9,10-seco-cyclopentanohydrophenanthrene Ring System Or 9,10-seco Cyclopentanohydrophenanthrene Ring System Having A Bond Between The 3- And 5-positions (e.g., Vitamin D Compounds, Cholecalciferols, Activated 7-dehydrocholesterols, Dihydrotachysterols, 3,5 Cyclovitamin D Compounds, Etc.) Patents (Class 552/653)
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Publication number: 20130324750Abstract: Disclosed are methods of purifying the compound (20R)-2-methylene-19-nor-24-difluoro-1?,25-dihydroxyvitamin D3 to obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals.Type: ApplicationFiled: March 14, 2013Publication date: December 5, 2013Applicant: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Agnieszka Flores, James B. Thoden, Hazel M. Holden
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Publication number: 20130324751Abstract: Disclosed are methods of purifying the compound (20R)-19-nor-24-difluoro-1?,25-dihydroxyvitamin D3 to obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals.Type: ApplicationFiled: March 14, 2013Publication date: December 5, 2013Applicant: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Agnieszka Flores, James B. Thoden, Hazel M. Holden
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Publication number: 20130295083Abstract: A method of treating islet cell transplant patients is described herein. The method comprises the steps of a) identifying an islet cell transplant patient, b) treating the patient with 2AMD or 2AMD analog and c) observing a prolonged period of normal glycemia is disclosed. A composition for treatment of islet cell transplant patient is disclosed as well, wherein the composition comprises 50-400 ng/day of 2AMD or 2AMD analog.Type: ApplicationFiled: February 20, 2013Publication date: November 7, 2013Applicant: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Carol M. Kiekhaefer
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Patent number: 8575136Abstract: Compounds of formula I are provided where X1 and X2 are independently selected from H or hydroxy protecting groups. Such compounds are used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.Type: GrantFiled: April 6, 2007Date of Patent: November 5, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Lori A. Plum, Margaret Clagett-Dame, Rafal Barycki
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Publication number: 20130252927Abstract: The present invention relates to treating/preventing conditions associated with an increased level of eotaxin in a human with 25-hydroxyvitamin D3 (calcifediol). Optionally, vitamin D3 may be used together with 25-hydroxyvitamin D3.Type: ApplicationFiled: December 5, 2011Publication date: September 26, 2013Applicant: DSM IP ASSETS, B.V.Inventors: Stephanie Krammer-Lukas, Elisabeth Stoecklin, Joseph Schwager, Swen Wolfram
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Publication number: 20130236540Abstract: Methods and compositions for treating 25-hydroxyvitamin D insufficiency and deficiency in a patient are described herein. The method includes orally administering to the patient a delayed, sustained release formulation including a first ingredient selected from the group consisting of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, or a combination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, or it includes gradually administering to the patient a sterile intravenous formulation including a first ingredient selected from the group consisting of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, or a combination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3.Type: ApplicationFiled: March 22, 2013Publication date: September 12, 2013Inventors: Charles W. Bishop, Keith H. Crawford, Eric J. Messner
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Patent number: 8518917Abstract: This invention discloses 2-methylene-19-nor-vitamin D analogs, and specifically (20S)-25-hydroxy-2-methylene-19-nor-vitamin D3 and (20R)-25-hydroxy-2-methylene-19-nor-vitamin D3, as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. Although these compounds have relatively low calcemic activities they may also be useful in the treatment of bone diseases due to their ability to act as prodrugs in vivo.Type: GrantFiled: October 21, 2011Date of Patent: August 27, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Izabela Sibliska, Lori A. Plum, Margaret Clagett-Dame, Rafal R. Sicinski, Katarzyna M. Barycka, Katarzyna Plonska-Ocypa, Rafal Barycki
