Preparation and use of compounds as protease inhibitors

A compound having the structural formula

• or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein
• Q is a bond or —N(R5)—;
• T is a bond, —O—, —C(O)—;
• —S—, —N(R5)—, —S(O)—, —S(O)2— or —C(R6′R7′)—;
• U is a bond or —C(R6)(R7)—;
• Y is C or N;
• Z is C or N;
• ring A, including variables Y and Z, is a three- to nine-membered cycloalkyl, cycloalkenyl, heterocylcyl, heterocyclenyl, aryl, and heteroaryl ring having 0 to 7, preferably 0 to 4, heteroatoms independently selected from the group consisting of O, S, N and —N(R)—, wherein ring A is unsubstituted or substituted with 1 to 5 independently selected R1 moieties and/or oxo when ring A is cycloalkyl, cycloalkenyl, heterocyclyl or heterocyclenyl;
• where,
• R is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl, —OR15, C(O)R8, —C(O)OR9, —S(O)R10, —S(O)2R10, —C(O)N(R11)(R12), —S(O)N(R11)(R12), and —S(O)2N(R11)(R12);
• R1 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR15, —C(O)R15, —C(O)OR15, —C(O)N(R15)(R16), —S(O)0-2R15, —S(O)N(R15)(R16), S(O)1-2—N(R15)(R16), S(O)2N(R15)(R16), —C(═NOR15)R16, —P(O)(OR15)(OR16), —N(R15)(R16), —N(R15)C(O)R16, —N(R15)S(O)R16, —N(R15)S(O)2R16, N(R15)S(O)2N(R16)(R7), —N(R15)S(O)N(R16)(R17), —N(R15)C(O)N(R16)(R17), and —N(R15)C(O)OR16;
• and optionally:
• i) when ring A is disubstituted with two R1 groups on the same carbon atom, the two R1 groups together with the ring carbon atom form a 3- to 7-membered cycloalkyl, cycloalkenyl, heterocyclyl or heterocyclenyl ring having 0 to 4, preferably 0 to 2, heteroatoms, independently selected from the group consisting of O, N, S, or —N(R)—, which is optionally substituted by 1 to 5 R14 groups;
• or
• ii) when ring A is disubstituted with either:
• a) two R1 groups;
• or b) a R group and a R1 group, the two R1 groups or the R group and R1 group together with the ring A atoms to which they are attached form a 3- to 7-membered cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl or heteroaryl ring having 0 to 4, preferably 0 to 2 heteroatoms, independently selected from the group consisting of O, N, S, or —N(R)—, which is optionally substituted by 1 to 5 R14 groups;
• R2 is independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heterocycloalkenylaryl, —OR15, —CN, —C(O)R8, —C(O)OR9, —S(O)R10, —S(O)2R10, —C(O)N(R11)(R12), —S(O)N(R11)(R12), —S(O)2N(R11)(R12), —NO2, —N═C(R8)2 and —N(R8)2;
• R3, R4, R6 and R7 are independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heterocycloalkenylaryl, halo, —CH2—O—Si(R9)(R10)(R19), —SH, —CN, —OR9, —C(O)R8, —C(O)OR9, —C(O)N(R11)(R12), —SR19, —S(O)N(R11)(R12), —S(O)2N(R11)(R12), —N(R11)(R12), —N(R11)C(O)R8, —N(R11)S(O)R10, —N(R11)S(O)2R10—, —N(R11)C(O)N(R12)(R13), —N(R11)C(O)OR9 and —C(═NOH)R8;
• and optionally,
• (i) R3 and R4, together with the carbon to which they are attached, form a 3- to 8-membered cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl or heteroaryl ring having 0 to 3 heteroatoms independently selected from the group consisting of O, N, S, and —N(R)—, which is optionally substituted by 1 to 5 R14 groups and/or oxo, when said ring is cycloalkyl, cycloalkenyl, heterocyclyl, or heterocyclenyl ring;
