 and R2 is independently: (1)-H, (2) -C1-6 alkyl, (3)-C1-6 haloalkyl, (4) -O-C1-6 alkyl, (5) -O-C1-6 haloalkyl, (6)-OH (7) halo, (8)-NO2, (9)-CN, (10) -C1-6 alkyl-ORa, (11) -C0-6 alkyl-C(=O)Ra, (12) -C0-6 alkyl-C02Ra, (13) -C0-6 alkyl-SRa, (14)-N (Ra) 2, (15)-Ci-6 alkyl-N (Ra) 2, (16) -C0-6 alkyl-C (=O) N (Ra) 2, (17)-Ci-6 alkyl-N (Ra)-C (Ra) =O, (18)-S02Ra, (19)-N (Ra) S02Ra, (20)-C2-5 alkenyl, (21) -O-C1-6 alkyl-ORa, (22) -O-C1-6 alkyl-SRa, (2) -O-C1-6 alkyl-NH-CO2Ra, (24) -O-C2-6 alkyl-N (Ra) 2, (25)-N (Ra)-Cl-6 alkyl-SRa, (26)-N (Ra)-Cl-6 alkyl-ORa, (27)-N (Ra)-C1-6 alkyl-N (Ra) 2, (28)-N (Ra) -C1-6 alkyl-N (Ra)-C (Ra) =O, (29)-Rk, (30) -C1-6 alkyl substituted with 1 or 2 Rk groups, (31)-C1-6 haloalkyl substituted with 1 or 2 Rk groups, (32) -C2-5 alkenyl-Rk, (33) -C2-5 alkynyl-Rk, (34)-O-Rk (35) -O-C1-6 alkyl-Rk, (36)-S S(O) n-Rk, (37)-S (O) n-C1-6 alkyl-Rk, (38) -O-C1-6 alkyl-ORk, (39) -O-C1-6 alkyl-O-C1-6 alkyl-Rk, (40) -O-C1-6 alkyl-S (O) nRk, (41)-C1 6 alkyl (ORb) (Rk), (42)-C1-6 alkyl (ORb) (-C1-6 alkyl-Rk), (43)-Cp-6 alkyl-N (Rb) (Rk), (44) -C0-6 alkyl-N (Rb) (-Cl-6 alkyl-Rk), (45) -C1-6 alkyl S (O) n-Rk, (46) -C1-6 alkyl S (O) n-C1-6 alkyl-Rk, (47) -C0-6 alkyl C (O)-Rk, or (48) -C0-6 alkyl C (O)-C1-6 alkyl-Rk, each of R3 and R4 is independently (1)-H, (2) halo, (3)-CN, (4)-N02, (5)-OH, (6) C1-6 alkyl, (7) Cl-6 haloalkyl, (8)-O-C1 (alkyl, (9) -O-C1-6 haloalkyl, (10)-Ci-6 alkyl-ORa, (110 -C0-6 alkyl-C(=O)Ra, (12) -C0-6 alkyl-C02Ra, (13) -C0-6 alkyl-SRa, (14)-N (Ra) 2, (15)-Ci-6 alkyl-N (Ra) 2, (16) -C0-6 alkyl-C (=O) N (Ra) 2, (17)-S02Ra, (18)-N (Ra) SO2Ra, (19) -C2-5 alkenyl, (20) -O-C1- alkyl-ORa, (21) -O-C1- alkyl-SRa, (22) -O-C1-6 alkyl-NH-CO2Ra, (23) -O-C2-6 alkyl-N (Ra) 2, or (24) oxo; each Ra is independently -H,-C1-6 alkyl, or -C1-6 haloalkyl ; each Rb is independently: (1)-H, (2) -C1-4 alkyl (3) -C1-4 haloalkyl, (4) -Rk, (5) -C2-3 alkenyl, (6)-C1 4 alkyl-Rk, (7) -C2-3 alkenyl-Rk, (8)-S (O) n-Rk, or (9)-C (ORb -Rk; each Rc is independently (1)-H, (2) -C1-6 alkyl, (3)-Cl-6 alkyl substituted with-N (Ra) 2, or (4) -C1-4 alkyl-aryl, wherein aryl is optionally substituted with 1 to 5 substituents independently selected from halogen, Cl-6 alkyl, Cl-6 haloalkyl,-O-C1-6 alkyl,-O-C1-6 haloalkyl,-S-C1-6 alkyl,-CN, and-OH; each Rk is independently carbocycle or heterocycle, wherein the carbocycle and heterocycle are unsubstituted or substituted with from 1 to 5 substituents each of which is independently selected from (a) halogen, (b) -C1-6 alkyl (c) -C1-6 haloalkyl, (d) -O-C1-6 alkyl, (e) -O-C1-6 haloalkyl, (f) -S-C1-6 alkyl, (g)-CN, (h)-OH, (i) oxo, -C0-6 alkyl-C (=O) N (Ra) 2, (k)-Cp-6 alkyl-C (=O) Ra, (1)-N (Ra)-C (=O) Ra, (m)-N (Ra)-CO2Ra, (n)-Cl-6 alkyl-N (Ra)-C (=O) Ra, (o)-N (Ra) 2, -C1-6 alkyl-N (Ra) 2, (q)-Cl-6 alkyl-ORa, (r)-Cp-6 alkyl-C02Ra, (s)-Cp-6 alkyl-O-C1-6 alkyl-ORa, (t)-S02Ra, (u)-S02N (Ra) 2, (v)-Cp-6 alkyl-C02-C2-5 alkenyl, (w) aryl, (x) aryloxy-, (y) -C1-4 alkyl substituted with aryl, (z) heteromonocycle, (aa) -C1-4 alkyl substituted with a heteromonocycle, (bb) heteromonocyclylcarbonyl-Co-6 alkyl-, and (cc) N-heteromonocyclyl-N-C1-6 alkyl-amino-; wherein the aryl group in (w) aryl, (x) aryloxy, and (y) -C1-4 alkyl substituted with aryl, is optionally substituted with from 1 to 4 substituents independently selected from halogen, Cl-6 alkyl,-O-C1-6 alkyl, Cul-6 alkyl substituted with N (Ra) 2, C1-6 haloalkyl, and-OH; and wherein the heteromonocyclyl group in (z) heteromonocycle, (aa)-C1-4 alkyl substituted with a heteromonocycle, (bb) heteromonocyclyl-carbonyl-Co-6 alkyl-, and (cc) N heteromonocyclyl-N-Cl-6 alkyl-amino-is optionally substituted with from 1 to 4 substituents independently selected from halogen, C1-6 alkyl,-O-C1-6 alkyl, Cl-6 haloalkyl, oxo, and-OH; and each n is independently an integer equal to 0,1 or 2; or a pharmaceutically acceptable salt thereof. The present invention also includes pharmaceutical compositions containing a compound of the present invention and methods of preparing such pharmaceutical compositions. The present invention further includes methods of treating AIDS, methods of delaying the onset of AIDS, methods of preventing AIDS, methods of preventing infection by HIV, and methods of treating infection by HIV. Other embodiments, aspects and features of the present invention are either further described in or will be apparent from the ensuing description, examples and appended claims. DETAILED DESCRIPTION OF THE INVENTION The present invention includes the aza-and polyaza-naphthalenyl carboxamides of Formula (I) above. These compounds and pharmaceutically acceptable salts thereof are HIV integrase inhibitors. A first embodiment of the invention is a compound of Formula (I), wherein each of Ql, Q2, Q3 and Q4 is independently (1)-H, (2)-C1 6 alkyl, (3)-Cl-6 fluoroalkyl, (4)-0-Cl-6 alkyl, (5) -O-C1-6 fluoroalkyl, (6) halo, (7)-CN, (8)-Ci-6 alkyl-ORa, (9)-Cp-6 alkyl-C (=O) Ra, (10)-Cp-6 alkyl-CO2Ra, (11) -C0-6 alkyl-SRa, (12)-N (Ra) 2, (13) -C1-6 alkyl-N (Ra) 2, (14)-Cp-6 alkyl-C (=O) N (Ra) 2, (15) -C1-6 alkyl-N (Ra)-C (Ra) =O, (16) -SO2Ra, (17)-N (Ra) SO2Ra, (18)-C2-5 alkynyl, (19)-C2-5 alkynyl-CH2N (Ra) 2, (20) -C2-5 alkynyl-CH2ORa, EMI11.1 (22)-N (Ra)-C1-6 alkyl-SRa, (23)-N (Ra)-C1-6 alkyl-ORa, (24) -N (Ra)-Cl-6 alkyl-N (Ra) 2, (25)-N (Ra)-C1-6 alkyl-N (Ra)-C (Ra) =O, (26)-Rk, (27) -C1-6 alkyl substituted with Rk, (28) -C1-6 fluoroalkyl substituted with Rk, (29) -C2-5 alkenyl-Rk, (30) -C2-5 alkynyl-Rk, (31)-O-Rk, (32) O-C1-4 alkyl-Rk, (33)-S S(O) n-Rk, (34)-S (O) n-C1-4 alkyl-Rk, (35) -O-C1-6 alkyl-ORk, (36) -O-C1-6 alkyl-O-C1-4 alkyl-Rk, (37) -O-C1-6 alkyl-SRk, (38)-N -N(Rc)-Rk, (39)-N (Rc)-Cl-6 allcyl substituted with one or two Rk groups, (40)-N (Rc)-Cl-6 alkyl-ORk, (41)-C (=0) N-Ci-6 alkyl-Rk, (42) -C2-5 alkynyl-CH2S(O) n-Ra, or (43)-C (=NRa)-N (Ra) 2 ; each of Rl and R2 is independently: (1)-H, (2)-C1-6 alkyl, (3) -C1-6 fluoroalkyl, (4) -O-C1-6 alkyl, (5) -O-C1-6 fluoroalkyl, (6)-OH, (7) halo, (8)-NO2, (9)-CN, (10)-Cl-6 alkyl-ORa, (11) -C0-6 alkyl-C(=O) Ra, (12) -C0-6 alkylCO2Ra, (13) -C0-6 alkyl-SRa, (14)-N (Ra) 2, (15)-Cl-6 alkyl N (Ra) 2, (16) -C0-6 alkyl-C (=O) N (Ra) 2, (17) -C1-6 alkyl-N (Ra)-C (Ra) =O, -SO2Ra, (19)-N (Ra) S02Ra, (20)-C2-5 alkenyl, (21) -O-C1-6 alkyl-ORa, (22) -O-C1-6 alkyl-SRa, (23) -O-C1-6 alkyl-NH-CO2Ra, (24)-0-C2-6 alkyl-N (Ra) 2, (25)-N (Ra)-C1-6 alkyl-SRa, (26)-N (Ra) -Cl-6 alkyl-ORa, (27)-N (Ra)-C1-6 alkyl-N (Ra) 2, (28)-N (Ra)-Cl-6 alkyl-N (Ra)-C (Ra) =O, (29)-Rk, (30)-C1-6 alkyl substituted with 1 or 2 Rk groups, (31) -C1-6 fluoroalkyl substituted with 1 or 2 Rk groups, (32)-C2-5 alkenyl-Rk, (33)-C2-5 alkynyl-Rk, (34) -O-Rk, (35)-0-CI-4 alkyl-Rk, (36)-S S(O) n-Rk, (37)-S (O) n-C1-4 alkyl-Rk, (38) -O-C1-6 alkyl-ORk, (39) -O-C1-6 alkyl-O-C1-4 alkyl-Rk, (40) -O-C1-6 alkyl-SRk, (41) -C1-6 alkyl (ORb) (Rk), (42) -C1-6 alkyl (ORb) (-C1-4 alkyl-Rk), (43) -C0-6 alkyl-N (Rb) (Rk), (44) -C0-6 alkyl-N (Rb) (-C1-4 alkyl-Rk), (45) -C1-6 alkyl S (O) n-Rk, (46)-C1-6 alkyl S (O) n-C1-4 alkyl-Rk, (47) -C0-6 alkyl C (O)-Rk, or (48) -C0-6 alkyl C (O)-C1-4 alkyl-Rk, each of R3 and R4 is independently (1)-H, (2) halo, (3)-CN, (4)-NO2, (5)-OH, (6) C1-6 alkyl, (7) C1-6 fluoroalkyl, (8) -O-C1-6 alkyl, (9) -O-C1-6 fluoroalkyl, (10) -C1-6 alkyl-ORa, (11) -C0-6 alkyl-C(=O) Ra, (12) -C0-6 alkyl-CO2Ra, (13) -C0-6 alkyl-SRa, (14)-N (Ra) 2, (15)-C1-6 alkyl N (Ra) 2, (16) -C0-6 alkyl-C (=O) N (Ra) 2, (17) -SO2Ra, (18)-N (Ra) S02Ra (19)-C2-5 alkenyl, (20) -O-C1-6 alkyl-ORa, (21) -O-C1-6 alkyl-SRa, (22) -O-C1-6 alkyl-NH-CO2Ra, (23) -O-C2-6 alkyl-N (Ra) 2, or (24) oxo each Ra is independently -H, -C1-6 alkyl, or -C1-6 fluoroalkyl ; each Rb is independently: (1)-H, (2)-C1 4 alkyl, (3)-C1¯4 fluoroalkyl, (4) -Rk, (5)-C2-3 alkenyl, (6) -C1-4 alkyl-Rk, (7) -c2-3 alkenyl-Rk, (8)-S (O) n-Rk, or (9)-C (O)-Rk ; each Rc is independently (1)-H, (2) -C1-6 alkyl, (3)-C1-6 alkyl substituted with-N (Ra) 2, or (4) -C1-4 alkyl-aryl, wherein aryl is optionally substituted with 1 to 5 substituents independently selected from halogen, C1-6 alkyl, Cl¯6 fluoroalkyl,-O-C1-6 alkyl,-O-C1-6 fluoroalkyl,-S-C1-6 alkyl,-CN, and-OH; each Rk is independently carbocycle or heterocycle, wherein the carbocycle and heterocycle are unsubstituted or substituted with from 1 to 5 substituents each of which is independently selected from (a) halogen, (b) Cl-6 alkyl, (c) CI-6 fluoroalkyl, (d) -O-C1-6 alkyl, (e)-O-C1-6 fluoroalkyl, -S-C1-6 alkyl, (g)-CN, (h)-OH, (i) oxo, -(CH2)0-3C(=O)N(Ra)2, (k)- (CH2) 0-3C (=0) Ra, (1)-N (Ra)-C (=O) Ra, (m)-N -C(=O)ORa, (n) -(CH2)1-3N(Ra)-C(=O)Ra, (o)-N (Ra) 2, (p)-C1-6 allcyl-N (Ra) 2, (q) aryl, (r) aryloxy-, (s)-C1-4 alkyl substituted with aryl, (t) heteromonocycle, (u) -C1-4 alkyl substituted with a heteromonocycle, (v) heteromonocyclylcarbonyl-Co-6 alkyl-, and (w) N-heteromonocyclyl-N-C1¯ alkyl-amino- ; wherein the aryl group in (q) aryl, (r) aryloxy, and (s)-Cl-4 alkyl substituted with aryl, is optionally substituted with from 1 to 3 substituents independently selected from halogen, Cl-6 alkyl,-O-C1-6 alkyl, Cul-6 alkyl substituted with N (Ra) 2, Cl-6 fluoroalkyl, and-OH; and wherein the heteromonocyclyl group in (t) heteromonocycle, (u) -C1-4 alkyl substituted with a heteromonocycle, (v) heteromonocyclyl-carbonyl-C0-6 alkyl-, and (w) N heteromonocyclyl-N-Cl-6 alkyl-amino-is optionally substituted with from 1 to 3 substituents independently selected from halogen, Cl-6 alkyl,-O-Cl¯6 alkyl, C1-6 fluoroalkyl, oxo, and-OH; and all other variables are as originally defined; or a pharmaceutically acceptable salt thereof. A second embodiment of the invention is a compound of Formula (I), wherein each Ra is independently-H or-C1 6 alkyl ; each Rc is independently (1)-H, (2) -C1-4 alkyl, (3)-C1 4 alkyl substituted with-N (Ra) 2, or (4) -C1-4 alkyl-phenyl, wherein the phenyl is optionally substituted with 1 to 5 substituents independently selected from halogen, C1-6 alkyl, C1-6 fluoroalkyl, -O-C1-6 alkyl, -C-C1-6 fluoroalkyl,-S-C1 6 alkyl,-CN, and-OH; each Rk is independently: (1) aryl selected from phenyl and naphthyl, wherein aryl is unsubstituted or substituted with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) C1-6 fluoroalkyl, (d)-O-C1-6 alkyl, (e)-O-C1-6 fluoroalkyl, (f) phenyl, (g) -S-C1-6 alkyl, (h)-CN, (i)-OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (i) halogen, (ii) C1-6 alkyl, (iii) C1-6 fluoroalkyl, and (iv)-OH, (k)-N (Ra) 2, (1)-C1 6 alkyl-N (Ra) 2, ) (p) -(CH2)0-3C(=O)N(Ra)2, and ) -(CH2)0-3C(=O)Ra; (2) -C3-7 cycloalktyl, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (a) halogen, (b) Cl-6 alkyl, (c)-O-Cl-6 alkyl, (d) CI-6 fluoroalkyl, (e)-O-C1 6 fluoroalkyl, (f)-CN, (h) phenyl, and (j) -OH ; (3)-C3-7 cycloalkyl fused with a phenyl ring, unsubstituted or substituted with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) -O-C1-6 alkyl, (d) C1-6 fluoroalkyl, (e)-O-C1-6 fluoroalkyl, (f)-CN, and (g)-OH; (4) a 5-or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein the heteroaromatic ring is unsubstituted or substituted on nitrogen or carbon with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1 6 alkyl, (c) Cl-6 fluoroalkyl, (d)-O-C1-6 alkyl, (e)-O-C1-6 fluoroalkyl, (f) phenyl, (g)-S-1-6 alkyl, (h)-CN, (i)-OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (i) halogen, (ii) C1-6 alkyl, (iii) Cl-6 fluoroalkyl, and (iv)-OH, (k)-N (Ra) 2, (1)-Cl-6 alkyl-N (Ra) 2, ) (n) oxo, -(CH2)0-3C(=O)N(Ra)2, and ) -(CH2)0-3C(=O)Ra; (5) a 5-or 6-membered saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein the heterocyclic ring is unsubstituted or substituted with from 1 to 4 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) -O-C1- (alkyl, (d) CI-6 fluoroalkyl, (e)-O-C1-6 fluoroalkyl, (f)-CN, (g) oxo, (h) phenyl (i) benzyl, (j) phenylethyl, (k)-OH, -(CH2)0-3C(=O)N(Ra)2, (m)- (CH2) 0-3C (=O) Ra, (n)-N (Ra)-C (=O) Ra, (o)-N (Ra)-C (=O) ORa, (p)- (CH2) 1-3N (Ra)-C (=O) Ra, (q)-N (Ra) 2, (r)- (CH2) 1-3N (Ra) 2, -(CH2)0-3C(=O)Rt, (t)-Rt, (u)-N (Ra) Rt, and (v) -(CH2)1-3Rt; or (6) an 8-to 10-membered heterobicyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein the heterobicyclic ring is saturated or unsaturated and is unsubstituted or substituted with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c)-O-C1 6 alkyl, (d) CI-6 fluoroalkyl, (e)-O-C1-6 fluoroalkyl, (f)-CN, (g) =O, and (h)-OH; and Rt is naphthyl or a 5-or 6-membered heteromonocylic ring containing from 1 to 4 nitrogen atoms, wherein the heteromonocyclic ring is saturated or unsaturated, and wherein the naphthyl or the heteromonocyclic ring is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, oxo, C1 4 alkyl, and-O-C 4 alkyl ; and all other variables are as originally defined; or a pharmaceutically acceptable salt thereof. A third embodiment is identical to the second embodiment, except that all other variables are as defined in the first embodiment, instead of being as originally defined. A fourth embodiment of the present invention is a compound of Formula I, wherein A is a 5-or 6-membered saturated heterocyclic ring which contains 1 or 2 nitrogen atoms one of which is directly attached to the exocyclic carbonyl moiety, zero or 1 heteroatoms selected from oxygen and sulfur, and a balance of carbon atoms; wherein the heterocyclic ring is optionally fused to a phenyl ring or to a second 5-or 6-membered heterocyclic ring which is saturated or unsaturated and which contains 1 or 2 nitrogen atoms, zero or 1 heteroatoms selected from oxygen and sulfur, and a balance of carbon atoms, wherein the second heterocyclic ring is optionally fused to a phenyl ring ; and all other variables are as originally defined; or a pharmaceutically acceptable salt thereof. A fifth embodiment is identical to the fourth embodiment, except that all other variables are as defined in the first embodiment, instead of being as originally defined. A first class of the present invention is compounds of Formula I, wherein A is pyrrolidinyl, piperidinyl, piperazinyl, imidazolidinyl, morpholinyl, thiomorpholinyl, indolinyl, or isoindolinyl; and all other variables are as defined in the fourth embodiment; or a pharmaceutically acceptable salt thereof. A second class is identical to the first class, except that all other variables are as defined in the fifth embodiment, instead of being as defined in the fourth embodiment. A sixth embodiment of the present invention is a compound of Formula I, wherein XisN ; Y is C-Q2; zl is C-Q3; Z2 is C-Q4; Z3 is CH; Q2 is (1)-H, (2)-C1-6 alkyl, (3)-C1-6 fluoroalkyl, (4) -O-C1-6 alkyl, (5) -O-C1-6 fluoroalkyl, (6) halo, (7)-CN, (8) -C1-6 alkyl-oRa, (9)-Cp-6 alkyl-C (=O) Ra, (10)-Cp-6 alkyl-C02Ra, (11)-C0-6 alkyl-SRa, (12)-N (Ra) 2, (13) -C1-6 alkyl-N (Ra) 2, (14)-Cp-6 alkyl-C (=O) N (Ra) 2, (15)-Cl-6 alkyl-N (Ra)-C (Ra) =O, (16) -SO2Ra, (17)-N (Ra) SO2Ra, (18)-C2-5 alkynyl, (19) -C2-5 alkynyl-CH2N (Ra) 2, (20) -C2-5 alkynyl-CH20Ra, EMI22.1 (22)-N (Ra)-Cl-6 alkyl-SRa, (23)-N (Ra)-C1-6 alkyl-ORa, (24)-N (Ra)-C1-6 alkyl-N (Ra) 2, (25)-N (Ra)-C1-6 alkyl-N (Ra)-C (Ra) =O, -Rk, (27) -C1-6 alkyl substituted with Rk, (28) -C1-6 fluoroalkyl