CA2588415C - 2-methylene-19,26,27-trinor-(20s)-1-alpha-hydroxyvitamin d3 and its uses - Google Patents
2-methylene-19,26,27-trinor-(20s)-1-alpha-hydroxyvitamin d3 and its uses Download PDFInfo
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- CA2588415C CA2588415C CA2588415A CA2588415A CA2588415C CA 2588415 C CA2588415 C CA 2588415C CA 2588415 A CA2588415 A CA 2588415A CA 2588415 A CA2588415 A CA 2588415A CA 2588415 C CA2588415 C CA 2588415C
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/24—All rings being cycloaliphatic the ring system containing nine carbon atoms, e.g. perhydroindane
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Diabetes (AREA)
- Immunology (AREA)
- Hematology (AREA)
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- Dermatology (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Child & Adolescent Psychology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Transplantation (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62996504P | 2004-11-22 | 2004-11-22 | |
| US60/629,965 | 2004-11-22 | ||
| PCT/US2005/041671 WO2006057886A2 (en) | 2004-11-22 | 2005-11-18 | 2-METHYLENE-19,26,27-TRINOR-(20S)-1α-HYDROXYVITAMIN D3 AND ITS USES |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2588415A1 CA2588415A1 (en) | 2006-06-01 |
| CA2588415C true CA2588415C (en) | 2012-07-10 |
Family
ID=36203195
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2588415A Expired - Fee Related CA2588415C (en) | 2004-11-22 | 2005-11-18 | 2-methylene-19,26,27-trinor-(20s)-1-alpha-hydroxyvitamin d3 and its uses |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US7244719B2 (https=) |
| EP (1) | EP1828113B1 (https=) |
| JP (1) | JP2008520691A (https=) |
| AT (1) | ATE467614T1 (https=) |
| AU (1) | AU2005309791A1 (https=) |
| CA (1) | CA2588415C (https=) |
| DE (1) | DE602005021245D1 (https=) |
| MX (1) | MX2007006543A (https=) |
| NZ (1) | NZ555281A (https=) |
| WO (1) | WO2006057886A2 (https=) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8404667B2 (en) * | 2006-12-29 | 2013-03-26 | Wisconsin Alumni Research Foundation | Compounds, compositions, kits and methods of use to orally and topically treat acne and other skin conditions by 19-Nor vitamin D analog |
| US7713951B2 (en) * | 2004-04-09 | 2010-05-11 | Wisconsin Alumni Research Foundation | 2-alkylidene-18,19-dinor-vitamin D compounds |
| US8193169B2 (en) * | 2006-04-06 | 2012-06-05 | Wisconsin Alumni Research Foundation | (20R)-2α-methyl-19,26,2-trinor-vitamin D analogs |
| US8193170B2 (en) * | 2008-07-10 | 2012-06-05 | Wisconsin Alumni Research Foundation | 2-methylene-19,26-dinor-(20R,22E,25R)-vitamin D analogs |
| US8399439B2 (en) * | 2008-07-10 | 2013-03-19 | Wisconsin Alumni Research Foundation | 2-methylene-19,26-dinor-(20S,22E,25R)-vitamin D analogs |
| US7879829B2 (en) * | 2008-07-10 | 2011-02-01 | Wisconsin Alumni Research Foundation | 19-nor-vitamin D analogs with 1,2-dihydrofuran ring |
| US7648974B1 (en) * | 2008-07-10 | 2010-01-19 | Wisconsin Alumni Research Foundation | 19-nor-vitamin D analogs with 3,2-dihydrofuran ring |
| EP2525799B1 (en) | 2009-10-02 | 2014-09-03 | Wisconsin Alumni Research Foundation | (20s,22e)-2-methylene-19-nor-22-ene-1alpha,25-dihydroxyvitamin d3 analogs |
