Warner-lambert Company

Schering Corporation

James A Bristol

Ila Sircar

Raymond G Lovey

Bharat Kalidas Trivedi

Walter H Moos

Chester Puchalski

Richard William Skeean

Edward W Badger

Novel 4,5-dihydro-4,4-dialkyl-6-(substituted)phenyl-3(2H)-pyridazinones having unexpected activity for use as cardiotonic and antihypertensive agents.

4,5-dihydro-4,4-dialkyl-6-(substituted)phenyl-3(2H)-pyridazinones useful

Substituted 4,5-dihydro-6-(substituted)phenyl-3(2H)-pyridazinone compounds and 6-(substituted)phenyl-3(2H)-pyridazinone compounds and pharmaceutically acceptable salts thereof are useful as cardiotonic and antihypertensive agents. Said compounds cause a significant increase in myocardial contractility in the dog. Said compounds also cause a decrease in blood pressure in the spontaneously hypertensive rat. Said compounds are produced by reacting substituted .gamma.-oxobenzenebutanoic acids with suitably substituted hydrazines to provide 4,5-dihydro-6-(substituted)phenyl-3(2H)-pyridazinones which are dehydrogenated to 6-(substituted)phenyl-3(2H)-pyridazinones. Both the intermediate 4,5-dihydro-6-(substituted)phenyl-3(2H)-pyridazinones and the 6-(substituted)phenyl-3(2H)-pyridazinones are useful as cardiotonic and antihypertensive agents.

Substituted 4,5-dihydro-6-(substituted)-phenyl-3(2H)-pyridazinones and

A novel method of producing 4,5-dihydro-6-(substituted)phenyl-5-methyl-3(2H)-pyridazinone compounds and the corresponding pharmaceutically acceptable salt compounds is provided as well as pharmaceutical compositions containing one or more of the compounds as active components of the compositions for their pharmacological activity, particularly their cardiotonic and/or antihypertensive activity. Said 5-methylpyridazinone compounds have greatly improved cardiotonic activity in vivo that causes, for example, a significant increase in myocardial contractility in the dog. Said compounds also cause a decrease in blood pressure in the spontaneously hypertensive rat. Said compounds are produced by a stepwise procedure in which one reacts a substituted morpholineacetonitrile with crotononitrile to obtain the corresponding 4-(substituted)-.beta.-methyl.gamma.-oxobenzenebutanoic acid and reacts the latter acid with hydrazine to provide the 4,5-dihydro-6-(substituted)phenyl-5-methyl-3(2 ,uns/H/ )-pyridazinone product.

4,5-dihydro-6-(substituted)phenyl-5-methyl-3-(2H)-pyridazinones and

Substituted 2,5-dihydro- and 2,4,4a,5-tetrahydro-3H-indeno[1,2-c]pyridazin-3-ones and pharmaceutically acceptable salts thereof are useful as cardiotonic and antihypertensive agents.

Substituted indeno-pyridazinones

N.sup.6 -Tricyclic adenosines and pharmaceutically acceptable acid addition salts having highly desirable central nervous system and cardiovascular properties, processes for their manufacture and pharmaceutical composition and methods for using said compounds and compositions are described.

N.sup.6 -tricyclic adenosines for treating hypertension

N.sup.6 -Substituted diarylalkyladenosines and pharmaceutically acceptable acid addition salts having highly desirable central nervous system and cardiovascular properties, processes for their manufacture and pharmaceutical compositions and methods for using said compounds and compositions are described.

N.sup.6 -substituted adenosines and method of use

N.sup.6 -substituted adenosines for treating pain

(S)-N.sup.6 -2-Hydroxypropyladenosines and pharmaceutically acceptable acid addition salts having highly desirable antihypertensive properties, processes for their manufacture and pharmaceutical compositions and methods for using said compounds and compositions are described.

(S)-N.sup.6 -2-hydroxypropyladenosines

Certain 2(1H)-pyridinones are cardiotonic agents. Methods for their preparation and use are disclosed.

Cardiotonic 2(1H)-pyridinones

Indeno[1,2-c]pyridazin-3-one derivatives useful as cardiotonic and

N.sup.6 -Tricyclic adenosines and pharmaceutically acceptable acid addition salts having highly desirable central nervous system and cardiovascular properties, processes for their manufacture and pharmaceutical compositions and methods for using said compounds and compositions are described.

N.sup.6 -tricyclic adenosines

4,5-Dihydro-6-[(substituted)-1H-imidazol-4-yl or 5-yl]-3(2H)-pyridazinones 6-[(substituted)-1H- imidazol-4-yl or 5-yl]-3(2H)-pyridazinones and pharmaceutically acceptable acid addition salts thereof are useful as cardiotonic and antihypertensive agents. The above compounds cause a significant increase in myocardial contractility in the dog and also cause a decrease in blood pressure in the spontaneously hypertensive rat. The compounds are produced by reacting the appropriate .gamma.-oxo-imidazolebutanoic acid with a suitably substituted hydrazine to provide 4,5-dihydro-6-(substituted)imidazolyl-3(2H)-pyridazinones which are oxidized to 6-(substituted)imidazolyl-3(2H)-pyridazinones.

4,5-Dihydro-6-[(substituted)-1H-imidazol-4-yl or

There are disclosed herein certain substituted imidazo[1,2-a]pyrazine compounds which are useful in the treatment of peptic ulcer diseases.

Imidazo[1,2-a]pyrazines

Substituted phenyl-pyridinones as cardiotonic agents

There are disclosed herein certain substituted imidazo[1,2-b]pyridazine compounds which are useful in the treatment of peptic ulcer diseases.

Growing community of inventors

Ann Arbor, MI, United States of America

James A Bristol