公开(公告)号：US20190185508A1

公开(公告)日：2019-06-20

申请号：US16212163

申请日：2018-12-06

Applicant: Merck Sharp & Dohme Corp. ,  Idenix Pharmaceuticals LLC

Inventor： Francois-Rene Alexandre ,  Izzat Raheem

IPC: C07H19/23 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/7064 ,  C07H19/16 ,  A61P31/18

CPC classification number: C07H19/23 ,  A61K31/7064 ,  A61K31/7072 ,  A61K31/7076 ,  A61P31/18 ,  C07H19/16

Abstract: The present invention is directed to deuterated 4′-substituted nucleoside derivatives of Formula I and their use in the inhibition of HIV reverse transcriptase, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS and/or ARC.

公开(公告)号：US20170088577A1

公开(公告)日：2017-03-30

申请号：US15379415

申请日：2016-12-14

Applicant: Idenix Pharmaceuticals LLC ,  Universita degli Studi di Cagliari ,  Centre National De La Recherche Scientifique ,  Universite de Montpellier

Inventor： Richard STORER ,  Gilles GOSSELIN ,  Jean-Pierre SOMMADOSSI ,  Paolo LACOLLA

IPC: C07H19/16 ,  A61K38/21 ,  A61K9/20 ,  A61K9/48 ,  C07H19/056 ,  A61K31/7068 ,  A61K31/7076 ,  A61K31/7072 ,  A61K31/7056 ,  A61K31/708 ,  A61K45/06 ,  C07H19/06

CPC classification number: C07H19/16 ,  A61K9/20 ,  A61K9/48 ,  A61K31/675 ,  A61K31/7056 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/708 ,  A61K38/21 ,  A61K38/212 ,  A61K45/06 ,  A61K47/60 ,  C07H19/00 ,  C07H19/04 ,  C07H19/048 ,  C07H19/056 ,  C07H19/06 ,  C07H19/22 ,  A61K2300/00

Abstract: 2′ and/or 3′ prodrugs of 1′, 2′, 3′ or 4′-branchednucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions.

公开(公告)号：US20170066779A1

公开(公告)日：2017-03-09

申请号：US15123170

申请日：2015-03-04

Applicant: IDENIX Pharmaceuticals LLC

Inventor： Adel M. Moussa ,  Benjamin Alexander Mayes ,  Alistair James Stewart

IPC: C07D495/04 ,  A61K31/4184 ,  A61K45/06

CPC classification number: C07D495/04 ,  A61K31/4184 ,  A61K45/06 ,  C07B2200/13

Abstract: Provided herein are crystalline and salt forms of methyl N-{(1R)-2-[(2S)-2-{5-[4-(6-{2-[(2S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl} pyrrolidin-2-yl]-3H-benzimidazol-5-yl}thieno[3,2-b]thiophen-3-yl)phenyl]-1H-imidazol-2-yl}pyrrolidin-1-yl]-2-oxo-1-phenylethyl} carbamate, a Flaviviridae, including hepatitis C, virus inhibitor, pharmaceutical compositions comprising the compound, and processes of preparation thereof. Also provided are methods of its use for the treatment of a Flaviviridae, including HCV, infection in a subject in need thereof.

Abstract translation: 本文提供的是N - {（1R）-2 - [（2S）-2- {5- [4-（6- {2 - [（2S）-1 - {（2S）-2 - [（甲氧基羰基）氨基] -3-甲基丁酰基}吡咯烷-2-基] -3H-苯并咪唑-5-基}噻吩并[3,2-b]噻吩-3-基）苯基〕-1H-咪唑-2-基） 吡咯烷-1-基] -2-氧代-1-苯基乙基}氨基甲酸酯，黄病毒科，包括丙型肝炎病毒抑制剂，包含该化合物的药物组合物及其制备方法。 还提供了其用于治疗有需要的受试者中的黄病毒科（包括HCV）感染的方法。

公开(公告)号：US20170044205A1

公开(公告)日：2017-02-16

申请号：US15304506

申请日：2015-04-16

Applicant: IDENIX PHARMACEUTICALS LLC

Inventor： David DUKHAN ,  Cyril B. DOUSSON ,  Gilles GOSSELIN ,  Jean-Laurent PAPARIN ,  Guillaume BRANDT ,  Rachid RAHALI ,  Aurelien SALANSON ,  François-René ALEXANDRE

