University of Connecticut

Other

Promiliad Biopharma Inc.

Dennis L Wright

Amy C Anderson

Eric William Scocchera

Santosh Keshipeddy

James A Remington

Michael Henry Cynamon

David B Bolstad

Daniel A Ivanyo

David J Phelps

Kishore Viswanathan

Phillip M Pelphrey

Tammy M Joska

Erin S D Bolstad

Paola Bargagna-Mohan

Michael N Lombardo

Veljko Popov

Michael Van Heyst

Ben A Bahr

Sophia Ononye

Stephanie Reeve

Grant Sormunen

Narendran Gummudipundi Dayanandan

Kathleen Mary Frey

Royce Mohan

Janet Leigh Paulsen

Janet L Paulsen

Kathleen M Frey

Eric W Scocchera

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 present disclosure relates to compounds and methods for labeling and/or detecting proteins in vivo, and methods for probing mitochondrial structure and/or dynamics.

Methods of use for intermediate filament protein probes

The compositions and methods described herein relate generally to substituted tropolone derivatives, which, among other features, are useful as histone deacetylase (HDAC) inhibitors.

Substituted tropolone derivatives and methods of use

Compounds of Formula I and Formula IA are inhibitors of dihydrofolate reductase and are suitable for use in compositions and methods for dihydrofolate reductase inhibition or, more specifically, treatment of a fungal infection, a bacterial infection or a protozoal infection, and, in specific embodiments, treatment of a fungal infection caused byor: wherein R, R, R, R, R, A, B, E, V, W, X, Y and Z are as defined herein.

Heterocyclic and cyclic analogs of propargyl-linked inhibitors of dihydrofolate reductase

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

The compositions and methods described herein discloses 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.

Inhibitors of dihydrofolate reductase with antibacterial antiprotozoal, antifungal and anticancer properties

Compounds useful for promoting lysosomal processes and thereby ameliorating the disruption of cellular and functional integrity induced by A&#x3b2; and other protein and glycoconjugate species are provided. Methods for the treatment of neurodegenerative diseases that involve protein accumulation and aggregation in the brain, such as Alzheimer's, Parkinson's and Huntington's Disease, are also provided.

Compounds for lysosomal modulation and methods of use

A rail brace assembly for bracing a rail with respect to a tie plate. The rail brace assembly includes a brace member, a locking member, a retention member and a spring clip fastener. The brace member has a top surface adapted to engage a head fishing surface of the rail, a bottom surface adapted to engage a base fishing surface of the rail, a front friction surface and an outwardly extending toe. The retention member is adapted to be attached to the tie plate and includes a bore adapted to receive a first end of the fastener and a recess adapted to receive the toe of the brace member to thereby prevent vertical movement of the brace member and the rail. The locking member has a front surface, a rear friction surface adapted to engage the front friction surface of the brace member, and a pair of spaced apart outwardly extending legs which straddle the retention member. A first end of the fastener is inserted into the bore of the retention member and a second end of the fastener biases the rear friction surface of the locking member into interlocking engagement with the front friction surface of the brace member to thereby inhibit lateral movement of the brace member with respect to the locking member.

Lateral and vertical rail brace assembly

A direct assay for chloramphenicol acetyl transferase (CAT) has been presented wherein the assay reagent comprises chloramphenicol, an acyl CoA compound, and a tetrazolium salt, and wherein the reagent does not have any added coupling redox enzymes. In one embodiment, the reagent is mixed with the test sample and the presence of CAT is detected by an optical response. In a second embodiment, the reagent is mixed with a test sample containing CAT and the optical response is quantitated by comparison with standards to measure CAT activity in the test sample. In another embodiment, an exogenous electron carrier such as phenazines may be used to enhance the detection of CAT. The assay for the presence or activity of CAT can be used in a high-throughput screening assay or to detect CAT as a reporter gene for measuring the expression of a gene of interest. Kits containing the reagents are also provided.

Direct chloramphenicol acetyl transferase assay

A non-radioactive method of detecting the enzymes beta galactosidase or beta glucosidase directly or for the detection of a ligand and antiligand complex is provided wherein beta galactosidase or the complex labelled with beta galactosidase or a tracer having beta galactosidase conjugated thereto is reacted with 5-bromo-4-chloro-3-indolyl-B-D-galactoside and a tetrazolium salt to produce a colored formazan or a color change indicative of the presence of beta galactosidase, or wherein beta glucosidase or the complex labelled with the beta glucosidase or a tracer having beta glucosidase conjugated thereto is reacted with 5-bromo-4-chloro-3-indolyl-B-D-glucoside and a tetrazolium salt to produce a colored formazan or a color change indicative of the presence of beta glucosidase. Optionally, the galactosidase-galactoside determination or the glucosidase-glucoside determination may further include catalyst phenazine methosulfate (PMS) as a reactant. The preferred tetrazolium salt is dimethylthiazol diphenyl tetrazolium (MTT). A solution or composition of 5-bromo-4-chloro-3-indolyl-B-D-galactoside or 5-bromo-4-chloro-3-indolyl-B-D-glucoside, and a tetrazolium salt, as well as a test kit including the same, is also provided for carrying out the chromogenic method of detection.

Enzymatic method for detecting a labelled segment and a solution or

A non-radioactive method of detecting a ligand and antiligand complex labelled with alkaline phosphatase or a tracer having alkaline phosphatase conjugated thereto comprises reacting the complex with bromo-chloro-indolyl phosphate (BCIP), phenazine methosulfate (PMS) and dimethylthiazol diphenyl tetrazolium (MTT) and allowing the reaction to proceed to produce a colored formazan or a color change indicative of the presence of the labelled complex. A solution or composition of bromo-chloro-indolyl phosphate (BCIP), phenazine methosulfate (PMS) and dimethylthiazol diphenyl tetrazolium (MTT), as well as a test kit including the same, is also provided for carrying out the chromogenic method of detection.

Non-radioactive method for detecting a labelled segment and a solution

A furnace basket having a flat bottom and an upright peripheral wall formed of a gridwork of transverse rods pressure welded together. The rod portions which form the wall are reinforced by means of peripheral rods welded thereto.

Furnace basket

A hearth construction having a plurality of sections each of which has a first plurality of parallel, stainless steel I-beams connected in spaced relation by a plurality of transverse stainless steel I-beams. The top surfaces of the longitudinal and transverse I-beams are co-planar to provide a furnace floor for supporting work loads to be heat treated. In each section there are three elongated beams with the outer beams in each section having extensions at one end thereof. The ends of the extensions are situated in the furnace vestibule and have chamfered ends to facilitate loading and unloading of the work loads. Each section has a plurality of pairs of pier plates. The pairs are longitudinally spaced along the elongated beams at a distance corresponding to pier blocks which are situated on and extend from the furnace subfloor. The spacing between the plates in each pair dimensionally conforms to the pier blocks. The sections are then installed over the pier blocks with each pair of plates engaging opposite sides of the corresponding pier block.

Growing community of inventors

Farmington, CT, United States of America

Dennis L Wright