Pró-drogas de análogos de nucleotìdeo de fosfonato e métodos para selecionar e preparar as mesmas

• Main Authors: HARLAN H. CHAPMAN, JOHN C. ROHLOFF, GONG-XIN HE, TOMAS CIHLAR, MICHAEL R. KERNAN, MARK L. SPARACINO, MARK W. BECKER, EUGENE J. EISENBERG, ERNEST J. PRISBE, WILLIAM A. LEE
• Format: Patent
• Language: Portuguese
• Published: 24.06.2003
• Edition: 7
• Subjects: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS OR TEST PAPERS THEREFOR; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; DERIVATIVES THEREOF; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES; MEASURING; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MUTATION OR GENETIC ENGINEERING; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; PHYSICS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROCESSES OF PREPARING SUCH COMPOSITIONS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; SUGARS; TESTING; VINEGAR; WINE

"PRó-DROGAS DE ANáLOGOS DE NUCLEOTìDEO DE FOSFONATO E MéTODOS PARA SELECIONAR E PREPARAR AS MESMAS". A presente invenção refere-se a método que é fornecido para avaliar pró-drogas de análogos de nucleotídeo de metoxifosfonato para identificar pró-drogas seletivamente alvejando tecidos desejados com atividade antiviral ou antitumor. Este método tem induzido à identificação de novos éster-amidatos misturados de PMPA para terapia retroviral ou hepadnaviral, incluindo compostos de estrutura (5a) tendo grupos substituintes como aqui definido. Composições destes compostos em excipientes farmaceuticamente aceitáveis e seu uso em terapia e profilaxia são fornecidas. Também fornecido é um método para o uso de alcóxido de magnésio para a preparação de materiais de partida e compostos para uso aqui. A novel method is provided for screening prodrugs of methoxyphosphonate nucleotide analogues to identify prodrugs selectively targeting desired tissues with antiviral or antitumor activity. This method has led to the identification of novel mixed ester-amidates of PMPA for retroviral or hepadnaviral therapy, including compounds of structure (5a) having substituent groups as defined herein. Compositions of these novel compounds in pharmaceutically acceptable excipients and their use in therapy and prophylaxis are provided. Also provided is an improved method for the use of magnesium alkoxide for the preparation of starting materials and compounds for use herein.