Tsrl, Inc.

The United States of America, as Represented by the Secretary, Department of Health and Human Services

University of Southern California

University of Michigan

Sinevir Therapeutics LLC

The United States of America as Represented by the Nih Division of Extramural Inventions and Technology Resources (Deitr)

John Hilfinger

Charles E McKenna

Boris A Kashemirov

Gordon L Amidon

Alvin H Schmaier

Michaela Serpi

Henry Mosberg

Valeria M Zakharova

Phillip Kish

Ivan S Krylov

Larryn W Peterson

Jae Seung Kim

Paul Kijek

Chi Pham

Kanokkarn Saejueng

Larryn Peterson

Fernanda F Marques

Ulrika Tehler

A new class of neuramidase inhibitor prodrugs is provided characterized by a prodrug moiety of a carboxyl group modified to form a carbonyl ethoxy amino acid, a carbonyl ethoxy dipeptide or a carbonyl ethoxy tripeptide, a guanidine group modified to form a carbonyl ethoxy amino acid, a carbonyl ethoxy dipeptide, a carbonyl ethoxy tripeptide; a primary alcohol modified to form an esterified single amino acid, dipeptide or tripeptide of zanavimir of the unaltered therapeutic agent. Exemplary therapeutic agents so modified to form prodrugs include zanavimir, oseltamivir and peramivir. The prodrug has increased oral bioavailability relative to the unaltered neuraminidase inhibitor and is effective in the inhibition of viral infections involving neuraminidase in the viral reproductive cycle.

Prodrugs of neuraminidase inhibitors

A tyrosine-based (phosphonylmethoxyalkyl)purine or -pyrimidine conjugate is provided. In some embodiments, the conjugate includes tyrosine based amino acid or dipeptide moieties of (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine or its cytosine analog. A method of synthesizing such conjugates based on Boc-protected amino acid or dipeptides is also provided. In addition, a method of isomerizing an (S,S)-diastereoisomer to an (S,R)-diastereoisomer of an amino acid-based or dipeptide-based conjugate by a process including transesterification is provided. A method of inhibiting viral infection and a method of treating viral infection based on (phosphonylmethoxyalkyl)purine or -pyrimidine conjugates is also provided.

Tyrosine-based prodrugs of antiviral agents

A pharmaceutical composition is provided that includes an active ingredient in the form of a powder or granule, a water soluble high molecular weight excipient and a water insoluble hydrophilic amphiphilic excipient. These ingredients are solution mixed and dried to form a modified pharmaceutical ingredient in simultaneous contact with both the water soluble high molecular weight excipient and the water insoluble hydrophilic amphiphilic excipient. Adjuvants are compacted about the modified pharmaceutical ingredient as well as a release control agent. The release control agent being present at levels from 1 to 40 total weight percent of the pharmaceutical composition.

Methods and composition of extended delivery of water insoluble drugs

Cidofovir or foscarnet based compounds having an amino acid or dipeptide esters are provided as prodrugs.

Phosphonyl ester conjugates as prodrugs

The invention relates to synthetic peptide analogs of D-Arg-Oic-Pro-Gly-Phe and methods of their use to inhibit human platelet aggregation, thrombosis and cell activation mediated by PAR1 and PAR4.

Synthetic peptide inhibitors of thrombin and thrombin activation of protease activated receptors 1 and 4

Cidofovir-based compounds having an amino acid, dipeptide or tripeptide attached to a cidofovir or cyclic cidofovir framework. The compounds show enhanced oral bioavailability and increased binding to the PepT1 transporter. The present invention also provides compositions and methods for treating virus infections, and a method of preparing cidofovir.

Cidofovir peptide conjugates as prodrugs

A dipeptide or tripeptide carrier system for active agent delivery to cells has an N-terminus natural amino acid and an active agent covalently bonded to a side chain of one of the remaining amino acid bases. The system is amenable to formulation as an oral administrant. The active agent being a therapeutic, a fluorescent dye, or contrast agent where the active agent has a molecular weight of less than 500 atomic mass units. An optional linker is provided intermediate between the active agent and the linking side chain.

Short peptide carrier system for cellular delivery of agent

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Ann Arbor, MI, United States of America

John Hilfinger