公开(公告)号：WO2016198948A1

公开(公告)日：2016-12-15

申请号：PCT/IB2016/000874

申请日：2016-06-08

Applicant: NEWSOUTH INNOVATIONS PTY LIMITED ,  METRO BIOTECH, LLC

Inventor： WU, Lindsay ,  SINCLAIR, David, A. ,  MEETZE, Kyle

IPC: C12N9/12 ,  C07H19/00 ,  C12P19/30 ,  C12N11/18 ,  C12N11/00

CPC classification number: C12P19/30 ,  C07H19/048 ,  C12N9/12 ,  C12N9/1235 ,  C12N11/10 ,  C12N11/18 ,  C12P19/02 ,  C12Y207/06001

Abstract: Enzyme-based systems and methods for synthesizing the NAD precursors NMN and NaMN are disclosed. Such methods and systems utilize a mutated form of phosphoribosylpyrophosphate synthetase (PRS) that is superactive and/or other enzyme or enzyme combinations that are immobilized onto a solid surface. The methods and systems substantially increase the efficiency and yield of NAD precursor synthesis.

Abstract translation: 公开了用于合成NAD前体NMN和NaMN的基于酶的体系和方法。 这样的方法和系统利用突变形式的磷酸核糖焦磷酸合成酶（PRS），其是超活性的和/或固定在固体表面上的其它酶或酶组合。 所述方法和系统显着提高NAD前体合成的效率和产率。

公开(公告)号：WO2016196941A1

公开(公告)日：2016-12-08

申请号：PCT/US2016/035729

申请日：2016-06-03

Applicant: CHROMADEX, INC. ,  THE QUEEN'S UNIVERSITY OF BELFAST

Inventor： MIGAUD, Marie Eugenie ,  REDPATH, Philip ,  CROSSEY, Kerri ,  CUNNINGHAM, Richard ,  RHONEMUS, Troy ,  VENKATARAMAN, Sylesh

IPC: A01N43/40 ,  A61K31/44

CPC classification number: C07H19/048 ,  C07F9/582 ,  C07F9/65583 ,  C07F9/65616 ,  C07H1/04 ,  C07H19/04 ,  C07H19/20

Abstract: A synthetic process is provided for the preparation of phosphorylated analogs of nicotinamide riboside ("NR") having the formula (I), or salts thereof, and reduced or modified derivatives thereof, having the formula (II), wherein X - , Y 1 , Y 2 , Z 1 , Z 2 , n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as defined herein. The present disclosure also relates to the preparation of phosphorylated analogs of nicotinic acid riboside ("NAR") having the formula (I), or salts thereof, and reduced or modified derivatives thereof, having the formula (II). Generally solvent-free conditions are employed using appropriate mechano-chemical techniques as described. (I) (II)

Abstract translation: 提供了一种合成方法，用于制备具有式（I）的烟酰胺核苷（“NR”）或其盐以及具有式（II）的还原或修饰的衍生物的磷酸化类似物，其中X，Y 1， Y2，Z1，Z2，n，R1，R2，R3，R4，R5，R6和R7如本文所定义。 本公开还涉及具有式（I）的烟酸核糖苷（“NAR”）的磷酸化类似物或其盐以及具有式（II）的还原或修饰的衍生物的制备。 一般使用无溶剂条件，使用所述的适当的机械化学技术。 （一）（二）

公开(公告)号：WO2016149395A1

公开(公告)日：2016-09-22

申请号：PCT/US2016/022682

申请日：2016-03-16

Applicant: CHROMADEX INC. ,  THE QUEEN'S UNIVERSITY OF BELFAST

Inventor： DELLINGER, Ryan ,  MIGAUD, Marie, Eugenie ,  REDPATH, Philip ,  RHONEMUS, Troy ,  CUNNINGHAM, Richard

IPC: C07H19/048 ,  A61K31/706

CPC classification number: C07H19/048 ,  A61K8/675 ,  A61Q19/00 ,  A61Q19/004 ,  A61Q19/007 ,  A61Q19/08

Abstract: Derivatives of nicotinic acid riboside (NAR), nicotinamide riboside (NR), and reduced NAR and NR, including 1-(2', 3', 5'-triacetyl-beta-D-ribofuranosyl)-1,4-dihydronicotinic acid (4a), and compositions containing the same and/or reduced derivative forms of nicotinamide riboside including 1-(2',3',5'-triacetyl-beta-D-ribofuranosyl)-1,4-nicotinamide (2), are provided for use in the care of treatment of skin and skin conditions. In some embodiments, the invention relates to pharmaceutical compositions and cosmetic compositions containing one or more NR, NAR, NRH, or NARH derivatives, or prodrugs or salts thereof. In further embodiments, the invention relates to methods of using one or more NR, NAR, NRH, or NARH derivatives, or prodrugs, solvates, or salts thereof, to promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival and overall cell and tissue health.

