Merck + Co., Inc.

Chan-Hwa Kuo

Tesfaye Biftu

David Taub

Norman L Wendler

Conrad Santini

Robert M Burk

Arthur A Patchett

Michael H Fisher

William H Parsons

Ann E Weber

Danqing D Feng

Mitree M Ponpipom

Robert L Bugianesi

John J Acton, Iii

Yuan-Ching P Chiang

Gui-Bai Liang

Elizabeth M Naylor

Narindar N Girotra

Gregory D Berger

Claude Dufresne

James D Bergstrom

Robert W Marquis, Jr

Lori L Whiting

Sandra P Plevyak

Oxadiazole substituted benzenesulfonamides are selective .beta..sub.3 adrenergic receptor agonists with very little .beta..sub.1 and .beta..sub.2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in cells. The compounds thus have potent activity in the treatment of Type II diabetes and obesity. The compounds can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduced neurogenic inflammation or as antidepressant agents. The compounds are prepared by coupling an aminoalkylphenyl-sulfonamide with an appropriately substituted epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for increasing gut motility are also disclosed.

Oxadiazole benzenesulfonamides as selective .beta..sub.3 Agonist for the

Cholesterol lowering compounds

This invention is directed to compounds of formula (I) which are novel C3- or C5-acyl sulfonamide, carboxamic acid or tetrazolyl analogs of the Zaragozic acids. These compounds inhibit the enzyme squalene synthase and are useful as cholesterol lowering agents. ##STR1##

Mevinolin is converted to its 4a',5'-dihydro derivative by a route involving protection of the 3',4'-double bond followed by reduction of the 4a',5'-double bond followed by deprotection of the 3',4'-positions.

Process for 4a'(R),5'-dihydromevinolin

Hydrogenation of the natural fermentation product, mevinolin, MK-803, results in the production of dihydro- and tetra-hydro derivatives and hydrogenation of the naturally occurring dihydromevinolin results in the formation of a tetrahydro derivative. These several products with the exception of cis-(4.alpha..beta., 8.alpha..beta.-)-tetrahydromevinolin are potent inhibitors of cholesterol biosynthesis.

Hypocholesterolemic hydrogenation products and process of preparation

Disclosed is a novel stereospecific synthesis of Prostaglandin E.sub.1.

Prostaglandin E.sub.1 intermediate

6 .alpha.-Carboxy-5.alpha. (1-hydroxyethyl)-2-cyclohexene-1-heptanoic acid, .gamma. - lactone, and lower alkyl and aralkyl esters thereof, are useful intermediates for the production of Prostaglandin E.sub.1.

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South Plainfield, NJ, United States of America

Chan-Hwa Kuo