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Patent number: 8519169Abstract: A method of purifying 1?-hydroxy-20-methyl-2-methylene-19,24,25,26,27-pentanorvitamin D3 to obtain 1?-hydroxy-20-methyl-2-methylene-19,24,25,26,27-pentanorvitamin D3 in crystalline form. The method includes the steps of preparing a solvent of either ethyl formate or a mixture of ethyl formate and hexane, dissolving a product containing 1?-hydroxy-20-methyl-2-methylene-19,24,25,26,27-pentanorvitamin D3 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 1?-hydroxy-20-methyl-2-methylene-19,24,25,26,27-pentanorvitamin D3 crystals, and recovering the 1?-hydroxy-20-methyl-2-methylene-19,24,25,26,27-pentanorvitamin D3 crystals.Type: GrantFiled: August 17, 2012Date of Patent: August 27, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Agnieszka Glebocka, James B. Thoden, Hazel M. Holden
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Publication number: 20130210781Abstract: To provide a novel vitamin D3 derivative useful as a therapeutic agent for osteoporosis. Provided is a vitamin D3 derivative represented by the following formula (1) or a medicinally acceptable solvate thereof: wherein R1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkylcarbonyloxyalkyl group with each alkyl having 1 to 6 carbon atoms, or an arylcarbonyloxyalkyl group with the aryl having 6 to 10 carbon atoms and the alkyl having 1 to 6 carbon atoms; R2 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms or, together with the other R2 and the carbon atom to which they are bound to, may form a cyclic alkyl group having 3 to 6 carbon atoms; R3 represents an alkyl group having 1 to 6 carbon atoms or, together with the other R3 and the carbon atom to which they are bound to, may form a cyclic alkyl group having 3 to 6 carbon atoms; X represents an oxygen atom or a methylene group; and n represents an integer of 1 or 2.Type: ApplicationFiled: October 24, 2011Publication date: August 15, 2013Applicant: TEIJIN PHARMA LIMITEDInventors: Hiroshi Saito, Masato Komiyama, Eiji Ochiai, Kenichiro Takagi, Takayuki Chida, Mariko Fujita, Keiichiro Imaizumi, Toshiyuki Kaneko
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Publication number: 20130178449Abstract: This invention discloses 2-methylene-20(21)-dehydro-19,24,25,26,27-pentanor-vitamin D analogs, and specifically 2-methylene-20(21)-dehydro-19,24,25,26,27-pentanor-1?-hydroxyvitamin D3, 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 lower activity in vivo on bone calcium mobilization and lower in vivo intestinal calcium transport activity as compared to the native hormone 1?,25-dihydroxyvitamin D3, and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as secondary hyperparathyroidism and renal osteodystrophy.Type: ApplicationFiled: July 12, 2012Publication date: July 11, 2013Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Hector F. DeLuca, Margaret Clagett-Dame, Lori A. Plum, Agnieska Glebocka, Rafal R. Sicinski
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Publication number: 20130178450Abstract: Methods and compositions for increasing the production or activity of catalase in an animal are disclosed. The methods comprise administering vitamin D to the animal in an amount effective to increase catalase production or activity. Methods for treating catalase deficiency, extending the prime years of an animal's life, promoting health and wellness of an animal, and improving the quality of life for an animal through the vitamin D-mediated increase in catalase production or activity are also disclosed. Methods of screening for vitamin D mimetics based on their ability to increase the production or activity of catalase in cells in a manner similar to vitamin D are also disclosed.Type: ApplicationFiled: May 18, 2011Publication date: July 11, 2013Applicant: Nestec SAInventors: Rondo Paul Middleton, Nongnuch Inpanbutr
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Publication number: 20130172588Abstract: The present application provides a novel method for generation of a vitamin D2 compound using a continuous flow photoisomerization reactor. A compound represented by formula I: [structure] as further defined herein, is mixed with a solvent and a sensitizer, and is then passed through the continuous flow photoisomerization reactor. If X3 and X4 of formula II is tert-butyldimethylsilyl, then formula II is mixed with a deprotection reagent to obtain the vitamin D2 analog.Type: ApplicationFiled: September 1, 2011Publication date: July 4, 2013Applicant: GENZYME CORPORATIONInventors: William Edward Bauta, Bruce Girard Anderson, William R. Cantrell, JR.