substituted with Rk, (29)-C2-5 alkenyl-Rk, (31) -C2-5 alkynyl-Rk, (31) -O-Rk, (32)-0-Cl-4 alkyl-Rk, (33)-S S(O) n-Rk, (34)-S (O) n-C1-4 alkyl-Rk, (35) -O-C1-6 alkyl-ORk, (36) -O-C1-6 alkyl-O-C1-4 alkyl-Rk, (37) -O-C1-6 alkyl-SRk, (38)-N (Rc)-Rk, (39)-N (Rc)-Cl-6 alkyl substituted with one or two Rk groups, (40)-N (Rc)-Cl-6 alkyl-ORk, (41)-C (=O) N-C1-6 alkyl-Rk, (42) -C2-5 alkynyl-CH2S(O)n-Ra, or (43)-C (=NRa)-N (Ra) 2 ; each of Q3 and Q4 is independently: (1)-H, (2)-C1 6 alkyl, (3) -C1-6 fluoroalkyl, (4) -O-C1-6 alkyl, (5)-O-Cl-6 fluoroalkyl, (6) halo, (7)-CN, (8) -C1-6 alkyl-ORa, (9)-Cp-6 alkyl-C (=O) Ra, (10)-Cp-6 alkyl-C02Ra, (11)-SRa, (12)-N (Ra) 2, (13) -C1-6 alkyl -N (Ra) 2, (14)-Cp-6 alkyl-C (=O) N (Ra) 2, (15) -SO2Ra, (16)-N (Ra) SO2Ra (17)-Rk, or (18) -C1-6 alkyl substituted with Rk; and all other variables are as originally defined; or a pharmaceutically acceptable salt thereof. A seventh embodiment is identical to the sixth embodiment, except that all other variables are as defined in the first embodiment, instead of being as originally defined. An eighth embodiment of the present invention is a compound of Formula I, wherein Q3 is : (1)-H, (2) -C1-6 alkyl, (3) -C1-6 fluoroalkyl, (4) -O-C1-6 alkyl, (5) -O-C1-6 fluoroalkyl, (6) halo, (7)-CN, -C1-6 alkyl-ORa, (9)-Cp-6 alkyl-C (=O) Ra, (10)-Cp-6 alkyl-C02Ra, (11)-SRa, (12)-N (Ra) 2, (13) -C1-6 alkyl-N (Ra) 2, (14)-Cp-6 alkyl-C (=O) N (Ra) 2, (15) -SO2Ra, (16)-N (Ra) SO2Ra (17)-Rk, or (18)-C1 6 alkyl substituted with Rk; Q4 is: (1)-H, (2) -C1-6 alkyl, (3) -C1-6 fluoroalkyl, (4) -O-C1-6 alkyl, (5) -O-C1-6 fluoroalkyl, (6) halo, (7)-CN, (8) -C1-6 alkyl-ORa, (9) -C0-6 alkyl-C (=O) Ra, (10) -C0-6 alkyl-C02Ra, (11) -SRa, (12)-N (Ra) 2, (13) -C1-6 alkyl -N (Ra) 2, -C0-6 alkyl-C(=O)N(Ra)2, (15) -SO2Ra, or (16)-N (Ra) S02Ra ; and all other variables are as defined in the sixth embodiment; or a pharmaceutically acceptable salt thereof. A ninth embodiment is identical to the eighth embodiment, except that all other variables are as defined in the seventh embodiment, instead of being as defined in the sixth embodiment. In an aspect of each of the eighth and ninth embodiments, Q3 and Q4 are both-H. A tenth embodiment of the present invention is a compound of Formula II: EMI25.1 wherein A is EMI25.2 denotes the point of attachment; Zl is N or C-Q3; Q2 is (1)-H, (2) -C1-4 alkyl, (3) -C1-4 fluoroalkyl, (4) -O-C1-4 alkyl, (5) -O-C1-4 fluoroalkyl, (6) halo, (7)-CN, (8) -C1-4 alkyl-ORa, (9) -(CH2)0-2C(=O)Ra, (10) -(CH20)0-2CO2Ra, (11) -(CH2)0-2SRa, (12)-N (Ra) 2, (13) C1-4 alkyl -N (Ra) 2, (14) -(CH2)0-2C(=O) N (Ra) 2, (15) -SO2Ra, (16)-N (Ra) SO2Ra, (17) -C2-3 alkynyl, (18) -C#C-CH2N(Ra)2 (19)-C=C-CH20Ra (20)-N (Ra)-Cl 4 alkyl-SRa, (21)-N (Ra)-Cl-4 alkyl-ORa, (22)-N (Ra)-C1-4 alkyl-N (Ra) 2, (23)-N (Ra)-Cl-4 alkyl-N (Ra)-C (Ra) =O, (24) -Rk, (25) -Cl-4 alkyl substituted with Rk, (26) -C1-4 fluoroalkyl substituted with Rk, (27) -C2-5 alkenyl-Rk, (28) -C2-5 alkynyl-Rk, (29)-0-Rk, (30) -C-C1-4 alkyl-Rk, (31)-S S(O)n-Rk, (32)-N (Rc)-Rk, (33)-N (Rc)-C1-4 alkyl substituted with one or two Rk groups, (34)-N (Rc)-C1-4 alkyl-ORk, (35)-C (=O) N-C1-4 alkyl-Rk, (36) -C#C-CH2SRa (37) -C#C-CH2SO2Ra; Q3 is (1)-H, (2) -C1-4 alkyl, (3) -C1-4 fluoroalkyl, (4)-O-C1-4 alkyl, (5) -O-C1-4 fluroalkyl, (6) halo selected from-F,-Cl, and-Br, (7)-CN, (8)-Ci-4 alkyl-ORa, or (9) -C1-4 alkyl substituted with Rk; Q4 is : (1)-H, (2) -C1-4 alkyl, (3)-C1-4 fluoroalkyl, (4) -O-C1-4 alkyl, (5) -O-C1-4 fluoroalkyl, (6) halo selected from-F,-Cl, and-Br, (7)-CN, (8)-Ci-6 alkyl-ORa, (9)-N (Ra) 2, or (10) -C1-6 alkyl -N(Ra)2 ; each of RI and R2 is independently: (1)-H, (2) -C1-4 alkyl, (3)-C1-4 fluoroalkyl, (4) -O-C1-4 alkyl, (5) -O-C1-4 fluoroalkyl, (6)-OH, (7) halo, (8)-CN, (9)-Ci-4 alkyl-ORa, (10) -(CH2)0-2C(=O)Ra, (11) -(CH2)0-2CO2Ra, (12) -(CH2)O0-2SRa, (13)-N (Ra) 2, (14)-Cl-4 alkyl N (Ra) 2, (15) -(CH2)0-2C(=O)N(Ra)2, (16) -C1-4 alkyl-N (Ra)-C (Ra) =O, -SO2Ra, (18)-N (Ra) S02Ra, (19)-0-CI-4 alkyl-ORa, (20)-0-Cl-4 alkyl-SRa, (21) -O-C1-4 alkyl-NH-CO2Ra, (22) -O-C2-4 alkyl-N (Ra) 2, (23)-N (Ra)-Ci-4 alkyl-SRa, (24)-N (Ra)-Cl-4 alkyl-ORa, (25)-N (Ra)-Cl-4 alkyl-N (Ra) 2, (26)-N (Ra)-Ci-4 alkyl-N (Ra)-C (Ra) =O, (27) -Rk, (28)-C1 4 alkyl substituted with 1 or 2 Rk groups, (29) -C1-4 fluoroalkyl substituted with 1 or 2 Rk groups, (30) -O-Rk, (31) -O-C1-4 alkyl-Rk, (32)-S S(O) n-Rk, (33)-S (O) n-C1-4 alkyl-Rk, (34)-0-Cl-4 alkyl-ORk, (35) -O-C1-4 alkyl-O-C1-4 alkyl-Rk, (36)-0-CI-4 alkyl-SRk, or (37) -C0-4 alkyl-n (Rb) (Rk) ; each of R3 and R4 is independently (1)-H, (2) halo, (3)-CN, (4)-OH, (5) C1 4 alkyl, (6) C1-4 fluoroalkyl, (7) -O-C1-4 alkyl, (8)-O-C1 4 fluoroalkyl, (9)-Ci-4 alkyl-ORa, (10) -O-C1-4 alkyl-ORa, (11) -O-C1-4 alkyl-SRa, (12) -O-C1-4 alkyl-NH-CO2Ra, or (13)-0-C2-4 alkyl-N (Ra) 2 ; each Ra is independently-H or -C1-4 alkyl ; each Rb is independently: (1)-H, (2) -C1-4 alkyl, (3) -C1-4 fluoroalkyl, (4) -Rk, (5) -C1-4 alkyl-Rk, (6)-S (O) n-Rk, or (7)-C (=ORb ( each Rc is independently (1)-H, (2) -C1-4 alkyl, (3) -C1-4 alkyl substituted with-N (Ra) 2, or (4) -C1-4 alkyl-phenyl, wherein the phenyl is optionally substituted with 1 to 3 substituents independently selected from halogen, C1-4 alkyl, C1-4 fluoroalkyl, -O-C1-4 alkyl, -O-C1-4 fluoroalkyl,-S-C1-4 alkyl,-CN, and-OH; each Rk is independently: (1) aryl selected from phenyl and naphthyl, wherein aryl is unsubstituted or substituted with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) C1-6 fluoroalkyl, (d)-O-C1 6 alkyl, (e) -O-C1-6 fluoroalkyl, (f) phenyl, (g) -S-C1-6 alkyl, (h)-CN, (i)-OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (i) halogen, (ii) C1-6 alkyl, (iii) C1-6 fluoroalkyl, and (iv)-OH, (k)-N (Ra) 2, (1)-Cl-6 alkyl-N (Ra) 2, ) -(CH2)0-3C(=O)N(Ra)2, and (q)- (CH2) 0-3C 0) Ra ; (2)-C3-7 cycloalkyl, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c)-O-C1-6 alkyl, (d) C1-6 fluoroalkyl, (e)-O-C1-6 fluoroalkyl, (f)-CN, (h) phenyl, and (j) -OH ; (3)-C3-7 cycloalkyl fused with a phenyl ring, unsubstituted or substituted with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c)-O-C1-6 alkyl, (d) C1-6 fluoroalkyl, (e) -O-C1-6 fluoroalkyl, (f)-CN, and (g)-OH; (4) a 5-or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein the heteroaromatic ring is unsubstituted or substituted on nitrogen or carbon with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1 6 alkyl, (c) Cul-6 fluoroalkyl, (d)-O-C1 6 alkyl, (e) -O-C1-6 fluoroalkyl, (f) phenyl, (g)-S-C1-6 alkyl, (h)-CN, (i)-OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (i) halogen, (ii) C1-6 alkyl, (iii) C1-6 fluoroalkyl, and (iv)-OH, (k)-N (Ra) 2, (1)-Ci-6 alkyl-N (Ra) 2, ) (n) oxo, ) -(H2)0-3C(=O)N(Ra)2, and ) -(CH2)0-3C(=O)Ra; (5) a 5-or 6-membered saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein the heterocyclic ring is unsubstituted or substituted with from 1 to 4 substituents independently selected from: (a) halogen, (b) Cl-6 alkyl, (c)-O-C1 6 alkyl, (d) C1-6 fluoroalkyl, (e)-O-Cl 6 fluoroalkyl, -CN, (g) oxo, (h) phenyl, (i) benzyl, (j) phenylethyl, (k)-OH, (1)- (CH2) 0-3C (=) N (Ra) 2, ) -(CH2)0-3C(=O)Ra, (n)-N (Ra)-C (=0) Ra, (o)-N (Ra)-C (=O) ORa, (q) -N(Ra)2, (r) -(CH2)1-3N(Ra)2, (s) -(CH2)0-3C(=O)Rt, (t)-Rt, (u)-N (Ra) Rt, and (v)- (CH2) 1-3Rt ; or (6) an 8-to 10-membered heterobicyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein the heterobicyclic ring is saturated or unsaturated, and is unsubstituted or substituted with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1 6 alkyl, (c) -O-C1-6 alkyl, (d) C1-6 fluoroalkyl, (e)-O-C1-6 fluoroalkyl, -CN, (g) =O, and (h)-OH; Rt is naphthyl or a 5-or 6-membered heteromonocylic ring containing from 1 to 4 nitrogen atoms, wherein the heteromonocyclic ring is saturated or unsaturated, and wherein the naphthyl or the heteromonocyclic ring is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, oxo, C1 4 alkyl, and-O-C 4 alkyl ; and n is an integer equal to 0,1 or 2; or a pharmaceutically acceptable salt thereof. In an aspect of the tenth embodiment, Zl is CH, and Q4 is-H. A third class of the present invention is compounds of Formula m : EMI33.1 wherein G is: (1) NH optionally substituted by either Rl or R2, (2) CH2 optionally substituted by either or both RI and R2, or (3)-S (O) n wherein n is an integer equal to zero, 1 or 2; Q2is (1)-H, (2) methyl, (3) ethyl, (4) CF3, (5) methoxy, (6) ethoxy (7)-OCF3 (8) halo selected from--Cl and-Br, (9)-CN, (10)-CH20H, (11)-CH20CH3 (12) -(CH2)0-2CO2CH3, (13)-SRa, (14)-N (Ra) 2, (15) -SO2Ra, (16) -C#C-CH2ORa (17)-N (Ra)- (CH2) 1-3SRa (18)-N (Ra)- (CH2) 1-30Ra (19)-N (Ra)-(CH2) 1-3N (Ra) 2, (20)-N (Ra)-(CH2)1-3N(Ra)-C(Ra)=O, (21) -Rk, (22)- (CH2) l-4Rk, (23) -C#C-CH2Rk (24)-0-Rk, -S-Rk, -SO2-Rk, (27)-N -N(Rc)-Rk, (28)-N (Rc)-(CH2)1-4H substituted with one or two Rk groups, (29)-N (Rc)-(CH2)1-4ORk, (30)-C (=O) N-(CH2)1-4Rk, (31) -C#C-CH2SRa, (32) -C#C-CH2SO2Ra; each of Rl and R2 is independently: (1)-H, (2) methyl, (3) ethyl, (4) CF3, (5) methoxy, (6) ethoxy (7)-OCF3 (8) halo selected from-F,-Cl and-Br, (9)-CN, (10)-CH20Ra, (11)-C02Ra, (12) -SRa, (13)-N (Ra) 2, (14)- (CH2) 1-3N (Ra) 2, (15) -SO2Ra, (16) -(CH2)1-2N(Ra)-C(Ra)=O, (17) -Rk, (18)- (CH2) 1-3H substituted with 1 or 2 Rk groups, (19) -O-Rk, or (20) -O-(CH2)1-3Rk; each Ra is independently-H or-C1 4 alkyl ; each Rc is independently-H,-C1 4 alkyl, or-(CH2) l-3N (Ra) 2; each Rk is independently: (1) phenyl which is unsubstituted or substituted with from 1 to 4 substituents independently selected from: (a) halogen selected from-F,-Cl, and-Br, (b) methyl, (c)-CF3, (d) methoxy, (e)-OCF3, (f) phenyl, (g)-S-CH3, (h)-CN, (i)-OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (i) halogen selected from-F,-Cl, and-Br, (ii) methyl, (iii)-CF3, and (iv)-OH, (k)-N (Ra) 2, (1)- (CH2) 1-3N (Ra) 2, (m)-Rt, ) -(CH2)0-3C(=O)N(Ra)2, and ) -(CH2)0-3C(=O)Ra; (2)-C3-6 cycloalkyl, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (a) halogen selected from-F,-Cl, and-Br, (b) methyl, (c)-CF3, (d) methoxy, (e)-OCF3, (f)-CN, (h) phenyl, and (j)-OH ; (3) a 5-or 6-membered heteroaromatic ring selected from thienyl, pyridyl, imidazolyl, pyrrolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isooxazolyl, pyrazinyl, pyirimidinyl, triazolyl, tetrazolyl, furanyl, and pyridazinyl, wherein the heteroaromatic ring is unsubstituted or substituted on nitrogen or carbon with 1 or 2 substituents independently selected from: (a) halogen selected from-F,-Cl, and-Br, (b) methyl, (c)-CF3, (d) methoxy, (e)-OCF3, (f) phenyl, (9)-S-Cl-6 alkyl, (h)-CN, (i)-OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (i) halogen selected from-F,-Cl, and-Br, (ii) methyl, (iii)-CF3, and (iv)-OH, (k)-N (Ra) 2, (1)-Ci-6 alkyl-N (Ra) 2, (m)-Rt, (n) oxo, (o) -(CH2)0-3C(=O) N (Ra) 2, and -(CH2)0-3C(=O)Ra; (4) a 5-or 6-membered saturated heterocyclic ring selected from piperidinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isooxazolidinyl, pyrrolidinyl, imidazolidinyl, piperazinyl, tetrahydrofuranyl, and pyrazolidinyl, wherein the heterocyclic ring is unsubstituted or substituted with 1 or 2 substituents independently selected from: (a) halogen selected from-F,-Cl, and-Br, (b) methyl, (c)-CF3, (d) methoxy, (e)-OCF3, (f)-CN, (g) =0, (h) phenyl, (i) benzyl, (j) phenylethyl, (k)-OH, (1) -(CH2)0-3C(=O)N(Ra)2, (m)- (CH2) 0. 3C (=0) Ra, (n) N (Ra)-C (=O) Ra, (o) N (Ra)-C (=O) ORa, (p) (CH2) l 3N (Ra)-C (=O) Ra, (q) N (Ra) 2, (r) (CH2) 1-3N (Ra) 2 (s)-(CH2) 0 3C (=O) Rt, (t)-Rt, (u)-N (Ra) Rt, and (v)- (CH2) 1-3Rt ; and (5) an 8-to 10-membered heterobicyclic ring selected from indolyl, benzotriazolyl, benzoimidazolyl, imidazo [4,5-b] pyridinyl, dihydroimidazo [4,5-b] pyridinyl, pyrazolo [4,3-c] pyridinyl, dihydropyrazolo [4,3c] pyridinyl, tetrahydropyrazolo [4,3-c] pyridinyl, pyrrolo [1, 2-a] pyrazinyl, dihydropyrrolo [1, 2-a] pyrazinyl, tetrahydropyrrolo [1, 2-a] pyrazinyl, octahydropyrrolo [1, 2-a] pyrazinyl, isoindolyl, indazolyl, indolinyl, isoindolinyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, chromanyl, and isochromanyl, wherein the bicyclic ring is unsubstituted or substituted with 1 or 2 substituents independently selected from: (a) halogen selected from-F,-Cl, and-Br, (b) methyl, (c)-CF3, (d) methoxy, (e)-OCP3, (f)-CN, (g) =O, and (h)-OH; and Rt is selected from pyrrolidinyl, pyrazolidinyl, imidazolinyl, piperidinyl, piperazinyl, pyrrolyl, pyridyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyrazinyl, pyrimidinyl, and pyradizinyl; any one of which is unsubstituted or substituted with 1 or 2 substituents independently selected from-F,-Cl,-Br, oxo, methyl, and methoxy; or a pharmaceutically acceptable salt thereof. A sub-class of the present invention is compounds of Formula (IV): EMI39.1 wherein each of the variables is as defined in the third class of the invention; or a pharmaceutically acceptable salt thereof. Exemplary compounds of the invention include compounds selected from the group consisting of 7- [ (3-phenylpyrrolidin-1-yl) carbonyl]-1,6-naphthyridin-8-ol; 7- [ (3-benzylpiperidin-1-yl) carbonyl]-1, 6-naphthyridin-8-ol; and pharmaceutically acceptable salts thereof. Other embodiments of the invention include compounds of Formula (I), (II), (III), or (IV), wherein each variable is independently as defined in any one of the preceding embodiments, classes, sub-classes or aspects. Other embodiments of the present invention include the following: (a) A pharmaceutical composition comprising a compound of Formula (I) and a pharmaceutically acceptable carrier. (b) The pharmaceutical composition of (a), further comprising at least one antiviral selected from the group consisting of HIV protease inhibitors, nonnucleoside HIV reverse transcriptase inhibitors, and nucleoside HIV reverse transcriptase inhibitors. (c) A method of inhibiting HIV integrase in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of Formula (I). (d) A method of preventing or treating infection by HIV in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of Formula (I). (e) The method of (d), wherein the compound of Formula (I) is administered in combination with a therapeutically effective amount of at least one antiviral selected from the group consisting of HIV protease inhibitors, nonnucleoside HIV reverse transcriptase inhibitors, and nucleoside HIV reverse transcriptase inhibitors. (f) A method of preventing, treating or delaying the onset of AIDS in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of a compound of Formula (I). (g) The method of (f), wherein the compound is administered in combination with a therapeutically effective amount of at least one antiviral selected from the group consisting of HIV protease inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, and nucleoside HIV reverse transcriptase inhibitors (h) A method of inhibiting HIV integrase in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the composition of (a) or (b). (i) A method of preventing or treating infection by HIV in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the composition of (a) or (b). (j) A method of preventing, treating or delaying