US 2013/0210801 A1 · 2-QUINOLINYL-ACETIC ACID DERIVATIVES AS HIV ANTIVIRAL COMPOUNDS

Abstract

The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula (I).

A compound of formula I:

wherein:
G1 is N, G2 is CR8, and the dashed bond is a double bond;
or
G1 is CR5, G2 is N, and the dashed bond is a double bond;
or
G1 is CR5, G2 is NR13, the dashed bond is a single bond, and R7 is an oxo (═O) group;
or
G1 is CR5, G2 is NR13, the dashed bond is a single bond, and R7 and R13 together with the atoms to which they are attached form a heteroaryl, wherein the heteroaryl is optionally substituted with one or more Z1 groups;
R1 is R1a or R1b;
R2 is R2a or R2b;
R3 is R3a or R3b;
R3′ is R3a′ or R3b′;
R4 is R4a or R4b;
R5 is R5a or R5b;
R6 is R6a or R6b;
R7 is R7a or R7b;
R8 is R8a or R8b;
R13 is R13a or R13b;
R1a is selected from:
a) H, halo, (C1-C6)alkyl and (C1-C6)haloalkyl;
b) (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, nitro, cyano, aryl, heterocycle and heteroaryl;
c) —C(O)—R11, —SO2—R11, —(C1-C6)alkyl-R11, —(C1-C6)alkyl-C(═O)—R11, —(C1-C6)alkyl-O—R11, —(C1-C6)alkyl-O—R11, —(C1-C6)alkyl-S —R11, —(C1-C6)alkyl-S(O)—R11 and —(C1-C6)alkyl-SO2—R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl;
and
d) —N(R9)R10, —C(═O)—N(R9)R10, —O—C(═O)—N(R9)R10, —SO2—N(R9)R10, —(C1-C6)alkyl-N(R9)R10, —(C1-C6)alkyl-C(═O)—N(R9)R10, —(C1-C6)alkyl-O—C(═O)—N(R9)R10 and —(C1-C6)alkyl-SO2—N(R9)R10, wherein each R9 is independently selected from H, (C1-C6)alkyl and (C3-C7)cycloalkyl, and each R10 is independently selected from R11, —(C1-C6)alkyl-R11, —SO2—R11, —C(═O)—R11, —C(═O)OR11 and —C(═O)N(R9)R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl;
and wherein any aryl, heterocycle or heteroaryl of R1a is optionally substituted with one or more Z10 groups;
R1b is selected from:
a) —(C1-C6)alkyl-O—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S(O)—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-SO2—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-SO2—(C1-C6)alkyl-Z13, —C(O)—(C1-C6)alkyl-Z13, —O—(C1-C6)alkyl-Z13, —S—(C1-C6)alkyl-Z13, —S(O)—(C1-C6)alkyl-Z13, —SO2—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-Z14, —(C1-C6)alkyl-C(O)—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-C(O)—O(C1-C6)alkyl-Z13, —(C1-C6)alkyl-O—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-S—(C1-C6)alkyl-Z13, —(C2-C6)alkenyl-(C1-C6)haloalkyl, —(C2-C6)alkynyl-(C1-C6)haloalkyl, —(C3-C7)halocarbocycle, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle, —NRaSO2Oaryl, —(C2-C6)alkenyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-aryl, —(C2-C6)alkenyl-heteroaryl, —(C2-C6)alkenyl-heterocycle, —(C2-C6)alkynyl-(C3-C7)carbocycle, —(C2-C6)alkynyl-aryl, —(C2-C6)alkynyl-heteroaryl —(C2-C6)alkynyl-heterocycle, —(C3-C7)carbocycle-Z1 and -halo(C1-C6)alkyl-Z3, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C7)carbocycle, (C3-C7)halocarbocycle, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heterocycle and heteroaryl, either alone or as part of a group, is optionally substituted with one or more Z1 groups;
b) spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle, wherein any spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle is optionally substituted with one or more Z1 groups, wherein two Z1 groups together with the atom or atoms to which they are attached optionally form a (C3-C7)carbocycle or heterocycle, wherein the (C3-C7)carbocycle or heterocycle is optionally substituted with one or more Z1 groups;
c) (C1-C6)alkyl, wherein (C1-C6)alkyl is substituted with one or more Z2 groups and optionally substituted with one or more Z1 groups;
d) —X(C1-C6)alkyl, —X(C1-C6)haloalkyl, —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle, wherein any —X(C1-C6)alkyl and —X(C1-C6)haloalkyl is substituted with one or more Z3 groups and optionally substituted with one or more Z1 groups, and wherein any —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle, is substituted with one or more Z4 groups and optionally substituted with one or more Z1 groups;
e) aryl, heteroaryl, heterocycle, —Xaryl, —Xheteroaryl and —Xheterocycle, wherein any aryl heteroaryl and heterocycle, either alone or as part of a group, is substituted with one or more Z5 groups and optionally substituted with one or more Z1 groups;
f) (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl, and (C2-C6)alkynyl, wherein (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl and (C2-C6)alkynyl are each substituted with one or more Z6 groups and optionally substituted with one or more Z1 groups;
and
g) —NReRf, —C(O)NReRf, —OC(O)NReRf, —SO2NReRf, —(C1-C6)alkyl-NReRf, —(C1-C6)alkylC(O)—NReRf, —(C1-C6)alkyl-O—C(O)—NReRf and —(C1-C6)alkyl-SO2NReRf, wherein each any (C1-C6)alkyl, as part of a group, is optionally substituted with one or more Z1 groups;
R2a is selected from:
a) H, (C1-C6)alkyl and —O(C1-C6)alkyl;
b) (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle, heteroaryl, halo, nitro and cyano;
c) —C(═O)—R11, —C(═O)—O—R11, —S—R11, —S(O)—R11, —SO2—R11, —(C1-C6)alkyl-R11, —(C1-C6)alkyl-C(═O)—O—R11, —(C1-C6)alkyl-O—R11, —(C1-C6)alkyl-S—R11, —(C1-C6)alkyl-S(O)—R11 and —(C1-C6)alkyl-SO2—R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl and heterocycle and heteroaryl, wherein aryl, heterocycle and heteroaryl are each optionally substituted with one or more Z11 groups;
d) —OH, —O(C2-C6)alkenyl, —O(C2-C6)alkynyl, —O(C1-C6)haloalkyl, —O(C3-C7)cycloalkyl, —Oaryl, —Oheterocycle and —Oheteroaryl;
and
e) —N(R9)R10, —C(═O)—N(R9)R10, —O—C(═)—N(R9)R10, —SO2—N(R9)R10, —(C1-C6)alkyl-N(R9)R10, —(C1-C6)alkyl-C(═O)—N(R9)R10, —(C1-C6)alkyl-O—C(═O)—N(R9)R10, and —(C1-C6)alkyl-SO2—N(R9)R10, wherein each R9 is independently selected from H, (C1-C6)alkyl and (C3-C7)cycloalkyl, and each R10 is independently selected from R11, —(C1-C6)alkyl-R11, —SO2—R11, —C(═O)—R11, —C(═O)OR11 and —C(═O)N(R9)R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl;
