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1. 发明申请

WO2009073506A2 NUCLEOSIDE PRODRUGS AND USES THEREOF 审中-公开
标题翻译：核苷酸原料及其用途
公开(公告)号：WO2009073506A2
公开(公告)日：2009-06-11
申请号：PCT/US2008/084828
申请日：2008-11-26
申请人： METABASIS THERAPEUTICS INC. , HECKER, Scott J. , REDDY, K. Raja
发明人： HECKER, Scott J. , REDDY, K. Raja
CPC分类号： C07H19/10
摘要： This application provides compositions or compounds as disclosed herein that are suitable for treating hepatic viral diseases, such as hepatitis C (HCV).
摘要翻译：本申请提供了本文公开的适用于治疗肝病毒疾病如丙型肝炎（HCV）的组合物或化合物。

2. 发明申请

WO2009069095A2 ANTIVIRAL NUCLEOSIDE COMPOUNDS 审中-公开
标题翻译：杀虫剂核苷酸化合物
公开(公告)号：WO2009069095A2
公开(公告)日：2009-06-04
申请号：PCT/IB2008/054985
申请日：2008-11-27
申请人： METABASIS THERAPEUTICS, INC. , BOOKSER, Brett C. , HECKER, Scott J. , REDDY, K. Raja , SMITH, David Bernard , SUN, Zhili
发明人： BOOKSER, Brett C. , HECKER, Scott J. , REDDY, K. Raja , SMITH, David Bernard , SUN, Zhili
CPC分类号： C07H19/10 , C07H19/20
摘要： Compounds having the formula I or II wherein R 1 , R 2 , B, and V are as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.
摘要翻译：具有式I或II的化合物，其中R 1，R 2，B和V如本文所定义，是丙型肝炎病毒NS5b聚合酶抑制剂。还公开了用于治疗HCV感染和抑制HCV复制的组合物和方法。

3. 发明申请

WO2003095665A3 PMEA AND PMPA CYCLIC PRODUCING SYNTHESIS 审中-公开
公开(公告)号：WO2003095665A3
公开(公告)日：2003-11-20
申请号：PCT/US2003/014822
申请日：2003-05-12
申请人： METABASIS THERAPEUTICS, INC. , KOPCHO, Joseph J. , REDDY, K. Raja , MATELICH, Michael C. , UGARKAR, Bheemarao G.
发明人： KOPCHO, Joseph J. , REDDY, K. Raja , MATELICH, Michael C. , UGARKAR, Bheemarao G.
IPC分类号： C07F9/6574
摘要： The method of preparing compounds of Formula I is described: Formula Iwherein:M and V are cis to one another and MPO3H2 is a phosphonic acid selected from the group consisting of 9-(2-phosphonylmethoxyethyl)adenine, and (R)-9-(2-phosphonylmethoxypropyl)adenine; wherein V is phenyl, optionally substituted with 1-2 substituents selected from a group consisting of fluoro, chloro, and bromo; comprising:coupling a chiral 1-phenylpropane-1,3-diol, wherein the phenyl may be optionally substituted, with MPOCl2 or an N-6 substituted analogue thereof.Additionally, methods and salt forms are described that enable isolation and purification of the desired isomer.

