Sri International

Wan-Ru Chao

Masato Tanabe

Richard H Peters

Ling Jong

Wesley K Chong

John G Johansson

Nurulain Zaveri

David F Crowe

Kazuhiko Shigeno

Jyanwei Liu

Dennis Mitsugu Yasuda

Mitchell A Avery

Kenneth J Ryan

Ahlem Bensari

Peter D Hobbs

Nathan Collins

Keith R Laderoute

Lidia Sambucetti

Dominic Dinh

Joy M Calaoagan

Khalid Amin

The disclosure provides compositions and methods for treating multiple myeloma. In some embodiments, the compositions comprise (E)-3-hydroxy-21-[2'-(N,N-dimethylamino)ethoxy]-19-norpregna-1,3,5(10),17(20)-tetraene or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutical carrier.

Compositions and method for the treatment of multiple myeloma

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

Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of indole-3-carbinol metabolites wherein the structures and substituents of the compounds are selected to enhance the compounds' overall efficacy, particularly with respect to therapeutic activity, oral bioavailability, long-term safety, patient tolerability, and therapeutic window. The compounds are useful not only in treatment of cancer but also in prevention of cancer. One preferred class of the novel compounds has the structure of formula (IV) wherein:

Analogs of indole-3-carbinol metabolites as chemotherapeutic and chemopreventive agents

Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of indole-3-carbinol metabolites wherein the structures and substituents of the compounds are selected to enhance the compounds' overall efficacy, particularly with respect to therapeutic activity, oral bioavailability, long-term safety, patient tolerability, and therapeutic window. The compounds are useful not only in treatment of cancer but also in prevention of cancer. One preferred class of the novel compounds have the structure of formula (III) wherein R, R, R, R, R, R, R, R, R, R, R, and Rare defined herein. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.

Compounds useful as chemotherapeutic, chemopreventive, and antiangiogenic agents are provided. The compounds are flavanoids, including flavanones, flavanols, and chalcones. The compounds have the structure of formula (I) wherein Rthrough Rand Rthrough Rare defined herein, and &#x3b1;, &#x3b2;, and &#x3b3; are optional bonds, providing that when &#x3b1; is absent, &#x3b2; is present, and when &#x3b2; is absent, &#x3b1; is present. When &#x3b1; is present, preferred Rmoieties are selected from O, S, NH and CH, and when &#x3b1; is absent, preferred Rgroups are selected from OH, SH, NHand CH. When &#x3b3; is present, the preferred Rsubstituent is O, while when &#x3b3; is absent, the preferred Rsubstituent is OH. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.

Flavanoid compounds as chemotherapeutic, chemopreventive, and antiangiogenic agents

Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of polyphenol catechins that occur in green tea, such as epigallocatichin-3-gallate (EGCG), and have the structure of formula (I) wherein Rthrough Rare defined herein. Preferred Rmoieties are selected from O, S, NH and CH, and in exemplary compounds, Ris O and Ris a tri-substituted aroyloxy substituent, such as a 3,4,5-substituted benzoyloxy group. Pharmaceutical compositions are provided as well, as are methods of chemotherapy and chemoprevention.

Analogs of green tea polyphenols as chemotherapeutic and chemopreventive agents

Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of indole-3-carbinol metabolites wherein the structures and substituents of the compounds are selected to enhance the compounds' overall efficacy, particularly with respect to therapeutic activity, oral bioavailability, long-term safety, patient tolerability, and therapeutic window. The compounds are useful not only in treatment of cancer but also in prevention of cancer. One preferred class of the novel compounds have the structure of formula (I) wherein R, R, R, R, R, R, R, R, R, R, R, and Rare defined herein. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.

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.

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Sunnyvale, CA, United States of America

Wan-Ru Chao