Merrell Dow Pharmaceuticals

The Dow Chemical Company

Merrell Pharmaceuticals, Inc.

Robert J Cregge

Gary A Flynn

Shyam Sunder

Thomas L Fevig

Patrick W Shum

Norton P Peet

Catherine A Alexander

Viviane Van Dorsselaer

Daniel G Schirlin

Robert A Farr

Nelsen L Lentz

Celine Tarnus

Jeffrey S Sabol

John E Coutant

David A Janowick

Daniel T Kohlman

The present invention relates to novel aminoacetylmercapto derivatives useful as inhibitors of enkephalinase and ACE.

Aminoacetylmercapto derivatives useful as inhibitors of enkephalinase

2,3-Dihydro-1-(8-methyl-1,2,4-triazolo [4,3-b]pyridazin-6-yl)-4(1H)-pyridinone has been prepared in substantially pure form and has been found to be useful for alleviating bronchial spasms in mammals. Synthesis of this material through phenylselenyl intermediates is described.

2,3-dihydro-

The present invention relates to compounds which are 4-hydroxy-4-alkenylcyclohexanecarboxylic acid derivatives possessing leukotriene antagonist activity. The compounds are useful in the treatment of allergic diseases, particularly in the treatment of human asthma. They are prepared by the reaction of an appropriate oxaspiro compound with a mercaptoalkanoic acid derivative.

4-hydroxy-4-(substituted alkenyl)cyclohexanecarboxylic acids

The present invention is directed to 2-hydroxy-4-alkylidenecyclohexanealkanoic acids having a mercaptoalkanoic acid substituent at the 3-position. Esters and amides corresponding to the acids referred to above are also encompassed by the present invention. These compounds are useful in the treatment of bronchial asthma and they are obtained by the reaction of an appropriate 2,3-epoxy-4-alkylidenecyclohexanealkanoate with a mercapto alkanoic acid ester in the presence of a tertiary amine. The indicated process gives the esters of the present invention which can be hydrolyzed to the corresponding free acids by standard procedures. The compounds described can be subjected to other known reactions to give the other compounds of the present invention.

Cyclohexanealkanoic acids

8-Methyl-1,2,4-triazolo[4,3-b]pyridazines having a hydroxyalkylamino substituent at the 6-position are described herein. The compounds involved are useful as bronchodilator agents and they are prepared by the reaction of 6-chloro-8-methyl-1,2,4-triazolo[4,3-b]-pyridazine with an appropriate amino alcohol.

6-Hydroxyalkylamino-8-methyl-1,2,4-triazolo-[4,3-b]pyridazine and

Substituted tetrahydroimidazo[2,1-a]phthalazine compounds such as 6-methylamino-7,8,9,10-tetrahydroimidazo[2,1-a]phthalazine are prepared by reacting a 6-halo-7,8,9,10-tetrahydroimidazo[1,2-a]phthalazine with an appropriate amine. The compounds are useful as bronchodilators.

6-Substituted tetrahydroimidazo[2,1-a]phthalazines and use as

Substituted tetrahydropyridazino[1,6-a]benzimidazole compounds such as 2-methylamino-6,7,8,9-tetrahydropyridazino[1,6-a]benzimidazole are prepared by reacting a 2-halo-6,7,8,9-tetrahydropyridazino[1,6-a]benzimidazole with an appropriate amine. The compounds are useful as bronchodilators.

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Zionsville, IN, United States of America

Robert J Cregge