Heterocyclic analogs of propargyl-linked inhibitors of dihydrofolate reductase

US8853228B2 · kind B2 · utility

Assignee

• UNIVERSITY OF CONNECTICUT · US

Inventors

• Amy C. Anderson
• Dennis L. Wright · Farmington, US
• Kathleen Mary Frey · Manchester, US
• Janet Leigh Paulsen · Manchester, US
• Eric William Scocchera · Mansfield Center, US
• Kishore Viswanathan · Mansfield Center, US

Key dates

• Filing date: Nov 7, 2011
• Grant date: Oct 7, 2014
• Expiry date: Nov 7, 2031

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02A50/30
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The compositions and methods described herein disclose the design, synthesis and testing of compounds that act as inhibitors of DHFR. The basic scaffold of these inhibitors includes a 2,4-diaminopyrimidine ring with a propargyl linker to another substituted aryl, bicyclo or heteroaryl ring. These DHFR inhibitors are potent and selective for many different pathogenic organisms, including the DHFR enzyme from bacteria such as Bacillus anthracis and methicillin-resistant Staphylococcus aureus, fungi such as Candida glabrata, Candida albicans and Cryptococcus neoformans and protozoa such as Cryptosporidium hominis and Toxoplasma gondii. These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.