Wisconsin Alumni Research Foundation

Other

Lori A Plum

Hector Floyd Deluca

Margaret Clagett-Dame

Pawel Grzywacz

Rafal R Sicinski

Hector F Deluca

Rafal Barycki

Grazia Chiellini

Agnieszka Glebocka

Bulli Padmaja Tadi

Izabela K Sibilska

Agnieszka Flores

Julia B Zella

Hazel Holden

James Thoden

Katarzyna Plonska-Ocypa

Margaret Clagette-Dame

Sumithra Gowlugari

Nirca J Nieves

Katarzyna M Barycka

Katarzyna Sokolowska

Yanping F Wang

Steven Marling

Mary E Kaiser

James B Thoden

Hazel M Holden

Thomas A Brown

Jamie M Ahrens

Antonio Mouriño

Nirupama K Shevde

Hau Zhe Ke

Izabela Sibliska

Jamie Nehring

Ehren N Rudolph

Nircaq J Nieves

Moisés A Rivera-Bermúdez

Margaret Ciagett-Dame

John W Pike

Hector Deluca

Pawel K Grzywacz

Katarzyna Plonskaocypa

Angieszka Glebocka

Yangping F Wang

Angieszka A Flores

James Wonkee Kim

Disclosed are methods of purifying the compound (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24,25-trihydroxy-19-nor-vitamin Dto obtain the compound in crystalline form. The methods typically include the steps of dissolving (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24,25-trihydroxy-19-nor-vitamin Din a solvent comprising ethyl acetate and hexane to form a solution, allowing crystals of (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24,25-trihydroxy-19-nor-vitamin Dto form and precipitate from the solution, and recovering the crystals of (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24,25-trihydroxy-19-nor-vitamin Dfrom the solution.

Procedure for crystallization of (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24-25-trihydroxy-19-nor-vitamin D

A method of treating an MS patient with homosalate, octyl salicylate, or a combination is disclosed.

Use of homosalate and octyl salicylate to treat multiple sclerosis

Disclosed are 1&#x3b1;,25-dihydroxy-24,24-difluoro-2-methylene-19-nor-vitamin D analogs and their pharmaceutical uses. These new vitamin D analogs are 19-nor-vitamin D analogs having two fluorine atom substitutions at the 24 position (C-24) in the side chain and optionally having a 2-methylene substituent.

(20S)-1-&#x3b1;,25-dihydroxy-24,24-difluoro-19-nor-vitamin Danalogs and their pharmaceutical uses

This invention discloses 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-vitamin D analogs, and specifically 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-1&#x3b1;-hydroxyvitamin D, and pharmaceutical uses therefor. This compound exhibits relatively high transcription activity as well as 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 shows low activity in vivo on bone calcium mobilization, 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-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-vitamin D analogs

Disclosed are methods of administering 2-methylene-19-nor-(20S)-1&#x3b1;,25-dihydroxyvitamin Dto treat primary hyperparathyroidism and/or to treat and/or prevent the symptoms of primary hyperparathyroidism in as subject having or at risk for developing primary hyperparathyroidism, preferably without inducing hypercalcemia in the patient.

Use of 2-methylene-19-NOR-(20S)-1-alpha,25-dihydroxyvitamin D3 to treat primary hyperparathyroidism

Disclosed are pharmaceutical compositions and methods of combination therapy that include or utilize low doses of 2-methylene-19-nor-(20S)-1&#x3b1;,25-dihydroxyvitamin Dand a calcimimetic to treat and/or prevent secondary hyperparathyroidism and/or its accompanying symptoms in a subject having or at risk for developing secondary hyperparathyroidism.

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Disclosed are methods of administering 2-methylene-19-nor-(20S)-1&#x3b1;,25-dihydroxyvitamin Dto treat and/or prevent secondary hyperparathyroidism and/or its accompanying symptoms in a subject having or at risk for developing secondary hyperparathyroidism.

Cyclopropane-containing vitamin D analogs of formulas I and IV are provided. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions. 

Disclosed are methods of administering 2-methylene-19-nor-(20S)-1&#x3b1;,25-dihydroxyvitamin Dto treat and/or prevent secondary hyperparathyroidism and/or its accompanying symptoms in a subject having or at risk for developing secondary hyperparathyroidism, including a subject previously administered a calcimimetic.

