公开(公告)号：WO2012158552A2

公开(公告)日：2012-11-22

申请号：PCT/US2012/037612

申请日：2012-05-11

Applicant: UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. ,  CHU, Chung, K. ,  WANG, Jianing

Inventor： CHU, Chung, K. ,  WANG, Jianing

CPC classification number: C07D473/34 ,  A61K45/06 ,  C07D239/54 ,  C07D473/30

Abstract: The present invention relates to 2'-Fluoro-6'-methylene carbocyclic nucleosides, pharmaceutical compositions containing these nucleosides and their use in the treatment or prophylaxis of a number of viral infections and secondary disease states and conditions thereof, especially including Hepatitis B virus (HBV) and secondary disease states and conditions thereof (cirrhosis and liver cancer), Heptatitis C virus (HCV), Herpes Simplex virus I and II (HSV-1 and HSV-2), cytomegalovirus (CMV), Varicella-Zoster Virus (VZV) and Epstein Barr virus (EBV) and secondary cancers which occur thereof (lymphoma, nasopharyngeal cancer, including drug resistant (especially including lamivudine and/or adefovir resistant) and other mutant forms of these viruses, especially HBV.

Abstract translation: 本发明涉及2'-氟-6'-亚甲基碳环核苷，含有这些核苷的药物组合物及其在治疗或预防多种病毒感染及其继发性疾病状态及其病症中的用途，特别是包括乙型肝炎病毒（ HBV）和继发性疾病状态和病症（肝硬化和肝癌），丙型肝炎病毒（HCV），单纯疱疹病毒I和II型（HSV-1和HSV-2），巨细胞病毒（CMV），水痘带状疱疹病毒（VZV） ）和爱泼斯坦巴尔病毒（EBV）和其发生的继发性癌症（淋巴瘤，鼻咽癌，包括耐药性（特别是包括拉米夫定和/或阿德福韦抗性）以及这些病毒的其他突变形式，特别是HBV。

公开(公告)号：WO1992010496A1

公开(公告)日：1992-06-25

申请号：PCT/US1991009123

申请日：1991-12-05

Applicant: UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

Inventor： UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. ,  CHU, Chung, K. ,  BEACH, J., Warren ,  JEONG, Lak-Shin

IPC: C07D475/00

CPC classification number: A61K31/7076 ,  A61K31/675 ,  A61K31/704 ,  C07D327/04 ,  C07D411/04 ,  C07D473/00 ,  C07D497/08

Abstract: An asymmetric process for the preparation of enantiomerically pure beta -L-(-)-1,3-oxathiolane-nucleosides that includes the initial preparation of the key chiral intermediates (2R,5R) and (2R,5S)-5-(O-protected)-2-(protected-oxymethyl)-1,3-oxathiolane from 1,6-thioanhydro-L-gulose. The 2R,5(R,S)-5-(O-protected)-2-(protected-oxymethyl)-1,3-oxathiolane is condensed with a desired heterocyclic base, typically a purine or pyrimidine base, to provide the product nucleoside. The synthesis can be used to prepare the pharmaceutically important compound, beta -L-(-)-1-[(2 beta ,4 beta )-2-(hydroxymethyl)-4-(1,3-thioxolane)]cytosine ( beta -L-(-)BCH-189).

Abstract translation: 用于制备对映体纯的β-L-（ - ） - 1,3-氧硫杂环戊烷 - 核苷的不对称方法，包括关键手性中间体（2R，5R）和（2R，5S）-5-（O 保护的）-2-（保护的 - 氧甲基）-1,3-氧硫杂环戊烷，由1,6-硫代氢化-L-古洛糖。 将2R，5（R，S）-5-（O-保护的）-2-（保护的 - 氧甲基）-1,3-氧硫杂环戊烷与所需的杂环碱（通常为嘌呤或嘧啶碱基）缩合，得到产物 核苷。 该合成可用于制备药学上重要的化合物，β-L-（ - ） - 1 - [（2β，4β）-2-（羟甲基）-4-（1,3-硫代羟烷基）]胞嘧啶 -L（ - ） - BCH-189）。

公开(公告)号：WO1991010670A1

公开(公告)日：1991-07-25

申请号：PCT/US1991000051

申请日：1991-01-02

Applicant: UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

Inventor： UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. ,  CHU, Chung, K.

