University of Georgia Research Foundation, Inc.

Emory University

Yale University

Other

Sloan-kettering Institute for Cancer Research

Research, Incorporated

Anterogen Co. Ltd.

University of Iowa Research Foundation

The Uab Research Foundation

Georgetown University

Health Research, Inc.

The University of Newcastle Upon Tyne

Medical College of Georgia Research Institute, Inc.

Pharmasset, Inc.

Stereochemical Genetics, Inc.

Chung K Chu

Raymond F Schinazi

Yung-Chi Cheng

Yongseok Choi

Jinfa Du

Junxing Shi

Dennis C Liotta

J Jeffrey McAtee

Kyeong Lee

Joon H Hong

Jianing Wang

Balakrishna S Pai

Kyoichi A Watanabe

Jack J Fox

Uma Sharan Singh

Fucheng Qu

Gang-Qing Yao

Brent E Korba

John L Gerin

Bud Tennant

Dennis Michael Marcus

Gang-Oing Yao

John L Casey

Varughese Alexander Mulamootttil

Paul J Cote

Ram C Mishra

Jean-Pierre Sommadossi

Michael J Otto

Karen S Anderson

J Warren Beach

Ling Li

William M Shafer

Charles R West

Uri Reichman

Chung I Hong

Lakshmi Kotra

Lawrence B Hendry

Jelena Mann

Yongseok Chai

Kostantine K Manouilov

Derek A Mann

Lakshimi Kotra

Lak-Shin Jeong

Virendra B Mahesh

Yaoquan Chen

Chunguang Wang

Kosaku Hirota

Konstantine Manouilov

Giuseppe Gumina

Youhoon Chong

Adrian Staffin Ray

Yang Zhenjun

Varughese Alexander Mulamoottil

Raymond Schinazi

Kostantin Manouilov

In an embodiment, the invention is directed to prodrug compounds of L-BHDU according to the chemical structure I:

Prodrugs of L-BHDU and methods of treating viral infections

The present invention relates to 2'-Fluoro-6&#x2032;-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.

2'-fluoro-6&#x2032;-methylene carbocyclic nucleosides and methods of treating viral infections

The invention provides a new convergent approach for the synthesis of 2'-fluoro-6&#x2032;-methylene-carbocyclic adenosine (FMCA) and 2&#x2032;-fluoro-6&#x2032;-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R, 4R)-3-tert-butoxy-4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.

Synthesis of 2'-fluoro-6&#x2032;-methylene-carbocyclic adenosine (FMCA) and 2&#x2032;-fluoro-6&#x2032;methylene-carbocyclic guanosine (FMCG)

2'-Fluoro-6&#x2032;-methylene carbocyclic nucleosides and methods of treating viral infections

The invention provides a new convergent approach for the synthesis of 2'-fluoro-6&#x2032;-methylene-carbocyclic adenosine (FMCA) and 2&#x2032;-fluoro-6&#x2032;-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R,4R)-3-tert-butoxy-4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.

Synthesis of 2'-fluoro-6&#x2032;-methylene-carbocyclic adenosine (FMCA) and 2&#x2032;-fluoro-6&#x2032;-methylene-carbocyclic guanosine (FMCG)

2'-Fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae: wherein

2' Fluoronucleosides

The present invention relates to 2'-Fluoro-6&#x2032;-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), Hepatitis 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.

Compounds, methods, and compositions for the treatment of infections in or exposure to humans and other host animals of Flaviviridae viruses, including HCV, that includes the administration of an effective amount of a spiro[2.4]heptane as described herein or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable carrier, are provided. The spiro[2.4]heptane compounds either possess antiviral activity, or are metabolized to a compound that exhibits such activity.

Spiro[2.4]heptanes for treatment of Flaviviridae infections

2'-fluoronucleosides

The present invention relates to 2'-Fluoro-6&#x2032;-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), Hepatitis 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.

2'-fluoro-6&#x2032;methylene carbocyclic nucleosides and methods of treating viral infections

Spiro[2.4]heptanes for treatment of flaviviridae infections

The present invention relates to 2'-Fluoro-6&#x2032;-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.

Growing community of inventors

Athens, GA, United States of America

Chung K Chu