| 主权项 |
1. A compound of Formula (I): or a pharmaceutically acceptable salt, wherein:
R5 is selected from the group consisting of halogen, N(R′)2, OCOR′, NHCOR′, N(COR′)COR′, SCOR′, OCOOR′, and NHCOOR′,each R′ is independently H, a lower alkyl (C1-C6), lower haloalkyl (C1-C6), lower alkoxy (C1-C6), lower alkenyl (C2-C6), lower alkynyl (C2-C6), lower cycloalkyl (C3-C6) aryl, heteroaryl, alkylaryl, or arylalkyl, wherein the groups can be substituted with one or more hydroxyalkyl, aminoalkyl, or alkoxyalkyl substituents,R3 and R4 are independently:(a) OR1 where R1 is H, C1-20 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, aryl, or heteroaryl optionally substituted with one to three substituents independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, (CH2)1-6CO2R1a, halogen, C1-6 haloalkyl, —N(R1a)2, C1-6 acylamino, —NHSO2C1-6 alkyl, —SO2N(R1a)2, —SO2C1-6 alkyl, COR1b, nitro and cyano;R1a is independently H or C1-6 alkyl;R1b is —OR1a or —N(R1a)2;(b) where R2a and R2b are:(i) independently selected from the group consisting of H, C1-10 alkyl, —(CH2)rNR1a2, C1-6 hydroxyalkyl, —CH2SH, —(CH2)2S (O)pMe, —(CH2)3NHC(═NH)NH2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH2)mCOR1b, aryl and aryl-C1-3 alkyl, said aryl groups optionally substituted with a group selected from the group consisting of hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano;(ii) R2a is H and R2b and R8 together are (CH2)2-4 to form a ring that comprises the adjoining N and C atoms;(iii) R2a and R2b together are (CH2)n to form a ring;(iv) R2a and R2b both are C1-6 alkyl; or(v) R2a is H and R2b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, —CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4′-OH)-Ph), CH2SH, or lower cycloalkyl;p is 0 to 2;r is 1 to 6;n is 4 or 5;m is 0 to 3R7 is H, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, halogen, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl;R8 is H, C1-3 alkyl, R2a or R2b and R8 together are (CH2)2-4 so as to form a ring that comprises the adjoining N and C atoms;(c) OH, an O attached lipid or phospholipid, an N or O attached peptide, an O attached cholesterol, or an O attached phytosterol;(d) R3 and R4 may come together to form a ring where W2 is selected from the group consisting of phenyl, optionally substituted with one to three substituents independently selected from the group consisting of C1-6 alkyl, CF3, C2-6 alkenyl, C1-6 alkoxy, OW1c, CO2R1a, COR1a, halogen, C1-6 haloalkyl, —N(R1a)2, C1-6 acylamino, CO2N(R1a)2, SR1a, —NHSO2C1-6 alkyl, —SO2N(R1a)2, —SO2C1-6 alkyl, COR1b, and cyano, and wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1-2 heteroatoms that are independently selected from the group consisting of N, O, and S with the provisos that:a) when there are two heteroatoms and one is O, then the other can not be O or S, andb) when there are two heteroatoms and one is S, then the other can not be O or S;R1a is independently H or C1-6 alkyl;R1b is —OR1a or —N(R1a)2;(e) where R9 is selected from the group consisting of H, C1-10 alkyl, and C1-10 alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, halogen, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl;R1c is H or C1-6 acyl; or(f) R3 and R4 may come together to form a ring where R2b is: (i) independently selected from the group consisting of H, C1-10 alkyl, —(CH2)rNR1a2, C1-6 hydroxyalkyl, —CH2SH, —(CH2)2S(O)pMe, —(CH2)3NHC(═NH)NH2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH2)mCOR1b, aryl and aryl-C1-3 alkyl, said aryl groups optionally substituted with a group selected from the group consisting of hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro, and cyano; (ii) R2b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, —CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, —CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4′-OH)-Ph), CH2SH, or lower cycloalkyl;p is 0 to 2;r is 1 to 6;m is 0 to 3A is NR1a, O, or SB is C1-10 alkyl, C1-6 hydroxyalkyl, aryl and aryl-C1-3 alkyl, heteroaryl or heteroaryl-C1-3 alkyl, said aryl and heteroaryl groups optionally substituted with a group selected from the group consisting of hydroxyl, C1-10 alkyl, C1-6 alkoxy, and halogen,R7 is H, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, halogen, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl;R8 is H, C1-3 alkyl, R2a or R2b and R8 together are (CH2)2-4 so as to form a ring that comprises the adjoining N and C atoms;W is N, CH, CF, CCN, CC≡CH, or CC(O)N(R′)2;Y is O or S; andZ is CH2CH2, CH2O, or OCH2. |