IPC: C07H01/00

CPC classification number: C07D405/04 ,  C07H19/06 ,  C07H19/16

Abstract: A method for the preparation of 2'-deoxynucleosides and 2',3'-dideoxy-2',3'-didehydronucleosides that includes the step of reacting a nucleoside having hydroxyl groups in the 2' and 3' positions with a mixture of acyl bromide or chloride and HX, wherein X is Br or Cl, at moderate temperature, to give a haloacyl nucleoside derivative that can be deprotected and reduced to form the desired compound.

公开(公告)号：WO2003000200A3

公开(公告)日：2003-01-03

申请号：PCT/US2002/020245

申请日：2002-06-24

Applicant: PHARMASSET LTD. ,  UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. ,  EMORY UNIVERSITY ,  CHU, Chung, K. ,  OTTO, Michael, J. ,  SHI, Junxing ,  SCHINAZI, Raymond, F. ,  CHOI, Yongseok ,  GUMINA, Giuseppe ,  CHONG, Youhoon ,  STUYVER, Lieven, J.

Inventor： CHU, Chung, K. ,  OTTO, Michael, J. ,  SHI, Junxing ,  SCHINAZI, Raymond, F. ,  CHOI, Yongseok ,  GUMINA, Giuseppe ,  CHONG, Youhoon ,  STUYVER, Lieven, J.

IPC: C07H19/06

Abstract: The present invention includes compounds and compositions of β-halonucleosides, as well as methods to treat HIV, HBV or abnormal cellular proliferation comprising administering said compounds or compositions.

公开(公告)号：WO1998020879A1

公开(公告)日：1998-05-22

申请号：PCT/US1997020647

申请日：1997-11-14

Applicant: YALE UNIVERSITY ,  THE UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

Inventor： YALE UNIVERSITY ,  THE UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. ,  CHENG, Yung-Chi ,  CHU, Chung, K. ,  QU, Fucheng

IPC: A61K31/505

CPC classification number: C07D405/04

Abstract: The present invention relates to the discovery that certain beta -L-dioxolane nucleoside analogs which contain a uracil base, and preferably, a 5-halosubstituted uracil base, exhibit unexpectedly high activity against Epstein-Barr virus (EBV), Varicella-Zoster virus (VZV) and Human Herpes Virus 8 (HV-8). In particular, the compounds according to the present invention show potent inhibition of the replication of the virus (viral growth) in combination with very low toxicity to the host cells (i.e., animal or human tissue). Compounds are useful for treating EBV, VZV and HV-8 infections in humans.

Abstract translation: 本发明涉及以下发现：含有尿嘧啶碱基，优选5-卤代尿嘧啶碱的某些β-L-二氧戊环核苷类似物对于爱泼斯坦 - 巴尔病毒（EBV），水痘带状疱疹病毒（水痘 - 带状疱疹病毒 VZV）和人疱疹病毒8（HV-8）。 特别地，根据本发明的化合物显示出对宿主细胞（即动物或人体组织）的非常低毒性的组合对病毒（病毒生长）的复制的有效抑制。 化合物可用于治疗人类的EBV，VZV和HV-8感染。

公开(公告)号：WO1991000867A1

公开(公告)日：1991-01-24

申请号：PCT/US1990003852

申请日：1990-07-10

Applicant: UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. ,  UAB RESEARCH FOUNDATION ,  SCHINAZI, Raymond, F. ,  SHAFER, William, M.

Inventor： UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. ,  UAB RESEARCH FOUNDATION ,  SOMMADOSSI, Jean-Pierre ,  CHU, Chung, K.