Abstract translation: 烟碱苷（NAR）衍生物，烟酰胺核苷（NR）和还原的NAR和NR，包括1-（2'，3'，5'-三乙酰基-β-D-呋喃核糖基）-1,4-二氢烟酸 提供了含有相同和/或还原的衍生物形式的包括1-（2'，3'，5'-三乙酰基-β-D-呋喃核糖基）-1,4-烟酰胺（2）的烟酰胺核苷的组合物 用于护理皮肤和皮肤状况的治疗。 在一些实施方案中，本发明涉及含有一种或多种NR，NAR，NRH或NARH衍生物或其前药或盐的药物组合物和化妆品组合物。 在进一步的实施方案中，本发明涉及使用一种或多种NR，NAR，NRH或NARH衍生物或其前药，溶剂合物或其盐来促进细胞中烟酰胺腺嘌呤二核苷酸（NAD +）的细胞内水平的增加的方法，以及 用于改善细胞和组织存活的组织以及整个细胞和组织的健康。

公开(公告)号：WO2011155855A1

公开(公告)日：2011-12-15

申请号：PCT/PL2011/000055

申请日：2011-06-01

Applicant: INSTYTUT CHEMII BIOORGANICZNEJ POLSKIEJ AKADEMII NAUK ,  CHMIELEWSKI, Marcin, Krzysztof

Inventor： CHMIELEWSKI, Marcin, Krzysztof

IPC: C07D213/74

CPC classification number: C07H19/048 ,  C07D213/74

Abstract: The subject of the invention is a new way of using thermolabile groups to protect a hydroxyl function, above all in nucleosides, nucleotides, oligomers, nucleic acids during the reactions of organic synthesis. The invention also covers new compounds that can be used to implement the procedure New compounds of general formula 1. New compounds of general formula 3. The way of using thermolabile groups to protect hydroxyl functions consists in a primary, secondary and tertiary hydroxyl group converting into a group of general formula 3 during the reaction between a compound of general formula 1 and a compound whose hydroxyl group is to be blocked. The blocking reaction is carried out by means of widely known methods appropriate for that purpose in the presence of a chemically basic catalyst. The obtained product has its hydroxyl group blocked. Then the compound with the group blocked can be used for the purposes of various chemical processes. After their completion, the hydroxyl group is unblocked by dissolving it in a solvent at a temperature of 50-95°C.

Abstract translation: 本发明的主题是在有机合成反应期间使用热不稳定基团来保护羟基官能团，尤其是在核苷，核苷酸，寡聚物，核酸中的新方法。 本发明还涵盖了可用于实施方法的新化合物。通式1的新化合物。通式3的新化合物。使用热不稳定基团保护羟基官能团的方式在于将伯，仲和叔羟基转化为 在通式1的化合物与其羟基被封闭的化合物反应期间通式3的基团。 通过在化学碱性催化剂存在下适用于该目的的广泛已知的方法进行封端反应。 所得产物的羟基被封闭。 那么具有封闭基团的化合物可以用于各种化学过程的目的。 完成后，通过在50-95℃的温度下将其溶解在溶剂中来解封羟基。

公开(公告)号：WO2011003018A3

公开(公告)日：2011-05-19

申请号：PCT/US2010040816

申请日：2010-07-01

Applicant: UNIV CORNELL ,  SAUVE ANTHONY A ,  CEN YANA

Inventor： SAUVE ANTHONY A ,  CEN YANA

IPC: C07H19/04 ,  A61K31/706 ,  A61P31/12 ,  A61P37/00 ,  C07H5/02

CPC classification number: C07H23/00 ,  C07H19/048 ,  C07H19/056 ,  C07H19/06 ,  C07H19/073 ,  C07H19/12 ,  C07H19/16 ,  C07H19/173 ,  C07H19/19

Abstract: Disclosed are halogenated 2-deoxy-lactone, 2'-deoxy-nucleosides, and derivatives thereof, for example, a compound of formula (I). Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one compound or salt of the invention, and a method of treating a disorder is selected from the group consisting of an abnormal cellular proliferation, a viral infection, and an autoimmune disorder.