R2b is selected from:
a) —(C1-C6)alkyl-O—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S(O)—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-SO2—(C1-C6)alkyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-(C1-C6)haloalkyl, —(C2-C6)alkynyl-(C1-C6)haloalkyl, —(C1-C6)alkyl-SO2—(C1-C6)alkyl-Z13, —C(O)—(C1-C6)alkyl-Z13, —O—(C1-C6)alkyl-Z13—S—(C1-C6)alkyl-Z13, —S(O)—(C1-C6)alkyl-Z13, —SO2—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-Z14, —(C1-C6)alkyl-C(O)—(C1-C6)alkyl-Z13—(C1-C6)alkyl-C(O)—O(C1-C6)alkyl-Z13, —(C1-C6)alkyl-O—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-S—(C1-C6)alkyl-Z″, —(C3-C7)halocarbocycle, —NRaSO2NRcR1i, —NRaSO2O(C3-C7)carbocycle, —NRaSO2Oaryl, —(C2-C6)alkenyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-aryl, —(C2-C6)alkenyl-heteroaryl, —(C2-C6)alkenyl-heterocycle, —(C2-C6)alkynyl-(C3-C7)carbocycle, —(C2-C6)alkynyl-aryl, —(C2-C6)alkynyl-heteroaryl, —(C2-C6)alkynyl-heterocycle, —(C3-C7)carbocycle-Z1 and -halo(C1-C6)alkyl-Z3, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C7)carbocycle, (C3-C7)halocarbocycle, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heterocycle and heteroaryl, either alone or as part of a group, is optionally substituted with one or more Z1 groups;
b) spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle, wherein any spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle is optionally substituted with one or more Z1 groups, and wherein two Z1 groups together with the atom or atoms to which they are attached optionally form a (C3-C7)carbocycle or heterocycle, wherein the (C3-C7)carbocycle or heterocycle is optionally substituted with one or more Z1 groups;
c) (C1-C6)alkyl, wherein (C1-C6)alkyl is substituted with one or more Z2 groups and optionally substituted with one or more Z1 groups;
d) —X(C1-C6)alkyl, —X(C1-C6)haloalkyl, —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle, wherein any —X(C1-C6)alkyl, —X(C1-C6)haloalkyl is substituted with one or more Z3 groups and optionally substituted with one or more Z1 groups, and wherein any —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle is substituted with one or more Z4 groups and optionally substituted with one or more Z1 groups;
e) aryl, heteroaryl, heterocycle, —Xaryl, —Xheteroaryl and —Xheterocycle, wherein any aryl heteroaryl and heterocycle, either alone or as part of a group, is substituted with one or more Z5 groups and optionally substituted with one or more Z1 groups;
f) (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl, and (C2-C6)alkynyl, wherein (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl and (C2-C6)alkynyl are each substituted with one or more Z6 groups and optionally substituted with one or more Z1 groups;
and
g) —NReRf, —C(O)NReRf, —OC(O)NReRf, —SO2NReRf, —(C1-C6)alkyl-NReRf, —(C1-C6)alkylC(O)—NReRf, —(C1-C6)alkyl-O—C(O)—NReRf and —(C1-C6)alkyl-SO2NReRf, wherein each (C1-C6)alkyl is optionally substituted with one or more Z1 groups;
R3a is (C1-C6)alkyl, (C1-C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C1-C6)alkyl-(C3-C7)cycloalkyl, —(C1-C6)alkyl-aryl, —(C1-C6)alkyl-heterocycle, —(C1-C6)alkyl-heteroaryl, —O(C1-C6)alkyl, —O(C1-C6)haloalkyl, —O(C2-C6)alkenyl, —O(C2-C6)alkynyl, —O(C3-C7)cycloalkyl, —Oaryl, —O(C1-C6)alkyl-(C3-C7)cycloalkyl, —O(C1-C6)alkyl-aryl, —O(C1-C6)alkyl-heterocycle or —O(C1-C6)alkyl-heteroaryl, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C2-C6)alkenyl or (C2-C6)alkynyl of R3a, either alone or as a group, is optionally substituted with one or more groups selected from —O(C1-C6)alkyl, halo, oxo and —CN, and wherein any (C3-C7)cycloalkyl, aryl, heterocycle or heteroaryl of R3a, either alone or as a group, is optionally substituted with one or more groups selected from (C1-C6)alkyl, —O(C1-C6)alkyl, halo, oxo and —CN;
and R3a′ is H;
R3b is —(C7-C14)alkyl, (C3-C7)carbocycle, aryl, heteroaryl, heterocycle, —(C1-C6)alkylOH, —(C1-C6)alkyl-O—(C1-C6)alkyl-Z12, —(C1-C6)alkyl-O—(C2-C6)alkenyl-Z12, —(C2-C6)alkyl-O—(C2-C6)alkynyl-Z12, —(C1-C6)alkyl-S—(C1-C6)alkyl-Z12, —(C1-C6)alkyl-S—(C2-C6)alkenyl-Z12, —(C1-C6)alkyl-S—(C2-C6)alkynyl-Z12, —(C1-C6)alkyl-S(O)—(C1-C6)alkyl-Z12, —(C1-C6)alkyl-S(O)—(C2-C6)alkenyl-Z12, —(C1-C6)alkyl-S(O)—(C2-C6)alkynyl-Z12, —(C1-C6)alkyl-SO2—(C1-C6)alkyl-Z12, —(C1-C6)alkyl-SO2—(C2-C6)alkenyl-Z12, —(C1-C6)alkyl-SO2—(C2-C6)alkynyl-Z12, —(C1-C6)alkyl-NRaRb, —(C1-C6)alkylOC(O)—NRcRd, —(C1-C6)alkyl-NRa—C(O)—ORb, —(C1-C6)alkyl-NRa—C(O)—NRaRb, —(C1-C6)alkyl-SO2(C1-C6)alkyl, —(C1-C6)alkyl-SO2NRcRd, —(C1-C6)alkyl-NRaSO2NRcRd, —(C1-C6)alkyl-NRaSO2O(C3-C7)carbocycle, —(C1-C6)alkyl-NRaSO2Oaryl, —(C1-C6)alkyl-NRa—SO2—(C1-C6)alkyl, —(C1-C6)alkyl-NRa—SO2-halo(C1-C6)alkyl, —(C1-C6)alkyl-NRa—SO2—(C2-C6)alkenyl, —(C1-C6)alkyl-NRa—SO2—(C2-C6)alkynyl, —(C1-C6)alkyl-NRa—SO2—(C3-C7)carbocycle, —(C1-C6)alkyl-NRa—SO2-halo(C3-C7)carbocycle, —(C1-C6)alkyl-NRa—SO2-aryl, —(C1-C6)alkyl-NRa—SO2-heteroaryl, —(C1-C6)alkyl-NRa—SO2-heterocycle, —O(C7-C14)alkyl, —O(C1-C6)alkyl-NRaRb, —O(C1-C6)alkylOC(O)—NRcRd, —O(C1-C6)alkyl-NRa—C(O)—ORb, —O(C1-C6)alkyl-NRa—C(O)—NRaRb, —O(C1-C6)alkyl-NRa—SO2—(C1-C6)alkyl, —O(C1-C6)alkyl-NRa—SO2-halo(C1-C6)alkyl, —O(C1-C6)alkyl-NRa—SO2—(C2-C6)alkenyl, —O(C1-C6)alkyl-NRa—SO2—(C2-C6)alkynyl, —O(C1-C6)alkyl-NRa—SO2—(C3-C7)carbocycle, —O(C1-C6)alkyl-NRa—SO2-halo(C3-C7)carbocycle, —O(C1-C6)alkyl-NRa—SO2-aryl, —O(C1-C6)alkyl-NRa—SO2-heteroaryl, —O(C1-C6)alkyl-NRa—SO2-heterocycle, —O(C1-C6)alkyl-NRa—SO2—NRaRb, —O(C1-C6)alkyl-NRa—SO2—(C3-C7)carbocycle, —O(C1-C6)alkyl-NRa—SO2-halo(C3-C7)carbocycle, —O(C1-C6)alkyl-NRa—SO2-aryl, —O(C1-C6)alkyl-NRaSO2NReRa, —O(C1-C6)alkyl-NRaSO2O(C3-C7)carbocycle, —O(C1-C6)allyl-NRaSO2Oaryl, -Oheteroaryl, —Oheterocycle, —Sheteroaryl, —Sheterocycle, —S(O)heteroaryl, —S(O)heterocycle, —SO2heteroaryl or —SO2heterocycle, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, —(C7-C14)alkyl, (C2-C6)alkynyl, aryl, (C3-C7)carbocycle, heteroaryl or heterocycle of R3b, either alone or as a group, is optionally substituted with one or more Z1 groups;
