| 主权项 |
1. A compound having Formula I: or a pharmaceutically acceptable salt, or solvate thereof, wherein: Z1 is CR1b and Z2 is selected from the group consisting of N and N-oxide; R1a and R1b, which are identical or different, are selected from the group consisting of: a) hydrogen; b) halogen; c) hydroxy; d) cyano; e) optionally substituted alkyl; f) alkoxy; g) haloalkoxy; and h) haloalkyl; A1 is selected from the group consisting of: a) optionally substituted cycloalkyl; b) optionally substituted heterocyclo; c) optionally substituted aryl; and d) optionally substituted heteroaryl; X is selected from the group consisting of: a) —O—; b) —S—; c) —SO—; d) SO2— e) —(CR2R3)j—; f) —NR4—; and g) —SO2NH—;wherein:
at each occurrence R2 and R3, which are identical or different, are selected from the group consisting of hydrogen, fluoro, and optionally substituted alkyl; or each R2 and R3 are taken together to form an oxo group; or each R2 and R3 taken together with the carbon atom to which they are attached form a 3- to 8-membered optionally substituted cycloalkyl or optionally substituted heterocyclo; j is 0, 1, 2, or 3; and R4 is selected from the group consisting of hydrogen and optionally substituted alkyl; A2 is selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl; G is selected from the group consisting of: a) hydrogen; b) alkyl; c) cyano; wherein: R5a and R5b, which are identical or different, are selected from the group consisting of: a) hydrogen; b) optionally substituted alkyl; c) optionally substituted cycloalkyl; d) optionally substituted heterocyclo; e) optionally substituted aryl; f) optionally substituted heteroaryl; g) aralkyl; h) hydroxyalkyl; i) (cyano)alkyl; j) (heterocyclo)alkyl; k) (heteroaryl)alkyl; l) (amino)alkyl; m) (alkylamino)alkyl; n) (dialkylamino)alkyl, and o) —(CH2CH2O)m—R15a; or R5a and R5b taken together with the nitrogen atom to which they are attached form an optionally substituted 3- to 8-membered heterocyclo; R6a and R6b, which are identical or different, are selected from the group consisting of: a) hydrogen; b) optionally substituted alkyl; c) optionally substituted cycloalkyl; d) optionally substituted heterocyclo; e) optionally substituted aryl; f) optionally substituted heteroaryl; g) hydroxyalkyl h) (heterocyclo)alkyl; i) (heteroaryl)alkyl; j) (amino)alkyl; k) (alkylamino)alkyl; l) (dialkylamino)alkyl; m) (carboxamido)alkyl; n) (cyano)alkyl, and o) —(CH2CH2O)n—R15b; or R6a and R6b taken together with the nitrogen atom to which they are attached form an optionally substituted 3- to 8-membered heterocyclo; R7 is selected from the group consisting of: a) hydrogen; b) optionally substituted alkyl; c) optionally substituted cycloalkyl; d) optionally substituted heterocyclo; e) optionally substituted aryl; f) optionally substituted heteroaryl; g) (heterocyclo)alkyl; h) (heteroaryl)alkyl; i) (amino)alkyl; j) (alkylamino)alkyl; k) (dialkylamino)alkyl; and l) —(CH2CH2O)o—R15c; R8a and R8b, which are identical or different, are selected from the group consisting of: a) hydrogen; b) optionally substituted alkyl; and c) —(CH2CH2O)p—R15d; L is selected from the group consisting of —O— and —NR16—; R9 is selected from the group consisting of hydrogen, alkyl and —(CH2CH2O)q—R15e; R15a, R15b, R15c, R15d, and R15e, which are identical or different, are selected from the group consisting of hydrogen and optionally substituted alkyl; R16 is selected from the group consisting of hydrogen and optionally substituted alkyl; m, n, o, p, and q are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11; w is 0, 1, 2, 3, 4 or 5; x and y are each independently 1, 2, 3, or 4; E is selected from the group consisting of: a) hydrogen; b) halogen; c) alkyl; d) optionally substituted heteroaryl; e) optionally substituted heterocyclo; f) hydroxyalkyl; wherein: R17a and R17b, which are identical or different, are selected from the group consisting of: a) hydrogen; b) optionally substituted alkyl; c) —SO2R24a; d) —COR24b; e) optionally substituted aryl; f) optionally substituted heteroaryl; g) (heterocyclo)alkyl; h) (heteroaryl)alkyl; i) (amino)alkyl; j) (alkylamino)alkyl; k) (dialkylamino)alkyl; l) (carboxamido)alkyl; m) (cyano)alkyl; and n) hydroxyalkyl; or R17a and R17b taken together with the nitrogen atom to which they are attached form an optionally substituted 3- to 8-membered heterocyclo; R18a and R18b, which are identical or different, are selected from the group consisting of: a) hydrogen; b) optionally substituted alkyl; c) optionally substituted cycloalkyl; d) optionally substituted aryl; e) optionally substituted heteroaryl; f) (heterocyclo)alkyl; g) (heteroaryl)alkyl; and h) (dialkylamino)alkyl; or R18a and R18b taken together with the nitrogen atom to which they are attached form an optionally substituted 3- to 8-membered heterocyclo; R19 is selected from the group consisting of hydrogen and optionally substituted alkyl; R20a and R20b, which are identical or different, are selected from the group consisting of hydrogen and optionally substituted alkyl, wherein at least one of R20a and R20b is optionally substituted alkyl; R21a is selected from the group consisting of hydrogen and alkyl; R21b and R21c, which are identical or different, are selected from the group consisting of: a) hydrogen; b) optionally substituted alkyl; c) optionally substituted cycloalkyl; d) optionally substituted aryl; e) optionally substituted heteroaryl; f) (heterocyclo)alkyl; g) (heteroaryl)alkyl; and h) (dialkylamino)alkyl; or R21b and R21c taken together with the nitrogen atom to which they are attached form an optionally substituted 3- to 8-membered heterocyclo; R22 is selected from the group consisting of hydrogen and alkyl; R24a is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl; R24b is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl; t and u are each independently 0, 1, 2, or 3; and v is 1, 2, or 3; wherein: 1) G and E cannot both be hydrogen; 2) when G is alkyl, then E is not halogen; 3) when G is: w is 0, and E is: then R17a is not hydrogen or alkyl when R17b is hydrogen or alkyl; 4) when G is: w is 0, and E is: then u is 1, 2, or 3; 5) when G is: and R5a and R5b taken together with the nitrogen atom to which they are attached form an optionally substituted 3- to 8-membered heterocyclo, then said optional substituents are selected from the group consisting of halo, nitro, cyano, hydroxy, amino, alkylamino, dialkylamino, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, aryloxy, aralkyloxy, alkylthio, alkylcarbonyl, arylcarbonyl, ureido, guanidino, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclo, alkoxyalkyl, (amino)alkyl, hydroxyalkylamino, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl, (carboxamido)alkyl, mercaptoalkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl; 6) when G is: and w is 0, then E is not a morpholinyl group. |
