Warner-lambert Company

Parke-davis Company

Edward Faith Elslager

Rocco Dean Gogliotti

John Michael Domagala

Bharat Kalidas Trivedi

Gary Louis Bolton

Joseph P Sanchez

Leslie M Werbel

Terri Stoeber Purchase

Annette M Doherty

Sham Shridhar Nikam

Chitase Lee

Xue-min Cheng

Howard D Showalter

Brian Edward Kornberg

Daniele Marie Leonard

Kyunghye Ahn

Christopher Franklin Bigge

James C French

Gerard C Hokanson

Daniel Fred Ortwine

Josefino B Tunac

Anthony Denver Sercel

David B Capps

Donald F Worth

Vlad E Gregor

Tim A Smitka

Ellen M Berman

John H Wilton

Blanche D Graham

Wilbur R Leopold

Judith L Johnson

Stephen W Mamber

Isothiazolones having the general structure ##STR1## where A is a monocyclic or bicyclic ring which may contain up to 3 heteroatoms selected from O, S, and N; R.sup.1 and R.sup.2 are substituent groups such as alkyl, alkoxy, hydroxy, nitro, cyano, amino, and carboxy; and R.sup.5 is alkyl, cycloalkyl, phenyl, and Het. The isothiazolones are useful as anti-retroviral agents, anti-inflammatory agents, and anti-atherosclerotic agents.

Isothiazolones and pharmaceutical formulations

Isothiazolones

Arylthiol and dithiobisarylamide antibacterial and antiviral agents have the general formula ##STR1## where A is monocyclic or bicyclic aryl which can contain up to 3 heteroatoms selected from O, S, and N,

Arylthio compounds

Novel quinazoline inhibitors of endothelin converting enzyme are described, as well as methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin and in controlling hypertension, myocardial infarction and ischemia, metabolic, endocrinological, and neurological disorders, congestive heart failure, endotoxic and hemorrhagic shock, septic shock, subarachnoid hemorrhage, arrhythmias, asthma, acute and chronic renal failure, cyclosporin-A induced nephrotoxicity, angina, gastric mucosal damage, ischemic bowel disease, cancer, pulmonary hypertension, preeclampsia, atherosclerotic disorders including Raynaud's disease and restenosis, cerebral ischemia and vasospasm, and diabetes.

Quinazolines as inhibitors of endothelin converting enzyme

Isothiazolone compounds

Phenylthiols and dithiobisbenzamides are potent antibacterial and antiviral agents.

Arylthiol and dithiobisarylamide antibacterial and antiviral agents have the general formula ##STR1## where A is monocyclic or bicyclic aryl which can contain up to 3 heteroatoms selected from O, S, and N, R.sup.1 and R.sup.2 are substituent groups, X is ##STR2## or SO.sub.2 NR.sup.4 Z, Y is H or SZ when n is 1, a single bond when n is 2; R.sup.4 and Z can be hydrogen or alkyl.

Antibacterial and antiviral phenylthiols and dithiobisbenzamides have the formula ##STR1## where n is 1 or 2, Y is hydrogen when n is 1, and a single bond when n is 2; and R.sup.1 and R.sup.11 are substituent groups, R.sup.4 is hydrogen or alkyl, and Z is hydrogen, alkyl, cycloalkyl or sulfamoylphenyl.

5-Methyl-6-[[(3,4,5-trimethoxyphenyl)amino]-methyl]-2,4-quinazolinediamine (trimetrexate) has been shown to possess clinical activity against non-small cell lung cancer, head and neck squamous cancers, and breast cancer. The compound also demonstrates therapeutic synergy with several known antineoplastic agents. Methods of treating non-small cell lung cancer, head and neck cancers, and breast cancer by administering trimetrexate alone or in combination with other neoplastic agents is disclosed.

Method for treating non-small cell lung cancer, head and neck cancers

Acids, esters, imine acids, imine esters, and imine amides derived from 6-formyl-4,7,9-trihydroxy-1-phenazinecarboxylic acid, methyl ester and from 6-formyl-4,7,9-trihydroxy-8-methyl-1-phenazinecarboxylic acid, methyl ester demonstrate antimicrobial and antineoplastic activity. A purified strain of Streptomyces galanosa, NRRL 15738, is capable of producing 6-formyl-4,7,9-trihydroxy-8-methyl-1-phenazinecarboxylic acid, methyl ester in isolable quantities from a fermentation broth containing assimilable sources of carbon and nitrogen.

Antimicrobial and antitumor phenazine carboxaldehydes and derivatives

Substituted 2H-[1]benzopyrano[4,3,2-cd]indazoles, 2H-[1]benzothiopyrano[4,3,2-cd]indazoles, and 2H-[1]benzoselenino[4,3,2-cd]indazoles have demonstrated pharmacological activity against a broad spectrum of Gram-positive and Gram-negative bacteria, yeasts, and fungi, as well as activity against the L1210 and P388 murine leukemia cells lines. Pharmaceutical compositions containing the compounds and methods of employing the compounds in methods of treating bacterial or fungal infections and of inhibiting the growth of neoplasms in mammals are also disclosed.

Antibacterial benzo(chalcogeno)[4,3,2-cd]indazoles

Growing community of inventors

Ann Arbor, MI, United States of America

Edward Faith Elslager