Sri International

John G Johansson

Masato Tanabe

Wan-Ru Chao

Richard H Peters

Dennis Mitsugu Yasuda

Jyanwei Liu

Mitchell A Avery

Wesley K Chong

Kenneth J Ryan

David F Crowe

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 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.

A method is provided for isolating 5,7-diene-containing steroids, particularly 3.beta.-ols and esters of 3.beta.-ols, from a sterol mixture. The method involves (1) treating the mixture with a dienophile or with an oxidizable dienophile precursor in combination with an oxidizing agent so as to provide a Diels-Alder adduct of the 5,7-diene to be isolated, followed by (2) removal of the adduct from the mixture and (3) regeneration of the 5,7-diene with a suitable reducing agent. The invention also encompasses subsequent purification steps and intermediate modification of the Diels-Alder intermediate, e.g., wherein chemical conversion of the Diels-Alder adduct is effected prior to regeneration of the 5,7-diene. Novel compounds which are Diels-Alder adducts of 5,7-diene-containing steroids are provided as well.

Isolation of steroids containing a 5,7-diene functionality from a sterol

This invention relates to a stereoisomerically pure .DELTA..sup.2 compound of the formula (I): ##STR1## wherein: R.sup.1 is hydrogen or --(C.dbd.O)--R.sup.2, wherein:

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Menlo Park, CA, United States of America

John G Johansson