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Publication number: 20130157987Abstract: This present disclosure is directed to novel prodrugs of activated vitamin D3 compounds. The prodrugs can be designed to have one or more beneficial properties, such as selective inhibition of the enzyme CYP24, low calcemic activity, and anti-proliferative activity. Specifically, these prodrugs are 1-deoxy prohormones of active Vitamin D analogs, e.g. analogs of calcitriol. This disclosure is also directed to pharmaceutical and diagnostic compositions containing the prodrugs of the invention, and to their medical use, particularly as prodrugs in the treatment and/or prevention of diseases.Type: ApplicationFiled: January 13, 2011Publication date: June 20, 2013Applicants: JOHNS HOPKINS UNIVERSITY, CYTOCHROMA INC.Inventors: Gary H. Posner, Lindsey C. Hess, Alvin S. Kalinda, Rachel D. Slack, Uttam Saha, P. Martin Petkovich
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Publication number: 20130150598Abstract: The use of 25-OH D3 (calcifediol) to increase muscle strength, muscle function, or both is provided. Vitamin D3 (cholecalciferol) may optionally be used together with 25-OH D3. Forms and dosages of a pharmaceutical composition, as well as processes for manufacturing medicaments, are also disclosed.Type: ApplicationFiled: May 9, 2012Publication date: June 13, 2013Applicant: DSM IP ASSETS B.V.Inventors: Neil Robert BUCK, Wouter Claerhout, Bruno H. Leuenberger, Elisabeth Stoecklin, Kai Urban, Swen Wolfram
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Patent number: 8455467Abstract: This invention discloses 2-methylene-vitamin D analogs, and specifically (20S)-25-hydroxy-2-methylene-vitamin D3 and (20R)-25-hydroxy-2-methylene-vitamin D3, as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also have relatively high calcemic activities evidencing use in the treatment of bone diseases.Type: GrantFiled: October 9, 2012Date of Patent: June 4, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Lori A. Plum, Rafal Sicinski, Izabela Sibilska
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Patent number: 8455466Abstract: Compounds according to formula I in which formula R1 and R2, which may be the same or different, represent halogen, (C1-C6)hydrocarbyl, optionally substituted with one or two hydroxyl group or one or more fluorine atoms, or, together with the carbon atom to which they are both attached, R1 and R2 form a (C3-C6)carbocyclic ring, or one of R1 and R2 taken together with R3 forms a direct bond, such that a triple bond is constituted, or R1 and R2 represent both hydrogen; R3 when not forming a direct bond with one of R1 and R2 represents hydrogen or (C1-C3)hydrocarbyl; X represents (E)-ethylene, (Z)-ethylene, ethynylene, or a bond; Y and Z independently represent hydrogen or methyl; and prodrugs and stereo isomeric forms thereof are provided together with their use in therapy, and their use in the manufacture of medicaments.Type: GrantFiled: October 23, 2003Date of Patent: June 4, 2013Assignee: Leo Pharma A/SInventors: Ernst Torndal Binderup, Kai Holst Hansen, Claus Aage Svensgaard Bretting, Martin John Calverley
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Publication number: 20130137662Abstract: The present invention relates to the use canthaxanthin and/or 25-hydroxy vitamin D3 (25-OH D3) for improving reproductive performance of roosters. More particularly, the invention relates to the use of Canthaxanthin and/or 25-hydroxy canthaxanthin in the manufacture of a food or veterinary composition for improving reproductive performance of roosters.Type: ApplicationFiled: December 7, 2010Publication date: May 30, 2013Inventor: Jose Maria Hernandez
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Patent number: 8445468Abstract: This invention discloses (20S,22E)-2-methylene-19-nor-22-ene-1?,25-dihydroxyvitamin D3 analogs, and specifically(20S,22E)-2-methylene-19-nor-22-ene-1?,25-dihydroxyvitamin D3, and pharmaceutical uses therefor. This compound exhibits significant vitamin D receptor binding activity and 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, especially for the treatment or prevention of leukemia, colon cancer, breast cancer, skin cancer or prostate cancer.Type: GrantFiled: September 30, 2010Date of Patent: May 21, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Pawel Grzywacz, Lori A. Plum, Margaret Clagett-Dame