and R3b′ is H, (C1-C6)alkyl or —O(C1-C6)alkyl;
or R3b and R3b′ together with the carbon to which they are attached form a heterocycle or (C3-C7)carbocycle which heterocycle or (C3-C7)carbocycle of R3b and R3b′ together with the carbon to which they are attached is optionally substituted with one or more Z1 groups;
R4a is selected from aryl, heterocycle and heteroaryl, wherein any aryl, heterocycle and heteroaryl of R4a is optionally substituted with one or more groups each independently selected from halo, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, —OH, —O(C1-C6)alkyl, SH, —S(C1-C6)alkyl, —NH(C1-C6)alkyl and —N((C1-C6)alkyl)2, wherein (C1-C6)alkyl is optionally substituted with hydroxy, —O(C1-C6)alkyl, cyano and oxo;
R4b is selected from:
a) (C1-C6)alkyl, (C2-C6)alkenyl and (C2-C6)alkynyl, wherein (C1-C6)alkyl, (C2-C6)alkenyl and (C2-C6)alkynyl are each optionally substituted with one or more Z1 groups;
b) (C3-C14)carbocycle, wherein (C3-C14)carbocycle is optionally substituted with one or more Z1 groups, wherein two Z1 groups together with the atom or atoms to which they are attached optionally form a (C3-C7)carbocycle or heterocycle;
c) spiro-heterocycle and bridged-heterocycle, wherein spiro-heterocycle and bridged-heterocycle are each optionally substituted with one or more Z1 groups, and wherein two Z1 groups together with the atom or atoms to which they are attached optionally form a (C3-C7)carbocycle or heterocycle;
d) aryl, heteroaryl, spiro-heterocycle, fused-heterocycle and bridged-heterocycle, wherein aryl, heteroaryl, spiro-heterocycle, fused-heterocycle and bridged-heterocycle are each independently substituted with one or more Z7 groups and optionally substituted with one or more Z1 groups;
or
R4 and R3 together with the atoms to which they are attached form a macroheterocycle or a macrocarbocycle wherein any macroheterocycle or macrocarbocycle of R4 and R3 together with the atoms to which they are attached may be optionally substituted with one or more Z1 groups;
and R3′ is H, (C1-C6)alkyl or —O(C1-C6)alkyl;
R5a is selected from:
a) halo, nitro and cyano;
b) R11, —C(═O)—R11, —C(═O)—O—R11, —O—R11, —S—R11, —S(O)—R11, —SO2—R11, —(C1-C6)alkyl-R11, —(C1-C6)alkyl-C(═O)—R11, —(C1-C6)alkyl-C(═O)—O—R11, —(C1-C6)alkyl-O—R11, —(C1-C6)alkyl-S—R11, —(C1-C6)alkyl-S(O)—R11 and —(C1-C6)alkyl-SO2—R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl, wherein aryl, heterocycle and heteroaryl are each optionally substituted with one or more Z11 groups;
and
c) —N(R9)R10, —C(═O)—N(R9)R10, —O—C(═O)—N(R9)R10, —SO2—N(R9)R10, —(C1-C6)alkyl-N(R9)R10 (C1-C6)alkyl-C(═O)—N(R9)R10, —(C1-C6)alkyl-O—C(═O)—N(R9)R10, and a (C1-C6)alkyl-SO2—N(R9)R10, wherein each R9 is independently selected from H, (C1-C6)alkyl and (C3-C7)cycloalkyl, and each R10 is independently selected from R11, —(C1-C6)alkyl-R11, —SO2—R11, —C(═O)—R11, —C(═O)OR11 and —C(═O)N(R9)R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl;
R5b is selected from:
a) —(C1-C6)alkyl-O—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkylS(O)—(C1-C6)alkyl-(C3-C6)carbocycle, —(C1-C6)alkylSO2(C1-C6)alkyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-(C1-C6)haloalkyl, —(C2-C6)alkynyl-(C1-C6)haloalkyl, —(C3-C7)halocarbocycle, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle, —NRaSO2Oaryl, —(C2-C6)alkenyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-aryl, —(C2-C6)alkenyl-heteroaryl, —(C2-C6)alkenyl-heterocycle, —(C2-C6)alkynyl-(C3-C7)carbocycle, —(C2-C6)alkynyl-aryl, —(C2-C6)alkynyl-heteroaryl, —(C2-C6)alkynyl-heterocycle, —(C3-C7)carbocycle-Z1 and -halo(C1-C6)alkyl-Z3, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C7)carbocycle, —(C3-C7)halocarbocycle, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heterocycle and heteroaryl, either alone or as part of a group, is optionally substituted with one or more Z1 groups;
b) spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle, wherein any spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle is optionally substituted with one or more Z1 groups, wherein two Z1 groups together with the atom or atoms to which they are attached optionally form a (C3-C7)carbocycle or heterocycle, wherein the (C3-C7)carbocycle or heterocycle is optionally substituted with one or more Z1 groups;
c) (C1-C6)alkyl, wherein (C1-C6)alkyl is substituted with one or more Z2 groups and optionally substituted with one or more Z1 groups;
d) —X(C1-C6)alkyl, —X(C1-C6)haloalkyl, —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle, wherein any X(C1-C6)alkyl and —X(C1-C6)haloalkyl is substituted with one or more Z3 groups and optionally substituted with one or more Z1 groups, and wherein any —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle is independently substituted with one or more Z4 groups and optionally substituted with one or more Z1 groups;
e) aryl, heteroaryl, heterocycle, —Xaryl, —Xheteroaryl and —Xheterocycle, wherein any aryl, heteroaryl and heterocycle, either alone or as part of a group are each independently substituted with one or more Z5 groups and optionally substituted with one or more Z1 groups;
f) (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl, and (C2-C6)alkynyl, wherein (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl and (C2-C6)alkynyl are each independently substituted with one or more Z6 groups and optionally substituted with one or more Z1 groups;
and
g) —NReRf, —C(O)NReRf, —OC(O)NReRf, —SO2NReRf, —(C1-C6)alkyl-NReRf, —(C1-C6)alkylC(O)—NReRf, —(C1-C6)alkyl-O—C(O)—NReRf and —(C1-C6)alkyl-SO2NReRf, wherein any (C1-C6)alkyl, as part of a group, is optionally substituted with one or more Z1 groups;
R6a is selected from:
a) H, halo, (C1-C6)alkyl, and (C1-C6)haloalkyl;
