| 主权项 |
1. A compound of Formula 1Aor a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is H or Me, wherein, when R1 is Me it may be wholly or partially R or S or any mixture thereof; R2 is H, N3, F, (C1-8)alkyl, (C2-8)alkenyl or (C2-8)alkynyl; R4 is H or P(O) R6R7, wherein, when chirality exists at the phosphorous center of R4, it may be wholly or partially Rp or S, or any mixture thereof, R5 is O, CH2, CHF, CF2, or C═CH2, R3 is H or CN when R5 is O, and R3 is selected from the group consisting of CN, (C1-8)alkyl, (C2-8)alkenyl, (C2-8)alkynyl and (C1-8)Oalkyl when R5 is CH2, CHF, CF2, or C═CH2, R8 is selected from the group consisting of H, C(O)(C18)alkyl, C(O)(C1-8) branched alkyl, C(O)NH(C1-8)alkyl, or C(O)NH(C1-8)branched alkyl, or OR8 as it appears in Formula 1A is an ester derived from an alpha amino acid, R6 and R7 are independently selected from the group consisting of: (a) OR15 where R15 selected from the group consisting of H, Li, Na, K, C1-20alkyl, C3-6cycloalkyl, C1-4(alkyl)aryl, benzyl, C1-6haloalkyl, C2-3(alkyl)OC1-20alkyl, aryl, and heteroaryl, wherein aryl and heteroaryl groups are optionally substituted with zero to three substituents independently selected from the group consisting of (CH2)0-6CO2R16 and (CH2)0-6CON(R16)2; R16 is independently H, C1-20 alkyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, fluoro, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the substituents are C1-5 alkyl, or C1-5 alkyl substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, fluoro, C3-10 cycloalkyl, or cycloalkyl; (c) the ester of an L-amino acidwhere R17 is restricted to those occurring in natural L-amino acids, and R18 is H, C1-20 alkyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, fluoro, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the substituents are C1-5 alkyl, or C1-5 alkyl substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, fluoro, C3-10 cycloalkyl, or cycloalkyl;
(d) R6 and R7 can come together to form a ringwhere R19 is H, C1-20 alkyl, C1-20 alkenyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, fluoro, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl;
wherein the substituents are C1-5 alkyl, or C1-5 alkyl substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, fluoro, C3-10 cycloalkyl, or cycloalkyl; (e) R6 and R7 can come together to form a ring selected from the group consisting ofwhere:
R20 is O or NH, and R21 is selected from the group consisting of H, C1-20 alkyl, C1-20 alkenyl, the carbon chain derived from a fatty acid, and C1-20 alkyl substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, fluoro, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the substituents are C1-5 alkyl, or C1-5 alkyl substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, fluoro, C3-10 cycloalkyl, or cycloalkyl, Base is selected from the group consisting of: X1 is CH or N, R9 is NHOH, NHO(CO)(C1-20)alkyl, or NHO(CO)NH(C1-20)alkyl, R10 is H, F or CH3 and X2 is H, F, Cl or NH2. |