the onset of AIDS in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the composition of (a) or (b). Still other embodiments of the present invention include the following: (k) A pharmaceutical composition which comprises the product prepared by combining (e. g., mixing) an effective amount of a compound of Formula (I) and a pharmaceutically acceptable carrier. (1) A combination useful for inhibiting HIV integrase, for treating or preventing infection by HIV, or for preventing, treating or delaying the onset of AIDS, which is a therapeutically effective amount of a compound of Formula (I) and a therapeutically effective amount of an HIV infection/AIDS treatment agent selected from the group consisting of H1V/AIDS antiviral agents, immunomodulators, and anti-infective agents. (m) The combination of (1), wherein the HIV infection/AIDS treatment agent is an antiviral selected from the group consisting of HIV protease inhibitors, non-nucleoside HIV reverse transcriptase inhibitors and nucleoside HIV reverse transcriptase inhibitors. Additional embodiments of the invention include the pharmaceutical compositions and methods set forth in (a)- (j) above and the compositions and combinations set forth in (k)- (m), wherein the compound employed therein is a compound of one of the embodiments, classes, sub-classes, or aspects of compounds described above. In all of these embodiments, the compound may optionally be used in the form of a pharmaceutically acceptable salt. As used herein, the term"Ci-6 alkyi" (or"Ci-C6 alkyi") means linear or branched chain alkyl groups having from 1 to 6 carbon atoms and includes all of the hexyl alkyl and pentyl alkyl isomers as well as n-, iso-, sec-and t-butyl, n-and isopropyl, ethyl and methyl."Cl-4 alkyl"means n-, iso-, sec-and t-butyl, n-and isopropyl, ethyl and methyl. The term"Co"as employed in expressions such as"Cp-6 alkyl"means a direct covalent bond. The term"C2-5 alkenyl" (or"C2-C5 alkenyl") means linear or branched chain alkenyl groups having from 2 to 5 carbon atoms and includes all of the pentenyl isomers as well as 1-butenyl, 2-butenyl, 3-butenyl, isobutenyl, 1- propenyl, 2-propenyl, and ethenyl (or vinyl). Similar terms such as"C2-3 alkenyl" have an analogous meaning. The term"C2-5 alkynyl" (or"C2-C5 alkynyl") means linear or branched chain alkynyl groups having from 2 to 5 carbon atoms and includes all of the pentynyl isomers as well as 1-butynyl, 2-butynyl, 3-butynyl, 1-propynyl, 2propynyl, and ethynyl (or acetylenyl). Similar terms such as"C2-3 alkynyl"have an analogous meaning. The term"C3 7 cycloalkyl" (or"C3-C7 cycloalkyl") means a cyclic ring of an alkane having three to seven total carbon atoms (i. e., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl). The term"C3-6 cycloalkyl" refers to a cyclic ring selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Terms such as"C3-C5 cycloalkyl"have an analogous meaning. The term"halogen" (or"halo") refers to fluorine, chlorine, bromine and iodine (alternatively, fluoro, chloro, bromo, and iodo). The term"thio" (also referred to as"thioxo") means divalent sulfur; i. e., =S. The term''C1 6 haloalkyl" (which may alternatively be referred to as "C-C6 haloalkyl"or"halogenated C1-C6 alkyl") means a C1 to C6 linear or branched alkyl group as defined above with one or more halogen substituents. The term"Cl-4 haloalkyi"has an analogous meaning. The term"C 1-6 fluoroalkyl" (which may alternatively be referred to as ''C1-C6 fluoroalkyl"or"fluorinated C1-C6 alkyl") means a C 1 to C6 linear or branched alkyl group as defined above with one or more fluorine substituents. The term"Cl-4 fluoroalkyl" (or"C1-C4 fluoroalkyl"or"fluorinated Cl-C4 alkyl") has an analogous meaning. Representative examples of suitable fluoroalkyls include the series (CH2) 0-4CF3 (i. e., trifluoromethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-npropyl, etc.), 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 3,3,3-trifluoroisopropyl, 1,1,1,3,3,3-hexafluoroisopropyl, and perfluorohexyl. The term"carbocycle" (and variations thereof such as"carbocyclic"or "carbocyclyl") as used herein broadly refers to a C3 to C8 monocyclic, saturated or unsaturated ring or a C7 to C12 bicyclic ring system in which the rings are independent or fused and in which each ring is saturated or unsaturated. The carbocycle may be attached at any carbon atom which results in a stable compound. The fused bicyclic carbocycles are a subset of the carbocycles; i. e., the terrn"fused bicyclic carbocycle"generally refers to a C7 to Clo bicyclic ring system in which each ring is saturated or unsaturated and two adjacent carbon atoms are shared by each of the rings in the ring system. A subset of the fused bicyclic carbocycles are the fused bicyclic carbocycles in which one ring is a benzene ring and the other ring is saturated or unsaturated, with attachment via any carbon atom that results in a stable compound. Representative examples of this subset include the following: EMI42.1 As used herein, the term"fused carbocyclic ring system"refers to a carbocycle as defined above which is fused to a phenyl ring. Representative examples include: EMI43.1 The term"aryl"refers to aromatic mono-and poly-carbocyclic ring systems, wherein the individual carbocyclic rings in the polyring systems may be fused or attached to each other via a single bond. Suitable aryl groups include, but are not limited to, phenyl, naphthyl, and biphenylenyl. The term"heterocycle" (and variations thereof such as"heterocyclic" or"heterocyclyl") broadly refers to a 4-to 8-membered monocyclic ring, 7-to 12membered bicyclic ring system, or an 11 to 16-membered tricyclic ring system, any ring of which is saturated or unsaturated, and which consists of carbon atoms and one or more heteroatoms selected from N, O and S, and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. The heterocyclic ring may be attached at any heteroatom or carbon atom, provided that attachment results in the creation of a stable structure. When the heterocyclic ring has substituents, it is understood that the substituents may be attached to any atom in the ring, whether a heteroatom or a carbon atom, provided that a stable chemical structure results. Representative examples of heterocyclics include piperidinyl, piperazinyl, azepinyl, pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolidinyl, triazolyl, tetrazolyl, imidazolinyl, pyridyl (or pyridinyl), pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, quinoxazolinyl, isothiazolidinyl, quinolinyl, isoquinolinyl, benzimidazolyl, thiadazolyl, benzopyranyl, benzothiazolyl, benzoazolyl, furyl (or furanyl), tetrahydrofuryl (or tetrahydrofuranyl), tetrahydropuranyl, thienyl (alternatively thiophenyl), benzothiophenyl, oxadiazolyl, and benzo-1, 3-dioxacyclopentyl (alternatively, 1,3-benzodioxolyl). Representative examples of heterocyclics also include tetrahydrothienyl, tetrahydrodioxothienyl, thiadiazinanyl, dioxothiadiazinanyl, thiazinanyl, dioxothiazinanyl, dioxothiazolidinyl, and isodioxothiazolidinyl. Representative examples of heterocyclics also include the following bicyclics: indolyl, benzotriazolyl, imidazo [4,5-b] pyridinyl, dihydroimidazo [4,5-b] pyridinyl, pyrazolo [4,3-c] pyridinyl, dihydropyrazolo [4,3-c] pyridinyl, tetrahydropyrazolo [4,3c] pyridinyl, pyrrolo [1, 2-a] pyrazinyl, dihydropyrrolo [1, 2-a] pyrazinyl, tetrahydropyrrolo [1,2-a] pyrazinyl, octahydropyrrolo [1,2-a] pyrazinyl, isoindolyl, indazolyl, indolinyl, isoindolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, chromanyl, and isochromanyl. Additional representative examples of bicyclics include the following: phthalazinyl, purinyl, 1,6-naphthyridinyl, 1,8-napthyridinyl, dihydroindolyl, dihydroisoindolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, imidazo [1, 2-a] pyrimidinyl, 2,3-dihydroimidazo [2,1-b] [1, 3] thiazolyl, benzazepinyl, dihydrobenazepinyl, benzodiazepinyl, dihydrobenzodiazepinyl, and tetrahydrobenzodiazepinyl. Representative examples of heterocyclics also include the following tricyclics: phenothiazinyl, carbazolyl, beta-carbolinyl, tetrahydro-betacarbolinyl, acridinyl, phenazinyl, and phenoxazinyl. Representative examples of heterocyclics also include the following saturated monocyclics: hexahydropyrimidinyl, thiazinanyl (e. g., 1,2-thiazinanyl, alternatively named tetrahydro-1, 2-thiazinyl), thiazepanyl (e. g., 1,4-thiazepanyl, alternatively named hexahydro-1, 4-thiazepinyl), azepanyl (alternatively hexahydroazepinyl), thiadiazepanyl (e. g., 1,2,5-thiadiazepanyl), dithiazepanyl (e. g.,, 1,5,2,-dithiazepanyl), diazepanyl (e. g., 1,4-diazepanyl), and thiadiazinanyl (e. g., 1,2,6-thiadiazinanyl). A representative unsaturated heterocycle, optionally substituted, is EMI44.1 wherein p is an integer from zero to 4 and Ra is as defined above, and wherein each ring carbon is optionally and independently substituted with-C1¯4 alkyl. Representative examples of heterocyclics also include the following bicyclics: hexahydropyrazolo [4,3-c] pyridinyl (e. g., 3a, 4,5,6,7,7a-hexahydro-lHpyrazolo [4,3c] pyridinyl), hexahydropurinyl (e. g., 2,3,4,5,6,7-hexahydro-lH-purinyl), hexahydrooxazolo [3,4a] pyrazinyl, and 1,2,3,4-tetrahydro-1,8-naphthyridinyl. Fused ring heterocycles form a subset of the heterocycles as defined above; e. g., the term"fused bicyclic heterocycle"refers to a heteroatom-containing bicyclic ring system as defined in the preceding paragraph in which two adjacent atoms are shared by both rings. A subset of the fused bicyclic heterocycles is the fused bicyclic heterocycle containing carbon atoms and one or more heteroatoms selected from nitrogen, oxygen and sulfur, wherein one ring is a benzene ring and the other is a saturated or unsaturated heteroatom-containing ring. Representative examples of this subset include, but are not limited to, the following: EMI45.1 The term"heteromonocycle" (and variations thereof such as "heteromonocyclyl"or"heteromonocyclic") refers to a 4-to 8-membered monocyclic ring which is saturated or unsaturated, and which consists of carbon atoms and one or more heteroatoms selected from N, O and S, and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. The heterocyclic ring may be attached at any heteroatom or carbon atom, provided that attachment results in the creation of a stable structure. Representative examples of monoheterocycles are disclosed above. Heteroaromatics form another subset of the heterocycles as defined above; i. e., the term"heteroaromatic" (alternatively,"heteroaryl") generally refers to a heterocycle as defined above in which the ring system (whether mono-or poly-cyclic) is an aromatic ring system. The term"heteroaromatic ring"refers to a monocyclic heterocycle as defined above which is an aromatic heterocycle. Representative examples of heteroaromatics include pyridyl, pyrrolyl, pyrazinyl, pyrimidinyl, pyridazinyl, thienyl (or thiophenyl), thiazolyl, furanyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isooxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, and thiadiazolyl. Unless expressly set forth to the contrary, an"unsaturated"ring is a partially or fully unsaturated ring. For example, an"unsaturated monocyclic C6 carbocycle"refers to cyclohexene, cyclohexadine, and benzene. The present invention includes pharmaceutical compositions useful for inhibiting HIV integrase, comprising an effective amount of a compound of this invention, and a pharmaceutically acceptable carrier. Pharmaceutical compositions useful for treating infection by HIV, or for treating AIDS or ARC, are also encompassed by the present invention, as well as a method of inhibiting HIV integrase, and a method of treating infection by HIV, or of treating AIDS or ARC. Additionally, the present invention is directed to a pharmaceutical composition comprising a therapeutically effective amount of a compound of the present invention in combination with a therapeutically effective amount of an agent for treating HIV infection or AIDS selected from: (1) an antiviral agent useful for treating or preventing HIV infection or for treating AIDS (also referred to herein as an MV/AEDS antiviral agent), (2) an anti-infective agent, and (3) an immunomodulator. The present invention also includes a compound of the present invention for use in (a) inhibiting HIV protease, (b) preventing or treating infection by HIV, or (c) preventing, treating or delaying the onset of AIDS or ARC. The present invention also includes the use of a compound of the present invention as described above as a medicament for (a) inhibiting HIV integrase, (b) preventing or treating infection by HIV, or (c) preventing, treating or delaying the onset of AIDS or ARC. The present invention further includes the use of any of the HIV integrase inhibiting compounds of the present invention as described above in combination with one or more HIV/AIDS treatment agents selected from an HIV/AIDS antiviral agent, an antiinfective agent, and an immunomodulator as a medicament for (a) inhibiting HIV integrase, (b) preventing or treating infection by HIV, or (c) preventing, treating or delaying the onset of AIDS or ARC, said medicament comprising an effective amount of the HIV integrase inhibitor compound and an effective amount of the one or more treatment agents. The present invention also includes the use of a compound of the present invention as described above in the preparation of a medicament for (a) inhibiting HIV integrase, (b) preventing or treating infection by HIV, or (c) preventing, treating or delaying the onset of AIDS or ARC. The present invention further includes the use of any of the HIV integrase inhibiting compounds of the present invention as described above in combination with one or more HIV/AIDS treatment agents selected from an HIV/AIDS antiviral agent, an anti-infective agent, and an immunomodulator for the manufacture of a medicament for (a) inhibiting HIV integrase, (b) preventing or treating infection by HIV, or (c) preventing, treating or delaying the onset of AIDS or ARC, said medicament comprising an effective amount of the HIV integrase inhibitor compound and an effective amount of the one or more treatment agents. The compounds of the present invention may have asymmetric centers and may occur, except when specifically noted, as mixtures of stereoisomers or as individual diastereomers, or enantiomers, with all isomeric forms being included in the present invention. When any variable (e. g., Ra, Rb, RC, Rk, etc.) occurs more than one time in any constituent or in Formula I or in any other formula depicting and describing compounds of the invention, its definition on each occurrence is independent of its definition at every other occurrence. Also, combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. The term"substituted" (e. g., as in"phenyl ring, unsubstituted or substituted with from 1 to 5 substituents...") includes mono-and poly-substitution by a named substituent to the extent such single and multiple substitution is chemically allowed. For example, a