b) (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, nitro, cyano, aryl, heterocycle and heteroaryl;
c) —C(═O)—R11, —C(═O)—O—R11, —O—R11, —S—R11, —S(O)—R11, —SO2—R11, —(C1-C6)alkyl-R11, —(C1-C6)alkyl-C(═O)—R11, —(C1-C6)alkyl-C(═O)—O—R11, —(C1-C6)alkyl-O—R11, —(C1-C6)alkyl-S—R11, —(C1-C6)alkyl-S(O)—R11 and —(C1-C6)alkyl-SO2—R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl;
and
d) —N(R9)R10, —C(═O)—N(R9)R10, —O—C(═O)—N(R9)R10, —SO2—N(R9)R10, —(C1-C6)alkyl-N(R9)R10, —(C1-C6)alkyl-C(═O)—N(R9)R10, —(C1-C6)alkyl-O—C(═O)—N(R9)R10 and —(C1-C6)alkyl-SO2—N(R9)R10, wherein each R9 is independently selected from H, (C1-C6)alkyl and (C3-C7)cycloalkyl, and each R10 is independently selected from R11, —(C1-C6)alkyl-R11, —SO2—R11, —C(═O)—R11, —C(═O)OR11 and —C(═O)N(R9)R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl;
and wherein any aryl, heterocycle or heteroaryl of R6a is optionally substituted with one or more Z10 groups;
R6b is selected from:
a) —(C1-C6)alkyl-O—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S(O)—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-SO2—(C1-C6)alkyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-(C1-C6)haloalkyl, —(C2-C6)alkynyl-(C1-C6)haloalkyl, -halo(C3-C7)carbocycle, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle, —NRaSO2Oaryl, —(C2-C6)alkenyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-aryl, —(C2-C6)alkenyl-heteroaryl, —(C2-C6)alkenyl-heterocycle, —(C2-C6)alkynyl-(C3-C7)carbocycle, —(C2-C6)alkynyl-aryl, —(C2-C6)alkynyl-heteroaryl, —(C2-C6)alkynyl-heterocycle, —(C3-C7)carbocycle-Z1 and -halo(C1-C6)alkyl-Z3, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heterocycle and heteroaryl, either alone or as part of a group, is optionally substituted with one or more Z1 groups;
b) spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle, wherein any spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle is optionally substituted with one or more Z1 groups, wherein two Z1 groups together with the atom or atoms to which they are attached optionally form a carbocycle or heterocycle wherein the carbocycle or heterocycle is optionally substituted with one or more Z1 groups;
c) (C1-C6)alkyl, wherein (C1-C6)alkyl is substituted with one or more Z2 groups and optionally substituted with one or more Z1 groups;
d) —X(C1-C6)alkyl, —X(C1-C6)haloalkyl, —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle, wherein any —X(C1-C6)alkyl and —X(C1-C6)haloalkyl is substituted with one or more Z3 groups and optionally substituted with one or more Z1 groups, and wherein any —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle is substituted with one or more Z4 groups and optionally substituted with one or more Z1 groups;
e) aryl, heteroaryl, heterocycle, —Xaryl, —Xheteroaryl and —Xheterocycle, wherein any aryl, heteroaryl and heterocycle, either alone or as part of a group, is substituted with one or more Z5 groups and optionally substituted with one or more Z1 groups;
f) (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl, and (C2-C6)alkynyl, wherein (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl and (C2-C6)alkynyl are each independently substituted with one or more Z6 groups and optionally substituted with one or more Z1 groups;
and
g) —NReRf, —C(O)NReRf, —OC(O)NReRf, —SO2NReRf, —(C1-C6)alkyl-NReRf, —(C1-C6)alkylC(O)—NReRf, —(C1-C6)alkyl-O—C(O)—NReRf and —(C1-C6)alkyl-SO2NReRf wherein any (C1-C6)alkyl, as part of a group, is optionally substituted with one or more Z1 groups;
R7a is selected from:
a) H, halo, (C1-C6)alkyl and (C1-C6)haloalkyl;
b) (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, nitro, cyano, aryl, heterocycle and heteroaryl;
c) —C(═O)—R11, —C(═O)—O—R11, —O—R11, —S—R11, —S(O)—R11, —SO2—R11, —(C1-C6)alkyl-R11, —(C1-C6)alkyl-C(═O)—R11, —(C1-C6)alkyl-C(═O)—O—R11, —(C1-C6)alkyl-O—R11, —(C1-C6)alkyl-S—R11, —(C1-C6)alkyl-S(O)—R11 and —(C1-C6)alkyl-SO2—R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl;
and
d) —N(R9)R10, —C(═O)—N(R9)R10, —O—C(═O)—N(R9)R10, —SO2—N(R9)R10, —(C1-C6)alkyl-N(R9)R10, —(C1-C6)alkyl-C(═O)—N(R9)R10, —(C1-C6)alkyl-O—C(═O)—N(R9)R10 and —(C1-C6)alkyl-SO2—N(R9)R10, wherein each R9 is independently selected from H, (C1-C6)alkyl and (C3-C7)cycloalkyl, and each R10 is independently selected from R11, —(C1-C6)alkyl-R11, —SO2—R11, —C(═O)—R11, —C(═O)OR11 and —C(═O)N(R9)R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl;
and wherein any aryl, heterocycle or heteroaryl of R7a is optionally substituted with one or more Z10 groups;
R7b is selected from:
a) —(C1-C6)alkyl-SO2—(C1-C6)alkyl-Z13, —C(O)—(C1-C6)alkyl-Z13, —O—(C1-C6)alkyl-Z13, —S—(C1-C6)alkyl-Z13, —S(O)—(C1-C6)alkyl-Z13, —SO2—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-Z14, C6)alkyl-C(O)—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-C(O)—O(C1-C6)alkyl-Z13, —(C1-C6)alkyl-O—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-S—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-O(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S(O)—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-SO2—(C1-C6)alkyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-(C1-C6)haloalkyl, —(C2-C6)alkynyl-(C1-C6)haloalkyl, —(C3-C7)halocarbocycle, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle, —NRaSO2Oaryl, —(C2-C6)alkenyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-aryl, —(C2-C6)alkenyl-heteroaryl, —(C2-C6)alkenyl-heterocycle, —(C2-C6)alkynyl-(C3-C7)carbocycle, —(C2-C6)alkynyl-aryl, —(C2-C6)alkynyl-heteroaryl, —(C2-C6)alkynyl-heterocycle, —(C3-C7)carbocycle-Z1 and -halo(C1-C6)alkyl-Z3, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C7)carbocycle, (C3-C7)halocarbocycle, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heterocycle and heteroaryl, either alone or as part of a group, is optionally substituted with one or more Z1 groups;
b) spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle, wherein any spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle is optionally substituted with one or more Z1 groups, wherein two Z1 groups together with the atom or atoms to which they are attached optionally form a (C3-C7)carbocycle or heterocycle, wherein the (C3-C7)carbocycle or heterocycle is optionally substituted with one or more Z1 groups;
c) (C1-C6)alkyl, wherein (C1-C6)alkyl is substituted with one or more Z2 groups and optionally substituted with one or more Z1 groups;
d) —X(C1-C6)alkyl, —X(C1-C6)haloalkyl, —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle, wherein any —X(C1-C6)alkyl and —X(C1-C6)haloalkyl is substituted with one or more Z3 groups and optionally substituted with one or more Z1 groups, and wherein any —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle is substituted with one or more Z4 groups and optionally substituted with one or more Z1 groups;
e) aryl, heteroaryl, heterocycle, —Xaryl, —Xheteroaryl and —Xheterocycle, wherein any aryl, heteroaryl and heterocycle, either alone or as part of a group, is substituted with one or more Z5 groups and optionally substituted with one or more Z1 groups;
f) (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl and (C2-C6)alkynyl, wherein (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl and (C2-C6)alkynyl are each substituted with one or more Z6 groups and optionally substituted with one or more Z1 groups;
and
g) —NReRf, —C(O)NReRf, —OC(O)NReRf, —SO2NReRf, —(C1-C6)alkyl-NReRf, —(C1-C6)alkylC(O)—NReRf, —(C1-C6)alkyl-O—C(O)—NReRf and —(C1-C6)alkyl-SO2NReRf, wherein each (C1-C6)alkyl is optionally substituted with one or more Z1 groups;
R8a is selected from:
a) halo, nitro and cyano;
b) R11, —C(═O)—R11, —C(═O)—O—R11, —O—R11, —S—R11, —S(O)—R11, —SO2—R11, —(C1-C6)alkyl-R11, —(C1-C6)alkyl-C(═O)—R11, —(C1-C6)alkyl-C(═O)—O—R11, —(C1-C6)alkyl-O—R11, —(C1-C6)alkyl-S—R11, —(C1-C6)alkyl-S(O)—R11 and —(C1-C6)alkyl-SO2—R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl, wherein aryl, heterocycle and heteroaryl are each optionally substituted with one or more Z11 groups;
and
c) —N(R9)R10, —C(═O)—N(R9)R10, —O—C(═O)—N(R9)R10, —SO2—N(R9)R10, —(C1-C6)alkyl-N(R9)R10, —(C1-C6)alkyl-C(═O)—N(R9)R10, —(C1-C6)alkyl-O—C(═O)—N(R9)R10 and —(C1-C6)alkyl-SO2—N(R9)R10, wherein each R9 is independently selected from H, (C1-C6)alkyl and (C3-C7)cycloalkyl, and each R10 is independently selected from R11, —(C1-C6)alkyl-R11, —SO2—R11, —C(═O)—R11, —C(═O)OR11 and —C(═O)N(R9)R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl, wherein aryl, heterocycle and heteroaryl are each optionally substituted with one or more Z11 groups;
R8b is selected from:
a) —(C1-C6)alkyl-SO2—(C1-C6)alkyl-Z13, —C(O)—(C1-C6)alkyl-Z13, —O—(C1-C6)alkyl-Z13, —S—(C1-C6)alkyl-Z13, —S(O)—(C1-C6)alkyl-Z13, —SO2—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-Z14, —(C1-C6)alkyl-C(O)—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-C(O)—O(C1-C6)alkyl-Z13, —(C1-C6)alkyl-O—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-S—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-O—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S(O)—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-SO2—(C1-C6)alkyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-(C1-C6)haloalkyl, —(C2-C6)alkynyl-(C1-C6)haloalkyl, -halo(C3-C7)carbocycle, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle, —NRaSO2Oaryl, —(C2-C6)alkenyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-aryl, —(C2-C6)alkenyl-heteroaryl, —(C2-C6)alkenyl-heterocycle, —(C2-C6)alkynyl-(C3-C7)carbocycle, —(C2-C6)alkynyl-aryl, —(C2-C6)alkynyl-heteroaryl, —(C2-C6)alkynyl-heterocycle, —(C3-C7)carbocycle-Z1 and -halo(C1-C6)alkyl-Z3, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heterocycle and heteroaryl, either alone or as part of a group, is optionally substituted with one or more Z1 groups;
b) spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle, wherein any spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle is optionally substituted with one or more Z1 groups, wherein two Z1 groups together with the atom or atoms to which they are attached optionally form a (C3-C7)carbocycle or heterocycle wherein the (C3-C7)carbocycle or heterocycle is optionally substituted with one or more Z1 groups;
c) (C1-C6)alkyl, wherein (C1-C6)alkyl is substituted with one or more Z2 groups and optionally substituted with one or more Z1 groups;
d) —X(C1-C6)alkyl, —X(C1-C6)haloalkyl, —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle, wherein any —X(C1-C6)alkyl and —X(C1-C6)haloalkyl is substituted with one or more Z3 groups and optionally substituted with one or more Z1 groups, and wherein any —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle is substituted with one or more Z4 groups and optionally substituted with one or more Z1 groups;
e) aryl, heteroaryl, heterocycle, —Xaryl, —Xheteroaryl and —Xheterocycle, wherein any aryl, heteroaryl and heterocycle, either alone or as part of a group is substituted with one or more Z5 groups and optionally substituted with one or more Z1 groups;
f) (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl and (C2-C6)alkynyl, wherein (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl and (C2-C6)alkynyl are each independently substituted with one or more Z6 groups and optionally substituted with one or more Z1 groups;
and
g) —NReRf, —C(O)NReRf, —OC(O)NReRf, —SO2NReRf, —(C1-C6)alkyl-NReRf, —(C1-C6)alkylC(O)—NReRf, —(C1-C6)alkyl-O—C(O)—NReRf and —(C1-C6)alkyl-SO2NReRf, wherein each (C1-C6)alkyl is optionally substituted with one or more Z1 groups;
R13a is selected from:
a) R11, —C(═O)—R11, —C(═O)—O—R11, —O—R11, —S—R11, —S(O)—R11, —SO2—R11, —(C1-C6)alkyl-R11, —(C1-C6)alkyl-C(═O)—R11, —(C1-C6)alkyl-C(═O)—O—R11, —(C1-C6)alkyl-O—R11, —(C1-C6)alkyl-S—R11, —(C1-C6)alkyl-S(O)—R11 and —(C1-C6)alkyl-SO2—R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl, wherein aryl, heterocycle and heteroaryl are each optionally substituted with one or more Z11 groups;