IPC: C07H19/20 ,  A61K31/7068 ,  C07H19/10 ,  A61K31/7072 ,  A61K45/06 ,  A61K31/7076

CPC classification number: C07H19/20 ,  A61K31/7052 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/708 ,  A61K45/06 ,  C07H19/10 ,  C07H19/11

Abstract: Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 3′-substituted methyl or alkynyl nucleosides of Formula I: (I); or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein Base, PD, RA, RB1, RB2, RC and Z are as defined herein.

Abstract translation: 本文提供了用于治疗黄病毒科感染（包括HCV感染）的化合物，组合物和方法。 在某些实施方案中，公开了核苷衍生物的化合物和组合物，其可以单独施用或与其它抗病毒剂组合施用。 在某些实施方案中，化合物是式I的3'-取代的甲基或炔基核苷：（I）; 或其药学上可接受的盐，溶剂化物，立体异构形式，互变异构形式或其多晶型形式，其中碱，PD，RA，RB1，RB2，RC和Z如本文所定义。

公开(公告)号：US20170029456A1

公开(公告)日：2017-02-02

申请号：US15039176

申请日：2014-11-25

Applicant: IDENIX PHARMACEUTICALS LLC

Inventor： Cyril B. Dousson ,  David Dukhan ,  Christophe Claude Parsy

IPC: C07H19/207 ,  C07H19/10

CPC classification number: C07H19/207 ,  A61K31/7052 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/708 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20

Abstract: Provided herein are compounds, compositions and methods for the treatment of liver cancer such as hepatocellular carcinoma, cholangiocarcinoma, or biliary tract cancer. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-cancer agents. In certain embodiments, the compounds are nucleoside analogs of Formula I: (I); or a pharmaceutically acceptable salt thereof, wherein Base, Z1, Z2, Z3, Z4, V, W, X, Ar, R1 and R2 are as described herein.

Abstract translation: 本文提供了用于治疗肝癌如肝细胞癌，胆管癌或胆道癌的化合物，组合物和方法。 在某些实施方案中，公开了核苷衍生物的化合物和组合物，其可以单独施用或与其它抗癌剂组合施用。 在某些实施方案中，化合物是式I的核苷类似物：（I）; 或其药学上可接受的盐，其中基团，Z 1，Z 2，Z 3，Z 4，V，W，X，Ar，R 1和R 2如本文所述。

公开(公告)号：US20160271162A1

公开(公告)日：2016-09-22

申请号：US15033725

申请日：2014-10-30

Applicant: IDENIX PHARMACEUTICALS, LLC

Inventor： Adel M. Moussa ,  Benjamin Alexander Mayes ,  Alistair James Stewart

IPC: A61K31/7076 ,  A61K45/06 ,  A61K9/00 ,  C07H19/207

CPC classification number: A61K31/7076 ,  A61K9/0053 ,  A61K45/06 ,  C07H19/207

Abstract: Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are D-alanine phosphoramidate pronucleotides of 2′-methyl 2′-fluoro guanosine nucleoside which display remarkable efficacy and bioavailability for the treatment of for example, HCV infection in a human. In certain embodiments, the compounds are of Formula I or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof; where W and R are as described herein.

公开(公告)号：US20160166597A1

公开(公告)日：2016-06-16

申请号：US14972009

申请日：2015-12-16

Applicant: Idenix Pharmaceuticals, LLC ,  Universita Degli Studi Di Cagliari

Inventor： Jean-Pierre SOMMADOSSI ,  Paolo LACOLLA ,  David N. STANDRING ,  Vadim BICHKO ,  Lin QU

IPC: A61K31/7072 ,  C12Q1/70 ,  C12Q1/18 ,  A61K38/21

Abstract: The present invention discloses a method for the treatment of Flaviviridae infection that includes the administration of a 2′-branched nucleoside, or a pharmaceutically acceptable prodrug and/or salt thereof, to a human in need of therapy in combination or alternation with a drug that directly or indirectly induces a mutation in the viral genome at a location other than a mutation of a nucleotide that results in a change from serine to a different amino acid in the highly conserved consensus sequence, XRXSGXXXT (SEQ ID NO: 63), of domain B of the RNA polymerase region, or is associated with such a mutation. The invention also includes a method to detect a mutant strain of Flaviviridae and a method for its treatment.