carbocycle or heterocycle substituted with more than one substituent can have multiple substituents on the same ring atom to the extent it is chemically permitted. A ring sulfur atom in a saturated heterocycle can, for example, typically be substituted with 1 (-S (=O)-) or 2 oxo groups (-SO2-). The compounds of the present inventions are useful in the inhibition of HIV integrase, the prevention or treatment of infection by human immunodeficiency virus (HIV) and the treatment of consequent pathological conditions such as AIDS. Treating AIDS or preventing or treating infection by HIV is defined as including, but not limited to, treating a wide range of states of HIV infection: AIDS, ARC (AIDS related complex), both symptomatic and asymptomatic, and actual or potential exposure to HIV. For example, the compounds of this invention are useful in treating infection by HIV after suspected past exposure to HIV by e. g., blood transfusion, exchange of body fluids, bites, accidental needle stick, or exposure to patient blood during surgery. The compounds of this invention are useful in the preparation and execution of screening assays for antiviral compounds. For example, the compounds of this invention are useful for isolating enzyme mutants, which are excellent screening tools for more powerful antiviral compounds. Furthermore, the compounds of this invention are useful in establishing or determining the binding site of other antivirals to HIV integrase, e. g., by competitive inhibition. Thus the compounds of this invention are commercial products to be sold for these purposes. The present invention also provides for the use of a compound of Formula (I) to make a pharmaceutical composition useful for inhibiting HIV integrase and in the treatment of AIDS or ARC. The compounds of the present invention may be administered in the form of pharmaceutically acceptable salts. The term"pharmaceutically acceptable salt"is intended to include all acceptable salts such as acetate, lactobionate, benzenesulfonate, laurate, benzoate, malate, bicarbonate, maleate, bisulfate, mandelate, bitartrate, mesylate, borate, methylbromide, bromide, methylnitrate, calcium edetate, methylsulfate, camsylate, mucate, carbonate, napsylate, chloride, nitrate, clavulanate, N-methylglucamine, citrate, ammonium salt, dihydrochloride, oleate, edetate, oxalate, edisylate, pamoate (embonate), estolate, palmitate, esylate, pantothenate, fumarate, phosphate/diphosphate, gluceptate, polygalacturonate, gluconate, salicylate, glutamate, stearate, glycollylarsanilate, sulfate, hexylresorcinate, subacetate, hydrabamine, succinate, hydrobromide, tannate, hydrochloride, tartrate, hydroxynaphthoate, teoclate, iodide, tosylate, isothionate, triethiodide, lactate, panoate, valerate, and the like which can be used as a dosage form for modifying the solubility or hydrolysis characteristics or can be used in sustained release or pro-drug formulations. Depending on the particular functionality of the compound of the present invention, pharmaceutically acceptable salts of the compounds of this invention include those formed from cations such as sodium, potassium, aluminum, calcium, lithium, magnesium, zinc, and from bases such as ammonia, ethylenediamine, N-methyl-glutamine, lysine, arginine, ornithine, choline, N, N'- dibenzylethylene-diamine, chloroprocaine, diethanolamine, procaine, Nbenzylphenethyl-amine, diethylamine, piperazine, tris (hydroxymethyl) aminomethane, and tetramethylammonium hydroxide. These salts may be prepared by standard procedures, e. g. by reacting a free acid with a suitable organic or inorganic base. Where a basic group is present, such as amino, an acidic salt, i. e. hydrochloride, hydrobromide, acetate, pamoate, and the like, can be used as the dosage form. Also, in the case of an acid (-COOH) or alcohol group being present, pharmaceutically acceptable esters can be employed, e. g. acetate, maleate, pivaloyloxymethyl, and the like, and those esters known in the art for modifying solubility or hydrolysis characteristics for use as sustained release or prodrug formulations. For these purposes, the compounds of the present invention may be administered orally, parenterally (including subcutaneous injections, intravenous, intramuscular, intrasternal injection or infusion techniques), by inhalation spray, or rectally, in dosage unit formulations containing conventional non-toxic pharmaceutically-acceptable carriers, adjuvants and vehicles. The term"administration"and variants thereof (e. g.,"administering"a compound) in reference to a compound of the invention each mean providing the compound or a prodrug of the compound to the individual in need of treatment. When a compound of the invention or prodrug thereof is provided in combination with one or more other active agents (e. g., antiviral agents useful for treating HIV infection or AIDS),"administration"and its variants are each understood to include concurrent and sequential provision of the compound or prodrug thereof and other agents. Thus, in accordance with the present invention there is further provided a method of treating and a pharmaceutical composition for treating HIV infection and AIDS. The treatment involves administering to a subject in need of such treatment a pharmaceutical composition comprising a pharmaceutical carrier and a therapeutically-effective amount of a compound of the present invention. As used herein, the term"composition"is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. By"pharmaceutically acceptable"it is meant the carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. The term"subject," (alternatively referred to herein as"patient") as used herein refers to an animal, preferably a mammal, most preferably a human, who has been the object of treatment, observation or experiment. The term"therapeutically effective amount"as used herein means that amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, which includes alleviation of the symptoms of the disease being treated. These pharmaceutical compositions may be in the form of orallyadministrable suspensions or tablets or capsules, nasal sprays, sterile injectible preparations, for example, as sterile injectible aqueous or oleagenous suspensions or suppositories. When administered orally as a suspension, these compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may contain microcrystalline cellulose for imparting bulk, alginic acid or sodium alginate as a suspending agent, methylcellulose as a viscosity enhancer, and sweeteners/flavoring agents known in the art. As immediate release tablets, these compositions may contain microcrystalline cellulose, dicalcium phosphate, starch, magnesium stearate and lactose and/or other excipients, binders, extenders, disintegrants, diluents and lubricants known in the art. When administered by nasal aerosol or inhalation, these compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other solubilizing or dispersing agents known in the art. The injectible solutions or suspensions may be formulated according to known art, using suitable non-toxic, parenterally-acceptable diluents or solvents, such as mannitol, 1,3-butanediol, water, Ringer's solution or isotonic sodium chloride solution, or suitable dispersing or wetting and suspending agents, such as sterile, bland, fixed oils, including synthetic mono-or diglycerides, and fatty acids, including oleic acid. When rectally administered in the form of suppositories, these compositions may be prepared by mixing the drug with a suitable non-irritating excipient, such as cocoa butter, synthetic glyceride esters of polyethylene glycols, which are solid at ordinary temperatures, but liquefy and/or dissolve in the rectal cavity to release the drug. The compounds of this invention can be administered orally to humans in a dosage range of 0.1 to 1000 mg/kg body weight in divided doses. One preferred dosage range is 0.1 to 200 mg/kg body weight orally in divided doses. Another preferred dosage range is 0.5 to 100 mg/kg body weight orally in divided doses. For oral administration, the compositions are preferably provided in the form of tablets containing 1.0 to 1000 milligrams of the active ingredient, particularly 1.0,5.0,10.0, 15.0.20.0,25.0,50.0,75.0,100.0,150.0,200.0,250.0,300.0,400.0,500.0,600.0, 750.0,800.0,900.0, and 1000.0 milligrams of the active ingredient for the symptomatic adjustment of the dosage to the patient to be treated. It will be understood, however, that the specific dose level and frequency of dosage for any particular patient may be varied and will depend upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the host undergoing therapy. The present invention is also directed to combinations of the HIV integrase inhibitor compounds with one or more agents useful in the treatment of HIV infection or AIDS. For example, the compounds of this invention may be effectively administered, whether at periods of pre-exposure and/or post-exposure, in combination with effective amounts of the HIV/AIDS antivirals, imunomodulators, antiinfectives, or vaccines useful for treating HIV infection or AIDS, such as those in the following Table. ANTIVIRALS Drug Name Manufacturer Indication Amprenavir Glaxo Wellcome HIV infection, AIDS, 141 W94 ARC GW 141 (protease inhibitor) Abacavir Glaxo Welcome HIV infection, AIDS, GW 1592 ARC 1592U89 (reverse transcriptase inhibitor) Acemannan Carrington Labs ARC (Irving, TX) Acyclovir Burroughs Wellcome HIV infection, AIDS, ARC, in combination with AZT AD-439 Tanox Biosystems HIV infection, AIDS, ARC AD-519 Tanox Biosystems HIV infection, AIDS, ARC Adefovir dipivoxil Gilead Sciences HIV infection AL-721 Ethigen ARC, PGL, HIV positive, (Los Angeles, CA) AIDS Alpha Interferon Glaxo Wellcome Kaposi's sarcoma, HIV, in combination w/Retrovir Ansamycin Adria Laboratories ARC LM 427 (Dublin, OH) Erbamont (Stamford, CT) Antibody which Advanced Biotherapy AIDS, ARC neutralizes pH Concepts labile alpha aberrant (Rockville, MD) Interferon AR177 Aronex Pharm HIV infection, AIDS, ARC beta-fluoro-ddA Natl Cancer Institute AIDS-associated diseases BMS-232623 Bristol-Myers Squibb/HIV infection, AIDS, (CGP-73547) Novartis ARC (protease inhibitor) BMS-234475 Bristol-Myers Squibb/HIV infection, AIDS, (CGP-61755) Novartis ARC (protease inhibitor) CI-1012 Warner-Lambert HIV-1 infection Cidofovir Gilead Science CMV retinitis, herpes, papillomavirus Curdlan sulfate AJI Pharma USA HIV infection Cytomegalovirus immune Medlmmune CMV retinitis globin Cytovene Syntex sight threatening CMV Ganciclovir peripheral CMV retinitis Delaviridine Pharmacia-Upjohn HIV infection, AIDS, ARC (protease inhibitor) Dextran Sulfate Ueno Fine Chem. AIDS, ARC, HIV Ind. Ltd. (Osaka, Japan) positive asymptomatic ddC Hoffman-La Roche HIV infection, AIDS, ARC Dideoxycytidine ddI Bristol-Myers Squibb HIV infection, AIDS, ARC; Dideoxyinosine combination with AZT/d4T mozenavir AVID HIV infection, AIDS, (DMP-450) (Camden, NJ) ARC (protease inhibitor) EL10 Elan Corp, PLC HIV infection (Gainesville, GA) Efavirenz DuPont (SUSTIVA#), HIV infection, AIDS, (DMP 266) Merck (STOCRINU) ARC (-) 6-Chloro-4 (S)- (non-nucleoside RT cyclopropylethynyl-inhibitor) 4(S)-trifluoro-methyl 1, 4-dihydro-2H-3,1benzoxazin-2-one, Pamciclovir Smith Kline herpes zoster, herpes simplex FTC Emory University HIV infection, AIDS, ARC (reverse transcriptase inhibitor) GS 840 Gilead HIV infection, AIDS, ARC (reverse transcriptase inhibitor) HBY09. 7 Hoechst Marion Roussel HIV infection, AIDS, ARC (non-nucleoside reverse transcriptase inhibitor) Hypericin VIMRx Pharm. HIV infection, AIDS, ARC Recombinant Human Triton Biosciences AIDS, Kaposi's sarcoma, Interferon Beta (Almeda, CA) ARC Interferon alfa-n3 Interferon Sciences ARC, AIDS Indinavir Merck HIV infection, AIDS, ARC, asymptomatic HIV positive, also in combination with AZT/ddI/ddC Compound A Merck HIV infection, AIDS, ARC, asymptomatic HIV positive ISIS 2922 ISIS Pharmaceuticals CMV retinitis KNI-272 Nat'1 Cancer Institute HIV-assoc. diseases Lamivudine, 3TC Glaxo Wellcome HIV infection, AIDS, ARC (reverse transcriptase inhibitor); also with AZT Lobucavir Bristol-Myers Squibb CMV infection Nelfinavir Agouron HIV infection, AIDS, Pharmaceuticals ARC (protease inhibitor) Nevirapine Boeheringer HIV infection, AIDS, Ingleheim ARC (protease inhibitor) Novapren Novaferon Labs, Inc. HIV inhibitor (Akron, OH) Peptide T Peninsula Labs AIDS Octapeptide (Belmont, CA) Sequence Trisodium Astra Pharm. CMV retinitis, HIV infection, Phosphonoformate Products, Inc other CMV infections PNU-140690 Pharmacia Upjohn HIV infection, AIDS, ARC (protease inhibitor) Probucol Vyrex HIV infection, AIDS RBC-CD4 Sheffield Med. Tech HIV infection, AIDS, (Houston TX) ARC Ritonavir Abbott HIV infection, AIDS, (ABT-538) ARC (protease inhibitor) Saquinavir Hoffmann-LaRoche HIV infection, AIDS, ARC (protease inhibitor) Stavudine; d4T Bristol-Myers Squibb HIV infection, AIDS, ARC Didehydrodeoxythymidine Valaciclovir Glaxo Wellcome genital HSV & CMV infections Virazole Viratek/ICN asymptomatic HIV Ribavirin (Costa Mesa, CA) positive, LAS, ARC VX-478 Vertex HIV infection, AIDS, ARC Zalcitabine Hoffmann-La Roche HIV infection, AIDS, ARC, with AZT Zidovudine; AZT Glaxo Wellcome HIV infection, AIDS, ARC, Kaposi's sarcoma in combination with other therapies (reverse transcriptase inhibitor) ABT-378; Lopinavir Abbott HIV infection, AIDS, ARC (protease inhibitor) ABT-378/r; contains Abbott HIV infection, AIDS, ARC lopinavir and ritonavir; (protease inhibitor) Kaletra JE2147/AG1776 Agouron HIV infection, AIDS, ARC (protease inhibitor) T-20 Trimeris HIV infection, AIDS, ARC (fusion inhibitor) T-1249 Trimeris HIV infection, AIDS, ARC (fusion inhibitor) atazanavir Bristol-Myers-Squibb HIV infection, AIDS, ARC (BMS 232632) (protease inhibitor) PRO 542 Progenies HIV infection, AIDS, ARC (attachment inhibitor) PRO 140 Progenies HIV infection, AIDS, ARC (CCR5 co-receptor inhibitor) TAK-779 Takeda HIV infection, AIDS, ARC (injectable CCR5 receptor antagonist) DPC 681 & DPC 684 DuPont HIV infection, AIDS, ARC (protease inhibitors) DPC 961 & DPC 083 DuPont HIV infection AIDS, ARC (nonnucleoside reverse transcriptase inhibitors) Trizivir (contains abacavir, GlaxoSmithKline HIV infection, AIDS, ARC lamivudine, and (reverse transcriptase zidovudine) inhibitors) tipranavir (PNU-140690) Boehringer Ingelheim HIV infection, AIDS, ARC (purchased from (protease inhibitor) Pharmacia & Upjohn) tenofovir disoproxil Gilead HIV infection, AIDS, ARC fumarate (reverse transcriptase inhibitor) TMC-120 & TMC-125 Tibotec HIV infections, AIDS, ARC (non-nucleoside reverse transcriptase inhibitors) TMC-126 Tibotec HIV infection, AIDS, ARC (protease inhibitor) IMMUNO-MODULATORS Drug Name Manufacturer Indication AS-101 Wyeth-Ayerst AIDS Bropirimine Pharmacia Upjohn advanced AIDS Acemannan Carrington Labs, Inc. AIDS, ARC (Irving, TX) CL246, 738 American Cyanamid AIDS, Kaposi's sarcoma Lederle Labs EL10 Elan Corp, PLC HIV infection (Gainesville, GA) FP-21399 Fuki ImmunoPharm blocks