Sri International

Other

Japan Tobacco Inc.

Stanford Research Institute

Masato Tanabe

Richard H Peters

Wan-Ru Chao

David F Crowe

Ling Jong

John G Johansson

Dennis Mitsugu Yasuda

Wesley K Chong

Mitchell A Avery

George Detre

Kazuhiko Shigeno

Jyanwei Liu

Kenneth J Ryan

Peter D Hobbs

John A Lawson

Keith R Laderoute

Peters, Richard H

Anjali Pandey

Joy M Calaoagan

Khalid Amin

Syntheses of steroids such as 3-hydroxy-7&#x3b1;-methyl-21-[2'-methoxy-4&#x2032;-(diethylaminomethyl)-phenoxy]-19-norpregna-1,3,5(10)triene citrate ('SR 16234') and analogs thereof are provided, wherein 21-hydroxy-19-norpregna-4-en-3-one serves as a starting material or intermediate. The latter compound may be readily prepared from estrone-3-methyl ether. Certain intermediates in these syntheses also have value as therapeutic agents, for example in the treatment of prostate disorders such as prostatic cancer.

Synthesis of anti-estrogenic and other therapeutic steroids from 21-hydroxy-19-norpregna-4-en-3-one

Syntheses of steroids such as 3-hydroxy-7&agr;-methyl-21-&lsqb;2&prime;-methoxy-4&prime;-(diethylaminomethyl)-phenoxy&rsqb;-19-norpregna-1,3,5(10)triene citrate (&ldquo;SR 16234&rdquo;) and analogs thereof are provided, wherein 21-hydroxy-19-norpregna-4-en-3-one serves as a starting material or intermediate. The latter compound may be readily prepared from estrone-3-methyl ether. Certain intermediates in these syntheses also have value as therapeutic agents, for example in the treatment of prostate disorders such as prostatic cancer.

Novel anti-estrogenic compounds are provided which are useful to treat a variety of disorders, particularly estrogen-dependent disorders. Preferred compounds have a 1,3,5-estratriene nucleus, and are substituted at the C-17 or C-11 position with a molecular moiety which renders the compounds effective to competitively block the binding of estrogen to its receptor. Particularly preferred compounds are 17-desoxy-1,3,5-estratrienes. Therapeutic methods and pharmaceutical compositions are provided as well.

Anti-estrogenic steroids, and associated pharmaceutical compositions and methods of use

Novel anti-estrogenic compounds are provided which are useful to treat a variety of disorders, particularly estrogen-dependent disorders. Preferred compounds have a 1,3,5(10)-estratriene nucleus, and are substituted at the C-17 or C-11 position with a molecular moiety which renders the compounds effective to competitively block the binding of estrogen to its receptor. Particularly preferred compounds are 17-desoxy-1,3,5(10)-estratrienes. Therapeutic methods and pharmaceutical compositions are provided as well.

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

Anti-estrogenic steroids, and associated pharmaceutical compositions and

Novel compounds useful as inhibitors of estrone sulfatase are provided. The compounds have the structural formula (I) wherein r1 is an optional double bond, R.sup.1 and R.sup.2 are selected from the group consisting of hydrogen and lower alky, or together form a cyclic substituent (II) ##STR1## wherein Q is NH, O or CH.sub.2, and the other various substituents are as defined herein. Pharmaceutical compositions and methods for using the compounds of formula (I) to treat estrogen-dependent disorders are provided as well.

Estrone sulfamate inhibitors of estrone sulfatase, and associated

Novel compounds useful as inhibitors of estrone sulfatase are provided. The compounds have the structural formula (I) ##STR1## wherein X and Y, or Y and Z, form an oxathiazine dioxide ring or a dihydro-oxathiazine dioxide ring, and the other various substituents are as defined herein. Pharmaceutical compositions and methods for using the compounds of formula (I) to treat estrogen-dependent disorders are provided as well.

Steroid inhibitors of estrone sulfatase and associated pharmaceutical

Antiandrogenic agents and related pharmaceutical compositions and

Steriod inhibitors of estrone sulfatase and associated 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 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

Growing community of inventors

Palo Alto, CA, United States of America

Masato Tanabe