| WO2011041596A2 (en) | 2009-10-02 | 2011-04-07 | Wisconsin Alumni Research Foundation | 19-nor-vitamin d analogs with 1,2-or 3,2-cyclopentene ring |
| MX2012005936A (es) * | 2009-11-30 | 2012-09-07 | Wisconsin Alumni Res Found | 2-metilen-19,26-nor-(20s)-1a-hidroxivitamina d3. |
| US8604009B2 (en) | 2010-03-23 | 2013-12-10 | Wisconsin Alumni Research Foundation | (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D3 and (20R)-2-methylene-19-nor-22-dimethyl-1α,25-hydroxyvitamin D3 |
| CA2793727C (en) * | 2010-03-23 | 2017-01-03 | Wisconsin Alumni Research Foundation | Diastereomers of 2-methylene-19-nor-22-methyl-1.alpha.,25-dihydroxyvitamin d3 |
| US8664206B2 (en) | 2010-03-23 | 2014-03-04 | Wisconsin Alumni Research Foundation | Diastereomers of 2-methylene-19-nor-22-methyl-1α,25-dihydroxyvitamin D3 |
| AU2012271759B2 (en) * | 2011-06-14 | 2017-02-02 | Wisconsin Alumni Research Foundation | 3-desoxy-2-methylene-19-nor-vitamin D analogs and their uses |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3846811A (en) * | 1972-03-29 | 1974-11-05 | Canon Kk | Flash unit for use with camera |
| US4486333A (en) * | 1981-04-10 | 1984-12-04 | Felix Sebba | Preparation of biliquid foam compositions |
| US4666634A (en) * | 1984-12-05 | 1987-05-19 | Chugai Seiyaku Kabushiki Kaisha | vitamin D3 derivatives having a substituent at 2-position |
| US4800198A (en) * | 1985-04-23 | 1989-01-24 | Wisconsin Alumni Research Foundation | Method of inducing the differentiation of malignant cells with secosterol |
| CA1333616C (en) * | 1989-03-09 | 1994-12-20 | Hector F. Deluca | 19-nor-vitamin d compounds |
| US5459136A (en) * | 1990-08-24 | 1995-10-17 | Wisconsin Alumni Research Foundation | Methods using vitamin D compounds for improvement of skin conditions |
| US5086191A (en) * | 1991-05-28 | 1992-02-04 | Wisconsin Alumni Research Foundation | Intermediates for the synthesis of 19-nor vitamin D compounds |
| EP0619306B1 (en) * | 1993-04-05 | 1996-09-11 | Wisconsin Alumni Research Foundation | 19-Nor-vitamin D3 compounds with substituent at 2-position |
| US5552392A (en) * | 1993-11-03 | 1996-09-03 | Wisconsin Alumni Research Foundation | Method of treating hypoparathyroidism with (20S) vitamin D compounds |
| US5877168A (en) * | 1995-02-10 | 1999-03-02 | Chugai Seiyaku Kabushiki Kaisha | Vitamin D derivative with substituent at the 2β-position |
| US6392071B1 (en) * | 1997-03-17 | 2002-05-21 | Wisconsin Alumni: Research Foundation | 26,27-homologated-20-EPI-2-alkylidene-19-nor-vitamin D compounds |
| US5843928A (en) * | 1997-03-17 | 1998-12-01 | Wisconsin Alumni Research Foundation | 2-alkylidene-19-nor-vitamin D compounds |
| US6316642B1 (en) * | 1997-03-17 | 2001-11-13 | Wisconsin Alumni Research Foundation | 26,27-Homologated-20-EPI-2alkyl-19-nor-vitamin D compounds |
| US5945410A (en) * | 1997-03-17 | 1999-08-31 | Wisconsin Alumni Research Foundation | 2-alkyl-19-nor-vitamin D compounds |
| PL199123B1 (pl) * | 1999-04-23 | 2008-08-29 | Leo Pharm Prod Ltd | Niewodna kompozycja farmaceutyczna do stosowania naskórnego i jej zastosowanie |
| NZ522909A (en) * | 2000-05-31 | 2004-09-24 | Wisconsin Alumni Res Found | 2-ethyl and 2-ethylidene-19-nor-vitamin D compounds |
| MXPA03000406A (es) * | 2000-07-14 | 2003-06-06 | Wisconsin Alumni Res Found | Uso de 2-metilen-19-nor-20(s)-1 alfa,25-dihidroxivitamina d3 para incrementar la resistencia de los huesos. |