and
b) —C(═O)—N(R9)R10, —SO2—N(R9)R10, —(C1-C6)alkyl-N(R9)R10, —(C1-C6)alkyl-C(═O)—N(R9)R10, —(C1-C6)alkyl-O—C(═O)—N(R9)R10 and —(C1-C6)alkyl-SO2—N(R9)R10, wherein each R9 is independently selected from H, (C1-C6)alkyl and (C3-C7)cycloalkyl, and each R10 is independently selected from R11, —(C1-C6)alkyl-R11, —SO2—R11, —C(═O)—R11, —C(═O)OR11 and —C(═O)N(R9)R11, wherein each R11 is independently selected from H, (C1-C6)alkyl, —(C1-C6)alkylaryl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, aryl, heterocycle and heteroaryl, wherein aryl, heterocycle and heteroaryl are each optionally substituted with one or more Z11 groups;
R13b is selected from:
a) —(C1-C6)allyl-SO2—(C1-C6)alkyl-Z13, —C(O)—(C1-C6)alkyl-Z13, —O—(C1-C6)alkyl-Z13, —S—(C1-C6)alkyl-Z13, —S(O)—(C1-C6)alkyl-Z13, —SO2—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-Z14, —(C1-C6)alkyl-C(O)—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-C(O)—O(C1-C6)alkyl-Z13, —(C1-C6)alkyl-O—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-S—(C1-C6)alkyl-Z13, —(C1-C6)alkyl-O—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-S(O)—(C1-C6)alkyl-(C3-C7)carbocycle, —(C1-C6)alkyl-SO2—(C1-C6)alkyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-(C1-C6)haloalkyl, —(C2-C6)alkynyl-(C1-C6)haloalkyl, -halo(C3-C7)carbocycle, —(C2-C6)alkenyl-(C3-C7)carbocycle, —(C2-C6)alkenyl-aryl, —(C2-C6)alkenyl-heteroaryl, —(C2-C6)alkenyl-heterocycle, —(C2-C6)alkynyl-(C3-C7)carbocycle, —(C2-C6)alkynyl-aryl, —(C2-C6)alkynyl-heteroaryl, —(C2-C6)alkynyl-heterocycle, —(C3-C7)carbocycle-Z1, -halo(C1-C6)alkyl-Z3, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle and —NRaSO2Oaryl, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heterocycle and heteroaryl, either alone or as part of a group, is optionally substituted with one or more Z1 groups;
b) spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle, wherein spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle are optionally substituted with one or more Z1 groups, wherein two Z1 groups together with the atom or atoms to which they are attached optionally form a (C3-C7)carbocycle or heterocycle wherein the (C3-C7)carbocycle or heterocycle is optionally substituted with one or more Z1 groups;
c) (C1-C6)alkyl, wherein (C1-C6)alkyl is substituted with one or more Z2 groups and optionally substituted with one or more Z1 groups;
d) —X(C1-C6)alkyl, —X(C1-C6)haloalkyl, —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle, wherein any X(C1-C6)alkyl and —X(C1-C6)haloalkyl is substituted with one or more Z3 groups and optionally substituted with one or more Z1 groups, and wherein any —X(C2-C6)alkenyl, —X(C2-C6)alkynyl and —X(C3-C7)carbocycle, is substituted with one or more Z4 groups and optionally substituted with one or more Z1 groups;
e) aryl, heteroaryl, heterocycle, —Xaryl, —Xheteroaryl and —Xheterocycle, wherein any aryl, heteroaryl and heterocycle, either alone or as part of a group, is substituted with one or more Z5 groups and optionally substituted with one or more Z1 groups;
f) (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl and (C2-C6)alkynyl, wherein (C1-C6)haloalkyl, (C3-C7)carbocycle, (C2-C6)alkenyl and (C2-C6)alkynyl are each independently substituted with one or more Z6 groups and optionally substituted with one or more Z1 groups;
and
g) —C(O)NReRf, —SO2NReRf, —(C1-C6)alkyl-NReRf, —(C1-C6)alkylC(O)—NReRf, —(C1-C6)alkyl-O—C(O)—NReRf and —(C1-C6)alkyl-SO2NReRf, wherein each (C1-C6)alkyl is optionally substituted with one or more Z1 groups;
or any of R5a and R6a, R6a and R7a, R7a and R8a, R1 and R2 or R1 and R13 together with the atoms to which they are attached form a 5 or 6-membered carbocycle or a 4, 5, 6 or 7-membered heterocycle, wherein the 5 or 6-membered carbocycle or the 4, 5, 6 or 7-membered heterocycle is optionally substituted with one or more substituents each independently selected from halo, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, —OH, —O(C1-C6)alkyl, —SH, —S(C1-C6)alkyl, —NH2, —NH(C1-C6)alkyl and —N((C1-C6)alkyl)2;
or any of R5 and R6, R6 and R7 or R7 and R8, together with the atoms to which they are attached form a 5 or 6-membered carbocycle or a 4, 5, 6 or 7-membered heterocycle, wherein the 5 or 6-membered carbocycle or the 4, 5, 6 or 7-membered heterocycle are each independently substituted with one or more Z7 or Z8 groups, wherein when two Z7 groups are on same atom the two Z7 groups together with the atom to which they are attached optionally form a (C3-C7)carbocycle or 4, 5 or 6-membered heterocycle;
or any of R1 and R8, R1 and R2 or R1 and R13 together with the atoms to which they are attached form a 5 or 6-membered carbocycle or a 4, 5, 6 or 7-membered heterocycle, wherein the 5 or 6-membered carbocycle or the 4, 5, 6 or 7-membered heterocycle are each independently substituted with one or more Z7 or Z8 groups;
wherein when two Z7 groups are on same atom the two Z7 groups together with the atom to which they are attached optionally form a (C3-C7)carbocycle or 4, 5 or 6-membered heterocycle;
X is independently selected from O, —C(O)—, —C(O)O—, —S—, —S(O)—, —SO2—, —(C1-C6)alkylO—, —(C1-C6)alkylC(O)—, —(C1-C6)alkylC(O)O—, —(C1-C6)alkylS—, —(C1-C6)alkylS(O)— and —(C1-C6)alkylSO2—;