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Patent number: 8440647Abstract: This invention discloses 2?-methyl and 2?-methyl analogs of 19,26,27-trinor-(20S)-1?-hydroxyvitamin D3 and pharmaceutical uses therefor. These compounds exhibit 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. These compounds also have little, if any, calcemic activity and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. These compounds may also be used for the treatment or prevention of obesity.Type: GrantFiled: July 9, 2007Date of Patent: May 14, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Lori A. Plum, Pawel K. Grzywacz, Margaret Clagett-Dame
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Patent number: 8431112Abstract: A method of reducing photodegradation of cholecalciferol when exposed to UV radiation in a composition containing cholecalciferol comprising combining with cholecalciferol a compound of formula (I) in an amount effective to quench excited state energy from cholecalciferol and transfer the excited state energy from cholecalciferol to the compound of formula (I), wherein one of R1 and R2 is a straight or branched chain C1-C30 alkoxy radical, and the non-alkoxy R1 or R2 is hydrogen; and R3 is a straight or branched chain C1-C30 alkyl radical, thereby photostabilizing the cholecalciferol compound.Type: GrantFiled: January 5, 2012Date of Patent: April 30, 2013Assignee: Hallstar Innocations Corp.Inventors: Craig A. Bonda, Jean Zhang
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Publication number: 20130102567Abstract: This invention discloses 3-desoxy-2-methylene-vitamin D analogs, and specifically (20S)-3-desoxy-1?,25-dihydroxy-2-methylene-vitamin D3 and (20R)-3-desoxy-1?, 25-dihydroxy-2-methylene-vitamin D3 as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to monocytes thus evidencing use as anti-cancer agents especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also exhibit relatively high calcemic activity evidencing use in the treatment of bone diseases.Type: ApplicationFiled: October 3, 2012Publication date: April 25, 2013Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventor: WISCONSIN ALUMNI RESEARCH FOUNDATION
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Publication number: 20130102574Abstract: This invention discloses 2-methylene-vitamin D analogs, and specifically (20S)-1?,25-dihydroxy-2-methylene-vitamin D3 as well as (5E)-(20S)-1?,25-dihydroxy-2-methylene-vitamin D3 and (20R)-1?,25-dihydroxy-2-methylene-vitamin D3, as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also have relatively high calcemic activities evidencing use in the treatment of bone diseases.Type: ApplicationFiled: October 11, 2012Publication date: April 25, 2013Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventor: Wisconsin Alumni Research Foundation
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Publication number: 20130102573Abstract: This invention discloses 2-methylene-vitamin D analogs, and specifically (20S)-25-hydroxy-2-methylene-vitamin D3 and (20R)-25-hydroxy-2-methylene-vitamin D3, as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also have relatively high calcemic activities evidencing use in the treatment of bone diseases.Type: ApplicationFiled: October 9, 2012Publication date: April 25, 2013Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventor: WISCONSIN ALUMNI RESEARCH FOUNDATION
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Patent number: 8420839Abstract: A method of purifying 1?-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol to obtain 1?-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol in crystalline form using precipitation with hexane from ethyl acetate. A method of preparing 1?-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol crystals acceptable for X-ray experiment using precipitation with hexane from benzene by diffusive exchange of the solvents is also described.Type: GrantFiled: October 1, 2012Date of Patent: April 16, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal Barycki, James B. Thoden, Hazel M. Holden
