Abstract: This invention relates to compounds of structural formula (I): ##STR1## which are squalene synthase inhibitors and thus useful as cholesterol lowering agents. The compounds also exhibit antifungal activity and are inhibitors of farnesyl-protein transferase.
Type:
Grant
Filed:
August 21, 1992
Date of Patent:
December 14, 1993
Assignee:
Merck & Co., Inc.
Inventors:
Shieh-Shung T. Chen, Leeyuan Huang, John G. MacConnell, Jon D. Polishook, Raymond F. White
Abstract: This invention relates to compounds of structural formula ##STR1## which are inhibitors of squalene synthase and useful as cholesterol lowering agents.
Abstract: New Zaragozic acids have been isolated from a culture of MF5465. These compounds and their derivatives are active as squalene synthetase inhibitors and are useful in the treatment of hypercholesterolemia.
Abstract: Compounds of Structural Formula (I) ##STR1## are produced by directed biosynthesis. These compounds are squalene synthetase inhibitors useful as cholesterol-lowering agents.
Type:
Grant
Filed:
March 9, 1992
Date of Patent:
October 12, 1993
Assignee:
Merck & Co., Inc.
Inventors:
Kevin M. Byrne, Louis Kaplan, Mary N. Omstead
Abstract: Biosynthetic production of 7-[1',2',6',-7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1'( S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid, "triol acid", is accomplished by enzymatic hydrolysis of lovastatin acid or a salt thereof, by treating it with Clonostachys compactiuscula ATCC 38009 or ATCC 74178, or mutants thereof, or a cell-free extract derived therefrom, or a hydrolase derived therefrom. The triol acid and its lactone form are both inhibitors of HMG-CoA reductase and thus useful as anti-hypercholesterolemic agents, and may also serve as intermediates for preparation of other HMG-CoA reductase inhibitors. Also, in the synthesis of simvastatin by direct methylation of lovastatin, selective hydrolysis of residual lovastatin salt by treatment with Clonostachys compactiuscula ATCC 38009 or ATCC 74178 or mutants thereof or a cell-free extract derived therefrom, or a hydrolase derived therefrom yields the "triol" salt which can be easily separated from simvastatin.
Type:
Grant
Filed:
February 7, 1992
Date of Patent:
June 29, 1993
Assignee:
Merck & Co., Inc.
Inventors:
Michael J. Conder, Steven J. Cianciosi, William H. Cover, Rebecca L. Dabora, Eric T. Pisk, Robert W. Stieber, Bogdan Tehlewitz, Gregory L. Tewalt
Abstract: Avermectin derivatives are disclosed wherein the 4"-hydroxy group is replaced by a substituted alkylthio or acylthio group or an iodo 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 from the 4"- and 4'-trifluoromethanesulfonyl avermectin derivatives with halo- or sulfur-containing nucleophiles. The 4"- and 4'-.alpha.- and .beta.-trifluoromethane sulfonates are prepared selectively and converted into 4"- or 4'-alkyl- or acylsulfides, or iodides using the appropriate sulfur-containing or iodine nucleophile. Substituted sulfoxy and sulfonyl substituents at the 4"- and 4'-positions are prepared from oxidation of the corresponding substituted sulfides. The new compounds are potent anti-parasitic agents; in particular, the compounds are anthelmintic, insecticidal and acaricidal agents.