Wisconsin Alumni Research Foundation

Sumithra Gowlugari

Hector Floyd Deluca

Margaret Clagett-Dame

Rafal R Sicinski

Lori A Plum

Pawel Grzywacz

Hazel Holden

James Thoden

Hector F Deluca

This invention discloses 2&#x3b1;-methyl-19-nor-vitamin D analogs, and specifically 2&#x3b1;-methyl-19-nor-1&#x3b1;-hydroxy-homopregnacalciferol and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also has little, if any, calcemic activity and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. This compound may also be used for the treatment or prevention of obesity.

2&#x3b1;-methyl-19-nor-1&#x3b1;-hydroxy-homopregnacalciferol and its uses

A method of minimizing or reducing the toxicity of a retinoid having a free carboxyl group and the resulting modified retinoids are described. The method comprises the step of esterifying the carboxyl group of the retinoid with a highly sterically hindered compound, which is preferably a secondary or tertiary alcohol. The resulting retinoid esters are rendered much less toxic than the starting or parent retinoid. This process provides a retinoid ester analog of reduced toxicity so that it may be administered orally with minimal side effects and with a much greater therapeutic window. The modified retinoid compounds are useful in the treatment and prophylaxis of all diseases and disorders where retinoid compounds have been shown effective.

Modified retinoid compounds and their uses

2-Methylene-19-nor-24(S) and 24(R) derivatives of 1&#x3b1;,25-dihydroxyvitamin Dare disclosed. These compounds are characterized by minimal bone calcium mobilization activity and relatively high intestinal calcium transport activity. This results in novel therapeutic agents for the treatment of diseases such as renal osteodystrophy, autoimmune diseases, and osteoporosis. These compounds also exhibit pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as anticancer agents and for use treating skin diseases such as psoriasis 

2-methylene-19-nor-vitamin D2 compounds

A method of making 1&#x3b1;-hydroxy-2-methylene-19-nor-homopregnacalciferol. The method includes the steps of condensing a bicyclic ketone with an allylic phosphine oxide to produce a protected 19-nor-pregnacalciferol analog, thereafter cleaving the protecting group to form 22-alcohol, converting the alcohol to an ester, reducing the ester to 17&#x3b2;-isopropyl-19-nor-vitamin D analog, and finally deprotecting the 17&#x3b2;-isopropyl derivative to form the desired compound.

Method of synthesizing 1alpha-hydroxy-2-methylene-19-nor-homopregnacalciferol

A method of purifying 2-methylene-19-nor-20(S)-1&agr;-hydroxy-bis-homo-pregnacaciferol to obtain 2-methylene-19-nor-20(S)-1&agr;-hydroxy-bis-homo-pregnacalciferol in crystalline form. The method includes the steps of boiling a solvent such as acetone under inert atmosphere, dissolving a product containing 2-methylene-19-nor-20(S)-1&agr;-hydroxy-bis-homo-pregnacalciferol to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of 2-methylene-19-nor-20(S)-1&agr;-hydroxy-bis-homo-pregnacalciferol crystals, and recovering the 2-methylene-19-nor-20(S)-1&agr;-hydroxy-bis-homo-pregnacalciferol crystals.

2-methylene-19-nor-20(S)-1&agr;-hydroxy-bis-homo-pregnacalciferol in crystalline form

A method of making 1&agr;-hydroxy-2-methylene-19-nor-homopregnacalciferol. The method includes the steps of condensing a bicyclic ketone with an allylic phosphine oxide to produce a protected 19-nor-pregnacalciferol analog, thereafter cleaving the protecting group to form 22-alcohol, converting the alcohol to an ester, reducing the ester to 17&bgr;-isopropyl-19-nor-vitamin D analog, and finally deprotecting the 17&bgr;-isopropyl derivative to form the desired compound.

Method of synthesizing 1&agr;-hydroxy-2-methylene-19-nor-homopregnacalciferol

This invention discloses 1&agr;-hydroxy-2-methylene-19-nor-homopregnacalciferol and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also has little, if any, calcemic activity and therefore may be used to treat immune disorders in humans as well as renal osteodystrophy.

1&agr;-hydroxy-2-methylene-19-nor-homopregnacalciferol and its uses

This invention discloses 1&agr;-hydroxy-2-methylene-19-nor-homopregnacalciferol and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anticancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also has little, if any, calcemic activity and therefore may be used to treat immune disorders in humans as well as renal osteodystrophy.

Growing community of inventors

Fremont, CA, United States of America

Sumithra Gowlugari