中文摘要：本发明公开了一种组合物，由以下成分及其盐类、异构体组成：Y 1，Y2，X 1，X 2，R 1，R 2，R3，R4，R5， R6，R8和R9。本发明同时提供了这种组合物的应用：可作为炎症、自免疫疾病、过敏、传染病、癌症、癌症潜伏期病症治疗的调节剂，也可以用作疫苗佐剂。
 
外文摘要：A compound of Formula (I) wherein Y 1, Y2, X 1, X 2, R 1, R 2, R3, R4, R5, R6, R8, and R9 are as defined herein; and pharmaceutically acceptable salts and tautomers thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, in the treatment of diseases in which modulation of STING (Stimulator of Interferon Genes) is beneficial, for example inflammation, allergic and autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes and as vaccine adjuvants.
NOVELTY - Substituted cyclic purine dinucleotide compounds (I) are new.
USE - (I) are useful as a vaccine adjuvant for treating a disease including inflammation, allergic diseases, autoimmune diseases, HIV, AIDS, infectious diseases, cancer, pre-cancerous syndromes, hepatitis B virus, hepatitis C virus, influenza, skin warts, multiple sclerosis or allergic inflammation in a mammal (i.e. human) (all claimed).
主权项：Substituted cyclic purine dinucleotide compounds (I) of formulae (I-a)-(I-f) and their salts and isomers are new.
Y1, Y2, Y11, Y12, Y21, Y22 = CH2 or O;
X1, X2 = S or O;
R1, R11, R21, R31, R41, R51 = OH (when R2, R12, R22, R32, R42, and R52 are NH2) or NH2 (when R2, R12, R22, R32, R42 and R52 are H);
R3, R13, R23, R33, R43, R53 = OH (when R4, R14, R24, R34, R44 and R54 are NH2) or NH2 (when R4, R14, R24, R34, R44 and R54 are H);
R5, R6 = F, OH or OC(O)R7;
R8, R9 = H, CH2OC(O)R7, CH2OCO2R7, C! H2CH2SC(O)R7 or CH2CH2SSCH2R7;
R7 = 1-20C alkyl (substituted with 1-5 aryl, cycloalkyl, hydroxy or F), aryl, heteroaryl, heterocycloalkyl or cycloalkyl;
X11, X22, X31, X42 = S;
X12, X21, X32, X41, X51, X52 = O;
R15, R16 = F, OH or OC(O)R17;
R18, R19 = H, CH2OC(O)R17, CH2OCO2R17, CH2CH2SC(O)R17 or CH2CH2SSCH2R17;
R17 = R7;
R25, R26 = F, OH or OC(O)R27;
R28, R29 = H, CH2OC(O)R27, CH2OCO2R27, CH2CH2SC(O)R27 or CH2CH2SSCH2R27;
R27 = R7;
R35, R36 = F, OH or OC(O)R37;
R38, R39 = H, CH2OC(O)R37, CH2OCO2R37, CH2CH2SC(O)R37 or CH2CH2SSCH2R37;
R37 = R7;
R45, R46 = F, OH or OC(O)R47;
R48, R49 = H, CH2OC(O)R47, CH2OCO2R47, CH2CH2SC(O)R47 or CH2CH2SSCH2R47;
R47 = R7;
R55 = F, OH or OC(O)R7;
R56 = F;
R58, R59 = H, CH2OC(O)R57, CH2OCO2R57, CH2CH2SC(O)R57 or CH2CH2SSCH2R57; and
R57 = R7.
Provided that: when neither R5 or R6 are F, at least one of Y1 and Y2 is CH2; when both X1 and X2 are O, at least one of R8 and R9 is not H; when neither R15 or R16 ! are F, at least one of Y11 and Y12 is CH2; when neither R25 or! R26 are F, at least one of Y21 and Y22 is CH2; at least one of R35 and R36 is F; at least one of R45 and R46 is F; and at least one of R58 and R59 is not H. INDEPENDENT CLAIMS are also included for:
(1) a combination comprising (I) and at least one further agent;
(2) vaccine composition or immugenic composition comprising (I), and an antigen or antigen composition; and
(3) composition comprising 0.5-1000 mg of (I), and 0.5-1000 mg of a excipient.
申请号：WO2016IB57265
公开/公告号：WO2017093933A1
申请日：2016-12-01
公开/公告日：2017-06-08
申请/专利权人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY (GLAX-C)
发明/设计人：ADAMS, J L;DUFFY, K J;LIAN, Y;ADAMS, J
分类号：A61K39/39; C07F9/65746; C07H21/00; C07H21/02; C07H21/04; A61K2039/55511
主分类号：A61K31/7084; A61P31/12; A61P35/00; C07H21/00
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