| 主权项 |
1. A compound of formula I: wherein:
r is 0, 1 or 2;Ar is: R1 is selected from —COOR1a, —NHSO2R1b, —SO2NHR1d, —SO2OH, —C(O)NH—SO2R1c, —P(O)(OH)2, —CN, —OCH(R1e)—COOH, tetrazol-5-yl, where R1a is H, —C1-6 alkyl, —C1-3 alkylenearyl, —C1-3 alkyleneheteroaryl, —C3-7 cycloalkyl, —CH(C1-4alkyl)OC(O)R1aa, —C0-6alkylenemorpholine, R1aa is —O—C1-6alkyl, —O—C3-7cycloalkyl, —NR1abR1ac, or —CH(NH2)CH2COOCH3; R1ab and R1ac are independently selected from H, —C1-6alkyl, and benzyl, or are taken together as —(CH2)3-6—; R1b is R1c or —NHC(O)R1c; R1c is —C1-6alkyl, —C0-6alkylene-O—R1ca, —C1-5alkylene-NR1cbR1cc, —C0-4alkylenearyl or —C0-4alkyleneheteroaryl; R1ca is H, —C1-6alkyl, or —C1-6alkylene-O—C1-6alkyl; R1cb and R1cc are independently selected from H and —C1-6alkyl, or are taken together as —(CH2)2—O—(CH2)2— or —(CH2)2—N[C(O)CH3]—(CH2)2—; R1d is H, R1c, —C(O)R1c, or —C(O)NHR1c; R1e is —C1-4alkyl or aryl;
n is 0, 1, 2 or 3;each R2 is independently selected from halo, —NO2, —C1-6alkyl, —C2-6alkenyl, —C3-6cycloalkyl, —CN, —C(O)R2a, —C0-5alkylene-OR2b, —C0-5alkylene-NR2cR2d, —C0-3alkylenearyl, and —C0-3alkyleneheteroaryl; where R2a is H, —C1-6alkyl, —C3-6cycloalkyl, —OR2b, or —NR2cR2d; R2b is H, —C1-6alkyl, —C3-6cycloalkyl, or —C0-1alkylenearyl; and R2c and R2d are independently selected from H, —C1-4alkyl, and —C0-1alkylenearyl;R3 is selected from —C1-10alkyl, —C2-10alkenyl, —C3-10alkynyl, —C0-3alkylene-C3-7cycloalkyl, —C2-3alkenylene-C3-7cycloalkyl, —C2-3alkynylene-C3-7cycloalkyl, —C0-5alkylene-NR3a—C0-5alkylene-R3b, —C0-5alkylene-O—C0-5alkylene-R3b, —C0-5alkylene-S—C1-5alkylene-R3b, and —C0-3alkylenearyl; where R3a is H, —C1-6alkyl, —C3-7cycloalkyl, or —C0-3alkylenearyl; and R3b is H, —C1-6alkyl, —C3-7cycloalkyl, —C2-4alkenyl, —C2-4alkynyl, or aryl;X is —C1-12alkylene-, where at least one —CH2— moiety in the alkylene is replaced with a —NR4a—C(O)— or —C(O)—NR4a- moiety, where R4a is H, —OH, or —C1-4alkyl;R5 is selected from —C0-3alkylene-SR5a, —C0-3alkylene-C(O)NR5bR5c, —C0-3alkylene-NR5b—C(O)R5d, —NH—C0-1alkylene-P(O)(OR5e)2, —C0-3alkylene-P(O)OR5eR5f, —C0-2alkylene-CHR5g—COOH, —C0-3alkylene-C(O)NR5h—CHR5i—COOH, and —C0-3alkylene-S—SR5j; where R5a is H or —C(O)—R5aa; R5aa is —C1-6alkyl, —C0-6alkylene-C3-7cycloalkyl, -aminoC4-7cycloalkyl, —C0-6alkylenearyl, —C0-6alkyleneheteroaryl, —C0-6alkylenemorpholine, —C0-6alkylenepiperazine-CH3, —C0-6alkylenepiperidine, —C0-6alkylenepiperidine-CH3, —CH[N(R5ab)2]-aa where aa is an amino acid side chain, —C0-6alkylene-CH[N(R5ab)2]-R5ac, -2-pyrrolidine, -2-tetrahydrofuran, —C0-6alkylene-OR5ab, —O—C0-6alkylenearyl, —C1-2alkylene-OC(O)—C1-6alkyl, —C1-2alkylene-OC(O)—C0-6alkylenearyl, —O—C1-2alkylene-OC(O)O—C1-6alkyl, —C-4alkylene-COOH, or -arylene-COOH; R5ab is independently H or —C1-6alkyl; R5ac is H, —C1-6alkyl, —CH2—C3-7cycloalkyl or —COOH; R5b is H, —OH, —OC(O)R5ba, —CH2COOH, —O-benzyl, -pyridyl, or —OC(S)NR5bbR5bc; R5ba is H, —C1-6alkyl, aryl, —OCH2-aryl, —CH2O-aryl, or —NR5bbR5bc; R5bb and R5bc are independently selected from H and —C1-4alkyl; R5c is H, —C1-6alkyl, or —C(O)R5ca; R5ca is —C1-6alkyl, —C3-7cycloalkyl, aryl, or heteroaryl; R5d is H, —C1-4alkyl, —C0-3alkylenearyl, —NR5daR5db, —CH2SH, or —O—C1-6alkyl; R5da and R5db are independently selected from H and —C1-4alkyl; R5e is H, —C1-6alkyl, —C1-3alkylenearyl, —C1-3alkyleneheteroaryl, —C3-7cycloalkyl, —CH(CH3)OC(O)R5ea, R5ea is —O—C1-6alkyl, —O—C3-7cycloalkyl, —NR5ebR5ec, or —CH(NH2)CH2COOCH3; R5eb and R5ee are independently selected from H, —C1-4alkyl, and —C1-3alkylenearyl, or are taken together as —(CH2)3-6—; R5f is H, —C1-4alkyl, —C0-3alkylenearyl, —C1-3alkylene-NR5faR5fb, or —C1-3alkylene(aryl)-C0-3alkylene-NR5faR5fb; R5fa and R5fb are independently selected from H and —C1-4alkyl; R5g is H, —C1-6alkyl, —C1-3alkylenearyl, or —CH2—O—(CH2)2—OCH3; R5h is H or —C1-4alkyl; R5i is H, —C1-4alkyl, or —C0-3alkylenearyl; and R5j is —C1-6alkyl, aryl, or —CH2CH(NH2)COOH;
R6 is selected from —C1-6alkyl, —CH2O(CH2)2OCH3, —C1-6alkylene-O—C1-6alkyl, —C1-3alkylenearyl, —C0-3alkyleneheteroaryl, and —C0-3alkylene-C3-7cycloalkyl; andR7 is H or is taken together with R6 to form —C3-8cycloalkyl;wherein: each —CH2— group in —(CH2)r— is optionally substituted with 1 or 2 substituents independently selected from —C1-4alkyl and fluoro;each carbon atom in the alkylene moiety in X is optionally substituted with one or more R4b groups and one —CH2— moiety in X may be replaced with a group selected from —C3-8cycloalkylene-, —CR4d═CH—, and —CH═CR4d—; where R4b is —C0-5alkylene-COOR4c, —C1-6 alkyl, —C0-1alkylene-CONH2, —C1-2 alkylene-OH, —C0-3alkylene-C3 -7 cycloalkyl, 1H-indol-3-yl, benzyl, or hydroxybenzyl; R4c is H or —C1-4alkyl; and R4d is —CH2-thiophene or phenyl;each alkyl and each aryl in R1-3, R4a-4d, and R5-6 is optionally substituted with 1 to 7 fluoro atoms;Ar and each aryl and heteroaryl in R1-3 and R5-6 is optionally substituted with 1 to 3 substituents independently selected from —OH, —C1-6alkyl, —C2-4alkenyl, —C2-4alkynyl, —CN, halo, —O—C1-6alkyl, —S—C1-6alkyl, —S(O)—C1-6alkyl, —S(O)2—C1-4alkyl, -phenyl, —NO2, —NH2, —NH—C1-6alkyl and —N(C1-6alkyl)2, wherein each alkyl, alkenyl and alkynyl is optionally substituted with 1 to 5 fluoro atoms;and pharmaceutically acceptable salts thereof. |
