Aza-substituted inhibitors of human immunodeficiency virus replication

A compound of Formula II, or a pharmaceutically acceptable salt thereof:

• wherein R1 is isopropenyl or isopropyl;
• X is a phenyl or heteroaryl ring substituted with A, wherein A is at least one member selected from —H, halogen, hydroxyl, —C1-6 alkyl, —C2-6 alkenyl, —C1-6 alkoxy, and —COOR2;
• alternatively, X is selected from a single bond, —C1-6alkyl-, —C1-6alkylaryl-, —C2-6alkenyl-, —C2-6alkenylaryl-, —CO—, —SO2—, —C1-6alkylCO—, —C2-6alkenylCO—, —COalkylsubstituted C1-6 alkyl-, —COspiroalkylsubstitutedC1-6 alkyl-, —COarylsubstitutedC1-6 alkyl-, —COarylsubstituted C2-6 alkenyl-, —COheteroaryl-, —COaryl-, —COC1-6 alkylaryl-, —COC1-6 alkylheteroaryl-, —COalkylsubstituted C3-6 cycloalkyl-, —COC2-6 alkenylaryl-, —COC1-6 alkyl(NHR0)—, —C1-6 alkyl(CONHR0)—, —(COCO)NR0SO2—, —SO2C1-6 alkyl-, —SO2alkylsubstitutedC1-6 alkyl-, —SO2arylsubstituted C1-6 alkyl-, —SO2C1-6 alkylaryl-, —SO2C2-6 alkenylaryl-, —SO2aryl-, —SO2arylC1-6alkyl-, —SO2arylC2-6alkenyl-, —SO2heteroaryl-, -heteroaryl-Q0- and -aryl-Q0-;
• Q0 is selected from —C1-6 alkyl, -halo, —CF3 and —OC1-6 alkyl,
• R0 is H, —C1-6 alkyl, -alkylsubstituted C1-6 alkyl, -alkylsubstituted(C1-6)COOR6, -spiroalkylsubstituted(C1-6)COOR6, or -aryl substituted C1-6 alkyl;
• R2 is —H, —C1-6 alkyl, -alkylsubstituted C1-6 alkyl, or-arylsubstituted C1-6 alkyl;
• Y is selected from —COOR2, —C(O)NR2SO2R3, —C(O)NHSO2NR2R2, —NR2SO2R2, —SO2NR2R2, —C3-6 cycloalkyl-COOR2, —C2-6 alkenyl-COOR2, —C2-6 alkynyl-COOR2, —C1-6 alkyl-COOR2, —NHC(O)(CH2)p—COOR2, —SO2NR2C(O)R2, -tetrazole, and —CONHOH,
• wherein p is 1-6;
• alternatively, Y is selected from a phenyl or heteroaryl ring, optionally further substituted with 1 to 3 substituents selected from —H, -halo, -hydroxyl, —C1-6 alkyl, —C1-6 alkoxy, —COOR2, —CN, —NO2, —CF3, —SO2, —NR26R27, —CONR26R27, and —SO2NR26R27;
• alternatively, —X-Y is selected from
• R3 is —C1-6 alkyl or -alkylsubstituted C1-6 alkyl;
• Z is selected from —CO— and —CH2—;
• W is selected from —CH2OR2, —COOR2, —NR4R5, —CONR26R27, —CH2NR26R27, —NR4COR6, —NR4C(O)NR4R5, and —NR4COOR6;
• R4 is selected from —H, —C1-6 alkyl, —C1-6 alkyl-C(OR3)2—C3-6 cycloalkyl, —C1-6 substituted alkyl, —C1-6 alkyl-C3-6 cycloalkyl, —C1-6 alkyl-Q1, —C1-6 alkyl-C3-6 cycloalkyl-Q1, aryl, heteroaryl, substituted heteroaryl, —COR6, —COCOR6, —SO2R7, and —SO2NR2R2,
• wherein Q1 is selected from C3-10 carbocycle, substituted C3-10 carbocycle, C3-10 heterocycle, substituted C3-10 heterocycle, aryl, heteroaryl, substituted heteroaryl, halogen, —CF3, —OR2, —COOR2, —NR8R9, —CONR10R11 and —SO2R7;
• alternatively, R4 is selected from —C3-6 cycloalkyl, —C1-6 substituted alkyl, —C1-6 alkyl-heteroaryl, —C1-6 alkyl-substituted heteroaryl, —C1-6 alkyl-NR6R7, —C1-6 alkyl-CONR8R9, —C3-6 cycloalkyl-CONR8R9, —C3-6 cycloalkyl-(CH2)1-3—NR6R7, —(CH2)1-3—C3-6 cycloalkyl-NR6R7, —(CH2)1-3—C3-6 cycloalkyl-(CH2)1-3—NR6R7;
• —C1-6 alkyl-Q′1, C3-6 cycloalkyl-Q1, —COR10, —SO2R3, and
• wherein Q′1 is selected from-hydroxy, —COOR2, -halo, and —SO2Ra;
• Ra is C1-6 alkyl, NR2R2,
• Rb is —H, —C1-6 alkyl, —COR3, —SO2R3, —SONR3R3,
• R5 is selected from —H, —C1-6 alkyl, —C3-6 cycloalkyl, —C1-6 alkylsubstituted alkyl, —C1-6 alkyl-NR8R9, —COR6, —COCOR6, —SO2R7 and —SO2NR2R2;
