HIV INTEGRASE INHIBITORSHydroxy (tetra- or hexa-)hydronaphthyridine dione compounds of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: (I) wherein a, R¿1?, R¿2?, R¿3?, R¿4? and R¿5? are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.A compound of Formula H, or a pharmaceutically acceptable salt thereof:wherein:bond ' =^= ' in the ring is a single bond or a double bond;Xl and χ2 are each independently: (1) -H, (2) -Ci-6 alkyl, (3) -OH (4) -O-C i-6 alkyl, (5) -Ci-6 haloalkyl, (6) -O-C 1-6 haloalkyl, (7) halogen, (8) -CN, (9) -N(Ra)Rb, (10) -C(=O)N(Ra)Rb (11) -SRa, (12) -S(O)Ra, (13) SO2Ra, (16) -N(Ra)C(=0)Rb, (17) -N(Ra)C(=0)-C(=0)N(Ra)Rb (18) -HetA, (19) -C(=0)-HetA, or (20) HetB; wherein each HetA is independently a C4-5 azacycloalkyl or a C3-4 diazacycloalkyl, either of which is optionally substituted with 1 or 2 substituents each of which is independently oxo or Ci-6 alkyl; and with the proviso that when HetA is attached to the rest of the compound via the -C(=O)- moiety, the HetA is attached to the -C(=O)- via a ring N atom; and each HetB is independently a 5- or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from N, O and S, wherein the heteroaromatic ring is optionally substituted with from 1 to 4 substituents each of which is independently halogen, -Cj-6 alkyl, -Cj-6 haloalkyl, -O-Ci-6 alkyl, -O-Ci-6 haloalkyl, or hydroxy;or alternatively χ and χ2 are respectively located on adjacent carbons in the phenyl ring and together form methylenedioxy or ethylenedioxy;X3 is: (1) -H, (2) -Ci-6 alkyl, (3) -O-C 1-6 alkyl, (4) -C 1-6 haloalkyl, (5) -O-C 1-6 haloalkyl, or (6) halogen;R4 IS: (1) -Ci-6 alkyl, (2) -CO2Ra, (3) -C(=O)N(Ra)Rb, (5) -N(Ra)C(=O)Rb, (7) -C3-6 cycloalkyl, which is optionally substituted with from 1 to 4 substituents each of which is independently halogen, -Cj-6 alkyl, -CF3, -O-Ci-6 alkyl, or -OCF3, (8) -HetK, (9) -C(=0)-HetK, (10) -C(=0)N(Ra)-HetK, (11) -C(=O)N(Ra)-(CH2)0-2-(C3-6 cycloalkyl), wherein the cycloalkyl is optionally substituted with from 1 to 4 substituents each of which is independently halogen, -Ci-6 alkyl, -CF3, -O-Ci-6 alkyl, or -OCF3, or (12) -C(=O)N(Ra)-CH2-phenyl, wherein the phenyl is optionally substituted with from 1 to 4 substituents each of which is independently -Ci-6 alkyl, -O-Ci-6 alkyl, -CF3, -OCF3, or halogen; (13) -HetL, (14) -C(=O)N(Ra)Rc, or (15) halogen; wherein HetK is a 5- or 6-membered saturated heterocyclic ring containing a total of from 1 to 4 heteroatoms independently selected from 1 to 4 N atoms, from 0 to 2 O atoms, and from 0 to 2 S atoms, wherein the heterocyclic ring is optionally substituted with (i) from 1 to 4 substituents each of which is independently -Ci-6 alkyl, oxo, halogen, -C(=O)N(Ra)Rb, -C(=0)C(=0)N(Ra)Rb -C(=O)Ra, -CO2Ra, -SO2Ra, or -Sθ2N(Ra)Rb and (ii) from zero to 1 C3-6 cycloalkyl; and with the proviso that when HetK is attached to the rest of the compound via the -C(=0)- moiety, the HetK is attached to the -C(=0)- via a ring N atom; wherein HetL is a 5- or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from N, O and S, wherein the heteroaromatic ring is optionally substituted with from 1 