4. 发明申请

WO2004037161A2 NOVEL PHOSPHONIC ACID BASED PRODRUGS OF PMEA AND ITS ANALOGUES 审中-公开
标题翻译：新型磷酸酯基PMEA及其类似物的研究进展
公开(公告)号：WO2004037161A2
公开(公告)日：2004-05-06
申请号：PCT/US2003/014821
申请日：2003-05-12
申请人： METABASIS THERAPEUTICS, INC. , REDDY, K. Raja , ERION, Mark D. , MATELICH, Michael C. , KOPCHO, Joseph J.
发明人： REDDY, K. Raja , ERION, Mark D. , MATELICH, Michael C. , KOPCHO, Joseph J.
IPC分类号： A61K
CPC分类号： C07F9/65742 , C07F9/65616
摘要： Prodrugs of Formula I, their uses, their intermediates, and their method of manufacture are described: Formula 1wherein:M and V are cis to one another and MPO3H2 is a phosphonic acid selected from the group consisting of 9-(2-phosphonylmethoxyethyl)adenine, (R)-9-(2-phosphonylmethoxy propyl)adenine, 9-(2-phosphonylmethoxyethyl)guanine, 9-(2-phosphonylmethoxy ethyloxy)adenine, 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, 9-(3-hydroxy-2-phosphonylmethoxypropyl)guanine, and (S)-9-(3-fluoro-2-phosphonyl methoxypropyl)adenine;V is selected from a group consisting of phenyl, 2-pyridyl , 3-pyridyl, 4-pyridyl, 2-furanyl, 3-furanyl, 2-thienyl, and 3-thienyl, all optionally substituted with 1-3 substituents selected from a group consisting of F, Cl, Br, C1-C3 alkyl, CF3 and OR6;R6 is selected from the group consisting of C1-C3 alkyl, and CF3;and pharmaceutically acceptable salts thereof.
摘要翻译：描述了式I的前药，其用途，其中间体及其制备方法：式1其中M和V彼此是顺式的，MPO3H2是选自9-（2-膦酰基甲氧基乙基）腺嘌呤，（R）-9-（2-膦酰基甲氧基丙基）腺嘌呤，9-（2-膦酰基甲氧基乙基）鸟嘌呤，9-（2-膦酰基甲氧基乙氧基）腺嘌呤，9-（2-膦酰基甲氧基乙基）-2,6-二氨基嘌呤，（S ） - （3-羟基-2-膦酰基甲氧基丙基）胞嘧啶，（S）-9-（3-羟基-2-膦酰基甲氧基丙基）腺嘌呤，9-（3-羟基-2-膦酰基甲氧基丙基）鸟嘌呤和（S） - 9-（3-氟-2-膦酰基甲氧基丙基）腺嘌呤; V选自苯基，2-吡啶基，3-吡啶基，4-吡啶基，2-呋喃基，3-呋喃基，2-噻吩基和3 噻吩基，全部任选被1-3个选自F，Cl，Br，C 1 -C 3烷基，CF 3和OR 6的取代基取代; R 6选自C 1 -C 3烷基和CF 3;和药学上其可接受的盐。

5. 发明申请

WO2003095665A2 PROCESS FOR PREPARATION OF CYCLIC PRODRUGS OF PMEA AND PMPA 审中-公开
标题翻译：制备PMEA和PMPA循环产物的方法
公开(公告)号：WO2003095665A2
公开(公告)日：2003-11-20
申请号：PCT/US2003/014822
申请日：2003-05-12
申请人： METABASIS THERAPEUTICS, INC. , KOPCHO, Joseph J. , REDDY, K. Raja , MATELICH, Michael C. , UGARKAR, Bheemarao G.
发明人： KOPCHO, Joseph J. , REDDY, K. Raja , MATELICH, Michael C. , UGARKAR, Bheemarao G.
IPC分类号： C12Q
CPC分类号： C07F9/657181
摘要： The method of preparing compounds of Formula I is described: Formula Iwherein:M and V are cis to one another and MPO3H2 is a phosphonic acid selected from the group consisting of 9-(2-phosphonylmethoxyethyl)adenine, and (R)-9-(2-phosphonylmethoxypropyl)adenine; wherein V is phenyl, optionally substituted with 1-2 substituents selected from a group consisting of fluoro, chloro, and bromo; comprising:coupling a chiral 1-phenylpropane-1,3-diol, wherein the phenyl may be optionally substituted, with MPOCl2 or an N-6 substituted analogue thereof.Additionally, methods and salt forms are described that enable isolation and purification of the desired isomer.
摘要翻译：描述了制备式I化合物的方法：式I其中M和V彼此是顺式的，MPO3H2是选自9-（2-膦酰基甲氧基乙基）腺嘌呤和（R）-9- （2-膦酰基）腺嘌呤; 其中V是苯基，任选被1-2个选自氟，氯和溴的取代基取代; 包括：将手性1-苯基丙烷-1,3-二醇（其中苯基可以被任选取代）与MPOCl 2或其N-6取代的类似物偶联。此外，描述了能够分离和纯化所需的方法和盐形式的方法和盐形式异构体。

6. 发明公开

EP3366686A3 INHIBITORS OF DIACYLGLYCEROL O-ACYLTRANSFERASE 1 (DGAT-1) AND USES THEREOF 有权
公开(公告)号：EP3366686A3
公开(公告)日：2018-10-24
申请号：EP18150958.9
申请日：2010-03-19
申请人： Metabasis Therapeutics, Inc.
发明人： REDDY, K. Raja , STEBBINS, Jeff , BOYER, Serge, H. , ERION, Mark, D. , HECKER, Scott, J. , RAFFAELE, Nicholas, Brian , BOOKSER, Brett, C. , REDDY, Mali, Venkat
IPC分类号： C07D473/16 , C07D473/34 , C07D473/40 , C07F9/30 , C07F9/32 , C07F9/653 , C07F9/6561 , C07F9/6574 , A61K31/52 , A61K31/662 , A61K31/665 , A61K31/675 , A61P3/10 , A61P3/04 , A61K45/06
摘要： The invention pertains to use of DGAT-1 inhibitors to treat and/or prevent overweight, obesity and various diseases and disorders associated therewith. Other conditions also can be ameliorated or avoided, such as high postprandial triglycerides or diet-related hypertriglyceridemia, cardiovascular risk associated with excessive triglycerides, and insulin resistance/glucose intolerance in overweight patients, those with diabetes or other glucose metabolic disorders such as Syndrome X and/or polycystic ovary disease. Compounds and compositions suitable for use in the disclosed methods are also provided. The DGAT-1 inhibiting composition comprises a DGAT-1 inhibitor, the DGAT-1 inhibitor including a compound of Formula (I), pharmaceutically acceptable salts or stereoisomers thereof,