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Publication number: 20130090486Abstract: A method of purifying 1?-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol to obtain 1?-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol in crystalline form using precipitation with hexane from ethyl acetate. A method of preparing 1?-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol crystals acceptable for X-ray experiment using precipitation with hexane from benzene by diffusive exchange of the solvents is also described.Type: ApplicationFiled: October 1, 2012Publication date: April 11, 2013Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventor: WISCONSIN ALUMNI RESEARCH FOUNDATION
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Patent number: 8410080Abstract: This invention discloses 2-methylene-vitamin D analogs, and specifically (20S)-1?,25 -dihydroxy-2-methylene-vitamin D3 as well as (5E)-(20S)-1?,25-dihydroxy-2 -methylene-vitamin D3 and (20R)-1?,25-dihydroxy-2-methylene-vitamin D3, as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also have relatively high calcemic activities evidencing use in the treatment of bone diseases.Type: GrantFiled: October 11, 2012Date of Patent: April 2, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Lori A. Plum, Rafal R. Sicinski, Izabela Sibilska
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Patent number: 8404667Abstract: 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.Type: GrantFiled: December 28, 2007Date of Patent: March 26, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Margaret Clagett-Dame, Hector F. DeLuca, Nirca J. Nieves, Lori A. Plum, Mary E. Kaiser
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Patent number: 8404874Abstract: A method of purifying (20R,25S)-2-methylene-19,26-dinor-1?,25-dihydroxyvitamin D3 to obtain (20R,25S)-2-methylene-19,26-dinor-1?,25-dihydroxyvitamin D3 in crystalline form. The method includes the steps of preparing a solvent of methanol and water, dissolving a product containing (20R,25S)-2-methylene-19,26-dinor-1?,25-dihydroxyvitamin D3 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 (20R,25S)-2-methylene-19,26-dinor-1?,25-dihydroxyvitamin D3 crystals, and recovering the (20R,25S)-2-methylene-19,26-dinor-1?,25-dihydroxyvitamin D3 crystals.Type: GrantFiled: September 28, 2011Date of Patent: March 26, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Pawel Grzywacz, James B. Thoden, Hazel Holden
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Patent number: 8404666Abstract: Compounds of formula I, II or III are provided where X1, X2 and X3 are independently selected from H and hydroxy protecting groups and R1 and R2 are independently selected from H or straight or branched chain alkyl groups having from 1 to 8 carbon atoms, straight or branched chain alkenyl groups having from 2 to 8 carbon atoms, straight or branched chain hydroxy-substituted alkyl groups having from 1 to 8 carbon atoms, or straight and branched chain hydroxy-substituted alkenyl groups having from 2 to 8 carbon atoms; and R3 is independently selected from straight or branched chain alkyl groups having from 1 to 8 carbon atoms, straight or branched chain alkenyl groups having from 2 to 8 carbon atoms, straight or branched chain hydroxy-substituted alkyl groups having from 1 to 8 carbon atoms, or straight and branched chain hydroxy-substituted alkenyl groups having from 2 to 8 carbon atoms.Type: GrantFiled: April 6, 2007Date of Patent: March 26, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Lori A. Plum, Margaret Clagett-Dame, Pawel Grzywacz
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Patent number: 8399439Abstract: This invention discloses 2-methylene-19,26-dinor-(20S,22E,25R)-vitamin D analogs, and specifically 2-methylene-19,26-dinor-(20S,22E,25R)-1?,25-dihydroxyvitamin D3, and pharmaceutical uses therefor. This compound exhibits 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 no activity in vivo on bone calcium mobilization and relatively low intestinal calcium transport activity compared to the native hormone 1?,25-dihydroxyvitamin D3, 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.Type: GrantFiled: July 10, 2008Date of Patent: March 19, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Grazia Chiellini, Pawel Grzywacz, Lori A. Plum, Margaret Clagett-Dame
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Patent number: 8399438Abstract: This invention discloses 2?-methyl-19-nor-vitamin D analogs, and specifically 2?-methyl-19-nor-1?-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.Type: GrantFiled: November 18, 2005Date of Patent: March 19, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Rafal R. Sicinski, Lori A. Plum, Margaret Clagett-Dame, Sumithra Gowlugari