Use of 2-methylene-19-nor-(20S)-1&#x3b1;,25-dihydroxyvitamin D3 to prevent secondary hyperparathyroidism or the symptoms thereof

Disclosed are 2-methylene analogs of vitamin Dand related compounds, their biological activities, and various pharmaceutical uses for these analogs. Particularly disclosed are 1&#x3b1;-hydroxy-2-methylene-vitamin D, (20S)-1&#x3b1;-hydroxy-2-methylene-vitamin D, and (5E)-1&#x3b1;,25-dihydroxy-2-methylene-vitamin D, their biological activities, and various pharmaceutical uses for these compounds including methods of treating and/or preventing bone diseases and disorders.

Synthesis and biological activity of 2-methylene analogs of calcitriol and related compounds

Use of 2-methylene-19-nor-(20S)-1-alpha,25-dihydroxyvitamin D3 to treat secondary hyperparathyroidism in patients previously treated with calcimimetics

Disclosed are (22E)-2-methylene-22-dehydro-1,24,25-trihydroxy-19-nor-vitamin Dcompounds, their biological activities, and various pharmaceutical uses for these compounds. Particularly disclosed are (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24,25-trihydroxy-19-nor-vitamin Dand (22E)-(24S)-2-methylene-22-dehydro-1&#x3b1;,24,25-trihydroxy-19-nor-vitamin D, their biological activities, and various pharmaceutical uses for these compounds.

Oral and topical pharmaceutical compositions, kits and methods of treatment thereof for treating various skin disorder including acne, psoriasis, ichthyosis, photoaging, photodamaged skin, and, skin cancer. Exemplary vitamin D analogs as active pharmaceutical ingredients include 2-methylene-19-nor-20(S)-1&#x3b1;-hydroxy-bishomopregnacalciferol, 19-nor-26,27-dimethylene-20(S)-2-methylene-1&#x3b1;,25-dihydroxyvitamin D, 2-methylene-1&#x3b1;,25-dihydroxy-(17E)-17(20)-dehydro-19-nor-vitamin D, 2-methylene-19-nor-(24R)-1&#x3b1;,25-dihydroxyvitamin D, 2-methylene-(20R,25S)-19,26-dinor-1&#x3b1;,25-dihydroxyvitamin D, 2-methylene-19-nor-1&#x3b1;-hydroxy-pregnacalciferol, 1&#x3b1;-hydroxy-2-methylene-19-nor-homopregnacalciferol, (20R)-1&#x3b1;-hydroxy-2-methylene-19-nor-bishomopregnacalciferol, 2-methylene-19-nor-(20S)-1&#x3b1;-hydroxy-trishomopregnacalciferol, 2-methylene-23,23-difluoro-1&#x3b1;-hydroxy-19-nor-bishomopregnacalciferol, 2-methylene-(20S)-23,23-difluoro-1&#x3b1;-hydroxy-19-nor-bishomopregnancalciferol, (2-(3'hydroxypropyl-1&#x2032;,2&#x2032;-idene)-19,23,24-trinor-(20S)-1&#x3b1;-hydroxyvitamin D, 2-methylene-18,19-dinor-(20S)-1&#x3b1;,25-dihydroxyvitamin D, a stereoisomer thereof, a prodrug thereof in oral compositions, a salt thereof, and/or a solute thereof. Compounds that activate retinoic acid receptors, such as retinoyls and retinoyl esters, include 13-cis-retinoic acid, all-trans-retinoic acid, (2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexeneyl)nona-2,4,6,8-tetraenoic acid, 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraenoic acid, 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-napthoic acid, 4-[1-(3,5,5,8,8-pentamethyl-tetralin-2-yl)ethenyl]benzoic acid, retinobenzoic acid, ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl]pyridine-3-carboxylate, retinoyl t-butyrate, retinoyl pinacol, retinoyl cholesterol, an isomer thereof, a prodrug thereof for oral compositions, an ester thereof, a salt thereof, and/or, a solute thereof. Combinations of such active ingredients demonstrate synergistic efficacy.

Methods of use to orally and topically treat acne and other skin conditions by administering a 19-nor containing vitamin D analog with or without a retinoid

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Arena, WI, United States of America

Lori A Plum