HIV fusion with CD4+ cells Gamma Interferon Genentech ARC, in combination w/TNF (tumor necrosis factor) Granulocyte Genetics Institute AIDS Macrophage Colony Sandoz Stimulating Factor Granulocyte Hoeschst-Roussel AIDS Macrophage Colony Immunex Stimulating Factor Granulocyte Schering-Plough AIDS, combination w/AZT Macrophage Colony Stimulating Factor HIV Core Particle Rorer seropositive HIV Immunostimulant IL-2 Cetus AIDS, in combination Interleukin-2 w/AZT IL-2 Hoffman-La Roche AIDS, ARC, HIV, in Interleukin-2 Immunex combination w/AZT IL-2 Chiron AIDS, increase in CD4 cell Interleukin-2 counts (aldeslukin) Immune Globulin Cutter Biological pediatric AIDS, in Intravenous (Berkeley, CA) combination w/AZT (human) IMREG-1 Imreg AIDS, Kaposi's (New Orleans, LA) sarcoma, ARC, PGL IMREG-2 Imreg AIDS, Kaposi's sarcoma, (New Orleans, LA) ARC, PGL Imuthiol Diethyl Merieux Institute AIDS, ARC Dithio Carbamate Alpha-2 Schering Plough Kaposi's sarcoma w/AZT, Interferon AIDS Methionine-TNI Pharmaceutical AIDS, ARC Enkephalin (Chicago, IL) MTP-PE Ciba-Geigy Corp. Kaposi's sarcoma Muramyl-Tripeptide Granulocyte Amgen AIDS, in combination Colony Stimulating w/AZT Factor Remune Immune Response Corp. immunotherapeutic rCD4 Genentech AIDS, ARC Recombinant Soluble Human CD4 rCD4-IgG AIDS, ARC hybrids Recombinant Biogen AIDS, ARC Soluble Human CD4 Interferon Hoffman-La Roche Kaposi's sarcoma, AIDS, Alfa 2a ARC, in combination w/AZT SK & F106528 Smith Kline HIV infection Soluble T4 Thymopentin Immunobiology HIV infection Research Institute Tumor Necrosis Genentech ARC, in combination Factor; TNF w/gamma Interferon etanercept Immunex Corp rheumatoid arthritis (Enbrel&commat;) infliximab Centocor (Remicade0) rheumatoid arthritis and Crohn's disease ANTI-INFECTIVES Drug Name Manufacturer Indication Clindamycin with Pharmacia Upjohn PCP Primaquine Fluconazole Pfizer cryptococcal meningitis, candidiasis Pastille Squibb Corp. prevention of oral candidiasis Nystatin Pastille Ornidyl Merrell Dow PCP Eflornithine Pentamidine LyphoMed PCP treatment Isethionate (IM & IV) (Rosemont, IL) Trimethoprim antibacterial Trimethoprim/sulfa antibacterial Piritrexim Burroughs Wellcome PCP treatment Pentamidine Fisons Corporation PCP prophylaxis isethionate for inhalation Spiramycin Rhone-Poulenc cryptosporidia diarrhea Intraconazole-Janssen Pharm. histoplasmosis; cryptococcal R51211 meningitis Trimetrexate Warner-Lambert PCP OTHER Drug Name Manufacturer Indication Daunorubicin NeXstar, Sequus Karposi's sarcoma Recombinant Human Ortho Pharm. Corp. severe anemia assoc. with Erythropoietin AZT therapy Recombinant Human Serono AIDS-related wasting, Growth Hormone cachexia Leukotriene B4 Receptor-HIV infection Antagonist Megestrol Acetate Bristol-Myers Squibb treatment of anorexia assoc. w/AIDS Soluble CD4 Protein and-HIV infection Derivatives Testosterone Alza, Smith Kline AIDS-related wasting Total Enteral Norwich Eaton diarrhea and malabsorption, Nutrition Pharmaceuticals related to AIDS It will be understood that the scope of combinations of the compounds of this invention with HIV/AIDS antivirals, immunomodulators, anti-infectives or vaccines is not limited to the list in the above Table, but includes in principle any combination with any pharmaceutical composition useful for the treatment of HIV infection or AIDS. When employed in combination with the compounds of the invention, the HIV/AIDS antivirals and other agents are typically employed in their conventional dosage ranges and regimens as reported in the art, including the dosages described in the Physicians'Desk Reference, 54th edition, Medical Economics Company, 2000. The dosage ranges for a compound of the invention in these combinations are the same as those set forth above just before the Table. Preferred combinations are simultaneous or sequential treatments of a compound of the present invention and an inhibitor of HIV protease and/or a nonnucleoside inhibitor of HIV reverse transcriptase. An optional fourth component in the combination is a nucleoside inhibitor of HIV reverse transcriptase, such as AZT, 3TC, ddC or ddI. A preferred inhibitor of HIV protease is the sulfate salt of indinavir, which is N- (2 (R)-hydroxy-l (S)-indanyl)-2 (R)-phenylmethyl-4- (S)-hydroxy-5- (1- (4- (3-pyridyl-methyl)-2 (S)-N'- (t-butylcarboxamido)-piperazinyl))-pentaneamide ethanolate, and is synthesized according to US 5413999. Indinavir is generally administered at a dosage of 800 mg three times a day. Other preferred protease inhibitors are nelfinavir and ritonavir. Another preferred inhibitor of HIV protease is saquinavir which is administered in a dosage of 600 or 1200 mg tid. Still another preferred protease inhibitor is Compound A, which is N-(2 (R)-hydroxy-1 (S)-indanyl)- 2 (R)-phenylmethyl-4 (S)-hydroxy-5- (1- (4- (2-benzo [b] furanylmethyl)-2 (S)-N'- (t- butylcarboxamido) piperazinyl)) pentaneamide, preferably administered as the sulfate salt. Compound A can be prepared as described in US 5646148. Preferred nonnucleoside inhibitors of HIV reverse transcriptase include efavirenz. The preparation of ddC, ddI and AZT are also described in EPO 0,484,071. These combinations may have unexpected effects on limiting the spread and degree of infection of HIV. Preferred combinations include a compound of the present invention with the following (1) indinavir with efavirenz, and, optionally, AZT and/or 3TC and/or ddI and/or ddC; (2) indinavir, and any of AZT and/or ddI and/or ddC and/or 3TC, in particular, indinavir and AZT and 3TC; (3) stavudine and 3TC and/or zidovudine; (4) zidovudine and lamivudine and 141W94 and 1592U89; (5) zidovudine and lamivudine. Another preferred combination is a compound of the present invention with indinavir and Compound A and optionally with one or more of efavirenz, AZT, 3TC, ddI and ddC. In one embodiment of this combination, the weight ratio of indinavir to Compound A is from about 1: 1 to about 1: 2, wherein the amount of indinavir employed is in the range of from about 200 to about 1000 mg. Indinavir and Compound A can be administered concurrently or sequentially in either order from one to three times per day. In such combinations the compound of the present invention and other active agents may be administered together or separately. In addition, the administration of one agent may be prior to, concurrent to, or subsequent to the administration of other agent (s). Abbreviations used in the instant specification, particularly the Schemes and Examples, are as follows: DEAD = diethylazodicarboxylate DMF = N, N-dimethylformamide DMPU = 1, 3-dimethyl-3,4,5,6-tetrahydro-2 (1H)-pyrimidinone DMSO = dimethylsulfoxide EDC = 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide ES MS = electrospray mass spectrometry Et = ethyl FAB MS = fast atom bombardment mass spectrometry HPLC = high performance liquid chromatography HOBt = 1-hydroxy benzotriazole hydrate HPLC = high performance liquid chromatography i-Pr = isopropyl Me = methyl MsCl = methanesulfonyl chloride (or mesyl chloride) NBS = N-bromosuccinimide NIS = N-iodosuccinimide NMR = nuclear magnetic resonance Ph = phenyl PMBC1 =p-methoxybenzyl chloride NMR = nuclear magnetic resonance rt and RT = room temperature TFA = trifluoroacetic acid THF = tetrahydrofuran The compounds of the present invention can be readily prepared according to the following reaction schemes and examples, or modifications thereof, using readily available starting materials, reagents and conventional synthesis procedures. In these reactions, it is also possible to make use of variants which are themselves known to those of ordinary skill in this art, but are not mentioned in greater detail. Furthermore, other methods for preparing compounds of the invention will be readily apparent to the person of ordinary skill in the art in light of the following reaction schemes and examples. Unless otherwise indicated, all variables are as defined above. The compounds of the present invention can be prepared by the coupling of suitable (poly) azanaphthenyl carboxylic acids (or acid derivatives such as acid halides or esters) with the appropriate amines, as represented by the following general scheme: SCHEME 1 EMI64.1 Compound I Methods for coupling carboxylic acids with amines to form carboxamides are well known in the art. Suitable methods are described, for example, in Jerry March, Advanced Organic Chemistry, 3rd edition, John Wiley & Sons, 1985, pp. 370-376. Amines of formula 1-1 can be prepared using the methods described in Richard Larock, Comprehensive Organic Transformations, VCH Publishers Inc, 1989, pp 385438, or routine variations thereof. Azanaphthenyl and polyazanaphthenyl carboxylic acids of formula 1-2 can be prepared using methods described in Ochiai et al., Cher. Ber. 1937,70: 2018,2023; Albert et al., J. Allem. Soc. 1952,4985,4991; and Barlin et al., Aust. J. Chem. 1990,43: 1175-1181 ; or routine variations thereof. Schemes 2-16 below illustrate and expand upon the chemistry portrayed in Scheme 1. In Scheme 2, following the procedure set forth in Ornstein et al., J. Med. Chefs. 1989,32: 827-833, a cyclic anhydride such as quinolinic anhydride (i. e., Zl = Z2 = Z3 = CH in 2-1) can be opened with isopropanol to provide mono acid 2-2, which can be converted to the corresponding acyl chloride 2-3 (e. g., by refluxing thionyl chloride). Acyl chloride 2-3 can then be reduced (e. g., with NaBH4 or LiBH4) to the corresponding alcohol 2-4, which can be converted to the corresponding bromide through the action of bromine in the presence of triphenylphosphine. Alkylation of the bromide with the sodium anion of phenylsulfonamide 2-5 in a polar aprotic solvent like DMF can provide sulfonamide 2-6, which can be treated with a base (e. g., alkali metal alkoxide such as sodium methoxide) to provide the bicyclic ester 2-7 via a Dieckmann cyclization. Saponification of the ester (e. g., with aqueous NaOH at reflux) will afford the acid 28. The acid 2-8 can be activated with triphosgene and coupled with a variety of amines to provide the compounds of the invention 2-9. The starting anhydrides of formula 2-1 can be prepared via methods described in Philips et al., Justus Liebigs Ann. Chem. 1895,288: 2535; Bernthsen et al., Cliem. Ber. 1887; 20: 1209; Bly et al., J. Org. C7iem. 1964,29: 2128-2135 ; and Krapcho et al., J. Heterocycl. Chem. 1993,30: 1597-1606; or routine variations thereof. SCHEME 2 EMI65.1 <tb> <SEP> 0 <SEP> 0 <tb> <SEP> Z2 <tb> <SEP> Z2-iPrOH, <SEP> reflux <SEP> 11 <SEP> OH <SEP> SOC12 <tb> <SEP> 2 <tb> <SEP> 0 <SEP> 0 <SEP> t <tb> <SEP> O <SEP> O <SEP> reflux <tb> <SEP> 2-1 <SEP> 2-2 <tb> <SEP> 0 <tb> <SEP> 1 <SEP> 1 <tb> Z2-c <SEP> I <SEP> NaBH4., <SEP> z2,-0 <SEP> H <SEP> i. <SEP> Br2, <SEP> PPh3 <tb> <SEP> 3 <SEP> 3 <tb> N <SEP> N <SEP> ii. <SEP> NaH, <tb> <SEP> Nr <SEP> N <SEP> ii. <SEP> NaH, <tb> <SEP> 2-3 <SEP> 2-4 <SEP> PhO2SsNOMe <tb> <SEP> 2-3 <SEP> 2-4 <SEP> N <tb> <SEP> 2-5 <SEP> H <SEP> 0 <tb> <SEP> Ph02SN <SEP> OMe <tb> <SEP> Z1 <SEP> 1 <tb> <SEP> Zizi <SEP> <SEP> NaOMe <SEP> Z2. <SEP> N <SEP> NAOH <tb> <SEP> Nr-r <SEP> N <tb> <SEP> O <SEP> OH <SEP> O <tb> <SEP> 2-6 <SEP> 2-7 <tb> EMI66.1 Scheme 3 depicts an alternative synthesis in which alcohol 2-4 can undergo the Mitsunobu reaction with the phenylsulfonamide of glycine methyl ester to provide 3-1. The sulfonamide 3-1 can again be elaborated to provide the acid 2-8, which can be coupled with a variety of amines using standard reagents to provide the compounds of the invention 2-9. SCHEME 3 EMI66.2 EMI67.1 Scheme 3A depicts (for a napthyridine core) a variation of the synthesis shown in Scheme 3, wherein the acid 3A-2 is reacted with ethyl chloroformate to form the mixed anhydride 3A-3, which is reduced to alcohol 3A-4. EMI67.2 <tb> <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <tb> <SEP> iPrOH <SEP> CIC02Et <tb> <SEP> o <SEP> o <tb> <SEP> iPrOAc <SEP> OH <SEP> THF <SEP> 0 <tb> <SEP> v <tb> <SEP> O <SEP> i <SEP> i <SEP> O <SEP> Ets-N- <SEP> I <SEP> O <tb> <SEP> reflux <tb> <SEP> N <SEP> to <SEP> 10 <SEP> deg <SEP> C <tb> <SEP> o <SEP> o'o' <tb> <SEP> 3A-1 <SEP> 3A-2 <SEP> 3A-3 <tb> <SEP> .-. <SEP> 0/-C02Me <tb> <SEP> S-NH <tb> <SEP> o <SEP> S02PhCH3 <tb> <SEP> DEAD <tb> NaBH4 <SEP> OH <SEP> PPh3 <SEP> N'C02Me <tb> TUF <SEP> 0 <tb> <SEP> ('N <SEP> ! <SEP> t <tb> <SEP> O <tb> <SEP> 3A-4 <SEP> 3A-5 <tb> EMI68.1 Halogen substituted compounds of the present invention can be prepared as shown in Scheme 4. The acid chloride 2-3 can be reacted with glycine methyl ester to provide the amide 4-1. Dieckmann cyclization of the ester 4-1 with a sodium alkoxide base in an alcoholic solvent like methanol will provide phenol 4-2., which can be reacted with phosphorous oxychloride, followed by methanolysis of the intermediate phosphonate esters to provide 4-3. The ester bond of 4-3 can react selectively with suitable amines (e. g., 3-benzylpiperidine is depicted in Scheme 4) to provide the corresponding halogenated derivative 4-4. SCHEME 4 EMI68.2 EMI69.1 4-4 The preparation of compounds that feature additional substituents can be achieved as shown in Scheme 5. Oxidation of the alcohol 2-4 with manganese dioxide in an inert solvent such as methylene chloride will provide aldehyde 5-1. The addition of Grignard reagents (such as phenyl magnesium bromide) to aldehyde moiety 5-1 can occur regioselectively to provide the alcohol 5-2, which can then be elaborated to the compounds of the invention 5-6. SCHEME 5 EMI69.2 EMI70.1 <tb> <SEP> G <SEP> G <tb> <SEP> w <SEP> Naos <tb> <SEP> N <tb> ZvN/OMe <SEP> zvN/OH <tb> <SEP> N <tb> <SEP> 5-4 <SEP> OH <SEP> 0 <SEP> 5-5 <SEP> OH <SEP> 0 <tb> <SEP> rua <tb> <SEP> EDC,HOT <SEP> RU <tb> <SEP> A <tb> <SEP> NH <tb> <SEP> R2 <tb> <SEP> 4 <SEP> Ri <tb> <SEP> R <tb> <SEP> R3 <tb> <SEP> 4 <SEP> X <SEP> R <tb> IR <SEP> G <tb> <SEP> A <SEP> N <SEP> , <SEP> Zs <SEP> G <SEP> = <SEP> unsubstituted <tb> <SEP> R2 <SEP> N <SEP> or <SEP> substituted <SEP> alkyl, <tb> <SEP> 1 <SEP> 0 <SEP> OH <SEP> carbocycle <SEP> (e. <SEP> g., <tb> <SEP> R <SEP> aryl), <SEP> or <SEP> heterocycle <tb> <SEP> 5-6 <SEP> (e. <SEP> g., <SEP> heteroaryl) <tb> A further synthetic route to prepare compounds that are the subject of the invention is shown in Scheme 6. This methodology allows access to naphthyridine derivatives that are substituted at the 2,3,4 and 5 positions. Briefly, a 2-substituted 5-hydroxypyridine derivative 6-1 can be treated with bromine to undergo bromination at the 6 position to afford 6-2, which can be converted to the methoxypyridine 6-3 and then oxidized to the corresponding N-oxide 6-4. The Noxide can be nitrated to provide 6-5. Reduction of 6-5 with iron in the presence of ammonium chloride can provide the aniline 6-6, which can be reacted with an alpha, beta-unsaturated aldehyde or ketone in the presence of an acid catalyst like sulfuric acid to provide 6-7 via an annulation. The bromide 6-7 can be elaborated to the amide 6-9 via a sequence of carbonylation and amidation reactions. 2-Substituted 5-hydroxypyridine derivatives of formula 6-1 can be prepared via methods described in Sorm et al., Collect. Czech. Chem.. Commun.. 