each Z1 is independently selected from halo, —NO2, —OH, ═NORa, —SH, —CN, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C1-C6)haloalkyl, (C3-C7)carbocycle, —(C3-C7)halocarbocycle, -aryl, -heteroaryl, -heterocycle, —O(C1-C6)alkyl, —O(C2-C6)alkenyl, —O(C2-C6)alkynyl, —O(C1-C6)haloalkyl, —O(C3-C7)carbocycle, —O(C3-C7)halocarbocycle, —Oaryl, -Oheteroaryl, —Oheterocycle, —S(C1-C6)alkyl, —S(C2-C6)alkenyl, —S(C2-C6)alkynyl, —S(C1-C6)haloalkyl, —S(C3-C7)carbocycle, —S(C3-C7)halocarbocycle, —Saryl, —Sheteroaryl, —Sheterocycle, —S(O)(C1-C6)alkyl, —S(O)(C2-C6)alkenyl, —S(O)(C2-C6)alkynyl, —S(O)(C1-C6)haloalkyl, —S(O) (C3-C7)carbocycle, —S(O)(C3-C7)halocarbocycle, —SO2(C1-C6)alkyl, —S(O)aryl, —S(O)carbocycle, —S(O)heteroaryl, —S(O)heterocycle, —SO2(C2-C6)alkenyl, —SO2(C2-C6)alkynyl, —SO2(C1-C6)haloalkyl, —SO2(C3-C7)carbocycle, —SO2(C3-C7)halocarbocycle, —SO2aryl, —SO2heteroaryl, —SO2heterocycle, —SO2NRcRd, —NRaC(O)Ra, —NRaC(O)ORa, —NRaC(O)NRcRd—NRaSO2Rb, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle, —NRaSO2Oaryl, —OS(O)2Ra, —C(O)Ra, —C(O)ORb, —C(O)NRcRd, and —OC(O)NRcRd, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C3-C7)halocarbocycle, (C3-C7)carbocycle, (C3-C7)halocarbocycle, aryl, heteroaryl and heterocycle of Z1, either alone or as part of a group, is optionally substituted with one or more halogen, —OH, —ORb, —CN, —NRaC(O)2Rb, heteroaryl, heterocycle, —Oheteroaryl, —Oheterocycle, —NHheteroaryl, —NHheterocycle, or —S(O)2NRcRd;
each Z2 is independently selected from —NO2, —CN, Spiro-heterocycle, bridged-heterocycle, spiro-bicyclic carbocycle, bridged-bicyclic carbocycle, NRaSO2(C3-C7)carbocycle, —NRaSO2aryl, —NRaSO2heteroaryl, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle and —NRaSO2Oaryl;
each Z3 is independently selected from —NO2, —CN, —OH, oxo, ═NORa, thioxo, -aryl, -heterocycle, -heteroaryl, (C3-C7)carbocycle, —(C3-C7)halocarbocycle, —O(C1-C6)alkyl, —O(C3-C7)carbocycle, —Ohalo(C3-C7)carbocycle, —Oaryl, —Oheterocycle, —Oheteroaryl, —S(C1-C6)alkyl, —S(C3-C7)carbocycle, —S(C3-C7)halocarbocycle, —Saryl, —Sheterocycle, —Sheteroaryl, —S(O)(C1-C6)alkyl, —S(O)(C3-C7)carbocycle, —S(O)(C3-C7)halocarbocycle, —S(O)aryl, —S(O)heterocycle, —S(O)heteroaryl, —SO2(C1-C6)alkyl, —SO2(C3-C7)carbocycle, —SO2(C3-C7)halocarbocycle, SO2aryl, —SO2heterocycle, —SO2heteroaryl, —NRaRb, —NRaC(O)Rb, —C(O)NRcRd, —SO2NRcRd, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle and —NRaSO2Oaryl;
each Z4 is independently selected from halogen, —(C1-C6)alkyl, (C3-C7)carbocycle, -halo(C1-C6)alkyl, —NO2, —CN, —OH, oxo, ═NORa, thioxo, aryl, heterocycle, heteroaryl, (C3-C7)halocarbocycle, —O(C1-C6)alkyl, —O(C3-C7)carbocycle, —O(C3-C7)halocarbocycle, —Oaryl, —Oheterocycle, -Oheteroaryl, —S(C1-C6)alkyl, —S(C3-C7)carbocycle, —S(C3-C7)halocarbocycle, -Saryl, —Sheterocycle, —Sheteroaryl, —S(O)(C1-C6)alkyl, —S(O)(C3-C7)carbocycle, —S(O)(C3-C7)halocarbocycle, —S(O)aryl, —S(O)heterocycle, —S(O)heteroaryl, —SO2(C1-C6)alkyl, —SO2(C3-C7)carbocycle, —SO2(C3-C7)halocarbocycle, SO2aryl, —SO2heterocycle, —SO2heteroaryl, —NRaRb, —NRaC(O)Ra, —C(O)NRcRd, —SO2NRcRd, —NRaSO2NRaRd, —NRaSO2O(C3-C7)carbocycle and —NRaSO2Oaryl;
each Z5 is independently selected from —NO2, —CN, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle, —NRaSO2Oaryl, —NRaSO2(C1-C6)alkyl, —NRaSO2(C2-C6)alkenyl, —NRaSO2(C2-C6)alkynyl, —NRaSO2(C3-C7)carbocycle, —NRaSO2(C3-C7)halocarbocycle, —NRaSO2aryl, —NRaSO2heteroaryl, —NRaSO2heteroaryl, —NRaSO2heterocycle, —NRaC(O)alkyl, —NRaC(O)alkenyl, —NRaC(O)alkynyl, —NRaC(O) (C3-C7)carbocycle, —NRaC(O)(C3-C7)halocarbocycle, —NRaC(O)aryl, —NRaC(O)heteroaryl, —NRaC(O)heterocycle, NRaC(O)NReRd and NRaC(O)ORb;
each Z6 is independently selected from —NO2, —CN, —NRaRa, NRaC(O)Rb, —C(O)NRcRd, —(C3-C7)halocarbocycle, aryl, heteroaryl, heterocycle, —Oaryl, —Oheteroaryl, —Oheterocycle, —O(C3-C7)halocarbocycle, —O(C1-C6)alkyl, —O(C1-C6)alkyl-O—(C1-C6)alkyl, —O(C3-C7)carbocycle, —Ohalo(C1-C6)alkyl, —Saryl, —Sheteroaryl, —Sheterocycle, —S(C3-C7)halocarbocycle, —S(C1-C6)alkyl, —S(C3-C7)carbocycle, —S(C1-C6)haloalkyl, —S(O)aryl, —S(O)heteroaryl, —S(O)heterocycle, —S(O)(C3-C7)halocarbocycle, —S(O)(C1-C6)alkyl, —S(O)(C3-C7)carbocycle, —S(O)halo(C1-C6)alkyl, —SO2aryl, —SO2heteroaryl, —SO2heterocycle, —SO2(C1-C6)alkyl, —SO2halo(C1-C6)alkyl, —SO2(C3-C7)carbocycle, —SO2(C3-C7)halocarbocycle, —NRaSO2(C3-C7)halocarbocycle, —NRaSO2aryl, —NRaSO2heteroaryl, —NRaSO2heteroaryl, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle and —NRaSO2Oaryl;
each Z7 is independently selected from —NO2, ═NORa, —CN, —(C1-C6)alkyl-Z12, —(C2-C6)alkenyl-Z12, —(C2-C6)alkenylOH, —(C2-C6)alkynyl-Z12, —(C2-C6)alkynyl-OH, —(C1-C6)haloalkyl-Z12, —(C1-C6)haloalkylOH, —(C3-C7)carbocycle-Z12, —(C3-C7)carbocycleOH, (C3-C7)halocarbocycle, —(C1-C6)alkylNRcRd, —(C1-C6)alkylNRaC(O)Ra, —(C1-C6)alkylNRaSO2Ra, aryl, heteroaryl, heterocycle, —O(C1-C6)alkyl-Z12, —O(C2-C6)alkenyl, —O(C2-C6)alkynyl, —O(C1-C6)haloalkyl, —O(C3-C7)carbocycle, —O(C3-C7)halocarbocycle, —Oaryl, —O(C1-C6)alkylNRcRd, —O(C1-C6)alkylNRaC(O)Ra, —O(C1-C6)alkylNRaSO2Ra, —Oheteroaryl, —Oheterocycle, —S(C1-C6)alkyl-Z12, —S(C2-C6)alkenyl, —S(C2-C6)alkynyl, —S(C1-C6)haloalkyl, —S(C3-C7)carbocycle, —S(C3-C7)halocarbocycle, —S(C1-C6)alkylNRcRd, —S(C1-C6)alkylNRaC(O)Ra, —S(C1-C6)alkylNRaSO2Ra, —Saryl, —Sheteroaryl, —Sheterocycle, —S(O)(C1-C6)alkyl, —S(O)(C2-C6)alkenyl, —S(O)(C2-C6)alkynyl, —S(O)(C1-C6)haloalkyl, —S(O)(C3-C7)carbocycle, —S(O)(C3-C7)halocarbocycle, —SO2(C1-C6)alkyl, —S(O)(C1-C6)alkylNRcRd, —S(O)(C1-C6)alkylNRaC(O)Ra, —S(O)(C1-C6)alkylNRaSO2Ra, —S(O)aryl, —S(O)heteroaryl, —S(O)heterocycle, —SO2(C1-C6)alkyl, —SO2(C2-C6)alkenyl, —SO2(C2-C6)alkynyl, —SO2(C1-C6)haloalkyl, —SO2(C3-C7)carbocycle, —SO2(C3-C7)halocarbocycle, —SO2aryl, —SO2heteroaryl, —SO2heterocycle, —SO2(C1-C6)alkylNRcRd, —SO2(C1-C6)alkylNRaC(O)Ra, —SO2(C1-C6)alkylNRaSO2Ra, —SO2NRcRd, —NRaC(O)ORb, —NRaC(O)NRcRd—NRaSO2Rb, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle, —NRaSO2Oaryl, —OS(O)2Ra, —C(O)NRcRd, and —OC(O)NRcRd, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocycle, (C3-C7)halocarbocycle, aryl, heteroaryl and heterocycle of Z7, either alone or as part of a group, is optionally substituted with one or more halogen, —OH, —ORb, —CN, —NRaC(O)2Rb, heteroaryl, heterocycle, —Oheteroaryl, —Oheterocycle, —NHheteroaryl, —NHheterocycle, or —S(O)2NRcRd;
each Z8 is independently selected from —NO2 and —CN;
