Tucker, GA, United States
Tucker, GA, United States

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Patent
Cocrystal Pharma Inc. and Emory University | Date: 2016-04-15

The present invention is directed to compounds, compositions and methods for treating or preventing hepatitis C virus (HCV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment or prevention of HCV infection.


The present invention is directed to compounds, compositions and methods for treating or preventing Flaviviridae family of viruses (including HCV, Yellow fever, Dengue, Chikungunya and West Nile virus), RSV and influenza infection and cancer in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment or prevention of HCV infection.


Zhou L.,Emory University | Zhang H.-W.,Emory University | Tao S.,Emory University | Bassit L.,Emory University | And 16 more authors.
Journal of Medicinal Chemistry | Year: 2015

The conversion of selected β-d-2,6-diaminopurine nucleosides (DAPNs) to their phosphoramidate prodrug (PD) substantially blocks the conversion to the G-analog allowing for the generation of two bioactive nucleoside triphosphates (NTPs) in human hepatocytes. A variety of 2′-C-methyl DAPN-PDs were prepared and evaluated for inhibition of HCV viral replication in Huh-7 cells, cytotoxicity in various cell lines, and cellular pharmacology in both Huh-7 and primary human liver cells. The DAPN-PDs were pan-genotypic, effective against various HCV resistant mutants, and resistant variants could not be selected. 2′-C-Me-DAPN-TP and 2′-C-Me-GTP were chain terminators for genotype 1b HCV-pol, and single nucleotide incorporation assays revealed that 2′-C-Me-DAPN-TP was incorporated opposite U. No cytotoxicity was observed with our DAPN-PD when tested up to 50 μM. A novel, DAPN-PD, 15c, has been selected for further evaluation because of its good virologic and toxicologic profile and its ability to deliver two active metabolites, potentially simplifying HCV treatment. © 2015 American Chemical Society.


Schinazi R.F.,Emory University | Schinazi R.F.,Veterans Affairs Medical Center | Sivets G.G.,National Academy of Sciences of Belarus | Detorio M.A.,Emory University | And 4 more authors.
Heterocyclic Communications | Year: 2015

The synthesis of new 2,6-disubstituted purine 2′,3′-dideoxy-2′,3′-difluoro-D-arabino nucleosides is reported. Their ability to block HIV and HCV replication along with their cytotoxicity toward Huh-7 cells, human lymphocyte, CEM and Vero cells was also assessed. Among them, β-2,6-diaminopurine nucleoside 25 and guanosine derivative 27 demonstrate potent anti-HIV-1 activity (EC50 = 0.56 and 0.65 μm; EC90 = 4.2 and 3.1 μm) while displaying only moderate cytotoxicity in primary human lymphocytes. © 2015 by De Gruyter 2015.


Mahmoud S.,Emory University | Mahmoud S.,Helwan University | Li H.,Emory University | McBrayer T.R.,CocrystalPharma Inc. | And 5 more authors.
Nucleosides, Nucleotides and Nucleic Acids | Year: 2016

A novel series of tetrafluoro and hexafluoro acyclic nucleosides and their phosphoramidates were successfully prepared from commercially available 2,2,3,3-tetrafluoro-1,4-butanediol and 2,2,3,3,4,4-hexafluoro-1,5-pentanediol in four to six steps. Their ability to block HIV, HCV, HSV-1, and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM, and Vero cells was assessed. © 2016 Taylor & Francis Group, LLC


Patent
Cocrystal Pharma LLC and Emory University | Date: 2015-11-10

The present invention is directed to compounds, compositions and methods for treating or preventing hepatitis C virus (HCV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment or prevention of HCV infection.


PubMed | CoCrystal Pharma Inc. and Emory University
Type: Journal Article | Journal: ACS medicinal chemistry letters | Year: 2016

A variety of 2,6-modified purine 2-C-methylribonucleosides and their phosphoramidate prodrugs were synthesized and evaluated for inhibition of HCV RNA replication in Huh-7 cells and for cytotoxicity in various cell lines. Cellular pharmacology and HCV polymerase incorporation studies on the most potent and selective compound are reported.


PubMed | CoCrystal Pharma Inc. and Emory University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry letters | Year: 2015

The design and synthesis of new non-symmetrical NS5A inhibitors with sulfur containing amino acids is reported along with their ability to block HCV replication in an HCV 1b replicon system. These compounds display EC50 values in the picomolar range with a large therapeutic index (>10(6)). Moreover, cellular pharmacology studies show that our preferred compounds intracellularly deliver three potent NS5A inhibitors.


Zhou L.,Emory University | Zhang H.,Emory University | Tao S.,Emory University | Ehteshami M.,Emory University | And 7 more authors.
ACS Medicinal Chemistry Letters | Year: 2016

A variety of 2,6-modified purine 2′-C-methylribonucleosides and their phosphoramidate prodrugs were synthesized and evaluated for inhibition of HCV RNA replication in Huh-7 cells and for cytotoxicity in various cell lines. Cellular pharmacology and HCV polymerase incorporation studies on the most potent and selective compound are reported. © 2015 American Chemical Society.


PubMed | Cocrystal Pharma Inc. and Emory University
Type: | Journal: Bioorganic & medicinal chemistry letters | Year: 2017

New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV activity in the HepAD38 system, and cytotoxicity profiles of each of the new compounds has been assessed. Among them, five new iodo- and bromo-heteroarylpyrimidines analogs displayed anti-HBV activity in the low micromolar range.

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