• (ii) R6 and R7, together with the carbon to which they are attached form a 3- to 8-membered cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl or heteroaryl ring having 0 to 3 heteroatoms independently selected from the group consisting of O, N, S, or —N(R)—, which is optionally substituted by 1 to 5 R14 groups and/or oxo, when said ring is cycloalkyl, cycloalkenyl, heterocyclyl, or heterocyclenyl ring;
• (iii) when U is —C(R6)(R7)—, R3 and R6 together with the carbon atoms to which they are attached form a 3- to 7-membered cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl or heteroaryl ring having 0 to 4, preferably 0 to 2 heteroatoms, independently selected from the group consisting of O, N, S, or —N(R)—, which is optionally substituted by 1 to 5 R14 groups and/or oxo when said ring is cycloalkyl, cycloalkenyl, heterocyclyl, or heterocyclenyl ring;
• (iv) when T is —C(R6′)(R7′)—, R3 and R6′ together with the carbon atoms to which they are attached form a 3- to 7-membered cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl or heteroaryl ring having 0 to 4, preferably 0 to 2 heteroatoms, independently selected from the group consisting of O, N, S, or —N(R)—, which is optionally substituted by 1 to 5 R14 groups and/or oxo when said ring is a cycloalkyl, cycloalkenyl, heterocyclyl, or heterocyclenyl ring;
• (v) when T is —N(R5)—, R3 and R5 together with the atoms to which they are attached form a 3- to 7-membered heterocyclyl, heterocyclenyl, heteroaryl ring having 1 to 4, preferably 1 to 2, heteroatoms, independently selected from the group consisting of O, N, S, or —N(R)—, which is optionally substituted by 1 to 5 R14 groups and/or by oxo when said ring is heterocyclyl, or a heterocyclenyl ring;
• or
• (vi) a) R3 and R4, together with the carbon to which they are attached, or b) R6 and R7, together with the carbon to which they are attached, form one of the following multicyclic groups:
• wherein:
• M is independently —(CH2)—, —S—, —N(R19)—, —O—, —S(O)—, —S(O)2—, or —C(O)—;
• q is 0, 1, or 2;
• A and B are independently aryl, heteroaryl, cycloalkyl, cycloalkenyl or heterocyclyl;
• E is aryl or heteroaryl;
• and
• F is cycloalkyl, cycloalkenyl, heterocyclyl or heterocyclenyl
• provided that there are no adjacent oxygen and/or sulfur atoms present in the ring system and further provided that both (a) R3 and R4;
• and (b) R6 and R7 cannot be combined to form said multicyclic groups:
• at the same time;
• R5 is selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroaryl heterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heterocycloalkenylaryl, —CH2—O—Si(R9)(R10)(R19), —CN, —C(O)R8, —C(O)OR9, —C(O)N(R11)(R12), —SR19, —S(O)N(R11)(R12), —S(O)2N(R11)(R12), —N(R11)(R12), —N(R11)C(O)R8, —N(R11)S(O)R10, —N(R11)S(O)2R10—, —N(R11)C(O)N(R12)(R13), —N(R11)C(O)OR9 and —C(═NOH)R8;