IPC: C07H19/10

CPC classification number: C07H19/10 ,  A61K31/70 ,  C07H19/06 ,  C07H19/20 ,  Y02A50/475 ,  Y02A50/478 ,  Y02A50/481

Abstract: This invention provides compounds and pharmaceutical compositions that include compounds of formula (I) in which A, B and C are hydrogen, halogen, or azido; D is hydrogen, halogen, azido, or OH; A and B or C and D can be replaced with a double bond; R is an aldohexose, aldohexosamine, or N-acetyl aldohexosamine, W is O or S; X is O, S, or CH2; Y is a purine or pyrimidine base, Z is C, S, or O, and wherein when Z is S or O, A and C are not present. The compounds of this invention have enhanced pharmaceutical or biological activity or increased intracellular absorption compared to the corresponding parent nucleoside as a function of the 5'-diphosphohexose moiety. Many of these compounds have antiviral, including anti-HIV, activity. Others have antibacterial activity. In one embodiment, the invention is a method to treat HIV infection and opportunistic infections concomitantly.

Abstract translation: 本发明提供了包括其中A，B和C为氢，卤素或叠氮基的式（I）化合物的化合物和药物组合物; D是氢，卤素，叠氮基或OH; A和B或C和D可以用双键替换; R是羟基己糖，己二酰胺或N-乙酰基己糖胺，W是O或S; X是O，S或CH 2; Y是嘌呤或嘧啶碱，Z是C，S或O，并且其中当Z是S或O时，不存在A和C。 与作为5'-二磷酸己糖部分的函数的相应亲本核苷相比，本发明的化合物具有增强的药物或生物活性或增加的细胞内吸收。 这些化合物中的许多具有抗病毒，包括抗HIV，活性。 其他有抗菌活性。 在一个实施方案中，本发明是一种同时治疗HIV感染和机会性感染的方法。

公开(公告)号：WO2010090723A2

公开(公告)日：2010-08-12

申请号：PCT/US2010/000283

申请日：2010-02-02

Applicant: UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. ,  MANN, Jelena ,  CHU, Chung, K. ,  UNIVERSITY OF NEWCASTLE UPON TYNE ,  MANN, Derek, A.

Inventor： MANN, Jelena ,  CHU, Chung, K. ,  MANN, Derek, A.

IPC: A61K31/519 ,  A61K31/4196 ,  A61K31/437 ,  A61P1/16 ,  A61P1/00

CPC classification number: A61K31/4196 ,  A61K31/437 ,  A61K31/519

Abstract: The present invention relates to the discovery of an epigenetic relay pathway that controls hepatic stellate cell activation and the wound-healing response in fibrogenesis, including fibrogenesis of the injured liver. Methods of inhibiting fibrogenesis, including liver fibrogenesis and secondary disease states and conditions thereof, and in treating liver damage, including cirrhosis of the liver (which may be caused by viruses or chemicals, including alcohol), are aspects of the present invention. The methods utilize certain nucleoside compounds and/or antibodies which are optionally conjugated. Pharmaceutical compositions represent additional aspects of the invention.

Abstract translation: 本发明涉及一种控制肝星状细胞活化的表观遗传中继途径的发现和包括受伤肝脏的纤维形成在内的纤维发生中的伤口愈合反应。 抑制纤维发生的方法，包括肝纤维发生和继发性疾病状态及其条件，以及治疗肝损伤，包括肝硬化（其可由病毒或化学物质，包括酒精引起）是本发明的一个方面。 所述方法利用任选缀合的某些核苷化合物和/或抗体。 药物组合物代表本发明的另外的方面。

公开(公告)号：WO2004043402A2

公开(公告)日：2004-05-27

申请号：PCT/US2003/036224

申请日：2003-11-12

Applicant: PHARMASSET, LTD. ,  UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

Inventor： STUYVER, Lieven, J. ,  CHU, Chung, K.

