Warner-lambert Company

Edna Mcconnell Clark Foundation

US Government As Represented by the Secretary of the Army

Leslie M Werbel

Edward Faith Elslager

Donald F Worth

Annette M Doherty

Mark J Suto

Sham Shridhar Nikam

Chitase Lee

Xue-min Cheng

Howard D Showalter

Brian Edward Kornberg

Daniele Marie Leonard

Ellen M Berman

Kyunghye Ahn

Dennis Joseph McNamara

Daniel Fred Ortwine

Anthony Denver Sercel

David B Capps

James D Hoeschele

Edgar A Steck

William R Turner

Vlad E Gregor

Ernest Bueding

Judith L Johnson

Jocelyn H Hung

William Turner

Norman Colbry

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

The invention is selected, novel, and known analogs of isoquinolinones of the formula ##STR1## and pharmaceutically acceptable salts thereof; novel pharmaceutical compositions; and a method for enhancing the lethal effects for tumor cells to treatment having DNA damaging activity such as ionizing radiation or with chemotherapeutic agents.

Substituted dihydroisoquinolinones and related compounds as potentiators

Novel cyclodiamineplatinum(II) and platinum(IV) complexes which are useful in inhibiting the growth of malignant neoplasms, as well as novel pharmaceutical compositions and methods of use, as well as processes for their manufacture are herein described.

Novel neutral mixed ligand platinum(II) and platinum(IV) complexes

Novel 6-substituted-4(3H)-quinazolinones are described as well as methods for the preparation and pharmaceutical composition of same, which inhabit the enzyme thymidylate synthase (TS) and are thus useful as anticancer agents.

Substituted quinazolinones as anticancer agents

Certain .alpha.-[(2-nitro-1H-imidazol-1-yl)methyl]-aziridinylethanols and the corresponding aziridine-ring opened analogs are useful as radiation sensitizers for X-irradiation therapy of tumors.

2-nitroimidazole derivatives useful as radiosensitizers for hypoxic

The subject 8-[6-(N-heterocyclic-substituted)hexylamino]-6-methoxy lepidine erivatives have the formula: ##STR1## wherein Z represents methyl or, together with the two contiguous carbon atoms, the benzo moiety of a benzopiperazinyl derivative when Y is --N(R')--, n is an integer from 0 to 2; Y represents --O--, --S--, --S(O)--, --S(O).sub.2 --, and --N(R')--; R' represents hydrogen, alkyl, lower alkyl, R' substituted lower alkyl, cycloalkyl, aryl, sulfonyl, saturated 1,4-diazepinyl, lower alkyl N-cyanocarboximidothioate, or --C(O)R''; R' represents at least one of hydroxy, alkoxy, aralkoxy, amino, lower alkyl substituted amino, phenyl, halogenated phenyl, or sufonyl; and R'' represents lower alkyl, alkoxy, aralkoxy, amino, lower alkyl substituted amino or aryl substituted amino; and pharmaceutically acceptable salts thereof. These derivatives afford improvement in means for the chemotherapy of leishmaniasis when administered parenterally or orally to infected animals.

Anti-leishmanial lepidine 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

Substituted anthra[1,9-cd]pyrazol-6(2H-ones have antimicrobial activity. Methods for their preparation, use and pharmaceutical compositions are disclosed.

Antimicrobial substituted anthra[1,9-cd]pyrazol-6(2H)-ones

Substituted-phenyl derivatives of 5-(1,4-piperazinyl)-2,4-pyrimidinediamine are effective as antibacterial and antitumor agents. Methods of preparing such compounds, pharmaceutical compositions based thereon, and a method of treating bacterial infections in a mammal in need of such treatment are disclosed.

Diaminopyrimidines

A compound of the formula ##STR1## in which A is ##STR2## n is 1, 2 or 3, and R is phenyl optionally substituted with halogen, alkyl, phenyl, cyano, hydroxy, alkoxy, mercapto, sulfinyl, sulfonyl, amino, nitro, trifluoromethyl and/or naphthyl radicals; or a furan, thiophene, pyridine, benzofuran, dibenzothiophene or thianthrene radical, or a pharmacologically acceptable salt thereof, for treating schistosomiasis.

Phenylpiperazines which are useful in the treatment of schistosomiasis

The title compositions containing N,N-diethyl-5-methyl-2H-12-benzothiopyrano-4,3,2-cd-indazole-2-ethanamine as the free base (I) or pharmaceutically acceptable acid addition salt, and methods for their use are provided. The compositions are useful for treating tumors in warm blooded animals. ##STR1##

N,N-diethyl-5-methyl-2H-1-benzothiopyrano-4,3,2-cd-indazole-2-ethanamine

7-Chloro-3-substituted aryl-3,4-dihydro-1,9-(2H,1OH) and 10-hydroxy-acridinedioneimines and their pharmaceutically acceptable salts and a process for preparing them are disclosed and claimed. The compounds are useful in the treatment of protozoan diseases.

7-Chloro-3-substituted aryl-3,4-dihydro-1,9(2H,10H) and 10 hydroxy

2-Chloro-4-(4-lower alkyl-1-piperazinyl)benzenemethanol, N.sup..omega. -oxides and their acid addition salts. These compounds are prepared by oxidizing the corresponding 2-chloro-4-(4-lower alkyl-1-piperazinyl)benzenemethanol. In addition, pharmaceutical compositions comprising said N-oxides and methods for treating schistosomiasis are disclosed.

Growing community of inventors

Ann Arbor, MI, United States of America

Leslie M Werbel