Merck + Co., Inc.

Thomas L Shih

Michael H Fisher

Helmut H Mrozik

Matthew J Wyvratt

Peter T Meinke

Ann E Weber

William R Schoen

Hyun O Ok

Elizabeth M Naylor

Prasun K Chakravarty

Emma R Parmee

Steven L Colletti

Richard Berger

Sriram Tyagarajan

Dong Ok

Howard C H Kuo

Ronald C Newbold

Philip Eskola

The present invention relates to novel nodulosporic acid derivatives, which are acaricidal, antiparasitic, insecticidal and anthelmintic agents.

C1 to C4 side chain modified nodulisporic acid analogs

Nodulisporic acid derivatives

Novel avermectin and milbemycin derivatives are disclosed, where the C-24 and C-25 carbon atoms are substituted by hydrogen, alkyl, alkenyl, substituted alkyl or substituted alkenyl groups. These compounds can be further substituted at the 4'-, 5-, 13-, and 23-positions. The new C-24 and C-25 substituted avermect prepared by cleavage of known and suitably protected avermectin and milbemycin compounds. The new compounds are potent anti-parasitic agents, in particular, the compounds are anthelmintic, insecticidal and acaricidal agents.

24-and 25-substituted avermectin and milbemycin derivatives

There are disclosed certain novel compounds identified as heterocyclic-fused lactams which promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to increase the stature of those afflicted with a lack of a normal secretion of natural growth hormone. Growth promoting compositions containing such heterocyclic-fused lactams as the active ingredient thereof are also disclosed.

Heterocyclic-fused lactams promote release of growth hormone

Substituted sulfonamides 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.

Substituted sulfonamides as selective .beta.-3 agonists for the

Substituted sulfonamides as selective .beta..sub.3 agonists for the

Avermectin derivatives, wherein the C-17-21-25-dioxaspirane substructure has been modified to include substitutions of heteratomic nucleophilic thiols at the 23,24-.alpha.-epoxide. These compounds can be similarly substituted at the 4'-, 5-, 13, and 25-positions. The new C-23 and C-24 substituted avermectin derivatives are potent anthelmintic, insecticidal and acaricidal agents.

Avermectin derivatives

There are disclosed avermectin derivatives with a hydroxy and hydrocarbon substituents at the 5, 10, 13, 23, 4' and 4' positions which are prepared by the reaction of the 5, 10, 13, 23, 4' or 4' ketone compound with an organo-metallic Grignard reagent. The compounds are potent antiparasitic and anthelmintic agents in human and animal therapy and are potent pesticidical agents against agricultural pests. Compositions containing such compounds as the active agent are also disclosed.

Alkyl avermectin derivatives

There are disclosed novel avermectin reduction products. The compounds are prepared by selective catalytic hydrogenation of avermectin-like compounds or by reaction of selected double bonds with electrophylic reagents. The reduced avermectin compounds have utility as anti-parasitic agents and compositions for that use are also disclosed. The compounds are also highly potent insecticides against agricultural pests. The reduced avermectin compounds have increased stability towards light which prolongs their insecticidal activities when applied to field crops subject to irradiation by sunlight.

Reduced avermectin derivatives

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Edison, NJ, United States of America

Thomas L Shih