each Z9 is independently selected from —(C1-C6)alkyl and —O(C1-C6)alkyl;
each Z10 is independently selected from:
i) halo, oxo, thioxo, (C2-C6)alkenyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(C1-C6)alkyl-, —OH, —O(C1-C6)alkyl, —O(C1-C6)haloalkyl, —SH, —S(C1-C6)alkyl, —SO(C1-C6)alkyl, —SO2(C1-C6)alkyl, —NH2, —NH(C1-C6)alkyl and —N((C1-C6)alkyl)2;
ii) (C1-C6)alkyl optionally substituted with —OH, —O—(C1-C6)haloalkyl, or —O—(C1-C6)alkyl;
and
iii) aryl, heterocycle and heteroaryl, which aryl, heterocycle and heteroaryl is optionally substituted with halo, (C1-C6)alkyl or COOH;
each Z11 is independently selected from Z19, —C(═O)—NH2, —C(═O)—NH(C1-C4)alkyl, —C(═O)—N((C1-C4)alkyl)2, —C(═O)-aryl, —C(═O)-heterocycle and —C(═O)-heteroaryl;
each Z12 is independently selected from —NO2, ═NORa, thioxo, aryl, heterocycle, heteroaryl, (C3-C7)halocarbocycle, (C3-C7)carbocycle, —O(C3-C7)carbocycle, —Ohalo(C3-C7)carbocycle, —Oaryl, —Oheterocycle, —Oheteroaryl, —S(C1-C6)alkyl, —S(C3-C7)carbocycle, —Shalo(C3-C7)carbocycle, —Saryl, —Sheterocycle, —Sheteroaryl, —S(O)(C1-C6)alkyl, —S(O)(C3-C7)carbocycle, —S(O)halo(C3-C7)carbocycle, —S(O)aryl, —S(O)heterocycle, —S(O)heteroaryl, —SO2(C1-C6)alkyl, —SO2(C3-C7)carbocycle, —SO2(C3-C7)halocarbocycle, —SO2aryl, —SO2heterocycle, —SO2heteroaryl, —NRaRa, —NRaC(O)Rb, —C(O)NRcRd, —SO2NRcRd, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle and —NRaSO2Oaryl;
each Z13 is independently selected from —NO2, —OH, ═NORa, —SH, —CN, —(C3-C7)halocarbocycle, —O(C1-C6)alkyl, —O(C2-C6)alkenyl, —O(C2-C6)alkynyl, —O(C1-C6)haloalkyl, —O(C3-C7)carbocycle, —O(C3-C7)halocarbocycle, —Oaryl, —Oheteroaryl, —Oheterocycle, —S(C1-C6)alkyl, —S(C2-C6)alkenyl, —S(C2-C6)alkynyl, —S(C1-C6)haloalkyl, —S(C3-C7)carbocycle, —S(C3-C7)halocarbocycle, —Saryl, —Sheteroaryl, —Sheterocycle, —S(O)(C1-C6)alkyl, —S(O)(C2-C6)alkenyl, —S(O)(C2-C6)alkynyl, —S(O)(C1-C6)haloalkyl, —S(O)(C3-C7)carbocycle, —S(O)(C3-C7)halocarbocycle, —S(O)aryl, —S(O)heteroaryl, —S(O)heterocycle, —SO2(C1-C6)alkyl, —SO2(C2-C6)alkenyl, —SO2(C2-C6)alkynyl, —SO2(C1-C6)haloalkyl, —SO2(C3-C7)carbocycle, —SO2(C3-C7)halocarbocycle, —SO2aryl, —SO2heteroaryl, —SO2heterocycle, —SO2NRcRd, —NRcRd, —NRaC(O)Ra, —NRaC(O)ORb, —NRaC(O)NRcRd—NRaSO2Rb, —NRaSO2NRcRd, —NRaSO2O(C3-C7)carbocycle, —NRaSO2Oaryl, —OS(O)2Ra, —C(O)Ra, —C(O)ORb, —C(O)NRcRd, and —OC(O)NRcRd, wherein any (C1-C6)alkyl, (C1-C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocycle, (C3-C7)halocarbocycle, aryl, heteroaryl and heterocycle of Z13, either alone or as part of a group, is optionally substituted with one or more halogen, —OH, —ORb, —CN, —NRaC(O)2Rb, -heteroaryl, -heterocycle, —Oheteroaryl, —Oheterocycle, —NHheteroaryl, —NHheterocycle, or —S(O)2NRcRd;
each Z14 is independently selected from —NO2, ═NORa, —CN, —(C3-C7)halocarbocycle, —O(C3-C7)halocarbocycle, —S(C3-C7)halocarbocycle, —S(O)(C3-C7)halocarbocycle, —SO2(C3-C7)halocarbocycle, —NRaSO2NRcRd, —NRaSO2O(C3-C7)halocarbocycle, —NRaSO2Oaryl and —OS(O)2Ra, wherein any —(C3-C7)halocarbocycle of Z14, either alone or as part of a group, is optionally substituted with one or more halogen, —OH, —ORb, —CN, —NRaC(O)2Rb, -heteroaryl, -heterocycle, -Oheteroaryl, —Oheterocycle, —NHheteroaryl, —NHheterocycle, or —S(O)2NRcRd;
each Ra is independently H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocycle, heterocycle, aryl, aryl(C1-C6)alkyl-, heteroaryl or heteroaryl(C1-C6)alkyl-, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocycle, heterocycle, aryl or heteroaryl of Ra, either alone or as part of a group, is optionally substituted by one or more halogen, OH and cyano;
each Rb is independently (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocycle, heterocycle, aryl, aryl(C1-C6)alkyl-, heteroaryl or heteroaryl(C1-C6)alkyl-, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocycle, heterocycle, aryl or heteroaryl of Rb, either alone or as part of a group, is optionally substituted by one or more halogen, OH and cyano;
Rc and Rd are each independently selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocycle, aryl, aryl(C1-C6)alkyl-, heterocycle, heteroaryl and heteroaryl(C1-C6)alkyl-, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocycle, heterocycle, aryl and heteroaryl of Re or Rd, either alone or as part of a group, is optionally substituted by one or more halogen, OH and cyano;
or Rc and Rd together with the nitrogen to which they are attached form a heterocycle, wherein any heterocycle of Re and Rd together with the nitrogen to which they are attached is optionally substituted by one or more halogen, OH or cyano;
each Re is independently selected from —ORa, (C1-C6)alkyl and (C3-C7)carbocycle, wherein (C1-C6)alkyl and (C3-C7)carbocycle is substituted by one or more Z6 and optionally substituted with one or more Z1, (C2-C6)haloalkyl, (C2-C6)alkenyl and (C2-C6)alkynyl, wherein any (C2-C6)haloalkyl, (C2-C6)alkenyl and (C2-C6)alkynyl is optionally substituted with one or more Z1;
and aryl, heterocycle and heteroaryl wherein aryl, heterocycle and heteroaryl is substituted by one or more Z5;
each Rf is independently selected from —Rg, —OR., —(C1-C6)alkyl-Z6, —SO2Rg, —C(O)Rg, C(O)ORg and —C(O)NReRg;
and
each Rg is independently selected from H, —ORa, (C1-C6)alkyl, (C3-C7)carbocycle, (C1-C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heterocycle and heteroaryl, wherein any (C1-C6)alkyl, (C3-C7)carbocycle, (C1-C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heterocycle and heteroaryl of Rg is optionally substituted with one or more Z1 groups;
or a salt thereof.

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2-quinolinyl-acetic acid derivatives as hiv antiviral compounds

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2-quinolinyl-acetic acid derivatives as hiv antiviral compounds

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Abstract

Claims23