• R6′ and R7′ are independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heterocycloalkenylaryl, -halo, —CH2—O—Si(R9)(R10)(R19), —SH, —CN, —OR9, —C(O)R8, —C(O)OR9, —C(O)N(R11)(R12), —SR19, —S(O)N(R11)(R12), —S(O)2N(R11)(R12), —N(R11)(R12), —N(R11)C(O)R8, —N(R11)S(O)R10, —N(R11)S(O)2R10—, —N(R11)C(O)N(R12)(R13), —N(R11)C(O)OR9 and —C(═NOH)R8;
• or optionally R6′ and R7′ together with the carbon atom to which they are attached form a 3- to 8-membered cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl or heteroaryl ring having 0 to 3 heteroatoms independently selected from the group consisting of O, N, S, and —N(R)—, which is optionally substituted by 1 to 5 R14 groups and/or oxo, when said ring is cycloalkyl, cycloalkenyl, heterocyclyl, or heterocyclenyl ring provided that when there are at least two heteroatoms present, there cannot be any adjacent oxygen and/or sulfur atoms present in the ring system;
• R8 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —OR15, —N(R15)(R16), —N(R15)C(O)R16, —N(R15)S(O)R16, —N(R15)S(O)2R16, —N(R15)S(O)2N(R16)(R17), —N(R15)S(O)N(R16)(R17), —N(R15)C(O)N(R16)(R17) and —N(R15)C(O)OR16;
• R9 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl;
• R10 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and —N(R15)(R16);
• R11, R12 and R13 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —C(O)R8, —C(O)OR9, —S(O)R10, —S(O)2R10, —C(O)N(R15)(R16), —S(O)N(R15)(R16), —S(O)2N(R15)(R16) and —CN;
• R14 is 1-5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR15, —C(O)R15, —C(O)OR15, —C(O)N(R15)(R16), —SR15, —S(O)N(R15)(R16), —S(O)2N(R15)16—C(═NOR15)R16, —P(O)(OR15)(OR16), —N(R15)(R16), —N(R15)C(O)R16, —N(R15)S(O)R16, —N(R15)S(O)2R16, —N(R15)S(O)2N(R16)(R17), —N(R15)S(O)N(R16)(R17), —N(R15)C(O)N(R16)(R17) and —N(R15)C(O)OR16;
• R15, R16 and R17 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl, arylheterocycloalkyl, R18-alkyl, R18-cycloalkyl, R18-cycloalkylalkyl, R18-heterocycloalkyl, R18-heterocycloalkylalkyl, R18-aryl, R18-arylalkyl, R18-heteroaryl and R18-heteroarylalkyl;
• or
• wherein R23 numbers 0 to 5 substituents, m is 0 to 6 and n is 1 to 5;
• R18 is 1-5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, —NO2, halo, heteroaryl, HO-alkyoxyalkyl, —CF3, —CN, alkyl-CN, —C(O)R19, —C(O)OH, —C(O)OR19, —C(O)NHR20, —C(O)NH2, —C(O)NH2—C(O)N(alkyl)2, —C(O)N(alkyl)(aryl), —C(O)N(alkyl)(heteroaryl), —SR19, —S(O)2R20, —S(O)NH2, —S(O)NH(alkyl), —S(O)N(alkyl)(alkyl), —S(O)NH(aryl), —S(O)2NH2, —S(O)2NHR19, —S(O)2NH(heterocycloalkyl), —S(O)2N(alkyl)2, —S(O)2N(alkyl)(aryl), —OCF3, —OH, —OR20, —O-heterocycloalkyl, —O-cycloalkylalkyl, —O-heterocycloalkylalkyl, —NH2, —NHR20, —N(alkyl)2, —N(arylalkyl)2, —N(arylalkyl)-(heteroarylalkyl), —NHC(O)R20, —NHC(O)NH2, —NHC(O)NH(alkyl), —NHC(O)N(alkyl)(alkyl), —N(alkyl)C(O)NH(alkyl), —N(alkyl)C(O)N(alkyl)(alkyl), —NHS(O)2R20, —NHS(O)2NH(alkyl), —NHS(O)2N(alkyl)(alkyl), —N(alkyl)S(O)2NH(alkyl) and —N(alkyl)S(O)2N(alkyl)(alkyl);
