发明名称 Liposomal Formulations for Allosteric AKT Inhibitors
摘要 Disclosed herein is a lipid nanoparticle (LNP) composition comprising (a) an Akt inhibitor; (b) DSPC; (c) cholesterol; and (d) PEG-DMG. Also disclosed herein is a method for preparing the lipid composition using a scalable tangential flow micro-mixing technology.
申请公布号 US2016317444(A1) 申请公布日期 2016.11.03
申请号 US201415103911 申请日期 2014.12.12
申请人 SMITH Michael Hughes;GINDY Marian;MERCK SHARP & DOHME CORP. 发明人 Smith Michael Hughes;Gindy Marian
分类号 A61K9/127;A61K31/4375;A61K9/00 主分类号 A61K9/127
代理机构 代理人
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.
地址 Waltham MA US