Abstract translation: 公开了卤化2-脱氧内酯，2'-脱氧核苷及其衍生物，例如式（I）化合物。 还公开了包含药学上可接受的载体和至少一种本发明的化合物或盐的组合物，并且治疗病症的方法选自异常细胞增殖，病毒感染和自身免疫病症。

公开(公告)号：WO2011003018A2

公开(公告)日：2011-01-06

申请号：PCT/US2010/040816

申请日：2010-07-01

Applicant: CORNELL UNIVERSITY ,  SAUVE, Anthony, A. ,  CEN, Yana

Inventor： SAUVE, Anthony, A. ,  CEN, Yana

IPC: C07H19/04 ,  C07H5/02 ,  A61K31/706 ,  A61P37/00 ,  A61P31/12

CPC classification number: C07H23/00 ,  C07H19/048 ,  C07H19/056 ,  C07H19/06 ,  C07H19/073 ,  C07H19/12 ,  C07H19/16 ,  C07H19/173 ,  C07H19/19

Abstract: Disclosed are halogenated 2-deoxy-lactone, 2'-deoxy-nucleosides, and derivatives thereof, for example, a compound of formula (I). Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one compound or salt of the invention, and a method of treating a disorder is selected from the group consisting of an abnormal cellular proliferation, a viral infection, and an autoimmune disorder.

Abstract translation: 公开了卤化的2-脱氧内酯，2'-脱氧核苷及其衍生物，例如式（I）的化合物。 还公开了包含药学上可接受的载体和本发明的至少一种化合物或盐的组合物，治疗病症的方法选自异常细胞增殖，病毒感染和自身免疫性疾病。

公开(公告)号：WO2007061798A3

公开(公告)日：2007-07-12

申请号：PCT/US2006044580

申请日：2006-11-17

Applicant: CORNELL RES FOUNDATION INC ,  SAUVE ANTHONY ANDREW ,  YANG TIANLE

Inventor： SAUVE ANTHONY ANDREW ,  YANG TIANLE

IPC: A01N37/10 ,  A61K31/235

CPC classification number: A61K31/706 ,  A61K31/351 ,  A61K45/06 ,  C07H19/048

Abstract: The invention relates to compositions of nicotinoyl ribosides and nicotinamide riboside derivatives and their methods of use. In some embodiments, the invention relates to methods of making nicotinoyl ribosides. In some embodiments, the invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinoyl riboside. In further embodiments, the invention relates to methods of using nicotinoyl ribosides and nicotinamide riboside derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival.

Abstract translation: 本发明涉及烟酰基核糖苷和烟酰胺核苷衍生物的组合物及其使用方法。 在一些实施方案中，本发明涉及制备烟酰基核糖苷的方法。 在一些实施方案中，本发明涉及含有烟酰基核苷的药物组合物和营养补充剂。 在进一步的实施方案中，本发明涉及使用促进细胞和组织中细胞内水平的烟酰胺腺嘌呤二核苷酸（NAD +）增加细胞和组织存活的烟酰胺核糖苷和烟酰胺核苷衍生物的方法。

公开(公告)号：WO2006132808A1

公开(公告)日：2006-12-14

申请号：PCT/US2006/020131

申请日：2006-05-24

Applicant: SCINOPHARM TAIWAN, LTD. ,  SCHLOEMER, George

Inventor： SCHLOEMER, George ,  WANG, Lung-hu ,  LIU, Allen

IPC: C07H19/00 ,  C07H19/073

CPC classification number: C07H19/00 ,  C07H19/048 ,  C07H19/073 ,  C07H19/12 ,  C07H19/22 ,  Y02P20/55

