KADOW, JOHN F.,NAIDU, B. NARASIMHULU,ROMINE, JEFFREY LEE,SIVAPRAKASAM, PRASANNA,ST. LAURENT, DENIS R.
申请号：
CA2994512
公开号：
CA2994512A1
申请日:
2016.08.03
申请国别(地区):
CA
年份:
2017
代理人:
摘要：
Disclosed are compounds of Formula (I), including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS. In the compounds of formula (I), R1 is selected from H, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, (alkoxy)alkoxyalkyl, or (R6)alkyl； R2 is phenyl substituted with 1 R7 substituent and with 0-3 substituents selected from halo, alkyl, haloalkyl, alkoxy, and haloalkoxy； or R2 is selected from tetrahydroisoquinolinyl, ((Ar1)alkyl)tetrahydroisoquinolinyl, or ((N-alkoxycarbonyl)tetrahydroisoquinolinyl； R3 is is selected from tetrahydroisoquinolinyl or decahydroisoquinolinyl and is substituted with 0-3 substituents selected from halo, alkyl, and haloalkyl； or R3 is a [5-7.3-7.0-2] fused or bridged bicyclic amine and is substituted with 0-3 alkyl substituents； or R3 is selected from azetidinyl, pyrrolidinyl, piperidinyl, or homopiperidinyl and contains a spirocyclic moiety wherein the spirocyclic moiety, including the carbon atom to which it is attached, forms C3-7 cycloalkane, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, N-alkylpyrrolidinyl, piperidinyl, N-alkylpiperidinyl, homopiperidinyl, or N-alkylpiperidinyl, and wherein the spirocyclic moiety is substituted with 0-3 halo or alkyl substituents； R4 is selected from alkyl or haloalkyl； R5 is selected from H, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, (alkoxy)alkoxyalkyl, or (R6)alkyl； R6is selected from (oxetanyl)oxy, ((oxetanyl)alkoxy)alkyl, (tetrahydropyranyloxy)alkyl, (tetrahydropyranyl)alkoxy)alkyl, or (Rg)(R9)N； R7 is selected from (Ar1)alkoxy or ((Ar1)alkyl)HNCO； R8 is selected from hydrogen, alkyl, (cycloalkyl)alkyl, alkoxyalkyl, (tetrahydropyanyl)alkyl, tetrahydropyanyl, or alkoxyphenyl； R9 is selected from hydrogen or alkyl； or (R8)(R9)N taken together is selected from azetidinyl, pyrrolidinyl, piperidinyl, (spirocyclobutyl)piperidinyl, piperazi