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Publication number: 20130053587Abstract: A method of purifying 1?-hydroxy-20-methyl-2-methylene-19,24,25,26,27-pentanorvitamin D3 to obtain 1?-hydroxy-20-methyl-2-methylene-19,24,25,26,27-pentanorvitamin D3 in crystalline form. The method includes the steps of preparing a solvent of either ethyl formate or a mixture of ethyl formate and hexane, dissolving a product containing 1?-hydroxy-20-methyl-2-methylene-19,24,25,26,27-pentanorvitamin D3 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 1?-hydroxy-20-methyl-2-methylene-19,24,25,26,27-pentanorvitamin D3 crystals, and recovering the 1?-hydroxy-20-methyl-2-methylene-19,24,25,26,27-pentanorvitamin D3 crystals.Type: ApplicationFiled: August 17, 2012Publication date: February 28, 2013Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Hector F. DeLuca, Agnieszka Glebocka, James B. Thoden, Hazel M. Holden
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Publication number: 20130053356Abstract: Compounds of Formula I are provided where R1 and R2 are independently selected from H or hydroxy protecting groups. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.Type: ApplicationFiled: August 23, 2012Publication date: February 28, 2013Inventors: Hector F. DELUCA, Margaret Clagett-Dame, Lori A. Plum, Agnieszka Glebocka, Rafal Sicinski
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Patent number: 8377913Abstract: The invention relates to compounds that are vitamin D receptor activators, compositions comprising such compounds, methods of using such compounds and compositions, processes for preparing such compounds, and intermediates obtained during such processes.Type: GrantFiled: September 8, 2008Date of Patent: February 19, 2013Assignee: AbbVie Inc.Inventors: Thomas W. Von Geldern, Jufang H. Barkalow, David M. Barnes, Anthony R. Haight, John E. Hengeveld, Xiaofeng Li, Maureen A. McLaughlin, William T. Noonan, Zhonghua Pei, Jinshyun Ruth Wu-Wong
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Publication number: 20130039952Abstract: Calcipotriol monohydrate nanocrystals prepared by the process disclosed herein may be incorporated in a pharmaceutical composition for use in the prevention or treatment of dermal diseases and conditions.Type: ApplicationFiled: December 22, 2010Publication date: February 14, 2013Applicant: LEO PHARMA A/SInventor: Karsten Petersson
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Patent number: 8362287Abstract: The present invention relates to intermediates useful for the synthesis of calcipotriol or calcipotriol monohydrate, to methods of producing said intermediates, and to methods of stereoselectively reducing said intermediates.Type: GrantFiled: March 10, 2005Date of Patent: January 29, 2013Assignee: Leo Pharma A/SInventors: Thomas Peter Sabroe, Martin John Calverley
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Publication number: 20130023681Abstract: 1 a-hydroxy vitamin D2 (doxercalciferol) of exceptionally high purity and stability is prepared by a process involving chromatographically purifying 1 ?-hydroxyvitamin D2 monoacetate, chemically removing the acetate protectant group from the purified product to form 1 ?-hydroxyvitamin D2, and precipitating the 1 a-hydroxyvitamin D2 so formed from a mixed organic solvent consisting essentially of at least one C1-C6 dialkyl ether or C1-C6 alkyl ester, and at least one C5-C12 hydrocarbon.Type: ApplicationFiled: March 29, 2011Publication date: January 24, 2013Applicant: ALPHORA RESEARCH INC.Inventors: Graham McGowan, Boris Ivanovich Gorin
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Publication number: 20130006003Abstract: The present invention discloses the synthone of Formula (I), wherein R1 and R2 are the same or different and represent independently hydrogen atom or hydroxyl protecting group, and its use for preparation of 19-nor vitamin D derivatives of general Formula (IV), wherein represents single or double bond, p represents an integer 0 to 3, R1 and R2 represent independently hydrogen atom or hydroxyl protecting group, R3 represents hydrogen atom, CH3 or hydroxyl group, R4, R5 and R6 represent independently hydrogen atom, C1-C3-alkyl or hydroxyl group or two of R4, R5 and R6 substituents altogether form cyclopropyl group, in particular for preparation of paricalcitol.Type: ApplicationFiled: August 7, 2010Publication date: January 3, 2013Applicant: INSTYTUT FARMACEUTYCZNYInventors: Michal Chodynski, Malgorzata Krupa, Krzysztof Krajewski, Marek Kubiszewski, Andrzej Kutner, Anita Pietraszek, Kinga Trzcinska
