Sri International

Syntex (u.s.a.) Inc.

Agouron Pharmaceuticals, Inc.

Wesley K Chong

Masato Tanabe

Wan-Ru Chao

Mitchell A Avery

David F Crowe

Dennis Mitsugu Yasuda

John G Johansson

Jian Jeffrey Chen

Arlindo Lucas Castelhano

Melwyn A Abreo

Steven Lee Bender

Judith Gail Deal

James E Bupp

Novel antiandrogenic agents are provided. An exemplary group of compounds has the structural formula (I) ##STR1## wherein R.sup.1 through R.sup.10, a and b are as defined herein. Pharmaceutical compositions and methods for using the compounds of formula (I) to treat androgen-related clinical conditions are provided, as are methods and compositions for using the compounds as contraceptive agents.

Method and composition for effecting contraception in a mammalian male

The present invention is directed to compound of the formula I: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y, and ##STR2## are as defined herein. These compounds are useful for inhibiting the activity of a metalloproteinase by contacting the metalloproteinase with an effective amount of the inventive compounds.

Metalloproteinase inhibitors, pharmaceutical compositions containing

Antiandrogenic agents and related pharmaceutical compositions and

Novel antihypercholesterolemic agents are provided. An exemplary group of compounds has the structural formula (I) ##STR1## wherein R is a C-17 side chain, R.sup.1 is --OH, .dbd.O, or the like, and X and Y are CH, C--OH, C--OCH.sub.3 or C--Z. Methods of using the compound of formula (I) or other novel oxysterol analogs to treat hypercholesterolemia are provided, as are pharmaceutical compositions containing the compounds.

Antihypercholesterolemic compounds and related pharmaceutical

Novel antihypercholesterolemic agents are provided. An exemplary group of compounds has the structural formula (I) ##STR1## wherein R is a C-17 side chain, R.sup.1 is --OH, .dbd.O, or the like, and X and Y are N, N.fwdarw.O, CH, C--OH, C--OCH.sub.3 or C--Z. Methods of using the compound of formula (I) or other novel oxysterol analogs to treat hypercholesterolemia are provided, as are pharmaceutical compositions containing the compounds.

Polyoxoheterocyclic tetracycles related to the Chinese antimalarial natural product qinghaosu (artemisinin) are disclosed. These materials have a ##STR1## core structure with an oxygen (carbonyl or alkyl ether) at position 12 and in some cases one or two alkyl or aralkyl substituents at position 11. These materials have antimalarial properties.

Antimalarial analogs of artemisinin

A process for synthesizing oxygen-containing polyoxatetracycle compounds and in particular analogs of the antimalarial agent known as qinghaosu or artemisinin is disclosed. The process employs as a reactant an olefinically unsaturated bicyclic bridging ketone having nonenolizable bridgehead moieties for both of its alpha positions. This ketone is converted to a vinylsilane that is subjected to ozonolytic cleavage of its olefinic bond to yield a member of a family of unique carboxyl/carbonyl-substituted vinylsilanes which may in turn optionally be subjected to a wide range of reactions prior to a final ozonolysis/acidification step which closes the oxygen-containing ring structure. The various intermediates are claimed as aspects of this invention as are novel tetracycles and their use as antimalarials.

Growing community of inventors

Encinitas, CA, United States of America

Wesley K Chong