National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Department of Health

The United States of America

Other

Hyun K Kim

Richard P Blye

Pemmaraju Narasimha Rao

Carmie Kirk Acosta

James W Cessac

Anne Marie Simmons

Gabriel Bialy

Richard Blye

Charles L Carter

Josef Fried

Daniel H Fowler

Sydney Archer

Brian J Czerniecki

Peter A Cohen

Carl Djerassi

By Lucie Crabbe, Executor

Pierre Crabbe, Deceased

Egon R Diczfalusy

James E Burdett, Jr

Pemmaraju Narasinha Rao

Pemmaraju N Rao

James W Cessas

Methods of using 7&#x3b1;,11&#x3b2;-dimethyl-17&#x3b2;-hydroxy-4-estren-3-one bucyclate (I) and 7&#x3b1;,11&#x3b2;-dimethyl-17&#x3b2;-hydroxyestr-4-en-3-one 17-undecanoate (II) for various hormonal therapies, dosage forms comprising 7&#x3b1;,11&#x3b2;-dimethyl-17&#x3b2;-hydroxy-4-estren-3-one bucyclate and 7&#x3b1;,11&#x3b2;-dimethyl-17&#x3b2;-hydroxyestr-4-en-3-one 17-undecanoate, and processes for their preparation.

Method of making and using 7&#x3b1;, 11&#x3b2;-dimethyl-17&#x3b2;-hydroxyestr-4-en-3-one 17-undecanoate

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

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

Disclosed are compounds of the formula (I) wherein R is C-Calkyl, which may be optionally further substituted with one or more of C-Ccycloalkyl groups, or a C-Ccycloalkyl, which may be optionally substituted with one or more C-Calkyl groups, R' is hydrogen or lower alkyl, R&#x2033; is a C-Calkyl or halo, and the bond between C14 and C15 can be a single bond or double bond. Also disclosed are pharmaceutical compositions comprising such compounds and methods of use thereof. These compounds can find use in treating a number of diseases or conditions such as hypogonadism, osteoporosis, and anemia, in providing hormonal therapy and contraception, as an anabolic agent, and in suppressing the release of hormones such as the luteinizing hormone.

Nandrolone 17&#x3b2;-carbonates

Methods of using 7&#x3b1;,11&#x3b2;-dimethyl-17&#x3b2;-hydroxyestra-4,14-dien-3-one (III) and 17 esters thereof for various hormonal therapies, oral and parenteral dosage forms comprising these actives, and processes for their preparation.

Methods of making, using and pharmaceutical formulations comprising 7&#x3b1;, 11&#x3b2;-dimethyl-17&#x3b2;-hydroxyestra-4, 14-dien-3-one and 17 esters thereof

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.

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

Methods for the preparation of the 19-norprogesterone of formula I ##STR1## and its intermediates, in crystalline and amorphous forms are disclosed. The process is performed by (1) protecting the hydroxyl group of a compound of formula II ##STR2## (2) reacting the protected compound with an alkali or alkaline earth metal anion radical, (3) hydrolyzing the resulting compound, (4) ketalizing the carbonyl groups, (5) epoxidizing the compound, (6) opening the epoxide ring and introducing an N,N,dimethylamino-phenyl functional group into the axial position of C.sub.11, (7) deketalizing and dehydrating the resulting compound, and (8) acetylating to provide 17.alpha.-acetoxy-11.beta.-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-di ene-3,20-dione (I).

Method for preparing 17.alpha.-acetoxy-11.beta.-(4-N,

A method of isolating dendritic cells is described. This method involves elutriating peripheral blood samples in at least four flow rates from an elutriation rotor. Calcium ionophore is used to stimulate monocytes isolated during the process into dendritic cells. Treatments for diseases involving re-introduction of activated dentritic cells are also described.

Method for isolating dendritic cells

The invention presents 17.beta.-nitro and 11.beta., 17.beta.-dinitro esters of estradiol which are made from 3-acyloxy-17-keto- or 3,17-dihydroxy-1,3,5-estratrienes by processes known in the art. The compounds exhibit estrogenic activity.

Orally active derivatives of 1,3,5(10)-estratriene

Long-acting androgenic compositions comprising C.sub.4 -C.sub.6 cycloalkyl carboxylic acids of testosterone and a pharmaceutically acceptable carrier medium. The ester can be dissolved in an acceptable oily medium or suspended in an aqueous medium in the form of micronised particles or in the form of milled particles.

Long-acting androgenic compounds and pharmaceutical compositions thereof

A novel steroid, 7.alpha.-methylnorethindrone enanthate, having utility in prolonged suppression of fertility in female mammals, and methods for the use of the compound are claimed.

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Bethesda, MD, United States of America

Hyun K Kim