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Publication number: 20130005686Abstract: 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?-hydroxyvitamin D3, 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.Type: ApplicationFiled: June 26, 2012Publication date: January 3, 2013Applicant: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Margaret Clagett-Dame, Lori A. Plum, Rafal Barycki
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Publication number: 20120322775Abstract: This invention discloses 3-desoxy-2-methylene-19-nor-vitamin D analogs, and specifically (20S)-3-desoxy-2-methylene-1?,25-dihydroxy-19-nor-vitamin D3 and (20R)-3-desoxy-2-methylene-1?,25-dihydroxy-19-nor-vitamin D3 as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to monocytes thus evidencing use as anti-cancer agents especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also exhibit relatively high calcemic activity evidencing use in the treatment of bone diseases.Type: ApplicationFiled: June 13, 2012Publication date: December 20, 2012Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Hector F. DeLuca, Lori A. Plum, Rafal R. Sicinski, Izabela Sibilska, Margaret Clagett-Dame
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Publication number: 20120309719Abstract: 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.Type: ApplicationFiled: May 31, 2012Publication date: December 6, 2012Inventors: Hector DeLuca, Rafal Barycki, Lori Plum, Margaret Clagett-Dame
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Publication number: 20120309713Abstract: This invention discloses N-cyclopropyl-(20R)-2-methylene-19,26,27-trinor-25-aza-vitamin D analogs, and specifically N-cyclopropyl-(20R)-2-methylene-19,26,27-trinor-25-aza-1?-hydroxyvitamin D3 and pharmaceutical uses therefor. This compound exhibits relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of leukemia, colon cancer, breast cancer, skin cancer or prostate cancer.Type: ApplicationFiled: May 16, 2012Publication date: December 6, 2012Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: DeLuca F. Hector, Clagett-Dame Margaret, Plum A. Lori, Chiellini Grazia
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Publication number: 20120289723Abstract: Indene derivatives that are utilizable as intermediates in the synthesis of the vitamin D2 derivative paricalcitol, which is useful as pharmaceutical are efficiently prepared by subjecting a vitamin D2 derivative such as 25-hydroxyvitamin D2 to a two-steps oxidation reaction using an oxidizing agent such as potassium permanganates and sodium periodate in a suitable solvent such as methanol and ethanol.Type: ApplicationFiled: July 24, 2012Publication date: November 15, 2012Inventors: Asako TOYODA, Hazuki NAGAI
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Publication number: 20120283227Abstract: This invention discloses (20S)-24(p-toluenesulfonyloxy)-25,26,27-trinorvitamin D3 analogs, and especially (20S)-25,26,27-trinor-24-(p-methylphenylsulfonate)-vitamin D3, its biological activities, and pharmaceutical uses therefor. This compound exhibits relatively little calcemic activity and does not promote cellular differentiation of HL-60 leukemia cells, but rather kills the cells. This cell death activity is found in small cell lung carcinoma also, but not in prostate, bone or ovarian cancer cells. This compound thus causes specific cell death in the absence of changes in calcium levels and without general toxicity in an animal. Therefore it might serve as a useful therapy for treatment of some forms of cancer, such as leukemia and lung cancer.Type: ApplicationFiled: April 19, 2012Publication date: November 8, 2012Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Hector F. DeLuca, Margaret Clagett-Dame, Lori A. Plum, Rafal Barycki
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Publication number: 20120283228Abstract: This invention discloses 2?-methyl and 2?-methyl analogs of 19,26-dinor-1?,25-dihydroxyvitamin D3 and pharmaceutical uses therefor. These compounds exhibit in vitro biological activities 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. These compounds have little, if any, in vivo calcemic activity and therefore may be used to treat autoimmune disorders in humans as well as secondary hyperparathyroidism and renal osteodystrophy.Type: ApplicationFiled: May 3, 2012Publication date: November 8, 2012Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Hector F. DeLuca, Margaret Clagett-Dame, Pawel Grzywacz, Grazia Chiellini, Lori A. Plum
