Facile synthesis of the NNRTI microbicide MC-1220 and synthesis of its phosphoramidate prodrugs. Issue 3 (26th November 2015)

• Record Type: Journal Article
• Authors: Loksha, Yasser M.; Pedersen, Erik B.; La Colla, Paolo; Loddo, Roberta
• Is Part Of: Organic & biomolecular chemistry. Volume 14:Issue 3(2016)
• Page Start: 940
• Page End: 946
• Publication Date: 2015-11-26
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c5ob02055g
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A facile and novel synthetic route to MC-1220 was achieved by condensation of 4, 6-dichloro- N, N -5-trimethylpyrimidin-2-amine (1 ) with the sodium salt of 2, 6-difluorophenylacetonitrile, followed by methylation and strong acidic hydrolysis. Abstract : A facile and novel synthetic route to MC-1220 was achieved by condensation of 4, 6-dichloro- N, N -5-trimethylpyrimidin-2-amine (1 ) with the sodium salt of 2, 6-difluorophenylacetonitrile, followed by methylation and strong acidic hydrolysis. The prodrugs of MC-1220 were synthesized by reaction of chlorophosphoramidate derivatives (7a–e ) or α-acetobromoglucose with the sodium salt of MC-1220. The stability and anti-HIV-1 activity of phosphoramidate prodrugs turned out to be comparable to those of the parent drug MC-1220.