• or two R18 moieties on adjacent carbons can be linked together to form
• R19 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl or heteroarylalkyl;
• R20 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl;
• and wherein:
• i) each of the alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, cycloalkenylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heterocycloalkenylaryl, in R2, R3, R4, R5, R6, R6′, R7 and R7′;
• and
• ii) each of the alkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, arylcycloalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R, R1, R8, R9, R10, R11, R12, R13 and R14
• are independently unsubstituted or substituted by 1 to 5 R21 groups independently selected from the group consisting of alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heterocycloalkenylaryl, halo, —CN, —OR15, —C(O)R15, —C(O)OR15, —C(O)N(R15)(R16), —SR15, —S(O)N(R15)(R16), —CH(R15)(R16), —S(O)2N(R15)(R16), —C(═NOR15)R16, —P(O)(OR15)(OR16), —N(R15)(R16), -alkyl-N(R15)(R16), —N(R15)C(O)R16, —CH2—N(R15)C(O)R16, —CH2—N(R15)C(O)N(R16)(R17), —CH2—R15;
• —CH2N(R15)(R16), —N(R15)S(O)R16, —N(R15)S(O)2R16, —CH2—N(R15)S(O)2R16, —N(R15)S(O)2N(R16)(R17), —N(R15)S(O)N(R16)(R17), —N(R15)C(O)N(R16)(R17), —CH2—N(R15)C(O)N(R16)(R17), —N(R15)C(O)OR16, —CH2—N(R15)C(O)OR16, —S(O)R15, —N3, —NO2 and —S(O)2R15;
• and wherein each of the alkyl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R21 are independently unsubstituted or substituted by 1 to 5 R22 groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, halo, —CF3, —CN,
• —OR15, —C(O)R15, —C(O)OR15, -alkyl-C(O)OR15, C(O)N(R15)(R16), —SR15, —S(O)N(R15)(R15), —S(O)2N(R15)(R16), —C(═NOR15)R16, —P(O)(O15)(OR16), —N(R15)(R16), -alkyl-N(R15)(R16), —N(R15)C(O)R16, —CH2—N(R15)C(O)R16, —N(R15)S(O)R16, —N(R15)S(O)2R16, —CH2—N(R15)S(O)2R16, —N(R15)S(O)2N(R16)(R17), —N(R15)S(O)N(R16)(R17), —N(R15)C(O)N(R16)(R17), —CH2—N(R15)C(O)N(R16)(R17), —N(R15)C(O)OR16, —CH2—N(R15)C(O)OR16, —N3, —NO2, —S(O)R15 and —S(O)2R15;
• or two R21 or two R22 moieties on adjacent carbons can be linked together to form
• and when R21 or R22 are selected from the group consisting of —C(═NOR15)R16, —N(R15)C(O)R16, —CH2—N(R15)C(O)R16, —N(R15)S(O)R16, —N(R15)S(O)2R16, —CH2—N(R15)S(O)2R16, —N(R15)S(O)2N(R16)(R17), —N(R15)S(O)N(R16)(R17), —N(R15)C(O)N(R16)(R17), —CH2—N(R15)C(O)N(R16)(R17), —N(R15)C(O)OR16 and —CH2—N(R15)C(O)OR16, R15 and R16 together can be a C2 to C4 chain wherein, optionally, one, two or three ring carbons can be replaced by —C(O)— or —N(H)— and R15 and R16, together with the atoms to which they are attached, form a 5 to 7 membered ring, optionally substituted by R23;
• R23 is 1 to 5 groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR24, —C(O)R24, —C(O)OR24, —C(O)N(R24)(R25), —SR24, —S(O)N(R24)(R25), —S(O)2N(R24)(R25), —C(═NOR24)R25, —P(O)(OR24)(OR25), —N(R24)(R25), -alkyl-N(R24)(R25), —N(R24)C(O)R25, —CH2—N(R24)C(O)R25, —N(R24)S(O)R25, —N(R24)S(O)2R25, —CH2—N(R24)S(O)2R25, —N(R24)S(O)2N(R25)(R26), —N(R24)S(O)N(R25)(R26), —N(R24)C(O)N(R25)(R26), —CH2—N(R24)4C(O)N(R25)(R26), —N(R24)C(O)OR25, —CH2—N(R24)C(O)OR25, —S(O)R24 and —S(O)2R24;
