Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication

摘要

The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for making and using these compounds in the treatment of HIV infection.;

主权项

1. A compound of Formula I where: R1 is alkyl or haloalkyl; R2 is hydrogen or alkyl; R3 is hydrogen, halo, or alkyl; R4 is hydrogen, alkyl, or cycloalkyl; R5 is hydrogen, alkyl, or (Ar4)alkyl; Ar1 is phenyl or naphthyl and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; Ar2 is pyrrolyl, pyrazolyl, or triazolyl substituted with 0-2 alkyl substituents; Ar3 is phenyl substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; Ar4 is phenyl substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; X1 is alkylene, alkenylene, —CH2O—, —CH2OCH2—, —CH2N(R4)CH2—, or —CH2CON(R4)—; X2 is —O—, —Ar1—, —Ar2—, —CON(R5)—, —(Ar3)CH—, -((benzyloxy)CH2)CH—,)—, —O(Ar3)CH—, —CH2CON(R5)—, or —N(R5)COCON(R5)—; X3 is absent, —O—, alkyloxy, cycloalkyloxy, cycloalkyl, Ar3, (Ar3)O—, or ((Ar3)alkyl)O—; X4 is alkylene, alkenylene, alkyleneoxy, or alkenyleneoxy; X5 is absent or —O—; and X6 is azetidinyl, pyirolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl, and is substituted with 0-3 halo or alkyl substituents; or a pharmaceutically acceptable salt thereof.