Abstract: A process of preparing an alpha-anomer enriched 2- deoxy-2 , 2-dif luoro-D-ribofunanosyl sulfonate, which is useful as an intermediate in the preparation of a beta nucleoside, such as gemcitabine, an anti-tumor agent. A beta-2-deoxy-2, 2-difluoro-D-ribofunanosyl sulfonate is heated and converted to an alpha-2-deoxy-2, 2-difluoro-D- ribofunanosyl sulfonate in the absence of an effective amount of a sulfonate salt to facilitate the conversion. In addition, an anomeric mixture of an alpha-anomer and a beta-anomer of 2-deoxy-2, 2-difluoro-D-ribofunanosyl sulfonate can be dissolved in a mixture of water and a solvent and heated to produce a lactol, which may be further converted to jan alpha-anomer enriched 2-deoxy- 2 , 2-difluoro-D-ribofunanosyl sulfonate .

Abstract translation: 制备富含α-异头物的2-脱氧-2,2-二氟-D-核糖核酸磺酸的方法，其可用作制备β核苷的中间体，例如吉西他滨，抗肿瘤剂。 在不存在有效量的磺酸盐的情况下将β-2-脱氧-2,2-二氟-D-核糖核酸磺酸酯加热并转化成α-2-脱氧-2,2-二氟-D-核糖核酸磺酰基磺酸盐 以方便转换。 此外，可以将2-脱氧-2,2-二氟-D-核糖核酸磺酸的α-端基异构体和β-端基异构体的端基异构体混合物溶解在水和溶剂的混合物中，并加热产生内酯， 可以进一步转化成富含α-脱水异构体的2-脱氧-2,2-二氟-D-核糖核酸磺酰基。

公开(公告)号：WO2004072090A1

公开(公告)日：2004-08-26

申请号：PCT/US2004/003469

申请日：2004-02-06

Applicant: MERCK & CO. INC. ,  XU, Feng ,  BIO, Matthew, M. ,  COWDEN, Cameron, J. ,  SAVARY, Kimberly, A. ,  WILLIAMS, John, M. ,  YANG, Chunhua ,  WATERS, Majorie, See

Inventor： XU, Feng ,  BIO, Matthew, M. ,  COWDEN, Cameron, J. ,  SAVARY, Kimberly, A. ,  WILLIAMS, John, M. ,  YANG, Chunhua ,  WATERS, Majorie, See

IPC: C07H1/00

CPC classification number: C07D487/04 ,  C07H1/00 ,  C07H19/048 ,  C07H19/14 ,  Y02P20/55

Abstract: A process is provided for the preparation of branched-chain ribonucleosides of formula (I) from the 1,2- anhydro derivatives of fomula (II). The compounds of fomula (I) are inhibitors of HCV polymerase useful in the treatment of HCV infection.

Abstract translation: 提供了从式（II）的1,2-脱水衍生物制备式（I）的支链核糖核苷的方法。 （I）化合物是用于治疗HCV感染的HCV聚合酶抑制剂。

公开(公告)号：WO2003101198A1

公开(公告)日：2003-12-11

申请号：PCT/US2003/017284

申请日：2003-05-30

Applicant: ALBERT EINSTEIN COLLEGE OF MEDICINE OF ZESHIVA UNIVERSITY ,  SAUVE, Anthony, A. ,  SCHRAMM, Vern, L.

Inventor： SAUVE, Anthony, A. ,  SCHRAMM, Vern, L.

IPC: A01N43/04

CPC classification number: C07H19/052 ,  C07H19/048

Abstract: The present invention provides compounds having the formula: (I); Also provided are pro-drug compounds of the formula: (II); The invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds. Methods for inhibiting an ADP-ribosyl transferase, ADP-ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme using the above compounds, and methods for treating a disease or condition associated with an ADP-ribosyl transferase, ADP- `ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme in a subject using the above compounds are also provided.

Abstract translation: 本发明提供具有下式的化合物：（I）; 还提供了下式的前药化合物：（II）; 本发明还提供含有上述化合物的药物组合物，使用上述化合物作为药物的方法，以及制备上述化合物的方法。 使用上述化合物抑制ADP-核糖基转移酶，ADP-核糖基环化酶，ADP-核糖基水解酶或NAD依赖性脱乙酰酶的方法，以及用于治疗与ADP-核糖基转移酶ADP-核糖基转移酶ADP- 还提供了使用上述化合物的受试者中的环化酶，ADP-核糖基水解酶或NAD依赖性脱乙酰酶。