University of Virginia Patent Foundation

Other

The United States of America As Represented by the Department of Health

Allergan Sales, Inc.

Cavion, Inc.

Adenosine Therapeutics, LLC

Timothy L MacDonald

Kevin R Lynch

Joel M Linden

Gail W Sullivan

Jayson Michael Rieger

Lauren J Murphree

Robert Alan Figler

Mark D Okusa

Jerry L Nadler

Yugesh Kharel

Peng Cui

Robert Douglas Thompson

Thomas Allen Miller

Yves Pommier

Richard Littleton Guerrant

Lloyd S Gray

Ian J Sarembock

Doris M Haverstick

Andrew Kennedy

Paul S Hoffman

Thomas P Mathews

Thomas Eric Ballard, Jr

Jose S Madalengoitia

Webster L Santos

Irving L Kron

Christine Dieckhaus

W Michael Scheld

William F McCalmont

Charles D Thompson

Jaclyn R Patterson

Michael E Garst

Thomas E Richardson

John F Hunt

Brian R Wamhoff

Michael D Davis

Brian H Heasley

Benjamin M Gaston

Mahendra Devichand Chordia

Michelle S Higgin

Jeremy Clemens

Timothy Aj Haystead

George A Beller

David K Glover

Alaa S Awad

John W Vaughan

Christopher E Heise

Mithun Rajendra Raje

Tiffany N Heady

Joseph Houck

Nathan M Thielman

Aldo A Lima

Eric R Houpt

R Patrick Fadden

Marie Hanigan

Karen M Carter

Jr Thomas Eric Ballard

Richard L Guerrant

Lauren Murphree Mihalcik

The present disclosure describes carbamate analogs of mibefradil, as well as their compositions and methods of use. The compounds block the activity of one or more isoforms of voltage-gated calcium channels and are useful in the treatment of diseases including, e.g., cancer.

Calcium channel inhibitors

The present invention provides novel T type calcium channel inhibitors of formula (I), the use thereof in the treatment of a disease or condition in a mammal associated with influx of extracellular calcium via T type calcium channels, wherein Ris C-Calkyl, hydroxy, or C-Calkoxy; Z is NH, NCH, O, S, or CH; Y is NH, O, or CHwith the proviso that Y and Z are not the same; Ris H, halo, NH, C-Calkyl, hydroxy, or C-Calkoxy; m and n are independently selected from integers ranging from 1-5 with the proviso that m+n=an integer ranging from 2-9; and Ris H, halo, NH, C-Calkyl, hydroxy, or C-Calkoxy. 

T type calcium channel inhibitors

Imidamide (amidine) analogs that can inhibit the activity of sphingosine kinase 1 and sphingosine kinase 2 (SphK1 & SphK2) are provided. The compounds can prevent angiogenesis in tumors.

Imidamide sphingosine kinase inhibitors

The invention relates to inhibitors of Sphingosine Kinase enzymatic activity, and methods of treating diseases and disorders by administering inhibitors of Sphingosine Kinase enzymatic activity.

Long chain base sphingosine kinase inhibitors

The invention provides novel antimicrobial chemical entities based on a nitrothiazolide backbone that exhibit antibacterial and antiparasitic action against a wide range of human pathogens. The new classes of compounds show extended action against Gram positive bacteria including MRSA drug resistant pathogens. In the Gram-positive organisms, they specifically target and functionally inhibit microbial attachment to surfaces and biofilm formation. In Gram-negative bacteria, including enteroaggregativestrains, these compounds function as pilicides by inhibiting the assembly of pilin subunits into adhesive filaments. Several of these compounds show potent antimicrobial action against Gram positive bacteria, perhaps involving novel targets. Many of the benzothiophene derivatives exhibit antimicrobial activity in the low micrograms per ml range and in blocking biofilm formation in the nanomolar range; ranges considered are well within the range of utility as therapeutics.

Broad spectrum benzothiophene-nitrothiazolide and other antimicrobials

The invention provides for the use of antimicrobial chemical entities based on a nitrothiazolide backbone that exhibit anti-mycobacteria activity, including thecausing tuberculosis. Multiple compounds were synthesized and screened for anti-tuberculosis activity. Disclosed herein are a series of compounds with anti-tuberculosis activity, including six leads that completely inhibited bacterial growth at 5 micrograms per ml or less. Three of these compounds were tested to determine MIC and these ranged between 1 and 4 micrograms per ml against both drug susceptiblestrains and strains that are multi-drug resistant (MDR) including XDR strains. The compounds developed are derived from parent compound nitazoxanide, which had no inhibitory activity in the stringent testing format used herein. The derivatives were synthesized using a di-nitro-thiophene or 4-Chloro-5-Nitro-thiazole scaffold and R groups connected via a peptide bond (NHCO) to cyclic compounds such as benzene, thiophene or furans. Many of these compounds have broad spectrum activity against Gram positive bacteria including(MRSA) and. Several of these lead compounds were not toxic for mice at 200 mg/Kg doses administered over a period of three days. 

Compositions and methods for treating tuberculosis

Phthalazine analogs of a Lisofylline (LSF) and synthetic methods for preparation of such analogs are provided. Compounds of the invention have structural formula III: wherein 1) Ris hydrogen and Ris selected from Calkyl, Calkenyl, or Calkynyl; or a pharmaceutically acceptable salt thereof; or 2) Ris hydrogen and Ris selected from Calkyl, Calkyl, Calkenyl, or Calkynyl; or a pharmaceutically acceptable salt thereof; or 3) Rand Rare the same or different and are selected from Calkyl, Calkyl, Calkenyl, or Calkynyl; or a pharmaceutically acceptable salt thereof. The analogs of LSF provided have the ability to protect cell viability, particularly the ability to protect pancreatic &#x3b2;-cells, to induce insulin secretion.

Substituted phthalazines for inducing insulin secretion and protecting beta-cells

The present invention provides novel T type calcium channel inhibitors of formula (I), the use thereof in the treatment of a disease or condition in a mammal associated with influx of extracellular calcium via T type calcium channels, wherein

The present invention provides analogs of a Lysofylline (LSF), and synthetic methods for the preparation of such analogs. The have the active side chain moiety (5-R-hydroxyhexyl) of LSF and can have greater potency and oral bioavailability than LSF.

Lisofylline analogs and methods for use

Analogs of a Lisofylline (LSF), and synthetic methods for the preparation of such analogs are provided. The analogs of LSF provided have the ability to protect cell viability, particularly the ability to protect pancreatic &#x3b2;-cells.

Amidine analogs that can inhibit the activity of sphingosine kinase 1 and sphingosine kinase 2 (SphK1 & SphK2) are provided. The compounds can prevent angiogenesis in tumor cells.

Compositions and methods for inhibiting sphingosine kinase

The present invention provides &#x3b2;-hydroxy phosphonate compounds that are autotaxin inhibitors.

Phosphonate derivatives as autotaxin inhibitors

Growing community of inventors

Charlottesville, VA, United States of America

Timothy L MacDonald