Endorecherche, Inc.

Other

Yves M Merand

Fernand Labrie

Shankar Mohan Singh

Sylvain Gauthier

Joel A Sequeira

Donald Poirier

Alain Belanger

Van Luu-The

Marc Fournier

Nicholas DeAngelis

Shanshank Mahashabde

Louis Provencher

Novel methods of medical treatment and/or inhibition of development of diseases are disclosed for diseases that are sensitive to androgenic or estrogenic activity. The treatments utilize inhibitors of type 5 and/or type 3 17&bgr;-hydroxysteroid dehydrogenase. Novel inhibitors of type 5 17&bgr;-hydroxysteroid dehydrogenase are also disclosed, as are novel inhibitors of type 3 17&bgr;-hydroxysteroid dehydrogenase.

Inhibitors of type 5 and type 3 17&bgr;-hydroxysteroid dehydrogenase and methods for their use

Methods for treating sex steroid-dependent diseases by inhibiting sex steroid activity include administration of novel compounds which include an androgenic nucleus substituted at a ring carbon with at least one substituent specified herein. Such compounds may function by inhibiting sex steroid synthesis (both estrogen and androgen synthesis) and/or by antagonistically blocking androgen receptors.

Androgen derivatives for use in the inhibition of sex steroid activity

Certain benzopyran antiestrogens are disclosed for treating estrogen sensitive diseases such as breast cancer. Prodrug forms provide ease of manufacturing, good shelf life, and bioavailability, and preferred stereoisomers are shown to be more effective than racemic mixtures.

Benzopyran-containing compounds and method for their use

Androgen nucleus derivatives having specified substituents at the 17.alpha. position are disclosed for use as antiandrogens for the treatment of androgen-dependent diseases. In some preferred embodiments, the compound ##STR1## is formulated together with pharmaceutically acceptable diluent or carrier for topical use in the treatment of androgen-dependent diseases associated with the skin.

Antiandrogens

Pharmaceutical compositions for the topical treatment of androgen-related conditions, e.g., acne in humans containing an amount of the compound represented by formula II effective for the topical treatment of the androgen-related conditions, e.g., acne ##STR1## dissolved in an alcohol-water solvent system, such as ethanol-water �97.6:2.4(w/w)! and having an apparent pH in the range of about 3.5 to 4.5, and containing a gelling agent are disclosed.

Stable antiandrogenic gel composition

Inhibitors of sex steroid activity, for example those having the general structure ##STR1## may be used as part of a pharmaceutical composition to provide antiestrogenic effects and/or to suppress estrogen synthesis. Such pharmaceutical compositions are useful for the treatment of breast cancer or other diseases whose progress is aided by activation of sex steroid receptors.

Sex steroid activity inhibitors

Novel derivatives of estrogenic nuclei, contain a side-chain substitution of the formula --R.sup.1 �B--R.sup.2 --!.sub.x L--G and may be used in pharmaceutical compositions as sex steroid activity inhibitors useful in the treatment of both androgen-related and estrogen-related diseases.

Estrogen nucleus derivatives for use in the inhibition of sex steroid

Certain steroidal and non-steroidal compounds have been found to inhibit androgen and estrogen formation. Such inhibition may aid in the reduction of the activity of these hormones and may be useful in the treatment of diseases where, for example, inhibition of androgen or estrogen activity is desired. Preferred inhibitors also possess antiestrogenic activity, thus providing the advantage of a double inhibitory action both on estrogen formation and on estrogen action (blockade of estrogen receptors by antiestrogenic action).

Inhibitors of sex steroid biosynthesis and methods for their production

Inhibitors of testosterone 5.alpha.-reductase activity, for example those of formula: ##STR1## wherein novel substituents are provided at the R.sup.4, R.sup.6, R.sup.7, R.sup.17.alpha. and/or R.sup.17.beta. positions are useful for the treatment of diseases whose progress is aided by activation of androgen receptors, e.g., prostate cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, androgenic alopecia and the like.

Inhibitors for testosterone 5.alpha.-reductase activity

Anti-estrogenic compounds and compositions

Novel antiestrogenic compounds are disclosed for use in therapeutic preparations for treatment of estrogen-dependent diseases. The compounds are specified diphenylethane and diphenylethylene analogs which show strong affinity for estrogen receptors but substantially lack the capacity to activate such receptors or otherwise act as agonists.

Therapeutic antiestrogens

Certain steroidal and non-steroidal compounds have been found to inhibit androgen and estrogen formation. Such inhibition may aid in the reduction of the activity of these hormones and may be useful in the treatment of diseases where, for example, inhibition of androgen or estrogen acitivity is desired. Preferred inhibitors also possess antiestrogenic activity, thus providing the advantage of a double inhibitory action both on estrogen formation and on estrogen action.

Novel aromatase inhibitors are disclosed for use in therapeutic preparations for treatment of estrogen-dependent diseases. The compounds are specified 7.alpha.-substituted androstanedione and androstenedione derivatives which show a strong inhibitory activity towards aromatase. The invention includes synthesis and pharmaceutical compositions of said compounds.

Aromatase inhibitors

Novel compounds for the inhibition of sex steroid activity for the treatment of both androgen-related and estrogen-related diseases include for example 15- and 16-halo substituted compounds such as: ##STR1## The compounds are characterized by an estrogenic nucleus substituted with a substituent of the formula --R.sup.1 [B--R.sup.2 --].sub.x L--G wherein

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Ste-Foy, Canada

Yves M Merand