The United States of America, As Represented by the Secretary, Department of Health and Human Services

Evestra, Inc.

Southwest Foundation for Biomedical Research

Everstra, Inc.

James W Cessac

Pemmaraju Narasimha Rao

Hyun K Kim

Richard P Blye

Carmie Kirk Acosta

Klaus Nickisch

Anne Marie Simmons

Susan L Mooberry

Kesavaram Narkunan

Tina L Tinley

Baishakhi Das

Pemmaranu N Rao

Pemmaraju N Rao

Described herein are compounds which exhibit progesterone antagonistic effects and methods of treating cancer using such compounds.

Progesterone antagonists

The present invention relates, inter alia, to compounds having the general formula: in which R, R, R, Rand X are as defined by the present specification. In addition to providing the compounds of Formula I, the present invention provides methods wherein the compounds of Formula I are advantageously used, inter alia, to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat meningiomas; to treat uterine leiomyomas; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce cervical ripening; to induce labor; and for contraception.

Structural modification of 19-norprogesterone I: 17-&#x3b1;-substituted-11-&#x3b2;-substituted-4-aryl and 21-substituted 19-norpregnadienedione as new antiprogestational agents

Described herein are 3-(6,6-ethylene-17&#x3b2;-hydroxy-3-oxo-17&#x3b1;-pregna-4-ene-17&#x3b1;-yl)propionic acid &#x3b3;-lactone derivatives having progestational and aldosterone antagonistic activity. Also described herein are methods of preparing and using these novel compounds.

Progestational 3-(6,6-ethylene-17B-hydroxy-3-oxo-17A-pregna-4-ene-17A-yl)propionic acid G-lactones

A compound having the general formula: in which: Ris a member selected from the group consisting of &#x2014;OCH, &#x2014;SCH, &#x2014;N(CH), &#x2014;NHCH, &#x2014;CHO, &#x2014;COCHand &#x2014;CHOHCH; Ris a member selected from the group consisting of halogen, alkyl, acyl, hydroxy, alkoxy, acyloxy, alkyl carbonate, cypionyloxy, S-alkyl and S-acyl; Ris a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy; Ris a member selected from the group consisting of hydrogen and alkyl; and X is a member selected from the group consisting of &#x2550;O and &#x2550;N&#x2014;OR, wherein Ris a member selected from the group consisting of hydrogen and alkyl. In addition to providing the compounds of Formula I, the present invention provides methods wherein the compounds of Formula I are advantageously used, inter alia, to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce labor; and for contraception.

21-substituted progesterone derivatives as new antiprogestational agents

Described herein are bismethylene-17&#x3b1; carbolactone derivatives having progestational and/or antimineralocorticoid and/or aldosterone antagonistic activity. Also described herein are methods of preparing and using these novel compounds.

Bismethylene-17A carbolactones and related uses

The present invention relates, inter alia, to compounds having the general formula:in which: Ris a member selected from the group consisting of &#x2014;OCH, &#x2014;SCH, &#x2014;N(CH), &#x2014;NHCH, &#x2014;NCH, &#x2014;NCH, &#x2014;NCHO, &#x2014;CHO, &#x2014;CH(OH)CH, &#x2014;C(O)CH, &#x2014;O(CH)N(CH), and &#x2014;O(CH)NCH; Ris a member selected from the group consisting of hydrogen, halogen, alkyl, acyl, hydroxy, alkoxy (e.g., methoxy, ethoxy, vinyloxy, ethynyloxy, cyclopropyloxy, etc.), acyloxy (e.g., acetoxy, glycinate, etc.), alkylcarbonate, cypionyloxy, S-alkyl, &#x2014;SCN, S-acyl and &#x2014;OC(O)R, wherein Ris a functional group including, but not limited to, alkyl (e.g., methyl, ethyl, etc.), alkoxy ester (e.g., &#x2014;CHOCH) and alkoxy (&#x2014;OCH); Ris a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy; Ris a member selected from the group consisting of hydrogen and alkyl; and X is a member selected from the group consisting of &#x2550;O and &#x2550;N&#x2014;OR, wherein Ris a member selected from the group consisting of hydrogen and alkyl. In addition to providing the compounds of Formula I, the present invention provides methods wherein the compounds of Formula I are advantageously used, inter alia, to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat meningiomas; to treat uterine leiomyomas; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce cervical ripening; to induce labor; and for contraception.

A compound having the general formula:in which: Ris a member selected from the group consisting of &#x2014;OCH, &#x2014;SCH, &#x2014;N(CH), &#x2014;NHCH, &#x2014;CHO, &#x2014;COCHand &#x2014;CHOHCH; Ris a member selected from the group consisting of halogen, alkyl, acyl, hydroxy, alkoxy, acyloxy, alkyl carbonate, cypionyloxy, S-alkyl and S-acyl; Ris a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy; Ris a member selected from the group consisting of hydrogen and alkyl; and X is a member selected from the group consisting of &#x2550;O and &#x2550;N&#x2014;OR, wherein Ris a member selected from the group consisting of hydrogen and alkyl. In addition to providing the compounds of Formula I, the present invention provides methods wherein the compounds of Formula I are advantageously used, inter alia, to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce labor; and for contraception.

The application discloses novel 2-alkoxyestradiol analogs which exhibit anti-proliferative properties, and methods of making and using such compounds to inhibit undesired cell proliferation and tumor growth. Additionally, methods are disclosed of treating diseases associated with undesired angiogenesis and undesired proliferation, and methods of treating infectious disease wherein the infectious agent is particularly susceptible to inhibition by agents that disrupt microtubule organization and function.

2-alkoxyestradiol analogs with antiproliferative and antimitotic activity

A compound having general formula (I) in which R is a member selected from the group consisting of &mdash;OCH , &mdash;SCH , &mdash;N(CH ) , &mdash;NHCH , &mdash;CHO, &mdash;COCH and &mdash;CHOHCH ; R is a member selected from the group consisting of halogen, alkyl, acyl, hydroxy, alkoxy, acyloxy, alkyl carbonate, cypionyloxy, S-alkyl and S-acyl; R is a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy; R is a member selected from the group consisting of hydrogen and alkyl; and X is a member selected from the group consisting of &mdash;O and &mdash;N&mdash;OR , wherein R is a member selected from the group consisting of hydrogen and alkyl. In addition to providing the compounds of formula (I), the present invention provides methods wherein the compounds of formula (I) are advantageously used, inter alia, to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce labor; and for contraception.

PROCESS FOR PREPARING 17&agr;-ACETOXY-11&bgr;-&lsqb;4-N,N(DIMETHYLAMINO)PHENYL&rsqb;-21-METHOXY-19-NORPREGNA-4,9-DIENE-3,20-DIONE, INTERMEDIATES USEFUL IN THE PROCESS , AND PROCESSES FOR PREPARING SUCH INTERMEDIATES

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San Antonio, TX, United States of America

James W Cessac