| NZ524657A (en) * | 2000-09-08 | 2004-12-24 | Wisconsin Alumni Res Found | 1 alpha-hydroxy-2-methylene-19-nor-homopregnacalciferol and its therapeutic applications |
| NZ533424A (en) * | 2001-12-13 | 2006-08-31 | Wisconsin Alumni Res Found | Vitamin D derivative, methods of purifying and uses in treating psoriasis, cancer, autoimmune diseases, inflammatory diseases, skin conidtions and renal ostepdystrophy |
| US6627622B2 (en) * | 2002-02-18 | 2003-09-30 | Wisconsin Alumni Research Foundation | (20S)-1α-hydroxy-2-methylene-19-nor-bishomopregnacalciferol and its uses |
| US6566352B1 (en) * | 2002-02-18 | 2003-05-20 | Wisconsin Alumni Research Foudation | 1 α-hydroxy-2-methylene-19-nor-pregnacalciferol and its uses |
| HK1079766B (zh) * | 2002-03-29 | 2007-05-25 | 威斯康星校友研究基金会 | 合成1α-羟基-2-亚甲基-19-去甲-高孕钙化醇的方法 |
| US6846811B2 (en) | 2002-04-22 | 2005-01-25 | Wisconsin Alumni Research Foundation | (20S) 1α-hydroxy-2α-methyl and 2β-methyl-19-nor-vitamin D3 and their uses |
| MXPA06005887A (es) * | 2003-11-25 | 2006-06-27 | Wisconsin Alumni Res Found | Analogos de vitamina d para la prevencion y el tratamiento de la obesidad. |
| EP1694333A2 (en) * | 2003-11-25 | 2006-08-30 | Deltanoid Pharmaceuticals, Inc. | Methods for reducing body fat using vitamin d compounds |
| MX2007006261A (es) * | 2004-11-22 | 2007-07-10 | Wisconsin Alumni Res Found | Analogos de 17,20(z)-deshidro vitamina d y sus usos. |
| CA2588399A1 (en) * | 2004-11-22 | 2006-06-01 | Wisconsin Alumni Research Foundation | 2alpha-methyl-19-nor-(20s)-1alpha-hydroxy-bishomopregnacalciferol and its uses |
| AU2005309789A1 (en) * | 2004-11-22 | 2006-06-01 | Wisconsin Alumni Research Foundation | 2alpha-methyl and 2beta-methyl analogs of 19,26,27-trinor-(20S)-1alpha-hydroxyvitamin D3 and their uses |
-
2005
- 2005-11-18 DE DE602005021245T patent/DE602005021245D1/de not_active Expired - Lifetime
- 2005-11-18 AU AU2005309791A patent/AU2005309791A1/en not_active Abandoned
- 2005-11-18 AT AT05849147T patent/ATE467614T1/de not_active IP Right Cessation
- 2005-11-18 MX MX2007006543A patent/MX2007006543A/es active IP Right Grant
- 2005-11-18 US US11/283,306 patent/US7244719B2/en not_active Expired - Lifetime
- 2005-11-18 NZ NZ555281A patent/NZ555281A/en not_active IP Right Cessation
- 2005-11-18 EP EP05849147A patent/EP1828113B1/en not_active Expired - Lifetime
- 2005-11-18 WO PCT/US2005/041671 patent/WO2006057886A2/en not_active Ceased
- 2005-11-18 JP JP2007543229A patent/JP2008520691A/ja not_active Ceased
- 2005-11-18 CA CA2588415A patent/CA2588415C/en not_active Expired - Fee Related
-
2007
- 2007-07-09 US US11/775,087 patent/US7713952B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20060142246A1 (en) | 2006-06-29 |
| US7713952B2 (en) | 2010-05-11 |
| CA2588415A1 (en) | 2006-06-01 |
| DE602005021245D1 (de) | 2010-06-24 |
| EP1828113A2 (en) | 2007-09-05 |
| NZ555281A (en) | 2011-01-28 |
| ATE467614T1 (de) | 2010-05-15 |
| WO2006057886A2 (en) | 2006-06-01 |
| MX2007006543A (es) | 2007-07-25 |
| US7244719B2 (en) | 2007-07-17 |
| AU2005309791A1 (en) | 2006-06-01 |
| JP2008520691A (ja) | 2008-06-19 |
| US20070249567A1 (en) | 2007-10-25 |
| EP1828113B1 (en) | 2010-05-12 |
| WO2006057886A8 (en) | 2007-11-22 |
| WO2006057886A3 (en) | 2006-06-29 |
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