- Enhanced inhibition of orthopoxvirus replication in vitro by alkoxyalkyl esters of cidofovir and cyclic cidofovir
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The nucleotide phosphonates cidofovir (CDV) and cyclic cidofovir (cCDV) are potent antiviral compounds when administered parenterally but are not well absorbed orally. These compounds have been reported to have activity against orthopoxvirus replication i
- Kern, Earl R.,Hartline, Caroll,Harden, Emma,Keith, Kathy,Rodriguez, Natalie,Beadle, James R.,Hostetler, Karl Y.
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- Alkoxyalkyl esters of cidofovir and cyclic cidofovir exhibit multiple-log enhancement of antiviral activity against cytomegalovirus and herpesvirus replication in vitro
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The incidence of cytomegalovirus (CMV) retinitis is declining in AIDS patients but remains a significant clinical problem in patients with organ transplants and bone marrow transplants. Prophylaxis with ganciclovir (GCV) or valganciclovir reduces the incidence of CMV disease but may lead to the emergence of drug-resistant virus with mutations in the UL97 or UL54 gene. It would be useful to have other types of oral therapy for CMV disease. We synthesized hexadecyloxypropyl and octadecyloxyethyl derivatives of cyclic cidofovir (cCDV) and cidofovir (CDV) and found that these novel analogs had 2.5- to 4-log increases in antiviral activity against CMV compared to the activities of unmodified CDV and cCDV. Multiple-log increases in activity were noted against laboratory CMV strains and various CMV clinical isolates including GCV-resistant strains with mutations in the UL97 and UL54 genes. Preliminary cell studies suggest that the increase in antiviral activity may be partially explained by a much greater cell penetration of the novel analogs. 1-O-Hexadecyloxypropyl-CDV, 1-O-octadecyloxyethyl-CDV, and their corresponding cCDV analogs are worthy of further preclinical evaluation for treatment and prevention of CMV and herpes simplex virus infections in humans.
- Beadle, James R.,Hartline, Caroll,Aldern, Kathy A.,Rodriguez, Natalie,Harden, Emma,Kern, Earl R.,Hostetler, Karl Y.
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- Morphic forms of hexadecyloxypropyl-phosphonate esters and methods of synthesis thereof
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The disclosure describes methods of synthesis of phosphonate ester compounds. The methods according to the disclosure allow for large-scale preparation of phosphonate ester compounds having high purity and stability. Also disclosed are morphic forms of ph
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Page/Page column 56
(2015/03/03)
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- Phosphonate Ester Derivatives and Methods of Synthesis Thereof
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The disclosure describes methods of synthesis of phosphonate ester derivatives. Preferred methods according to the disclosure allow for large-scale preparation of phosphonate ester compounds having high purity. In some embodiments, preferred methods accor
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Page/Page column 22-23
(2012/03/26)
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- COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF POXVIRUS INFECTIONS
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The present application provides methods and compositions for combination therapy with antiviral compounds for the treatment of poxvirus infections, such as orthopox virus infections. In one embodiment, a method of treatment of a poxvirus infection is provided that comprises administering to a host in need thereof cidofovir, cyclic cidofovir, or a salt, ester, or prodrug thereof in combination or alternation with at least a second anti-poxvirus agent. The second anti-poxvirus agent is, for example, a biologic, such as a pegylated interferon.
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Page/Page column 33
(2008/06/13)
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- COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS AND OTHER MEDICAL DISORDERS
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The present application provides methods and compositions for improving the bioavailability of a lipid-containing antiviral compound, and in particular, an antiviral lipid-containing compound. In one embodiment, pharmaceutically acceptable compositions ar
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Page/Page column 45
(2008/06/13)
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- METHODS FOR PREPARATION OF NUCLEOSIDE PHOSPHONATE ESTERS
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A process is provided for the preparation of lipophilic monoesters of formula (3) and their stereoisomers. The process includes the steps of esterification of a phosphonate with a lipophilic alcohol, then allowing the resultant product to react with a sui
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Page/Page column 31
(2010/02/14)
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- PHOSPHONATE COMPOUNDS
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The present invention relates to phosphonate compounds, compositions containing them, processes for obtaining them, and their use for treating a variety of medical disorders, e.g., osteoporosis and other disorders of bone metabolism, cancer, viral infections, and the like.
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(2010/02/05)
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