wherein Q is:

and
Z is Z 1 ; and
Z 1 is

7. 发明授权

EP1504014B1 PROCESS FOR PREPARATION OF CYCLIC PRODRUGS OF PMEA AND PMPA 失效转让
标题翻译：用于生产PMEA和PMPA的前体药物循环
公开(公告)号：EP1504014B1
公开(公告)日：2015-12-02
申请号：EP03724549.5
申请日：2003-05-12
申请人： Metabasis Therapeutics, Inc.
发明人： KOPCHO, Joseph J. , REDDY, K. Raja , MATELICH, Michael C. , UGARKAR, Bheemarao G.
IPC分类号： C07F9/6574
CPC分类号： C07F9/657181

9. 发明公开

EP3366686A2 INHIBITORS OF DIACYLGLYCEROL O-ACYLTRANSFERASE 1 (DGAT-1) AND USES THEREOF 有权
公开(公告)号：EP3366686A2
公开(公告)日：2018-08-29
申请号：EP18150958.9
申请日：2010-03-19
申请人： Metabasis Therapeutics, Inc.
发明人： REDDY, K. Raja , STEBBINS, Jeff , BOYER, Serge, H. , ERION, Mark, D. , HECKER, Scott, J. , RAFFAELE, Nicholas, Brian , BOOKSER, Brett, C. , REDDY, Mali, Venkat
IPC分类号： C07D473/16 , C07D473/34 , C07D473/40 , C07F9/30 , C07F9/32 , C07F9/653 , C07F9/6561 , C07F9/6574 , A61K31/52 , A61K31/662 , A61K31/665 , A61K31/675 , A61P3/10 , A61P3/04 , A61K45/06
摘要： The invention pertains to use of DGAT-1 inhibitors to treat and/or prevent overweight, obesity and various diseases and disorders associated therewith. Other conditions also can be ameliorated or avoided, such as high postprandial triglycerides or diet-related hypertriglyceridemia, cardiovascular risk associated with excessive triglycerides, and insulin resistance/glucose intolerance in overweight patients, those with diabetes or other glucose metabolic disorders such as Syndrome X and/or polycystic ovary disease. Compounds and compositions suitable for use in the disclosed methods are also provided. The DGAT-1 inhibiting composition comprises a DGAT-1 inhibitor, the DGAT-1 inhibitor including a compound of Formula (I), pharmaceutically acceptable salts or stereoisomers thereof,

wherein Q is:

and
Z is Z 1 ; and
Z 1 is

10. 发明公开

EP1504014A2 PROCESS FOR PREPARATION OF CYCLIC PRODRUGS OF PMEA AND PMPA 失效转让
标题翻译：用于生产PMEA和PMPA的前体药物循环
公开(公告)号：EP1504014A2
公开(公告)日：2005-02-09
申请号：EP03724549.5
申请日：2003-05-12
申请人： Metabasis Therapeutics, Inc.
发明人： KOPCHO, Joseph J. , REDDY, K. Raja , MATELICH, Michael C. , UGARKAR, Bheemarao G.
IPC分类号： C07F9/6574
CPC分类号： C07F9/657181
摘要： The method of preparing compounds of Formula I is described: Formula Iwherein:M and V are cis to one another and MPO3H2 is a phosphonic acid selected from the group consisting of 9-(2-phosphonylmethoxyethyl)adenine, and (R)-9-(2-phosphonylmethoxypropyl)adenine; wherein V is phenyl, optionally substituted with 1-2 substituents selected from a group consisting of fluoro, chloro, and bromo; comprising:coupling a chiral 1-phenylpropane-1,3-diol, wherein the phenyl may be optionally substituted, with MPOCl2 or an N-6 substituted analogue thereof.Additionally, methods and salt forms are described that enable isolation and purification of the desired isomer.

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