• and wherein each of the alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkenyl and alkynyl groups in R23 are independently unsubstituted or substituted by 1 to 5 R27 groups independently selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, —CF3, —CN, —OR24, —C(O)R24, —C(O)OR24, alkyl-C(O)OR24C(O)N(R24)(R25), —SR24, —S(O)N(R24)(R25), —S(O)2N(R24)(R25), —C(═NOR24)R25, —P(O)(OR24)(OR25), —N(R24)(R25), -alkyl-N(R24)(R25)—N(R24)C(O)R25, —CH2—N(R24)C(O)R25, —N(R24)S(O)R25, —N(R24)S(O)2R25, —CH2—N(R24)S(O)2R25, —N(R24)S(O)2N(R25)(R26), —N(R24)S(O)N(R25)(R26), —N(R24)C(O)N(R25)(R26), —CH2—N(R24)C(O)N(R25)(R26), —N(R24)C(O)OR25, —CH2—N(R24)C(O)OR25, —S(O)R24 and —S(O)2R24;
• R24, R25 and R26 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl, R27-alkyl, R27-cycloalkyl, R27-cycloalkylalkyl, R27-heterocycloalkyl, R27-heterocycloalkylalkyl, R27-aryl, R27-arylalkyl, R27-heteroaryl and R27-heteroarylalkyl;
• R27 is 1-5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, arylalkyl, —NO2, halo, —CF3, —CN, alkyl-CN, —C(O)R28, —C(O)OH, —C(O)OR28, —C(O)NHR29, —C(O)N(alkyl)2, —C(O)N(alkyl)(aryl), —C(O)N(alkyl)(heteroaryl), —SR28, —S(O)2R29, —S(O)NH2, —S(O)NH(alkyl), —S(O)N(alkyl)(alkyl), —S(O)NH(aryl), —S(O)2NH2, —S(O)2NHR28, —S(O)2NH(aryl), —S(O)2NH(heterocycloalkyl), —S(O)2N(alkyl)2, —S(O)2N(alkyl)(aryl), —OH, —OR29, —O-heterocycloalkyl, —O-cycloalkylalkyl, —O-heterocycloalkylalkyl, —NH2, —NHR29, —N(alkyl)2, —N(arylalkyl)2, —N(arylalkyl)(heteroarylalkyl), —NHC(O)R29, —NHC(O)NH2, —NHC(O)NH(alkyl), —NHC(O)N(alkyl)(alkyl), —N(alkyl)C(O)NH(alkyl), —N(alkyl)C(O)N(alkyl)(alkyl), —NHS(O)2R29, —NHS(O)2NH(alkyl), —NHS(O)2N(alkyl)(alkyl), —N(alkyl)S(O)2NH(alkyl) and —N(alkyl)S(O)2N(alkyl)(alkyl);
• R28 is alkyl, alkenyl, alkynyl, cycloalkyl, arylalkyl or heteroarylalkyl;
• and
• R29 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl alkyl, heteroaryl or heteroarylalkyl;
• provided that:
• i) when U is a bond, Q is a bond, Y is N, and Z is C, then T is not —N(R5)—;
• ii) when U is —C(R6)(R7)—, Q is a bond, Y is N, and Z is C, then T is not —N(R5);
• iii) when Q is —N(R5)—, U is a bond, then T is not a bond;
• iv) when Q is —N(R5), T is a bond, Z is N and Y is C, then U is not a bond;
• v) when Q is —N(R5), Z is a N, Y is C and U is a bond, then T is not a bond, —C(O)—, or —C(R6′)(R7′)—;
• vi) when R3 and R4 are both phenyl, then A is not
• where
• R300 is H, an optionally substituted C1-C4 alkyl group, or together with the carbon to which it is attached and an adjacent ring carbon atom form a double bond;
• R400 is H or an optionally substituted C1-C4 alkyl group or
• R300 and R400 are taken together and form a 3- to 7-membered ring optionally containing one or two heteroatoms optionally selected from O, N and S;
• and
• j is 0, 1, 2, or 3, and
• vii) when Q is NR5 and T is a bond or —CR6′R7′, then
• is not a 3- to 7-membered cycloalkyl or cycloalkylether ring.