| 摘要 |
The present invention provides nucleoside phosphoramidate compounds of Formula I,;;where R1, R2a, R2b, R4, R5a, R5b, Rb5, Rb6 and D are as defined herein. The invention further includes pharmaceutical compositions comprising a compound of Formula I, methods of use of these compounds for treating a viral infection, and methods of producing these compounds. |
| 主权项 |
1. A compound represented by Formula I or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof: wherein: D is deuterium; R1 is selected from the group consisting of:
1) Hydrogen;2) R6; where R6 is selected from the group consisting of: hydrogen, hydroxy protecting group, —C(O)R7, —C(O)OR7, and —C(O)NR8aR8b; wherein R7 is selected from the group consisting of: substituted or unsubstituted —C1-C8 alkyl, substituted or unsubstituted —C2-C8 alkenyl, substituted or unsubstituted —C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclic; R8a and R8b are each independently selected from the group consisting of: hydrogen and R7; or alternatively R8a and R8b taken together with the nitrogen atom to which they are attached form a heterocyclic ring;3) —P(O)(OR7a)(OR7b); wherein R7a and R7b are each independently selected from the group consisting of a) hydrogen; and b) unsubstituted or substituted —C1-C8 alkyl;4) —P(O)(OR7a)—O—P(O)(OR7b)(OR7c); wherein R7a and R7b are previously defined; R7c is selected from the group consisting of a) hydrogen; and b) unsubstituted or substituted —C1-C8 alkyl;5) —P(O)(OR7a)—O—P(O)(OR7b)—O—P(O)(OR7c)(OR7d); wherein R7a, R7b and R7c are previously defined; R7d is selected from the group consisting of a) hydrogen; b) unsubstituted or substituted —C1-C8 alkyl; and6)where X is O or S; R9 is R7 wherein R7 is previously defined; R10, R11 and R12 are each independently selected from the group consisting of: a) hydrogen; b) unsubstituted or substituted —C1-C8 alkyl; c) R11 is hydrogen, R12 and R10 taken together with the intervening carbon and nitrogen atoms form a heterocyclic ring; d) R11 and R12 taken together with the carbon atom to which they are attached form a ring; and R13 is hydrogen or R7, wherein R7 is previously defined;
R2a is selected from the group consisting of:1) Hydrogen;2) Deuterium;3) Halogen;4) Nitrile;5) Substituted or unsubstituted —C1-C8 alkyl;6) Substituted or unsubstituted —C2-C8 alkenyl; and7) Substituted or unsubstituted —C2-C8 alkynyl; R2b is independently selected from the group consisting of:
1) Halogen; and2) OR9; R9 at each occurrence is selected from the group consisting of: hydrogen, hydroxy protecting group, R10b, —C(O)R10b, —C(O)OR10b, and —C(O)NR11aR11b; wherein R10b at each occurrence is independently selected from the group consisting of: substituted or unsubstituted —C1-C8 alkyl, substituted or unsubstituted —C2-C8 alkenyl, substituted or unsubstituted —C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclic; R11a and R11b at each occurrence are each independently selected from the group consisting of: hydrogen and R10b; or alternatively R11a and R11b taken together with the nitrogen atom to which they are attached form a heterocyclic ring; or R2a and R2b taken together with the carbon atom to which they are attached form a 3- to 6-membered cycloalkyl ring or a 3- to 6-membered heterrocycloalkyl ring containing one hereroatom selected from N, O, and S, each of which is optionally substituted; R4 is hydrogen, deuterium, N3, halogen or optionally substituted methyl; R5a and R5b are each independently selected from the group consisting of:
1) Hydrogen;2) Deuterium;3) Substituted or unsubstituted —C1-C8 alkyl;4) Substituted or unsubstituted —C2-C8 alkenyl; and5) Substituted or unsubstituted —C2-C8 alkynyl;or R5a and R5b are taken together with the carbon atom to which they are attached to form a group selected from —C3-C8 cycloalkyl, —C3-C8 cycloalkenyl, or —C3-C8 cycloalkynyl; and Rb5 and Rb6 are each independently selected from the group consisting of:
1) Hydrogen; and2) Deuterium. |
