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 integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.;

主权项

1. A compound of Formula I where: R1 is hydrogen, alkyl, or cycloalkyl; R2 is hydrogen or alkyl; R3 is hydrogen, alkyl or halo; R4 is cycloalkyl or Ar3; or R4 is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl, and is substituted with 0-3 alkyl substituents; R5 is independently hydrogen, alkyl, or (Ar4)alkyl; R6 is O, NR7, phenyl, or pyridinyl; R7 is hydrogen, alkyl, or benzyl; Ar1 is phenyl substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; Ar2 is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, or trizainyl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, and CON(R5)2; Ar3 is phenyl, napthyl, chromanyl, or dihydrobenzoxazinyl, and is 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 CH, CH2, O, S, or NR5; X2 is alkylene, haloalkyene, alkenylene, alkynylene, haloalkylene, or —(CH2)0-3—R6—(CH2)0-3—; and X3 is CH, CH2, CH2O, O, S, or NR5; or a pharmaceutically acceptable salt thereof.