Abstract translation: 本发明公开了一种治疗黄病毒科感染的方法，其包括将2支支链核苷或其药学上可接受的前药和/或盐给予需要与药物组合或替代的药物， 在高度保守的共有序列（XRXSGXXXT（SEQ ID NO：63））中，在导致从丝氨酸到不同氨基酸的变化的核苷酸突变以外的位置直接或间接诱导病毒基因组中的突变 B的RNA聚合酶区域，或与这样的突变有关。 本发明还包括检测黄病毒科突变菌株的方法及其治疗方法。

公开(公告)号：US20160002281A1

公开(公告)日：2016-01-07

申请号：US14856462

申请日：2015-09-16

Applicant: Idenix Pharmaceuticals LLC

Inventor： Benjamin Alexander MAYES ,  Adel M. MOUSSA ,  Alistair James STEWART ,  Gilles GOSSELIN ,  Christophe Claude PARSY ,  François-René ALEXANDRE ,  Jean-François GRIFFON ,  Dominique SURLERAUX ,  Cyril B. DOUSSON ,  Claire PIERRA ,  Houcine RAHALI

IPC: C07H19/20 ,  C07H19/10

CPC classification number: C07H19/20 ,  A61K31/403 ,  A61K31/4709 ,  A61K31/497 ,  A61K31/7056 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/708 ,  A61K38/21 ,  A61K38/55 ,  A61K45/06 ,  C07H19/10 ,  C07H19/16 ,  A61K2300/00

Abstract: Provided herein are compounds, compositions and methods for the treatment of liver disease and conditions, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

公开(公告)号：US20210024565A1

公开(公告)日：2021-01-28

申请号：US17061409

申请日：2020-10-01

Applicant: Idenix Pharmaceuticals LLC ,  Universita degli Studi di Cagliari ,  Centre National De La Recherche Scientifique ,  Universite de Montpellier

Inventor： Richard Storer ,  Gilles Gosselin ,  Jean-Pierre Sommadossi ,  Paolo La Colla

IPC: C07H19/16 ,  A61K47/60 ,  A61K31/675 ,  A61K31/7072 ,  A61K31/7076 ,  A61K38/21 ,  A61K45/06 ,  C07H19/00 ,  C07H19/04 ,  C07H19/048 ,  C07H19/22 ,  A61K31/7068 ,  A61K31/708 ,  C07H19/056 ,  C07H19/06 ,  A61K31/7056 ,  A61K9/20 ,  A61K9/48

Abstract: 2′ and/or 3′ prodrugs of 1′, 2′, 3′ or 4′-branched nucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions.

公开(公告)号：US10899788B2

公开(公告)日：2021-01-26

申请号：US16311363

申请日：2017-06-20

Applicant: Stephane Bogen ,  David Dukhan ,  Guillaume Brandt ,  Claire Pierra Rouviere ,  Cyril B. Dousson ,  Francois-Rene Alexandre ,  MERCK SHARP & DOHME CORP. ,  IDENIX PHARMACEUTICALS LLC

Inventor： Stephane Bogen ,  David Dukhan ,  Guillaume Brandt ,  Claire Pierra Rouviere ,  Cyril B. Dousson ,  Francois-Rene Alexandre

IPC: C07H19/11 ,  A61P31/14 ,  C07H19/213 ,  A61K45/06 ,  A61K31/7072 ,  A61K31/7076

Abstract: The present invention relates to Cyclic Phosphate Substituted Nucleoside Compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein in A, B, R1, R2, R3, Q and V are as defined herein. The present invention also relates to compositions comprising a Cyclic Phosphate Substituted Nucleoside Compound, and methods of using the Cyclic Phosphate Substituted Nucleoside Compounds for treating or preventing HCV infection in a patient.