1949, 14: 331,342; and Saksena et al., Tetrahedron Lett. 1993,34: 3267-3270: or routine variations thereof. SCHEME6 EMI71.1 <tb> <SEP> Q2 <SEP> Q2 <SEP> Q2 <tb> <SEP> N <SEP> Br2, <SEP> pyN <SEP> K2CO3, <SEP> MelNH202 <SEP> urea <tb> <SEP> Bu <SEP> ber <tb> <SEP> Br <SEP> Br <tb> <SEP> OH <SEP> OH <SEP> OMe <tb> <SEP> 6-1 <SEP> 6-2 <SEP> 6-3 <tb> <SEP> [py= <SEP> pyridine] <tb> <SEP> Q2 <SEP> Q2 <tb> <SEP> dz <tb> <SEP> N <SEP> H2SO4, <SEP> HN03N <SEP> Fe, <SEP> NH4CI <tb> <SEP> Br <SEP> Br <SEP> N02 <tb> <SEP> OMe <SEP> OMe <tb> <SEP> 6-4 <SEP> 6-5 <tb> <SEP> o <tb> <SEP> Q2 <SEP> Q2 <SEP> Q3 <tb> <SEP> Q4Q3 <SEP> 4 <tb> <SEP> ( <SEP> : <SEP> 15 <SEP> N <SEP> I <SEP> NaOAc, <SEP> CO, <SEP> MeOH <tb> 1s, <SEP> I, <SEP> > <tb> Br <SEP> NH2 <SEP> Br <SEP> N'Q5 <SEP> Ph2P <SEP> (CH2) <SEP> 3PPh2, <tb> <SEP> N <tb> <SEP> OMe <tb> <SEP> 6-6 <SEP> 6-7 <tb> <SEP> Q2 <SEP> Q3 <SEP> Q2 <SEP> Q3 <tb> <SEP> q. <SEP> Q4 <tb> <SEP> NA <SEP> solvent <SEP> reflux <SEP> < <tb> <SEP> MeO <SEP> ""Y-YNQS <tb> <SEP> 0 <SEP> OMe <SEP> 0 <SEP> OH <tb> <SEP> 6-8 <SEP> 6-9 <tb> <SEP> 4 <tb> <SEP> R <tb> <SEP> R3 <tb> <SEP> n/ <tb> <SEP> R1 <tb> Compounds of the invention that comprise an amino substituent at the 5 position can be prepared in the manner set forth in Schemes 7 and 8. Bromination of the phenol 7-1 occurs regioselectively upon treatment with NBS in an inert solvent like methylene chloride to afford 7-2. Reaction of this bromide with an amine at elevated temperatures in the presence of a polar solvent such as DMPU affords compounds of the invention 7-3. Similar reaction of the bromide 7-2 (Scheme 8) with a diamine such as ethylene diamine in DMF as solvent will afford the formylated derivative 8-1 in addition to the expected diaminoethane derivative. SCHEME 7 EMI72.1 EMI72.2 <tb> J1 <SEP> = <SEP> the <SEP> same <SEP> definition <SEP> as <SEP> in <SEP> Scheme <SEP> 6 <tb> RP, <SEP> Rq <SEP> = <SEP> H; <SEP> alkyl <SEP> ; <SEP> alkyl <SEP> substituted <SEP> with, <SEP> e. <SEP> g., <SEP> OH, <tb> <SEP> alkoxy, <SEP> carbocycle, <SEP> or <SEP> heterocycle <SEP> ; <SEP> (un) <SEP> substituted <tb> carbocycle, <SEP> or <SEP> (un) <SEP> substituted <SEP> heterocycle <tb> SCHEMES EMI73.1 7-2 8-1 Preparation of aryl and heteroaryl derivatives via palladium cross coupling of the chloride 9-1 and the requisite boronic acids are depicted in Scheme 9. SCHEME9 EMI73.2 <tb> <SEP> ci <tb> <SEP> 1 <tb> <SEP> 2 <tb> <SEP> N <SEP> PMBCI, <SEP> CS2CO3 <SEP> OMe <tb> <SEP> > <tb> z <SEP> N <SEP> OMe <SEP> DMF <SEP> n <SEP> S <SEP> Pd <SEP> (PPh3) <SEP> 4 <tb> <SEP> OH <SEP> 0 <SEP> 9-1 <tb> <SEP> 4-3/ <tb> <SEP> OMe <tb> <SEP> J2 <tb> <SEP> 71 <SEP> 1. <SEP> <tb> <SEP> N <tb> <SEP> OMe <SEP> I <SEP> I <tb> <SEP> solvent <SEP> reflux <SEP> z <SEP> N <tb> <SEP> 9-2 <SEP> 9-3 <SEP> OH <SEP> 0 <tb> <SEP> OMe <tb> <SEP> \ <tb> <SEP> OMe <tb> <SEP> J1 <SEP> = <SEP> same <SEP> definition <SEP> as <SEP> in <SEP> Scheme <SEP> 6 <tb> <SEP> J2 <SEP> = <SEP> (un) <SEP> substituted <SEP> aryl <SEP> or <SEP> heteroaryl <tb> (Hetero) aryloxy, (hetero) arylamino, and (heteroaryl) thioxy derivatives 10-2,11-2, and 12-2 respectively can be prepared as shown in Schemes 10 to 12, which exemplify the procedure for the naphthyridine core. The corresponding sulfone derivatives 12-2 can be obtained by oxidation of the sulfides 12-1 with either ozone or 3-chloroperbenzoic acid as shown in Scheme 12. SCHEME 10 EMI74.1 SCHEME 11 EMI74.2 SCHEME 12 EMI74.3 <SEP> L <tb> <SEP> Br <SEP> s"jz <tb> <SEP> J2-SH/Et3N <tb> <SEP> elevated <tb> <SEP> Nu <tb> O <SEP> OH <SEP> O <SEP> OH <tb> <SEP> 10-1 <SEP> 12-1 <tb> <SEP> oxid'n <tb> <SEP> 2 <tb> <SEP> lol <SEP> J2 <tb> <SEP> <tb> <SEP> JAZZ <tb> <SEP> dz <SEP> OH <tb> <SEP> o <SEP> OH <SEP> 12-2 <tb> Preparation of compounds of the invention substituted with an acetylene can be prepared according to Scheme 13, which exemplifies the procedure for the naphthyridine core. Following protection of the iodide 13-2 as its benzoate 13-3, the acetylenic group (for example propynol) can be appended by employing a suitable palladium catalyst in the presence of copper iodide. Aminolysis of the ester 13-4 will afford the amide 13-5 with concomitant deprotection of the benzoate ester. Alternately the ester 13-4 can be converted to the corresponding amine and sulfone derivatives as shown in Schemes 14 and 15. Scheme 16 shows that the preparation of the nitrile derivative 16-2 can be achieved via a palladium catalyzed cyanation of the iodide 13-4. SCHEME 13 EMI75.1 <SEP> I <tb> ¯N <SEP> NIS-'-N <SEP> BZ20, <SEP> CS2CO, <SEP> 3 <tb> <SEP> /OMe <SEP> N/OMe <SEP> DMF <tb> <SEP> Oh <SEP> O <tb> <SEP> OH <SEP> 0 <SEP> 13-2 <SEP> OH <SEP> 0 <SEP> [Bz <SEP> = <SEP> benzoyl] <tb> EMI76.1 <tb> <SEP> CH20H <tb> <SEP> N <tb> fTYN <SEP> == <tb> <SEP> /OMe <SEP> pH <SEP> I <SEP> N <tb> <SEP> o < so <SEP> O <SEP> Pd <SEP> (PPh3) <SEP> 2CI2, <SEP> N <tb> <SEP> 3) <SEP> 2cri2, <tb> <SEP> Cul, <SEP> NEt3, <SEP> DMF <SEP> O <SEP> O <SEP> O <tb> <SEP> / <tb> <SEP> 13-3 <SEP> 13-4 <tb> <SEP> \ <tb> <SEP> i.NaOH/ <tb> <SEP> ii. <SEP> Triphosgene, <SEP> NiPr2XJ1sH <tb> <SEP> Jl--H <tb> <SEP> 111 <tb> <SEP> N <SEP> N <SEP> il <tb> <SEP> N <SEP> J1 <tb> <SEP> OH <SEP> O <tb> <SEP> 13-5 <tb> SCHEME 14 EMI77.1 <tb> <SEP> OH <SEP> H2-AM <tb> <SEP> l <SEP> | <SEP> i. <SEP> MsCI, <SEP> NEt3, <SEP> CHCI3 <SEP> 14l <tb> <SEP> N <SEP> K2CO3 <tb> ome <SEP> amine <SEP> N <SEP> ol <SEP> Me <tb> <SEP> T <SEP> T <SEP> [1 <tb> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <tb> <SEP> 14-1 <SEP> 1-'H <tb> <SEP> 13-4 <tb> <SEP> CH2-AM <tb> AM= <SEP> acyclyl-, <SEP> cyclyl-, <SEP> or <tb> <SEP> heterocyclyl-amino <SEP> N <tb> <SEP> J1 <tb> <SEP> OH <SEP> O <tb> <SEP> 14-2 <tb> SCHEME 15 EMI78.1 <tb> <SEP> zu <tb> <SEP> OH <SEP> S, <SEP> rua <tb> <SEP> i. <SEP> MsCI, <SEP> NEt3, <SEP> CHCI3 <tb> <SEP> K2C03 <SEP> N <tb> <SEP> ZON <tb> <SEP> /OMe <SEP> Ra-SH <SEP> I <SEP> N/OMe <tb> <SEP> 0 <SEP> 0 <SEP> iii. <SEP> Oxone <SEP> 0 <SEP> 0 <tb> <SEP> zu <tb> <SEP> 'H <tb> <SEP> \ <tb> 13-4 <SEP> 15-1 <tb> <SEP> O, <SEP> O <tb> <SEP> Ra <tb> <SEP> N <tb> <SEP> N <SEP> J1 <tb> <SEP> OH <SEP> 0 <tb> CN/A <tb> <SEP> 15-2 <tb> SCHEME 16 EMI78.2 In the processes for preparing compounds of the present invention set forth in the foregoing schemes, functional groups in various moieties and substituents may be sensitive or reactive under the reaction conditions employed and/or in the presence of the reagents employed. Such sensitivity/reactivity can interfere with the progress of the desired reaction to reduce the yield of the desired product, or possibly even preclude its formation. Accordingly, it may be necessary or desirable to protect sensitive or reactive groups on any of the molecules concerned. Protection can be achieved by means of conventional protecting groups, such as those described in Protective Groups in Organic Chemistry, ed. J. F. W. McOmie, Plenum Press, 1973 and in T. W. Greene & P. G. M. Wuts, Protective Groups in Organic Synthesis, John Wiley & Sons, 1991. The protecting groups may be removed at a convenient subsequent stage using methods known in the art. Alternatively the interfering group can be introduced into the molecule subsequent to the reaction step of concern. For example, if one or more of the substituents Rl, R2, R3, and R4 in compound 1-1 can interfere with the coupling reaction between compounds 1-1 and 1-2 of Scheme 1, the substituent can be incorporated into the molecule in a post-coupling step to afford Compound I. The following examples serve only to illustrate the invention and its practice. The examples are not to be construed as limitations on the scope or spirit of the invention. EXAMPLE 1 7- [ (3-phenylpyrrolidin-1-yl) carbonyl]-1, 6-naphthyridin-8-ol EMI79.1 Step 1: Preparation of 3-{ [Methoxycarbonylmethyl-(toluene-4-sulfonyl) aminol-methyl-yridine-2-carboxxlic acid isopropyl ester Isopropyl 3- (hydroxymethyl) pyridine-2-carboxylate (prepared in accordance with P. Ornstein et. al. J. Med. Chem. 1989,32,827) (200g, 1.02 mol), methyl N- [ (4-methylphenyl) sulfonyl] glycinate (249g, 1.02 mol), and triphenylphosphine (403g, 1.5 mol) were dissolved in dry THF (3000mls) and cooled to zero degrees under N2. The diethylazodicarboxylate (DEAD) (267.6 g, 1.5 mol) was dissolved in dry THF (250 mls) and placed in a 500 ml addition funnel. The DEAD was added dropwise over 1 hour. The ice bath was removed and the reaction was allowed to warm slowly to RT. After 2 hours, the reaction was checked by HPLC (above conditions) and some glycinate remained. More starting reagents were added and the reaction was left to stir at RT. After 30 min, the reaction was checked again and saw a very small amount of the glycinate remaining. Concentrated reaction down to a reddish-orange oil that was carried onto the next step. Step 2: Preparation of methyl 8-hydroxy-1, 6-naphthyridine-7-carboxylate 3- { [Methoxyc arbonylmethyl-(toluene-4-sulfonyl)-amino]-methyl}- pyridine-2-carboxylic acid isopropyl ester (1.02 mol) was dissolved in dry methanol (4000ml) and cooled to zero degrees under nitrogen. Then via addition funnel, sodium methoxide (137.8g, 2.5 mol) was added slowly to avoid any exotherm. The reaction was stirred at zero degrees, and checked by HPLC after 1.5 hours and was found to be completed. The solvent was removed in vacuo to obtain a reddish-orange oil, which was partitioned between water (1L) and ethyl acetate (1L). The organic layer was back extracted with saturated sodium bicarbonate solution. The pH of the aqueous layer was adjusted to 7, and the layer was maintained at this pH while extracting with methylene chloride. The organic layer was dried with Na2SO4, filtered, and the solvent was removed in vacuo to obtain a tan solid. The solid was dissolved in hot ethyl acetate, and the solution was filtered while hot to filter out any insoluble material. The product precipitated upon cooling. The precipitate was then filtered and dried in a vacuum oven. The filtrate was recrystallized by concentrating the filtrate and redissolving the resulting solid in a minimal amount of methylene chloride. Sufficient ethyl acetate was added to turn the solution slightly cloudy, after which the solution was boiled to reduce the volume, cooled, and the resulting crystals were filtered out and dried in a vacuum oven. 1H NMR (CDC13,500MHz) 8 11.79 (5H, s), 9.20 (1H, dd, J= 1.7 and 6. lHz), 8.80 (1H, s), 8.30 (1H, dd, J=1. 5 and 9.7 Hz), 7.70 (1H, dd, J= 4.2 and 12.4 Hz) and 4.10 (3H, s) ppm. ES MS exact mass calculated for CloH8N203 204.1869 (MH+), found 205.1. Step 3: Preparation of 8-hydroxy-1, 6-naphthyl To a slurry of methyl 8-hydroxy-1, 6-naphthyridine-7-carboxylate from Example 1, Step 2 (1.50g, 7.35 mmol) in methanol (45ml) was added lithium hydroxide (22.0ml of a 1M aq. solution, 22.0 mmol) and the reaction was heated at 100 C for 7 hrs. Upon cooling to room temperature, hydrochloric acid (22.0ml of a 1M aq. solution, 22.0 mmol) was added and the reaction stirred for 16 hrs. The mixture was concentrated to a volume of 50 ml and neutralized with dilute NaHC03 (pH=7). The resulting precipitate was collected by filtration and washed with water and dried in vacuo to afford the title compound. FAB MS calcd for C9H6N203 191 (MH+), found 191. 1H NMR (d6DMSO, 400MHz) 8 9.20 (1H, m), 8.72 (1H, s), 8.58 (1H, m), 7.80 (1H, dd, J=8. 3 and 4.2 Hz) ppm. Step 4: Preparation of 7- [ (3-phenylpyrrolidin-1-yl) carbonyl]-1, 6-naphthyridin 8-ol Triphosgene (0.556g, 1.87 mmol) was added over 20 mins to a solution of the acid from Step 3. (0.89g, 4.68 mmol) and diisopropylethylamine 3.26 ml, 18. 7 mmol) in DMF (22 ml) at 0 C. The dark solution was allowed to warm to room temperature and stirred a further 1 hr. 3-phenylpyrrolidine (15.46 mg, 1.05 mmol) was treated with a portion of the above solution (0.58ml, 0.07 mmol) and the resulting mixture was stirred at room temperature for 16 hrs. The solution was treated with trifluroacetic acid (TFA) (0.025 ml) and purified by preparative HPLC. (Gilson semi preparative HPLC system and a YMC Combiprep Pro Column (50X20mm I. D., C18, S-5 um, 120A) (available from Waters) eluting with 5-95% acetonitrile/water (0.1% TFA) at 15 ml/min) to afford the title compound after lyophilization. 1H NMR (d6DMSO, 400MHz) 8 9.15 (1H, m), 8.91 (0. 5H, s), 8.87 (0. 5H, s), 8.628.50 (1H, m), 7.86-7.75 (1H, m), 4.37 (0.5H, dd, J=10.5 and 7.4Hz), 4.13 (0. 5H, m), 4.05-3.40 (4H, m), 2.32 (1H, m) and 2.07 (1H, m) ppm. FAB MS calcd for Cl9Hl7N302 320 (MH+), found 320. EXAMPLE 2 7- [ (3-benzylpiperidin-1-yl) carbonyl]-1, 6-naphthyridin-8-ol EMI82.1 The title compound was prepared using the procedure described in Example 1, Step 4 replacing 2-phenylpyrrolidine with 3-benzylpiperidine. 1H NMR (d6DMSO, 400MHz) 8 9.14 (1H, m), 8.89 (0. 5H, s), 8.73 (0. 5H, s), 8.58 (1H, m), 7.76 (1H, dd, J=8. 3 and 4.3Hz), 7.40-7.10 (3H, m), 7.05-6.60 (2H, m), 4.40 (1H, brd, J=10.3Hz), 4.30 (1H, d, J=11.5Hz) and 3.50-1.00 (9H, m) ppm. FAB MS calcd for C2lH2lN302 348 (MH+), found 348. EXAMPLE 3 Oral Composition As a specific embodiment of an oral composition of a compound of this invention, 50 mg of compound of Example 1 is formulated with sufficient finely divided lactose to provide a total amount of 580 to 590 mg to fill a size 0 hard gelatin capsule. EXAMPLE 4 HIV Integrase Assay: Strand Transfer Catalyzed by Recombinant Integrase Assays for the strand transfer activity of integrase were conducted in accordance with Wolfe, A. L. et al., J. Virol. 1996,70: 1424-1432, for recombinant integrase, except that: (i) the assays used preassembled integrase strand transfer complexes; (ii) the strand transfer reaction was performed in the presence of inhibitor in 2.5 mM MgCl2 using 0.5 to 5 nM of a 3'FITC labeled target DNA substrate (SEQ. ID. NO.: 1) 5'TGA CCA AGG GCT AAT TCA CT fitc 3' 3'fitc ACT GGT TCC CGA TTA AGT GA 5'; and (iii) strand transfer products were detected using an alkaline phosphatase conjugated anti-FITC antibody and a chemiluminescent alkaline phosphatase substrate. Representative compounds tested in the integrase assay demonstrated IC50's of less than about 100 micromolar. Further description on conducting the assay using preassembled complexes is found in Hazuda et al., J. Virol. 1997,71: 7005-7011; Hazuda et al., Drug Design and Discovery 1997,15: 17-24; and Hazuda et al., Science 2000,287: 646-650. EXAMPLE 5 Assay for inhibition of HIV replication Assays for the inhibition of acute HIV infection of T-lymphoid cells were conducted in accordance with Vacca, J. P. et al., (1994), Proc. Natl. Acad. Sci. USA 91,4096. Representative compounds tested in the present assay demonstrated IC95's of less than about 20 micromolar. While the foregoing specification teaches the principles of the present invention, with examples provided for the purpose of illustration, the practice of the invention encompasses all of the usual variations, adaptations and/or modifications that come within the scope of the following claims.

