University of Connecticut

Eric William Scocchera

Dennis L Wright

Amy C Anderson

Michael Henry Cynamon

Santosh Keshipeddy

Michael N Lombardo

Kathleen Mary Frey

Janet Leigh Paulsen

Kishore Viswanathan

Narendran Gummudipundi Dayanandan

Stephanie Reeve

The disclosure provides compounds of the formula I and the pharmaceutically acceptable salts thereof. The variables, e.g. R, R, R, R, A, B, J, V, W, M, J and Ar are defined herein. The disclosure also provides pharmaceutical compositions comprising a compound or salt of formula I and a pharmaceutically acceptable carrier, methods of inhibiting dihydrofolate reductase (DHFR) in vitro or in vivo with a compound or salt of formula I, and methods of treating a bacterial infections, fungal infections, and protozoal infections with a compound or salt of formula I. A compound or salt of formula I can be the first and only active ingredient used in a pharmaceutical composition or method of this disclosure or may be combined with one or more additional active ingredients that are not compounds or salts of formula I.

Zwitterionic propargyl-linked antifolates useful for treating bacterial infections

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 asand methicillin-resistant, fungi such asandand protozoa such asand. These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.

Heterocyclic analogs of propargyl-linked inhibitors of dihydrofolate reductase

Growing community of inventors

Vernon, CT, United States of America

Eric William Scocchera