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Publication number: 20120277180Abstract: Provided herein are methods and systems for identifying one or more cofactors such as vitamins for individuals based on the genetic makeup of the individual by detecting the presence or absence of at least one genetic variant, determining a predisposition to cofactor remediable condition, generating a personalized nutritional advice plan based on the genetic variant. Also provided herein are formulations of cofactors determined by the genetic make-up of the individual and methods of determining and producing these formulations.Type: ApplicationFiled: September 30, 2010Publication date: November 1, 2012Applicants: VITAPATH GENETICS, INC, THE REGENTS OF THE UNIVERSITY OF CALIFORNIAInventors: Nicholas Marini, Jasper Rine, Dennis Austin Gilbert, Bruce Cohen
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Publication number: 20120270839Abstract: Bromoacetoxycalcidiol (B3CD), which is structurally related to calcidiol, exhibits cytotoxic and apoptotic activity toward cancer cells, including highly aggressive neuroblastoma cells. A series of small molecules designed around the structure of B3CD is expected to have growth inhibitory and apoptogenic activities toward a wide range of malignancies. B3CD shows no apparent toxicity in vivo, indicating potential value as a chemotherapeutic agent which will be particularly useful in treating highly aggressive tumors.Type: ApplicationFiled: February 22, 2012Publication date: October 25, 2012Applicant: WOMEN AND INFANTS HOSPITAL OF RIInventors: Narasimha Swamy, Hema Malini K. Sundaresha
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Publication number: 20120258938Abstract: Provided herein are steroidal compounds that are androsta-5,7-dienes or pregna-5,7-dienes and ultraviolet B (UVB) conversion products thereof and cholecalciferol derivatives hydroxylated at one or more of C1, C17, C20, C23, C24, C25, and C26 which includes pharmaceutical, cosmeceutical or nutraceutical compositions of the steroidal compounds as shown in Tables 1A, 2A and 3. Also provided is a method for producing hydroxylated metabolites of cholecalciferol via CYP11A1, CYP24, CYP27A1, or CYP27B1 enzyme systems where the hydroxylase has an activity to hydroxylate position C1 or C20 or other position of the sidechain of a secosteroid or its 5,7-dieneal precursor and the hydroxylated metabolites so produced.Type: ApplicationFiled: April 30, 2012Publication date: October 11, 2012Inventors: Andrej Slominski, Robert C. Tuckey, Edith Tang, Elaine Tieu, Minh Nguyen, Zorica Janjetovic, Jianjun Chen, Wei Li, Yan Lu, Duane D. Miller, Jordan K. Zjawiony, Arnold E. Postlethwaite
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Publication number: 20120244627Abstract: Provided are methods of detecting the presence or amount of a dihydroxyvitamin D metabolite in a sample using mass spectrometry. The methods generally comprise associating an amine with a dihydroxyvitamin D metabolite in a sample, ionizing the adduct, and detecting the amount of the ion to determine the presence or amount of the vitamin D metabolite in the sample.Type: ApplicationFiled: October 19, 2010Publication date: September 27, 2012Applicant: Georgetown UniversityInventor: Steven J. Soldin
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Patent number: 8232263Abstract: This invention discloses 17,20(Z)-dehydro vitamin D analogs, and specifically 17(Z)-1?,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 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 may be used to treat autoimmune disorders and inflammatory diseases in humans as well as renal osteodystrophy and obesity. This compound also has significant calcemic activity making it a therapeutic agent for the treatment or prophylaxis of osteoporosis, osteomalacia, renal osteodystrophy and hypoparathyroidism.Type: GrantFiled: July 9, 2007Date of Patent: July 31, 2012Assignee: Wisconsin Alumni Research FoundationInventors: Hector F. DeLuca, Bulli Padmaja Tadi, Lori A. Plum, Margaret Clagett-Dame