Claims: WHAT IS CLAIMED IS: 1. A compound of Formula (I) : EMI84.1 wherein A is a 5-or 6-membered saturated or unsaturated heterocyclic ring which contains from 1 to 4 nitrogen atoms one of which is directly attached to the exocyclic carbonyl moiety, zero to 2 heteroatoms selected from oxygen and sulfur, and a balance of carbon atoms; wherein the heterocyclic ring is optionally fused to a phenyl ring or to a second 5-or 6-membered heterocyclic ring which is saturated or unsaturated and which contains from 1 to 4 nitrogen atoms, zero to 2 heteroatoms selected from oxygen and sulfur, and a balance of carbon atoms, wherein the second heterocyclic ring is optionally fused to a phenyl ring; A is substituted by R1, R2, R3, and R4; XisNorC-Ql ; Y is N or C-Q2, provided that X and Y are not both N; Z1 is N or C-Q3 ; Z2 is N or C-Q4 ; Z3 is N or CH ; each of Ql, Q2, Q3, and Q4 is independently (1)-H, (2)-C1 6 alkyl, (3)-Cl-6 haloalkyl, (4) -O-C1-6 alkyl, (5) -O-C1-6 haloalkyl, (6) halo, (7)-CN, (8)-Ci-6 alkyl-ORa, (9) -C0-6 alkyl-C (=O) Ra, (10) -C0-6 alkyl-C02Ra, (11) -C0-6 alkyl-SRa, (12)-N (Ra) 2, (13) -C1- alkyl-N (Ra) 2, (14) -C0-6 alkyl-C (=O) N (Ra) 2, (15) -C0-6 alkyl-G-C1 alkyl-C (=O) N (Ra) 2, wherein G is O, S, N (Ra), or N(SO2Ra), (16)-N (Ra)-C (Ra) =O, (17) -Ci-6 alkyl-N (Ra)-C (Ra) =O, ) -C(=O)-N(Ra)-C1-6 alkyl-[C(=O)]0-1-N(Ra)2, (19)-C (=O)-N (Ra)-C1-6 alkyl substituted with 1 or 2-ORa, (20) -C0-6 alkyl-S02Ra, )-CO-6 alkyl-N (Ra) S02Ra, (22) -C2- alkenyl, (23) -C2-6 alkenyl-C(=O)-N (Ra) 2, (24)-C2-5 alkynyl, (25)-C2-5 alkynyl-CH2N (Ra) 2, (26) -C2-5 alkynyl-CH2ORa, (27)-C2-5 alkynyl-CH2S (O) n-Ra, or EMI85.1 ) -C(=NRa)-N(Ra)2, (31)-N (Ra)-C1-6 alkyl-S (O) nRa, (32)-N (Ra)-C1-6 alkyl-ORa, (33)-N (Ra)-Ci-6 alkyl-N (Ra) 2, (34)-N (Ra)-C1-6 alkyl-N (Ra)-C (Ra) =O, (35)-N (Ra)-Co-6 alkyl- [C (=O) ] 1-2N (Ra) 2, (36)-N (Ra)-C1-6 alkyl-CO2Ra, (37)-N (Ra) C (=O) N (Ra)-C1-6 alkyl-C (=O) N (Ra) 2, (38)-N (Ra) C (=O)-C1-6 alkyl-N (Ra) 2, (39)-N (Ra)-SO2-N (Ra)2, (40)-Rk, (41)-C1-6 alkyl substituted with Rk, (42) -C1-6 haloalkyl substituted with Rk, (43) -C2-5 alkenyl-Rk, (44) -C2-5 alkynyl-Rk, )-CO-6 alkyl-O-Rk, (46) -C0-6 alkyl-O-C1-6 alkyl-Rk, (47) -C0-6 alkyl-S (O) n-Rk (48) -C0-6 alkyl-S (O) n-C1-6 alkyl-Rk, (49) -O-C1-6 alkyl-ORk, (50) -O-C1-6 alkyl-O-C1-6 alkyl-Rk, (51) -O-C1-6 alkyl-S (O) nRk, (52) -C0-6 alkyl-N (RC)-Rk, (53) -C0-6 alkyl-N (Rc)-C1-6 alkyl substituted with one or two Rk groups, (54) -C0-6 alkyl-N (Rc)-C1-6 alkyl-ORk, )-CO-6 alkyl-C (=O)-Rk, (56) -C0-6 alkyl-C (=O) N (Ra)-Rk, (57) -C0-6 alkyl-N (Ra) C (=O)-Rk, (58) -C0-6 alkyl-C (=O) N (Ra)-C1-6 alkyl-Rk, or (59) -C0-6 alkyl-N (Ra)-C0-6 alkyl-S(O) nRk; each of Rl and R2 is independently: (1)-H, (2)-C1-6 alkyl, (3)-C1-6 haloalkyl, (4) -O-C1-6 alkyl, (5) -O-C1-6 haloalkyl, (6)-OH (7) halo, (8)-N02, (9)-CN, (10)-Cl-6 alkyl-ORa, (11) -C0-6 alkyl-C (=O) Ra, (12) -C0-6 alkyl-CO2Ra, (13) -C0-6 alkyl-SRa, (14)-N (Ra) 2, (15) -C1-6 alkyl-N (Ra) 2, (16) -C0-6 alkyl-C (=O) N (Ra) 2, (17) -C1-6 alkyl-N (Ra)-C (Ra) =O, (18) -SO2Ra, (19)-N (Ra) S02Ra, (20)-C2-5 alkenyl, (21) -O-C1-6 alkyl-ORa, (22) -O-C1- alkyl-SRa, (23) -O-C1-6 alkyl-NH-CO2Ra, (24) -0-C2-6 alkyl-N (Ra) 2, (25)-N (Ra)-C1-6 alkyl-SRa, (26)-N (Ra)-C1-6 alkyl-ORa, (27)-N (Ra)-C1-6 alkyl-N (Ra) 2, (28)-N (Ra)-C1-6 alkyl-N (Ra)-C (Ra) =O, (29)-Rk, (30) -C1-6 alkyl substituted with 1 or 2 Rk groups, (31) -C1-6 haloalkyl substituted with 1 or 2 Rk groups, (32)-C2-5 alkenyl-Rk, (33) -C2-5 alkynyl-Rk, (34)-O-Rk -O-C1-6 alkyl-Rk, (36)-S S(O) n-Rk, (37)-S S(O) n-Cl-6 alkyl-Rk, (38) -O-C1-6 alkyl-ORk, (39) -O-C1-6 alkyl-O-C1-6 alkyl-Rk, (40) -O-C1-6 alkyl-S (O) nRk, (41)-C1-6 alkyl (ORb) (Rk), (42) -C1-6 alkyl (ORb)(-C1-6 alkyl-Rk), (43)-Cp-6 alkyl-N (Rb) (Rk), (44) -C0-6 alkyl-N (Rb) (-Cl-6 alkyl-Rk), (45) -C1-6 alkyl S (O) n-Rk, (46) -C1-6 alkyl S (O) n-Cl-6 alkyl-Rk, (47) -C0-6 alkyl C (O)-Rk, or (48) -C0-6 alkyl C (0)-Ci-6 alkyl-Rk, each of R3 and R4 is independently (1)-H, (2) halo, (3)-CN, (4)-N02, (5)-OH, (6) C1-6 alkyl, (7) C1-6 haloalkyl, (8) -O-C1-6 alkyl, (9) -O-C1-6 haloalkyl, (10)-Ci-6 alkyl-ORa, (11) -C0-6 alkyl-C(=O)Ra, (12) -C0-6 alkyl-CO2Ra, (13) -C0-6 alkyl-SRa, (14)-N (Ra) 2, (15)-Ci-6 alkyl-N (Ra) 2, (16) -C0-6 alkyl-C (=O) N (Ra) 2, (17) -SO2Ra, (18)-N (Ra) SO2Ra, (19)-C2-5 alkenyl, (20) -O-C1-6 alkyl-ORa, (21) -O-C1-6 alkyl-SRa, (22) -O-C1-6 alkyl-NH-CO2Ra, (23)-0-C2-6 alkyl-N (Ra) 2, or (24) oxo; each Ra is independently-H,-Cl-6 alkyl, or-C1-6 haloalkyl ; each Rb is independently: (1)-H, (2)-C1-4 alkyl, (3) -C1-4 haloalkyl, (4)-Rk, (5)-C2-3 alkenyl, (6)-Ci-4 alkyl-Rk, (7) -C2-3 alkenyl-Rk, (8)-S (O) n-Rk, or (9)-C (O)-Rk ; each Rc is independently (1)-H, (2) -C1-6 alkyl, (3) -C1-6 alkyl substituted with-N (Ra) 2, or (4) -C1-4 alkyl-aryl, wherein aryl is optionally substituted with 1 to 5 substituents independently selected from halogen, C1-6 alkyl, Cl-6 haloalkyl,-O-C1-6 alkyl,-O-C1-6 haloalkyl,-S-C1-6 alkyl,-CN, and-OH; each Rk is independently carbocycle or heterocycle, wherein the carbocycle and heterocycle are unsubstituted or substituted with from 1 to 5 substituents each of which is independently selected from (a) halogen, (b)-Cl-6 alkyl, (c) -C1-6 haloalkyl, (d) -O-C1-6 alkyl, (e) -O-C1- haloalkyl, -S-C1-6 alkyl, (g)-CN, (h)-OH, (i) oxo, (j) -C0-6 alkyl-C (=O) N (Ra) 2, (k)-Cp-6 alkyl-C (=O) Ra, (1)-N (Ra)-C (=O) Ra, (m)-N (Ra)-C02Ra, (n)-C1¯g alkyl-N (Ra)-C (=O) Ra, (o)-N (Ra) 2, -C1-6 alkyl-N (Ra) 2, (q) -C1-6 alkyl-ORa, (r)-Cp-6 alkyl-C02Ra, (s)-Cp-6 alkyl-C alkyl-ORa, (t) -SO2Ra, (u)-S02N (Ra) 2, (v) -Cp-6 alkyl-C02-C2-5 alkenyl, (w) aryl, (x) aryloxy-, (y) -C1-4 alkyl substituted with aryl, (z) heteromonocycle, (aa) -C1-4 alkyl substituted with a heteromonocycle, (bb) heteromonocyclylcarbonyl-Co-6 alkyl-, and (cc) N-heteromonocyclyl-N-C1-6 alkyl-amino-; wherein the aryl group in (w) aryl, (x) aryloxy, and (y)-C1-4 alkyl substituted with aryl, is optionally substituted with from 1 to 4 substituents independently selected from halogen, Cl-6 alkyl,-O-C1-6 alkyl, C1-6 alkyl substituted with N (Ra) 2, C1-6 haloalkyl, and-OH; and wherein the heteromonocyclyl group in (z) heteromonocycle, (aa) -C1-4 alkyl substituted with a heteromonocycle, (bb) heteromonocyclyl-carbonyl-Co-6 alkyl-, and (cc) Nheteromonocyclyl-N-C1-6 alkyl-amino-is optionally substituted with from 1 to 4 substituents independently selected from halogen, C1-6 alkyl,-O-C1-6 alkyl, Cl-6 haloalkyl, oxo, and-OH; and each n is independently an integer equal to 0,1 or 2; or a pharmaceutically acceptable salt thereof. 2. A compound according to claim 1, wherein: each of Ql, Q2, Q3 and Q4 is independently (1)-H, (2) -C1-6 alkyl, (3) -C1-6 fluoroalkyl, (4) -O-C1-6 alkyl, (5) -O-C1-6 fluoroalkyl, (6) halo, (7)-CN, (8)-Ci-6 alkyl-ORa, (9)-Cp-6 alkyl-C (=O) Ra, (10)-Cp-6 alkyl-C02Ra, (11) -C0-6 alkyl-SRa, (12)-N (Ra) 2, (13) -C1-6 alkyl -N (Ra) 2, (14) -C0-6 alkyl-C (=O) N (Ra) 2, (15) -C1-6 alkyl-N (Ra)-C (Ra) =O, (16) -SO2Ra, (17)-N (Ra) S02Ra, (18)-C2-5 alkynyl, (19)-C2-5 alkynyl-CH2N (Ra) 2, (20) -C2-5 alkynyl-CH2ORa, EMI91.1 (22)-N (Ra)-C1-6 alkyl-SRa, (23) -N (Ra)-C1-6 alkyl-ORa, (24)-N N(Ra)-C1-6 alkyl-N(Ra)2, (25)-N (Ra)-Ci-6 alkyl-N (Ra)-C (Ra) =O, (26)-Rk, (27)-Cl-6 alkyl substituted with Rk, (28) -C1-6 fluoroalkyl substituted with Rk, (29) -C2-5 alkenyl-Rk, (30)-C2-5 alkynyl-Rk, (31) -O-Rk, (32)-0-Cl-4 alkyl-Rk, (33)-S S(O) n-Rk, (34)-S (O) n-Cl-4 alkyl-Rk, (35) -O-C1-6 alkyl-ORk, (36) -O-C1-6 alkyl-O-C1-4 alkyl-Rk, (37)-0-Cl-6 alkyl-SRk, (38)-N (Rc)-Rk, (39)-N (Rc)-Cl-6 alkyl substituted with one or two Rk groups, (40)-N (Rc)-C1-6 alkyl-ORk, (41)-C (=O) N-C1-6 alkyl-Rk, (42)-C2-5 alkynyl-CH2S (O) n-Ra, or (43)-C(=NRa)-N (Ra) 2 ; each of RI and R2 is independently: (1)-H, (2) -C1-6 alkyl, (3) -C1-6 fluoroalkyl, (4) -O-C1-6 alkyl, (5) -O¯C1-6 fluoroalkyl, (6)-OH, (7) halo, (8)-NO2, (9)-CN, (10)-Cl-6 alkyl-ORa, (11)-Cp-6 alkyl-C (=O) Ra, (12) -C0-6 alkylCO2Ra, (13) -C0-6 alkyl-SRa, (14)-N (Ra) 2, (15)-Cl-6 alkyl N (Ra) 2, (16) -C0- alkyl-C (=O) N (Ra) 2, (17)-Cl-6 alkyl-N (Ra)-C (Ra) =O, (18) -SO2Ra, (19)-N (Ra) S02Ra, (20)-C2-5 alkenyl, (21) -O-C1-6 alkyl-ORa, (22) -O-C1-6 alkyl-SRa, (23) -O-C1-6 alkyl-NH-CO2Ra, (24) -O-C2-6 alkyl-N (Ra) 2, (25)-N (Ra) -C1-6 alkyl-SRa, (26)-N (Ra)-C 1-6 alkyl-ORa, (27)-N (Ra)-C1-6 alkyl-N (Ra) 2, (28)-N (Ra)-C1-6 alkyl-N (Ra)-C (Ra) =O, (29)-Rk, (30)-C1-6 alkyl substituted with 1 or 2 Rk groups, (31)-C1 fluoroalkyl substituted with 1 or 2 Rk groups, (32) -C2-6 alkenyl-Rk, (33) -C2-5 alkynyl-Rk, (34) -O-Rk, (35) -O-C1-4 alkyl-Rk, (36)-S S(O) n-Rk, (37)-S (O) n-C1-4 alkyl-Rk, (38) -O-C1-6 alkyl-ORk, (39) -O-C1-6 alkyl-O-C1-4 alkyl-Rk, (40) -O-C1-6 alkyl-SRk, (41) -C1-6 alkyl (ORb) (Rk), (42)-Cl-6 alkyl (ORb) (-C1-4 alkyl-Rk), (43) -C0-6 alkyl-N (Rb) (Rk), (44) -C0-6 alkyl-N (Rb) (-C1-4 alkyl-Rk), (45)-C1-6 alkyl S (O) n-Rk, (46) -C1-6 alkyl S (O) n-C1-4 alkyl-Rk, (47) -Cp-6 alkyl C (O)-Rk, or (48) -C0-6 alkyl C (O)-C1-4 alkyl-Rk, each of R3 and R4 is independently (1)-H, (2) halo, (3)-CN, (4) -NO2, (5)-OH, (6) C1-6 alkyl, (7) C1-6 fluoroalkyl, (8) -O-C1-6 alkyl, (9) -O-C1-6 fluoroalkyl, (10) -C1-6 alkyl-ORa, (11) -C0-6 alkyl-C(=O)Ra, (12)-Cp-6 alkyl-CO2Ra, (13)-Cp-6 6 alkyl-SRa, (14)-N (Ra) 2, (15) -C1-6 alkyl N (Ra) 2, (16)-Cp-6 alkyl-C (=O) N (Ra) 2, (17)-S02Ra, (18)-N (Ra) S02Ra, (19) -C2-5 alkenyl, (20) -O-C1-6 alkyl-ORa, (21) -O-C1-6 alkyl-Sra, (22) -O-C1-6 alkyl-NH-CO2Ra, (23) -O-C2-6 alkyl-N(Ra)2, or (24) oxo each Ra is independently-H,-C1-6 alkyl, or-C1-6 fluoroalkyl ; each Rb is independently: (1)-H, (2)-C1 4 alkyl, (3) -C1-4 fluoroalkyl, (4) -Rk, (5) -C2-3 alkenyl, (6) -C1-4 alkyl-Rk, (7) -C2-3 alkenyl-Rk, (8)-S (O) n-Rk, or (9)-C (O)-Rk ; each Rc is independently (1)-H, (2)-C1-6 alkyl, (3)-C1-6 alkyl substituted with-N (Ra) 2, or (4) -C1-4 alkyl-aryl, wherein aryl is optionally substituted with 1 to 5 substituents independently selected from halogen, Cl-6 alkyl, Cl-6 fluoroalkyl,-O-C1-6 alkyl,-O-Cl-6 fluoroalkyl,-S-C1-6 alkyl,-CN, and-OH; each Rk is independently carbocycle or heterocycle, wherein the carbocycle and heterocycle are unsubstituted or substituted with from 1 to 5 substituents each of which is independently selected from (a) halogen, (b) C1-6 alkyl, (c) C1- fluoroalkyl, (d) -O-C1-6 alkyl, (e) -O-C1-6 fluoroalkyl, (f) -S-C1-6 alkyl, (g)-CN, (h)-OH, (i) oxo, -(CH2)0-3C(=O)N(Ra)2, -(CH2)0-3C(=O)Ra, (1)-N (Ra)-C (=O) Ra, (m)-N (Ra)-C (=O) ORa, (n)- (CH2) 1-3N (Ra)-C (=O) Ra, (o)-N (Ra) 2, -C1-6 alkyl-N (Ra) 2, (q) aryl, (r) aryloxy-, (s)-C1-4 alkyl substituted with aryl, (t) heteromonocycle, (u)-C1 4 alkyl substituted with a heteromonocycle, (v) heteromonocyclylcarbonyl-Co-6 alkyl-, and (w) N-heteromonocyclyl-N-C1-6 alkyl-amino- ; wherein the aryl group in (q) aryl, (r) aryloxy, and (s)-Cl-4 alkyl substituted with aryl, is optionally substituted with from 1 to 3 substituents independently selected from halogen, C1- alkyl,-O-C1 6 alkyl, C1-6 alkyl substituted with N (Ra) 2, C1-6 fluoroalkyl, and-OH; and wherein the heteromonocyclyl group in (t) heteromonocycle, (u) -C1-4 alkyl substituted with a heteromonocycle, (v) heteromonocyclyl-carbonyl-Co-6 alkyl-, and (w) N heteromonocyclyl-N-C1¯6 alkyl-amino-is optionally substituted with from 1 to 3 substituents independently selected from halogen, C1-6 alkyl, -O-C1-6 alkyl, C1-6 fluoroalkyl, oxo, and-OH; or a pharmaceutically acceptable salt thereof. 