主权项 |
1. A lipid nanoparticle composition comprising:
(a) an Akt inhibitor; (b) DSPC; (c) cholesterol; and (d) PEG-DMG; wherein the Akt inhibitor is a compound of Formula C, or a tautomer thereof, or a pharmaceutically acceptable salt of a compound of Formula C or its tautomer: wherein: a is 0 or 1; b is 0 or 1; m is 0, 1 or 2; p is 0, 1 or 2; R2 is independently selected from: (C1-C6)alkyl, (C1-C6)alkoxy, —CO2H, halo, —OH and —NH2; ring Y is (C4-C7)cycloalkyl; R1 is selected from: —H, oxo, (C═O)aOb(C1-C10)alkyl, (C═O)aOb-aryl, (C═O)aOb(C2-C10)alkenyl, (C═O)aOb(C2-C10)alkynyl, —CO2H, halo, —OH, —Ob(C1-C6)perfluoroalkyl, (C═O)aNR7R8, CN, (C═O)aOb(C3-C8)cycloalkyl, —S(O)mNR7R8, —SH, —S(O)m(C1-C10)alkyl and (C═O)aOb-heterocyclyl, said alkyl, aryl, alkenyl, alkynyl, cycloalkyl, and heterocyclyl is optionally substituted with one or more substituents selected from R6; R6 is: (C═O)aObC1-C10 alkyl, (C═O)aObaryl, C2-C10 alkenyl, C2-C10 alkynyl, (C═O)aOb heterocyclyl, CO2H, halo, —CN, —OH, —ObC1-C6 perfluoroalkyl, —Oa(C═O)bNR7R8, oxo, —CHO, —(N═O)R7R8, —S(O)mNR7R8, —SH, —S(O)m-(C1-C10)alkyl or (C═O)aObC3-C8 cycloalkyl, said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one or more substituents selected from R6a; R6a is selected from: (C═O)aOb(C1-C10)alkyl, —Oa(C1-C3)perfluoroalkyl, (C0-C6)alkylene-S(O)mRa, —SH, oxo, —OH, halo, —CN, (C2-C10)alkenyl, (C2-C10)alkynyl, (C3-C6)cycloalkyl, (C0-C6)alkylene-aryl, (C0-C6)alkylene-heterocyclyl, (C0-C6)alkylene-N(Rb)2, C(O)Ra, (C0-C6)alkylene-CO2Ra, C(O)H, and (C0-C6)alkylene-CO2H, said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heterocyclyl is optionally substituted with up to three substituents selected from Rb, OH, (C1-C6)alkoxy, halogen, CO2H, CN, Oa(C═O)b(C1-C6)alkyl, oxo, and N(Rb)2; R7 and R8 are independently selected from: —H, (C═O)aOb(C1-C10)alkyl, (C═O)aOb(C3-C8)cycloalkyl, (C═O)aOb-aryl, (C═O)aOb-heterocyclyl, (C2-C10)alkenyl, (C2-C10)alkynyl, —SH, —SO2Ra, and (C═O)aNRb2, said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R6a, or R7 and R8 can be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 3-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, said monocyclic or bicyclic heterocycle optionally substituted with one or more substituents selected from R6a; Ra is (C1-C6)alkyl, (C3-C6)cycloalkyl, aryl, or heterocyclyl; and Rb is independently: —H, (C1-C6)alkyl, aryl, heterocyclyl, (C3-C6)cycloalkyl, (C═O)aOb(C1-C6)alkyl, or —S(O)mRa. |