to 4 substituents each of which is independently -Ci-6 alkyl or -OH;R5 IS: (1) -H, (2) -Ci-6 alkyl, (3) -C3-6 cycloalkyl, (4) -(CH2)l-2-C3-6 cycloalkyl, (5) -CH2-phenyl wherein the phenyl is optionally substituted with from 1 to 4 substituents each of which is indepedently halogen, Ci-6 alkyl, Ci-6 haloalkyl, -O-Ci-6 alkyl, or -O-C 1-6 haloalkyl, (6) -(CH2)l-2-HetD, wherein HetD is a 4- to 7-membered saturated heterocyclic ring containing from 1 to 2 heteroatoms independently selected from 1 to 2 N atoms, from zero to 1 O atom and from zero to 1 S atom, wherein the heterocyclic ring is attached to the rest of the molecule via a ring N atom, and the heterocyclic ring is optionally substituted with from 1 to 4 substituents each of which is independently -Ci-6 alkyl, -Ci-6 haloalkyl, -O- -ό alkyl, -O-Ci-6 haloalkyl, oxo, -C(=0)N(Ra)Rb -C(=0)Ra, -Cθ2Ra, -Sθ2Ra, or -Sθ2N(Ra)Rb, (7) phenyl which is optionally substituted with from 1 to 4 substituents each of which is independently -Ci-6 alkyl, -O-Ci-6 alkyl, -Ci-6 haloalkyl, -O-Ci-6 haloalkyl, -OH, halogen, -CN, -NO2, -C(=0)Ra, -Cθ2Ra, -Sθ2Ra, -N(Ra)C(=0)-Ci-6 haloalkyl, -N(Ra)C(=0)Rb, -N(Ra)C(=0)N(Ra)Rb, -N(Ra)Cθ2Rb, -N(Ra)Sθ2Rb, -C(=0)N(Rd)Re, or -SO2N(Rd)Re; (8) a 5- or 6-membered heteroaromatic ring containing from 1 to 4 heteroatoms independently selected from N, O and S, wherein the heteroaromatic ring is optionally substituted with from 1 to 4 substituents each of which is independently -Ci-6 alkyl, -Ci-6 haloalkyl, -O-Ci-6 alkyl, -O-Ci-6 haloalkyl, or -OH, (9) C 1 -6 alkyl substituted with -O-C 1 _6 alkyl, -CN, -N(Ra)Rb -C(=O)N(Ra)Rb -C(=O)Ra, -Cθ2Ra, -SO2Ra, or -SO2N(Ra)Rb 0r (10) -Ci-6 haloalkyl;each Ra is independently H or Ci-6 alkyl;each R is independently H or Ci-6 alkyl;RC is Ci-6 haloalkyl or -6 alkyl substituted with -CO2Ra, -SO2Ra, -SO2N(Ra)Rb, or N(Ra)Rb; andeach Rd and Re are independently H or Ci-6 alkyl, or together with the N atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring optionally conta...
ＨＩＶ 인테그라제 억제제화학식 I의 하이드록시 (테트라- 또는 헥사-)하이드로나프티리딘 디온 화합물은 HIV 인테그라제 억제제 및 HIV 복제 억제제이다. 당해 화합물은 HIV 감염의 예방 또는 치료, AIDS의 예방, 치료 및 개시 지연에 유용하다. 당해 화합물은 이 자체의 화합물로 또는 약제학적으로 허용되는 염 형태로, HIV 감염 및 AIDS에 사용된다. 약제학적 조성물에서 당해 화합물 및 이의 염은 성분으로 기타 항바이러스제, 항감염제, 면역조절제, 항생제 또는 백신과 임의 배합하여 사용될 수 있다. [화학식 I]  상기 식에서, X1, X2, R4 및 R5은 본원에 정의된 바와 같다. 화학식 I의 화합물 또는 이의 약제학적으로 허용되는 염. [화학식 I]  상기 식에서, X1이 (1) -H, (2) 브로모, (3) 클로로, (4) 플루오로, 또는 (5) 메톡시이고; X2가 (1) -H, (2) 브로모, (3) 클로로, (4) 플루오로, (5) 메톡시, (6) -C1-4 알킬, (7) -CF3, (8) -OCF3, (9) -CN, 또는 (10) -S02(C1-4 알킬)이고; R4가 (1) -CO2H, (2) -C(=O)-O-C1-4 알킬, (3) -C(=O)NH2, (4) -C(=O)NH-C1-4 알킬, (5) -C(=O)N(C1-4 알킬)2, (6) -C(=0)-NH-(CH2)2-3-0-C1-4 알킬, (7) -C(=O)-N(C1-4 알킬)-(CH2)2-3-O-C1-4 알킬, (8) -NHC(=O)-C1-4 알킬, (9) -N(C1-4 알킬)C(=O)-C1-4 알킬, (10) -NHS02-C1-4 알킬, (11) -N(C1-4 알킬)SO2-C1-4 알킬, (12) -C(=O)-HetK, 여기서 HetK가 이고, 당해 별표는 나머지 화합물의 부착 지점을 의미하고, (13) -C(=O)NH-(CH2)0-1-(C3-6 사이클로알킬), (14) -C(=O)N(C1-4 알킬)-(CH2)0-1-(C3-6 사이클로알킬), (15) -C(=O)NH-CH2-페닐, 또는 (16) -C(=O)N(C1-4 알킬)-CH2-페닐이고; R5가 (1) -H, (2) -C1-4 알킬, (3) 사이클로프로필, (4) 사이클로부틸, (5) -CH2-사이클로프로필, (6)-CH2-사이클로부틸, 또는 (7) -CH2-페닐이다. 