• with the proviso that only one of R4 or R5 can be selected from —COR6, —COCOR6, —SO2R7 and —SO2NR2R2;
• R6 is selected from —H, —C1-6 alkyl, —C1-6 alkyl-substitutedalkyl, —C3-6 cycloalkyl, —C3-6 substituted cycloalkyl-Q2, —C1-6 alkyl-Q2, —C1-6 alkyl-substitutedalkyl-Q2, —C3-6 cycloalkyl-Q2, aryl-Q2, —NR13R14, and —OR15;
• wherein Q2 is selected from C3-10 carbocycle, substituted C3-10 carbocycle, C3-10 heterocycle, substituted C3-10 heterocycle, aryl, heteroaryl, substituted heteroaryl, —OR2, —COOR2, —NR8R9, SO2R7, —CONHSO2R3, and —CONHSO2NR2R2;
• R7 is selected from —C1-6 alkyl, —C1-6 substituted alkyl, —C3-6 cycloalkyl, aryl, and heteroaryl;
• R8 and R9 are independently selected from —H, —C1-6 alkyl, —C1-6 substituted alkyl, aryl, heteroaryl, substituted aryl, substituted heteroaryl, —C1-6 alkyl-Q2, and —COOR3,
• alternatively R8 and R9 are taken together with the adjacent N to form a cycle selected from:
• V is selected from —CR24R25—, —SO2—, —O— and —NR12—;
• M is selected from —CHR24R25, —NR26R27, —SO2R7, —SO2NR3R3 and —OH;
• with the proviso that only one of R8 or R9 can be —COOR3;
• R10 and R11 are independently selected from —H, —C1-6 alkyl, —C1-6 substituted alkyl and —C3-6 cycloalkyl,
• alternatively R10 and R11 are taken together with the adjacent N to form a cycle such as
• R12 is selected from —C1-6 alkyl, —C1-6 alkyl-OH;
• —C1-6 alkyl, —C1-6 substituted alkyl,-C3-6 cycloalkyl, —COR7, —COONR22R23, —SORT, and —SONR24R25;
• R13 and R14 are independently selected from —H, —C1-6 alkyl, —C3-6 cycloalkyl, —C1-6 substituted alkyl, —C1-6 alkyl-Q3, —C1-6 alkyl-C3-6 cycloalkyl-Q3 and C1-6 substituted alkyl-Q3,
• alternatively R13 and R14 are taken together with the adjacent N to form a cycle selected from:
• Q3 is selected from heteroaryl, substituted heteroaryl, —NR20R21, —CONR2R2, —COOR2, —OR2, and —SO2R3;
• R15 is selected from —C1-6 alkyl, —C3-6 cycloalkyl, —C1-6 substituted alkyl, —C1-6 alkyl-Q3, —C1-6 alkyl-C3-6 cycloalkyl-Q3 and —C1-6 substituted alkyl-Q3,
• R16 is selected from —H, —C1-6 alkyl, —NR2R2, and —COOR3;
• R17 is selected from —H, —C1-6 alkyl, —COOR3, and aryl;
• R18 is selected from —COOR2 and —C1-6 alkyl-COOR2;
• R19 is selected from —H, —C1-6 alkyl, —C1-6 alkyl-Q4, —COR3, —COOR3,
• wherein Q4 is selected from —NR2R2 and —OR2;
• R20 and R21 are independently selected from —H, —C1-6 alkyl, —C1-6 substituted alkyl, —C1-6 substituted alkyl-OR2, and —COR3,
• alternatively R20 and R21 are taken together with the adjacent N to form a cycle selected from
• with the proviso that only one of R20 or R21 can be —COR3,
• R22 and R23 are independently selected from H, —C1-6 alkyl, —C1-6 substituted alkyl, and —C1-6 cycloalkyl,
• or R22 and R23 are taken together with the adjacent N to form a cycle selected from
• R24 and R25 are independently from the group of H, —C1-6 alkyl, —C1-6 substituted alkyl, —C1-6 alkyl-Q5, —C1-6 cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl,
• and Q5 is selected from halogen and SO2R3,
• R26 and R27 are independently selected from —H, —C1-6 alkyl, —C1-6 substituted alkyl, aryl, heteroaryl, substituted aryl, substituted heteroaryl, —C1-6 alkyl-Q2, and
• or alternatively R26 and R27 are taken together with the adjacent N to form a cycle selected from: