E. R. Squibb Sons, Inc.

Mmv Medicines for Malaria Venture

Perfuse Therapeutics, Inc.

University of Texas System

Fmc Corporation

University of Washington

Rutgers, the State University of New Jersey

St. Jude Children's Research Hospital

Monash University

Squibb & Sons, Inc.

Das, Jagabandhu

Floyd, David M.

Krapcho, John

Glaxosmithkline Investigacion Y Desarrollo, S.l.

David M Floyd

Philip D Stein

John Krapcho

Steven E Hall

Joel C Barrish

Raj N Misra

Jagabandhu Das

Christopher M Cimarusti

Philip Michael Sher

Spencer David Kimball

Alan W Fritz

Sevgi Gurkan

Steven Brandt

Karnail S Atwal

John K Thottathil

Joseph E Sundeen

George C Rovnyak

David J Matthews

John T Hunt

Jerome L Moniot

Melanie J Loots

Zhongli Ding

Susan A Charman

Margaret Phillips

Rodney Kiplin Guy

Spencer Knapp

William S DiMenna

Pradipsinh K Rathod

Jeremy Burrows

Alka Marwaha

Ramesh Gujjar

Donald C Monkhouse

Fangyi Zhu

Wendyam Armand Guiguemde

Ving G Lee

Steve Castro

Octavian R Kocy

Jose Coteron-Lopez

James D Pipkin

The present disclosure relates to the discovery that certain ocular diseases may be treated using Edonentan crystalline forms. Specific Edonentan crystalline form can be used alone or in combination with an intra-ocular pressure (TOP) reducing agent, a neuroprotective agent, or an anti-VEGF agent. Using Edonentan crystalline forms, alone or in combination with an additional agent, provides increased perfusion to the retina or reduced IOP in certain ocular diseases and reduces damage to retinal cells.

Compositions for treatment of ocular diseases

The present disclosure relates to the discovery that certain diseases of the eye that profoundly affect the human visual system and, as a result, quality of life, may be treated using Edonentan or A-182086. Edonentan or A-182086 can be used alone or in combination with an intra-ocular pressure (IOP) reducing agent, a neuroprotective agent, an anti-VEGF agent, or all, for example. Using Edonentan or A-182086, alone or in combination with an additional agent, provides increased perfusion to the retina in certain diseases and reduces damage to retinal cells.

Treatment of glaucoma using endothelin receptor antagonists

In one aspect, the invention relates to novel substituted 2-alkyl-1-oxo-N-phenyl-3-heteroaryl -1,2,3,4-tetrahydroisoquinoline-4-carboxamides; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating and/or preventing malaria. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Substituted 2-alkyl-1-OXO-N-phenyl-3-heteroaryl-1,2,3,4-tetrahydroisoquinoline-4-carboxamides for antimalarial therapies

Inhibitors of parasitic dihydroorotate dehydrogenase enzyme (DHOD) are candidate therapeutics for treating malaria. Illustrative of such therapeutic agents include the compound: and a triazolopyrimidine class of compounds that conform to Formula IX: and their solvates, stereoisomers, tautomers and pharmaceutically acceptable salts.

Antimalarial agents that are inhibitors of dihydroorotate dehydrogenase

7-Oxabicycloheptane substituted prostaglandin analogs useful in treating thrombotic and vasospastic disease have the structural formula ##STR1## wherein m is 1, 2 or 3; n is 1, 2, 3 or 4; Z is --(CH.sub.2).sub.2 --, --CH.dbd.CH-- or ##STR2## wherein Y is O, a single bond or vinyl, with the proviso that when n is O, if Z is ##STR3## then Y cannot be O, and when Z is --CH.dbd.CH--, n is 1, 2, 3 or 4; and when Y=vinyl, n=0; R is CO.sub.2 H, CO.sub.2 lower alkyl, CH.sub.2 OH, CO.sub.2 alkali metal, CONHSOR.sup.3, CONHR.sup.3a or --CH.sub.2 -5-tetrazolyl, X is O, S or NH; and where R.sup.1, R.sup.2, R.sup.3 and R.sup.3a are as defined herein.

7-oxabicycloheptyl substituted heterocyclic thioamide prostaglandin

7-Oxabicycloheptane substituted prostaglandin analogs useful in treating thrombotic and vasospastic disease have the structural formula ##STR1## wherein m is 1, 2 or 3; n is 1, 2, 3 or 4; Z is --(CH.sub.2).sub.2 --, --CH.dbd.CH-- or ##STR2## wherein Y is O, a single bond or vinyl, with the proviso that when n is O, if Z is ##STR3## then Y cannot be O, and when Z is --CH.dbd.CH--, n is 1, 2, 3 or 4; and when Y=vinyl, n=; R is CO.sub.2 H, CO.sub.2 lower alkyl, CH.sub.2 OH, CO.sub.2 alkali metal, CONHSOR.sup.3 m CONHR.sup.3a or --CH.sub.2 -5-tetrazolyl, X is O, S or NH; and where R.sup.1, R.sup.2, R.sup.3 and R.sup.3a are as defined herein.

7-Oxabicycloheptyl substituted heterocyclic amide or ester prostaglandin

7-Oxabicycloheptane substituted prostaglandin analogs useful in treating thrombotic and vasopastic disease have the structural formula ##STR1## wherein m is 1, 2 or 3; n is 1, 2, 3 or 4; Z is --(CH.sub.2).sub.2 --, --CH.dbd.CH-- or ##STR2## wherein Y is O, a single bond or vinyl, with the proviso that when n is 0, if Z is ##STR3## then Y cannot be O, and Z is --CH.dbd.CH--, n is 1, 2, 3 or 4; and when Y=vinyl, n=0; R is CO.sub.2 H, CO.sub.2 lower alkyl, CH.sub.2 OH, CO.sub.2 alkali metal, CONHSOR.sup.3, CONHR.sup.3a or --CH.sub.2 --5-tetrazolyl, X is O, S or NH; and where R.sup.1, R.sup.2, R.sup.3 and R.sup.3a are as defined herein.

7-oxabicycloheptyl substituted heterocyclic amide or ester prostaglandin

Novel cyclopropyl aza prostaglandin analogs are disclosed having the formula ##STR1## wherein A can be carbonyl, sulfonyl or a single bond. These compounds are useful, for example, as thromboxane antagonists.

Cyclopropyl aza prostaglandin analogs

The crystalline anhydrous form of [3S-[3.alpha.(Z), 4.beta.]]-3-[[(2-amino-4-thiazolyl) [(1-carboxy-1-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-1-azetidines ulfonic acid is prepared.

Crystalline anhydrous aztreonam

Vasodilating activity is exhibited by compounds having the formula ##STR1## wherein X can be --S--or --CH.sub.2 --; and

Benzazepine and benzothiazepine derivatives

Hypotensive activity is exhibited by compounds having the formulas ##STR1##

ACE-diuretics

Compounds of the formula ##STR1## wherein X is various imino or amino acids or esters are disclosed. These compounds possess angiotensin converting enzyme inhibition activity and depending upon the definition of X also possess enkephalinase inhibition activity.

Substituted urido amino and imino acids and esters

Hypotensive activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein R.sub.1 is hydrogen or alkyl;

Amino substituted benzenepropanols

Benzazepine derivatives useful, for example, as cardiovascular agents, are disclosed. These compounds have the general formula ##STR1## and pharmaceutically acceptable salts thereof.

3-substituted benzazepines

Vasodilating activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof.

Benzazepine derivatives

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Pennington, NJ, United States of America

David M Floyd