Abstract: Compounds of Formula I, stereoisomers, and pharmaceutically acceptable salts or prodrugs thereof, their preparation, and their uses for the treatment of hepatitis C viral infection are described:
Type:
Application
Filed:
November 6, 2006
Publication date:
August 2, 2007
Applicants:
Metabasis Therapeutics, Inc., Merck & Co., Inc.
Inventors:
Mark Erion, K. Reddy, Malcolm MacCoss, David Olsen
Abstract: Prodrugs of Formula I, their uses, their intermediates, and their method of manufacture are described: wherein: 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.
Type:
Grant
Filed:
May 12, 2003
Date of Patent:
May 8, 2007
Assignee:
Metabasis Therapeutics, Inc.
Inventors:
K. Raja Reddy, Mark D. Erion, Michael C. Matelich, Joseph J. Kopcho
Abstract: Novel cyclic phosphoramidate prodrugs of drugs of formula I in their use in delivery of drugs to the liver, their use in enhancing oral bioavailability, and their method of preparation are described.
Type:
Grant
Filed:
March 3, 2000
Date of Patent:
April 17, 2007
Assignee:
Metabasis Therapeutics, Inc.
Inventors:
Mark D. Erion, K. Raja Reddy, Serge H. Boyer
Abstract: The method of preparing compounds of Formula I is described: wherein: 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.
Type:
Grant
Filed:
May 12, 2003
Date of Patent:
March 20, 2007
Assignee:
Metabasis Therapeutics, Inc.
Inventors:
Joseph J. Kopcho, K. Raja Reddy, Michael C. Matelich, Bheemarao G. Ugarkar
Abstract: Compounds of Formula I, stereoisomers, and pharmaceutically acceptable salts or prodrugs thereof, their preparation, and their uses for the treatment of hepatitis C viral infection are described:
Abstract: Compounds of Formula I, their preparation and uses are described: wherein: M and V are cis to one another and MH is cytarabine; the 5? oxygen of said cytarabine is attached to the phosphorus; V is 4-pyridyl; and pharmaceutically acceptable prodrugs and salts thereof.
Abstract: Compounds of Formula I, their preparation and synthetic intermediates, and their use in the synthesis of prodrugs: wherein: V and L are trans relative to one another; V is selected from group consisting of carbocyclic aryl, substituted carbocyclic aryl, heteroaryl, and substituted heteroaryl; and L is a leaving group selected from the group consisting of halogen, alkyl sulfonate, aryloxy optionally substituted with 1–2 substituents, N-containing heteroaryl, and N-hydroxy-nitrogen containing heteroaryl; and salts thereof.
Type:
Grant
Filed:
October 31, 2003
Date of Patent:
December 12, 2006
Assignee:
Metabasis Therapeutics, Inc.
Inventors:
K. Raja Reddy, William Craigo, Zhili Sun, Serge Boyer, Bheemarao G. Ugarkar
Abstract: Novel purine compounds of the Formula 1, pharmacuetically acceptable prodrugs and salts thereof, and their use as fructose 1,6-bisphosphatase inhibitors
Type:
Grant
Filed:
July 7, 2003
Date of Patent:
November 22, 2005
Assignee:
Metabasis Therapeutics, Inc.
Inventors:
Qun Dang, Mark D. Erion, M. Rami Reddy, Edward D. Robinson, Srinivas Rao Kasibhatla, K. Raja Reddy
Abstract: Novel bisamidate phosphonate prodrugs of FBPase inhibitors of the Formula IA: and their use in the treatment of diabetes and other conditions associated with elevated blood glucose.
Type:
Grant
Filed:
December 22, 2000
Date of Patent:
November 15, 2005
Assignee:
Metabasis Therapeutics, Inc.
Inventors:
Tao Jiang, Srinivas Rao Kasibhatla, K. Raja Reddy
Abstract: Prodrugs of formula I, their uses, their intermediates, and their method of manufacturing are described: and pharmaceutically acceptable prodrugs and salts thereof.
Type:
Grant
Filed:
October 15, 2001
Date of Patent:
September 20, 2005
Assignee:
Metabasis Therapeutics, Inc.
Inventors:
Mark D. Erion, K. Raja Reddy, Edward D. Robinson, Bheemarao G. Ugarkar
Abstract: Novel FBPase inhibitors of the formula I are useful in the treatment of diabetes and other conditions associated with elevated blood glucose.
Type:
Grant
Filed:
March 7, 2001
Date of Patent:
July 19, 2005
Assignee:
Metabasis Therapeutics, Inc.
Inventors:
Brett C. Bookser, Qun Dang, K. Raja Reddy
Abstract: Pharmaceutical compositions containing an FBPase inhibitor and an insulin sensitizer are provided as well as methods for treating diabetes and diseases responding to increased glycemic control, an improvement in insulin sensitivity, a reduction in insulin levels, or an enhancement of insulin secretion.
Abstract: The present invention is directed towards novel cyclic phosph(oramid)ate prodrugs of alcohol, amine-, and thiol-containing drugs, their preparation, their synthetic intermediates, and their uses. Another aspect of the invention is the use of the prodrugs to treat diseases that benefit from enhanced drug distribution to the liver and like tissues and cells that express cytochrome P450, including hepatitis, cancer, liver fibrosis, malaria, other viral and parasitic infections, and metabolic diseases where the liver responsible for the overproduction of the biochemical end product, e.g. glucose (diabetes); cholesterol, fatty acids and triglycerides (hyperlipidemia) (atherosclerosis) (obesity). In one apsect, the invention is directed towards the use of the prodrugs to enhance oral drug delivery. In another aspect, the prodrugs are used to prolong pharmacodynamic half-life of the drug. In addition, the prodrug methodology of the current invention is used to achieve sustained delivery of the parent drug.
Abstract: This invention relates to novel human organic anion transporter polypeptides and genes encoding such polypeptides. The invention is directed towards the isolation, characterization and use of human organic anion transporter polypeptides for pharmacological screening of substrates, analogues of substrates, and modulators of human organic anion proteins. This invention also provides cell cultures, which stably contain nucleic acid sequences encoding human organic anion transport polypeptides. Such cell lines are useful for screening compounds in vitro to identify and characterize modulators, inhibitors and substrates of human organic anion transporter polypeptides.
Abstract: FBPase inhibitors of the formula I and X
are useful in the treatment of diabetes and other conditions associated with elevated blood glucose or excess glycogen storage.
Type:
Grant
Filed:
September 3, 1999
Date of Patent:
December 3, 2002
Assignee:
Metabasis Therapeutics, Inc.
Inventors:
Qun Dang, Srinivas Rao Kasibhatla, K. Raja Reddy, Mark D. Erion, M. Rami Reddy, Atul Agarwal
Abstract: The present invention is directed towards novel azaindole compounds which bind to the AMP site and are potent FBPase inhibitors. The present invention also is directed towards the clinical use of the novel FBPase inhibitors as a method of treatment or prevention of diseases responsive to lowered blood glucose levels.
Type:
Grant
Filed:
January 5, 2000
Date of Patent:
September 25, 2001
Assignee:
Metabasis Therapeutics, Inc.
Inventors:
K. Raja Reddy, Gerard R. Scarlato, Qun Dang, Mark D. Erion, Srinivas Rao Kasibhatla, M. Rami Reddy