IPC: A61K

CPC classification number: C07H19/16 ,  C07H19/06

Abstract: The present invention relates to 3’ substituted -2’, 3’-didehydro- 2’, 3’- dideoxy- β -L-nucleosides and their pharmaceutically acceptable salts and prodrugs thereof, for the treatment of infectious viral diseases, in general, particularly HBV and HIV viral infections and more particularly, HBV and HIV viral infections that are resistant to other antiviral drugs.

Abstract translation: 本发明涉及3'取代的-2'，3'-二脱氢-2'，3'-二脱氧-β-L-核苷及其药学上可接受的盐 及其前药一般用于治疗感染性病毒疾病，特别是HBV和HIV病毒感染，更特别是对其他抗病毒药物具有抗性的HBV和HIV病毒感染。

公开(公告)号：WO2002062123A2

公开(公告)日：2002-08-15

申请号：PCT/US2002/003371

申请日：2002-02-05

Applicant: YALE UNIVERSITY ,  THE UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

Inventor： ANDERSON, Karen, S. ,  CHU, Chung, K. ,  RAY, Adrian, Staffin ,  ZHENJUN, Yang

IPC: C07H19/16

CPC classification number: C07H19/16

Abstract: The present invention relates to novel compounds, compositions and methods for inhibiting the growth, elaboration and/or replication of HIV in human patients and to the prevention and treatment of human acquired immunodeficiency syndrome (AIDS) and other diseases caused by retroviral infection. More particularly, in preferred aspects, the present invention provides a method for the use of novel prodrug forms of 9-(2,3-Dideoxy-β-D-glycero-pent-2-enofuranosyl)guanine (d4G) for the prevention and treatment of both wild type and drug-resistant Human Immunodeficiency Virus (HIV), the causative pathogen of AIDS.

Abstract translation: 本发明涉及用于抑制人类患者中HIV的生长，制备和/或复制以及预防和治疗人类获得性免疫缺陷综合征（AIDS）和由逆转录病毒感染引起的其它疾病的新化合物，组合物和方法。 更具体地，在优选的方面，本发明提供了使用9-（2,3-二脱氧-β-D-甘油基 - 戊-2-烯呋喃糖基）鸟嘌呤（d4G）的新型前药形式用于预防和/ 治疗野生型和耐药性人类免疫缺陷病毒（HIV），艾滋病的病原体。

公开(公告)号：WO1992015598A1

公开(公告)日：1992-09-17

申请号：PCT/US1992001935

申请日：1992-03-06

Applicant: UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

Inventor： UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. ,  CHU, Chung, K. ,  CHEN, Yaoquan

IPC: C07H01/100

CPC classification number: C07H19/04

Abstract: An efficient process for the deoxygenation of 2'- and or 3'-hydroxyl groups of a nucleoside that includes reacting the hydroxyl group with 3-halopropionitrile or 2-nitroethylhalide and carbon disulfide in base to form a 2'- or 3'-(cyanoethylthio or nitroethylthio)thiocarbonyl, that is reductively eliminated and replaced with hydrogen. The deoxygenation process can be used in a wide variety of nucleoside syntheses that require the elimination of the 2'- or 3'-hydroxyl groups, including the preparation of 3'-substituted-2',3'-dideoxynucleosides such as 3'-azido-3'-deoxythymidine and 3'-azido-2',3'-dideoxyuridine.

Abstract translation: 使核苷的2'-或3'-羟基脱氧的有效方法包括使羟基与3-卤代丙腈或2-硝基乙基卤和二硫化碳在碱中反应形成2'-或3' - （ 氰基乙硫基或硝基乙硫基）硫代羰基，其被还原消除并用氢代替。 脱氧方法可用于需要消除2'-或3'-羟基的多种核苷合成，包括制备3'-取代-2'，3'-二脱氧核苷，例如3'- 叠氮基-3'-脱氧胸苷和3'-叠氮基-2'，3'-二脱氧尿苷。