Merck + Co., Inc.

Bruce O Linn

Helmut H Mrozik

Michael H Fisher

Howard Jones

Tsung-Ying Shen

Bruce E Witzel

Richard J Bochis

Peter Kulsa

Aino Lusi

Richard B Greenwald

Avermectin compounds are substituted at the 4', 4' or 13-postion hydroxy group with an alkylthioalkyl group and are optionally substituted at the other reactive positions of the avermectin molecule. The compounds are prepared by reacting protected avermectins, avermectin monosaccharides or avermectin aglycones with dialkylsulfoxides. The compounds are potent antiparasitic agents and compositions for such uses are also disclosed.

Alkylthio alkyl avermectins are active antiparasitic agents

There are disclosed derivatives of avermectin compounds wherein one or both of the 13-oleandrose saccharide groups lack the methyl group of the 3'- or 3'-methoxy. Such compounds are potent anthelmintic and antiparasitic agents.

Derivatives of 3'- and 3'-O-desmethyl avermectin compounds, compositions

Novel avermectin derivatives are disclosed, wherein the 4'-hydroxy group is replaced by a substituted acylamino or benzoylamino group. These avermectin derivatives can be further derivatized at the 5- and 23-positions as ketoximes or O-substituted ketoximes. The 4'-substituted avermectin derivatives are prepared by the acylation of the known 4'-aminoavermectins with acylating reagents. The new compounds are potent anti-parasitic agents, in particular, the compounds are anthelmintic, insecticidal and acaricidal agents.

Avermectin derivatives

There are disclosed novel avermectin compounds wherein the 4' or 4' hydroxy group is oxidized to an oxo group and replaced with a semicarbazone, carbonyl- or sulfonyl- hydrazone, hydrazone, or oxime, and optionally reduced to the corresponding semicarbazide, carbonyl- or sulfonyl-hydrazide or hydrazine. The semicarbozones and hydrazones are prepared from the 4' or 4' oxo compound using the corresponding semicarbazides or hydrazines. The compounds have utility as anti-parasitic agents and compounds for that use are also disclosed. The compounds are also highly potent insecticides against agricultural pests. Compositions for such uses are also disclosed.

Novel substituted and unsubstituted 13-(alkoxy)methoxy derivatives of the avermectin aglycones are useful as anthelmintic and antiparasitic agents. The compounds are also useful as pesticides and insecticides against agricultural pests. Included herein are novel intermediates useful in the process for preparing said avermectin aglycone derivatives. Compositions of said derivatives and methods of administering said compositions are also disclosed.

Substituted and unsubstituted 13-(alkoxy)methoxy derivatives of the

There are disclosed novel avermectin and milbemycin compounds wherein the 13-position is oxidized to a keto function. The 13-keto derivatives are prepared from the 13-hydroxy compounds by oxidizing the 13-position with a suitable oxidizing agent. The avermectin and milbemycin 13-keto derivatives are active in their own right and also serve as intermediates in the preparation of 13-imino and 13-amino derivatives. The 13-keto, imino and amino 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.

Avermectin and milbemycin 13-keto, 13-imino and 13-amino derivatives

Compounds of the efrotomycin class having a 4-hydroxy-2-pyridone terminal group are converted into 4-amino-4-dehydroxy compounds. The amino group may be substituted with various substituents. The processes for the preparation of such compounds are also disclosed. The amino derivatives have antimicrobial, and growth promotion properties and compositions for such uses are also disclosed.

4-Amino-4-dehydroxy derivatives of efrotomycin and related compounds

Complexes of pyromellitic diimide compounds which are ruminant feed additives and which improve feed efficiency are disclosed. The pyromellitic diimide compounds may be unsubstituted pyromellitic diimide itself, or one of the nitrogen atoms may be substituted with an alkyl or substituted alkyl group. The pyromellitic diimide nucleus may also be substituted. The pyromellitic diimide compound is complexed with a compound containing an amide, amidine or thioamide linkage. The complexing agent may be either cyclic or open chain. Compositions using the complexes as ruminant feed additives are also disclosed.

Pyromellitic diimide complexes

Novel substituted pyromellitic diimides are disclosed wherein the compounds are assymetrically substituted with a variety of substituent groups. Processes for the preparation of such compounds are also disclosed. The novel assymetrically substituted pyromellitic diimides are useful for administration to ruminant animals to increase feed efficiency, shift volatile fatty acid production in the ruminants from acetate with an increase in the more energetically efficient propionate and butyrate and to suppress methane formation in the rumen. Composition and methods of treatment utilizing said compounds as the active ingredient thereof are also disclosed.

Pyromellitic diimides and method of increasing feed efficiency in

Symmetrically substituted pyromellic diimides are disclosed wherein the compounds are substituted with a variety of substituent groups. The symmetrically substituted compounds are useful for administration to ruminant animals to increase feed efficiency, shift volatile fatty acid production in the ruminant from acetate with an increase in the more energetically efficient propionate and butyrate and to suppress methane formation in the rumen. Compositions and methods of treatment utilizing said compounds as the active ingredient thereof are also disclosed.

Symmetrically substituted pyromellitic diimides as ruminant feed

New substituted indenyl acetic acids and nontoxic pharmaceutically acceptable amides, esters and salts derived therefrom. The substituted indenyl acetic acids disclosed herein have anit-inflammatory, anti-pyretic and analgesic activity.

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Bridgewater, NJ, United States of America

Bruce O Linn