3. The compound according to claim 2, which is a compound of Formula (II) : EMI96.1 wherein A is EMI97.1 denotes the point of attachment; Z1 is N or C-Q3; Q2is (1)-H, (2)-C1-4 alkyl, (3) -C1-4 fluoroalkyl, (4) -O-C1-4 alkyl, (5) -O-C1-4 fluoroalkyl, (6) halo, (7)-CN, (8)-Ci-4 alkyl-ORa, (9)- (CH2) 0-2C (=O) Ra, (10) -(CH2)0-2CO2Ra, (11) -(CH2)0-2SRa, (12)-N (Ra) 2, (13) -C1-4 alkyl -N (Ra) 2, (14) -(CH2)0-2C(=O)N(Ra)2, (15)-S02Ra, (16)-N (Ra) SO2Ra, (17)-C2-3 alkynyl, (18) -C#C-CH2N(Ra)2 a (19) -C#C-CH2ORa (20)-N (Ra)-C1-4 alkyl-SRa, (21)-N (Ra)-C1-4 alkyl-ORa, (22)-N (Ra)-C1-4 alkyl-N (Ra) 2, (23)-N (Ra)-C1-4 alkyl-N (Ra)-C (Ra) =O, (24) -Rk, (25) -C1-4 alkyl substituted with Rk, (26) -C1-4 fluoroalkyl substituted with Rk, (27) -C2-5 alkenyl-Rk, (28)-C2-5 alkynyl-Rk, (29)-0-irk, (30) -O-C1-4 alkyl-Rk, (31)-S S(O) n-Rk, (32)-N (Rc)-Rk, (33)-N (Rc)-C1-4 alkyl substituted with one or two Rk groups, (34)-N (Rc)-Cl-4 alkyl-ORk, (35)-C (=O) N-Ci-4 alkyl-Rk, (36) -C#C-CH2SRa, or (37) -C#C-CH2SO2Ra; Q3 is (1)-H, (2) -C1-4 alkyl, (3) -C1-4 fluoroalkyl, (4) -O-C1-4 alkyl, (5) -O-C1-4 fluoroalkyl, (6) halo selected from-F,-Cl, and-Br, (7)-CN, (8) -C1-4 alkyl-ORa, or (9)-C1 4 alkyl substituted with Rk; Q4is : (1)-H, (2)-C1 4 alkyl, (3) -C1-4 fluoroalkyl, (4) -O-C1-4 alkyl, (5) -O-C1-4 fluoroalkyl, (6) halo selected from-F,-Cl, and-Br, (7)-CN, (8)-Ci-6 alkyl-ORa, (9)-N (Ra) 2, or (10) -C1-6 alkyl -N (Ra) 2 ; each of Rl and R2 is independently: (1)-H, (2)-C1 4 alkyl, (3)-C1 4fluoroalkyl, (4) -O-C1-4 alkyl, (5)-O-C1-4 fluoroalkyl, (6)-OH, (7) halo, (8)-CN, (9) -C1-4 alkyl-ORa, (10) -(CH2)0-2C(=O)Ra, (11)- (CH2) 0-2C02Ra, (12)- (CH2)0-2SRa, (13)-N (Ra) 2, (14)-C1-4 alkyl N (Ra) 2, (15) -(CH2)0-2C(=O)N(Ra)2, (16) -C1-4 alkyl-N (Ra)-C (Ra) =O, (17)-S02Ra (18)-N (Ra) SO2Ra, (19) -O-C1-4 alkyl-ORa, (20) -O-C1-4 alkyl-SRa, (21) -O-C1-4 alkyl-NH-CO2Ra, (22)-0-C2-4 alkyl-N (Ra) 2, (23)-N (Ra)-C1-4 alkyl-SRa, (24)-N (Ra)-C1-4 alkyl-ORa, (25)-N (Ra)-Cl-4 alkyl-N (Ra) 2, (26)-N (Ra)-C1-4 alkyl-N (Ra)-C (Ra) =O, (27)-Rk, (28) -C1 4 alkyl substituted with 1 or 2 Rk groups, (29)-C1-4 fluoroalkyl substituted with 1 or 2 Rk groups, (30) -O-Rk, (31) -O-C1-4 alkyl-Rk, (32)-S S(O) n-Rk, (33)-S (O) n-C1-4 alkyl-Rk, (34)-0-CI-4 alkyl-ORk, (35) -O-C1-4 alkyl-O-C1-4 alkyl-Rk, (36)-0-CI-4 alkyl-SRk, or (37) -C0-4 alkyl-N (Rb) (Rk); each of R3 and R4 is independently (1)-H, (2) halo, (3)-CN, (4)-OH, (5) C1-4 alkyl, (6) C1-4 fluoroalkyl, (7) -O-C1-4 alkyl, (8) -O-C1-4 fluoroalkyl, (9)-Ci-4 alkyl-ORa, (10)-0-Cl-4 alkyl-ORa, (11) -O-C1-4 alkyl-SRa, (12) -O-C1-4 alkyl-NH-CO2Ra, or (13)-0-C2-4 alkyl-N (Ra) 2; each Ra is independently-H or-C1 4 alkyl ; each Rb is independently: (1)-H, (2) -C1-4 alkyl, (3) -C1-4 fluoroalkyl, (4)-Rk (5) -C1-4 alkyl-Rk, (6)-S (O) n-Rk, or (7)-C (=O)-Rk ; each Rc is independently (1)-H, (2) -C1-4 alkyl, (3) -C1-4 alkyl substituted with-N (Ra) 2, or (4)-Ci-4 alkyl-phenyl, wherein the phenyl is optionally substituted with 1 to 3 substituents independently selected from halogen, C1-4 alkyl, C1-4 fluoroalkyl, -O-C1-4 alkyl, -O-C1-4 fluoroalkyl,-S-C1-4 alkyl,-CN, and-OH; each Rk is independently: (1) aryl selected from phenyl and naphthyl, wherein aryl is unsubstituted or substituted with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) Cl-6 fluoroalkyl, (d)-O-C1-6 alkyl, (e)-O-C1-6 fluoroalkyl, phenyl, (g) -S-C1-6 alkyl, (h)-CN, (i)-OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (i) halogen, (ii) C1- 6 alkyl, (iii) Cul-6 fluoroalkyl, and (iv)-OH, (k)-N (Ra) 2, (1)-Ci-6 alkyl-N (Ra) 2, ) (P)- (CH2) 0-3C () N (Ra) 2, and (q) -(CH2)0-3C(=O)Ra; (2)-C3-7 cycloalkyl, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c)-O-C1-6 alkyl, (d) CI-6 fluoroalkyl, (e)-O-C1 6 fluoroalkyl, (f)-CN, (h) phenyl, and (j)-OH ; (3)-C3-7 cycloalkyl fused with a phenyl ring, unsubstituted or substituted with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c)-O-C1-6 alkyl, (d) C1-6 fluoroalkyl, (e) -O-C1-6 fluoroalkyl, (f)-CN, and (g)-OH; (4) a 5-or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein the heteroaromatic ring is unsubstituted or substituted on nitrogen or carbon with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1 6 alkyl, (c) CI-6 fluoroalkyl, (d) -O-C1-6 alkyl, (e) -O-C1-6 fluoroalkyl, (f) phenyl, ) -S-C1-6 alkyl, (h)-CN, (i)-OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (i) halogen, (ii) C1-6 alkyl, (iii) C1-6 fluoroalkyl, and (iv)-OH, (k)-N (Ra) 2, (1) -C1-6 alkyl-N (Ra) 2, (m)-Rt, (n) oxo, ) -(CH2)0-3C(=O)N(Ra)2, and ) -(CH2)0-3C(=O)Ra; (5) a 5-or 6-membered saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein the heterocyclic ring is unsubstituted or substituted with from 1 to 4 substituents independently selected from: (a) halogen, (b) C1 6 alkyl, (c) -O-C1-6 alkyl, (d) Cl-6 fluoroalkyl, (e)-O-Cl-6 fluoroalkyl, (f)-CN, (g) oxo, (h) phenyl, (i) benzyl, (j) phenylethyl, (k)-OH, (1)- (CH2) 0-3C (=O) N (Ra) 2, ) -(CH2)0-3C(=O)Ra, (n)-N (Ra)-C (=O) Ra, (o)-N (Ra)-C (=O) ORa, )-OH2) 1-3N(Ra)-C(=O)Ra, (q)-N (Ra) 2, (r)- (CH2) 1-3N (Ra) 2, -(CH2)0-3C(=O)Rt, (t)-Rt, (u)-N (Ra) Rt, and (v)-(CH2) 1 3Rt ; or (6) an 8-to 10-membered heterobicyclic ring containing from 1 to 4 heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein the heterobicyclic ring is saturated or unsaturated, and is unsubstituted or substituted with from 1 to 5 substituents independently selected from: (a) halogen, (b) C1 6 alkyl, (c)-O-C1-6 alkyl, (d) C1-6 fluoroalkyl, (e) -O-C1- fluoroalkyl, (f)-CN, (g) =O, and (h)-OH; Rt is naphthyl or a 5-or 6-membered heteromonocylic ring containing from 1 to 4 nitrogen atoms, wherein the heteromonocyclic ring is saturated or unsaturated, and wherein the naphthyl or the heteromonocyclic ring is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, oxo, C1-4 alkyl, and -O-C1 4 alkyl ; and n is an integer equal to 0,1 or 2; or a pharmaceutically acceptable salt thereof. 4. The compound according to claim 3, wherein Zl is CH; and Q4 is-H; or a pharmaceutically acceptable salt thereof. 5. The compound according to claim 2, which is a compound of Formula (III) : EMI105.1 wherein G is: (1) NH optionally substituted by either Rl or R2, (2) CH2 optionally substituted by either or both R1 and R2, or (3)-S (O) n wherein n is an integer equal to zero, 1 or 2; Q2 is (1)-H, (2) methyl, (3) ethyl, (4) CF3, (5) methoxy, (6) ethoxy (7)-OCF3 (8) halo selected from--Cl and-Br, (9)-CN, (10)-CH20H, (11)-CH20CH3 (12) -(CH2)0-2 CO2CH3, (13)-SRa, (14)-N (Ra) 2, (15)-S02Ra, (16) -C#C-CH2ORa (17)-N (Ra)-(CH2)1-3SRa, (18)-N (Ra)- (CH2) 1-30Ra (19) -N(Ra)-(CH2)1-3N(Ra)2, (20)-N (Ra)-(CH2)1-3N(Ra)-C(Ra)=O, (21)-Rk, (22) -(CH2)1-4Rk, (23) -C#C-CH2Rk (24)-0-Rk, (25) -S-Rk, (26) -SO2-Rk, (27)-N -N(Rc)-Rk, (28)-N (Rc)- (CH2) 1-4H substituted with one or two Rk groups, (29)-N (Rc)- (CH2) 1-40Rk, (30)-C (=O) N-(CH2)1-4Rk, (31) -C#C-CH2SRa, or (32) -C#C-CH2SO2Ra; each of Rl and R2 is independently: (1)-H, (2) methyl, (3) ethyl, (4) CF3, (5) methoxy, (6) ethoxy (7)-OCF3 (8) halo selected from--Cl and-Br, (9)-CN, (10)-CH20Ra, (11)-C02Ra, (12)-SRa, (13)-N (Ra) 2, (14)- (CH2) 1-3N (Ra) 2, (15) -SO2Ra, (16) -(CH2)1-2N(Ra)-C(Ra)=O, (17)-Rk, (18)- (CH2) 1-3H substituted with 1 or 2 Rk groups, (19) -O-ORk, or (20) -O-(CH2)1-3Rk; each Ra is independently-H or -C1-4 alkyl ; each Rc is independently -H, -C1-4 alkyl, or -(CH2)1-3N(Ra)2; each Rk is independently: (1) phenyl which is unsubstituted or substituted with from 1 to 4 substituents independently selected from: (a) halogen selected from-F,-Cl, and-Br, (b) methyl, (c)-CF3, (d) methoxy, (e)-OCF3, (f) phenyl, (g)-S-CH3, (h)-CN, (i)-OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (i) halogen selected from-F,-Cl, and-Br, (ii) methyl, (iii)-CF3, and (iv)-OH, (lc)-N (Ra) 2, (1)- (CH2) l-3N (Ra) 2, (m)-Rt, (P)- (CH2) 0-3C () N (Ra) 2, and ) -(CH2)0-3C(=O)Ra; (2)-C3-6 cycloalkyl, unsubstituted or substituted with from 1 to 3 substituents independently selected from : (a) halogen selected from-F,-Cl, and-Br, (b) methyl, (c)-CF3, (d) methoxy, (e)-OCF3, (f)-CN, (h) phenyl, and (j)-OH ; (3) a 5-or 6-membered heteroaromatic ring selected from thienyl, pyridyl, imidazolyl, pyrrolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isooxazolyl, pyrazinyl, pyitimidinyl, triazolyl, tetrazolyl, furanyl, and pyridazinyl, wherein the heteroaromatic ring is unsubstituted or substituted on nitrogen or carbon with 1 or 2 substituents independently selected from: (a) halogen selected from-F,-Cl, and-Br, (b) methyl, (c)-CF3, (d) methoxy, (e)-OCF3, (f) phenyl, (g)-S-C1-6 alkyl, (h)-CN, (i)-OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from: (i) halogen selected from-F,-Cl, and-Br, (ii) methyl, (iii)-CF3, and (iv)-OH, (k)-N (Ra) 2, (1)-C1 6 alkyl-N (Ra) 2, (m)-Rt, (n) oxo, (o)- (CH2) 0-3C () N (Ra) 2, and (p) -(CH2)0-3C(=O)Ra; (4) a 5-or 6-membered saturated heterocyclic ring selected from piperidinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isooxazolidinyl, pyrrolidinyl, imidazolidinyl, piperazinyl, tetrahydrofuranyl, and pyrazolidinyl, wherein the heterocyclic ring is unsubstituted or substituted with 1 or 2 substituents independently selected from: (a) halogen selected from-F,-Cl, and-Br, (b) methyl, (c)-CF3, (d) methoxy, (e)-OCF3, (f)-CN, (g) =0, (h) phenyl, (i) benzyl, (j) phenylethyl, (k)-OH, (1)- (CH2) 0-3C (=O) N (Ra) 2, ) -(CH2)0-3C(=O)Ra, (n) N (Ra)-C (=0) Ra (o) N (Ra)-C (=O) ORa, (p) 1-3N(Ra)-C(=O)Ra, (q) N (Ra) 2, (r) (CH2) l-3N (Ra) 2, -(CH2)0-3C(=O)Rt, (t)-Rt, (u)-N (Ra) Rt, and (v)-(CH2) 1 3Rt ; and (5) an 8-to 10-membered heterobicyclic ring selected from indolyl, benzotriazolyl, benzoimidazolyl, imidazo [4,5-b] pyridinyl, dihydroimidazo [4,5-b] pyridinyl, pyrazolo [4,3-c] pyridinyl, dihydropyrazolo [4,3c] pyridinyl, tetrahydropyrazolo [4,3-c] pyridinyl, pyrrolo [1, 2-a] pyrazinyl, dihydropyrrolo [1,2-a] pyrazinyl, tetrahydropyrrolo [1,2-a] pyrazinyl, octahydropyrrolo [1, 2-a] pyrazinyl, isoindolyl, indazolyl, indolinyl, isoindolinyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, chromanyl, and isochromanyl, wherein the bicyclic ring is unsubstituted or substituted with 1 or 2 substituents independently selected from: (a) halogen selected from-F,-Cl, and-Br, (b) methyl, (c)-CF3, (d) methoxy, (e)-OCF3, (f)-CN, (g) =O, and (h)-OH; and Rt is selected from pyrrolidinyl, pyrazolidinyl, imidazolinyl, piperidinyl, piperazinyl, pyrrolyl, pyridyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyrazinyl, pyrimidinyl, and pyradizinyl; any one of which is unsubstituted or substituted with 1 or 2 substituents independently selected from-F,-Cl,-Br, oxo, methyl, and methoxy; or a pharmaceutically acceptable salt thereof. 6. The compound according to claim 5, which is a compound selected from a compound of Formula (IV) : EMI110.1 or a pharmaceutically acceptable salt thereof. 7. The compound according to claim 1, which is a compound selected from the group consisting of : 7- [ (3-phenylpyrrolidin-1-yl) carbonyl]-1, 6-naphthyridin-8-ol; 7- [ (3-benzylpiperidin-1-yl) carbonyl]-1,6-naphthyridin-8-ol; and pharmaceutically acceptable salts thereof. 8. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier. 9. A method of inhibiting HIV integrase in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound according to claim 1. 10. A method for preventing or treating infection by HIV or treating AIDS in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound according to claim 1.

Inventors: ANTHONY NEVILLE J, BENNETT JENNIFER J, GOMEZ ROBERT P, YOUNG STEVEN D, ANTHONY, NEVILLE, J., BENNETT, JENNIFER, J., GOMEZ, ROBERT, P., YOUNG, STEVEN, D.
Applicants: ANTHONY NEVILLE J, BENNETT JENNIFER J, GOMEZ ROBERT P, MERCK & CO INC, YOUNG STEVEN D, ANTHONY, NEVILLE, J., BENNETT, JENNIFER, J., GOMEZ, ROBERT, P., MERCK & CO., INC., YOUNG, STEVEN, D.
Application year: 2001
Main classification: A61K31
IPC codes: A61K31, A61P31, A61P43, C07D471