CA2794006C - (20s)-2-methylene-19-nor-22-dimethyl-1.alpha.,25-dihydroxyvitamin d3 and (20r)-2-methylene-19-nor-22-dimethyl-1.alpha.,25-hydroxyvitamin d3 - Google Patents
(20s)-2-methylene-19-nor-22-dimethyl-1.alpha.,25-dihydroxyvitamin d3 and (20r)-2-methylene-19-nor-22-dimethyl-1.alpha.,25-hydroxyvitamin d3 Download PDFInfo
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- CA2794006C CA2794006C CA2794006A CA2794006A CA2794006C CA 2794006 C CA2794006 C CA 2794006C CA 2794006 A CA2794006 A CA 2794006A CA 2794006 A CA2794006 A CA 2794006A CA 2794006 C CA2794006 C CA 2794006C
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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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
-
- 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
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- Health & Medical Sciences (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31663110P | 2010-03-23 | 2010-03-23 | |
| US61/316,631 | 2010-03-23 | ||
| PCT/US2011/029432 WO2011119610A2 (en) | 2010-03-23 | 2011-03-22 | (20S)-2-METHYLENE-19-NOR-22-DIMETHYL-1α,25- DIHYDROXYVITAMIN D3 AND (20R)-2-METHYLENE-19-NOR-22- DIMETHYL-1α,25-HYDROXYVITAMIN D3 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2794006A1 CA2794006A1 (en) | 2011-09-29 |
| CA2794006C true CA2794006C (en) | 2017-11-28 |
Family
ID=44170321
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2794006A Expired - Fee Related CA2794006C (en) | 2010-03-23 | 2011-03-22 | (20s)-2-methylene-19-nor-22-dimethyl-1.alpha.,25-dihydroxyvitamin d3 and (20r)-2-methylene-19-nor-22-dimethyl-1.alpha.,25-hydroxyvitamin d3 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8604009B2 (https=) |
| EP (1) | EP2556053B1 (https=) |
| JP (1) | JP5770261B2 (https=) |
| AU (1) | AU2011232633B2 (https=) |
| CA (1) | CA2794006C (https=) |
| ES (1) | ES2545403T3 (https=) |
| WO (1) | WO2011119610A2 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8884039B2 (en) | 2012-05-30 | 2014-11-11 | Wisconsin Alumni Research Foundation | Crystallization of (20R) and (20S) analogs of 2-methylene-19-nor-24-dimethyl-1α,25-dihydroxyvitamin D3 |
| SG11201408731WA (en) | 2012-06-29 | 2015-01-29 | Wisconsin Alumni Res Found | USE OF 2-METHYLENE-19-NOR-(20S)-1α,25-DIHYDROXYVITAMIN D<sb>3</sb> TO TREAT SECONDARY HYPERPARATHYROIDISM |
| US9539231B2 (en) | 2014-01-17 | 2017-01-10 | The Regents Of The University Of Colorado, A Body Corporate | Method for treating triple-negative breast cancer using AMPI-109 |
| US9539264B2 (en) | 2014-12-30 | 2017-01-10 | Wisconsin Alumni Research Foundation | Use of 2-methylene-19-nor-(20S)-1-alpha,25-dihydroxyvitamin D3 to treat secondary hyperparathyroidism in patients previously treated with calcimimetics |
| US10369161B2 (en) | 2014-12-30 | 2019-08-06 | Wisconsin Alumni Research Foundation | Use of 2-methylene-19-NOR-(20S)-1-alpha,25-dihydroxyvitamin D3 to treat primary hyperparathyroidism |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CA1333616C (en) * | 1989-03-09 | 1994-12-20 | Hector F. Deluca | 19-nor-vitamin d compounds |
| US5246925A (en) * | 1989-03-09 | 1993-09-21 | Wisconsin Alumni Research Foundation | 19-nor-vitamin D compounds for use in treating hyperparathyroidism |
| JPH0695892B2 (ja) | 1990-01-12 | 1994-11-30 | 伊藤忠飼料株式会社 | 体脂肪の畜積量を減少させる飼料 |
| US5086191A (en) | 1991-05-28 | 1992-02-04 | Wisconsin Alumni Research Foundation | Intermediates for the synthesis of 19-nor vitamin D compounds |
| DE69400495T2 (de) | 1993-04-05 | 1997-04-30 | Wisconsin Alumni Res Found | 19-Nor-vitamin-D3-Verbindung mit einem Substituent an die 2. Stelle |
| JP3210156B2 (ja) | 1993-10-18 | 2001-09-17 | マツダ株式会社 | 自動車の前部車体構造 |
| US5552392A (en) * | 1993-11-03 | 1996-09-03 | Wisconsin Alumni Research Foundation | Method of treating hypoparathyroidism with (20S) vitamin D compounds |
| US5945410A (en) * | 1997-03-17 | 1999-08-31 | Wisconsin Alumni Research Foundation | 2-alkyl-19-nor-vitamin D compounds |
| US6306844B1 (en) * | 1997-03-17 | 2001-10-23 | Wisconsin Alumni Research Foundation | Use of 2α-methyl-19-nor-20(S)-1α, 25-dihydroxyvitamin D3 to increase bone strength |
| 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 |
| US6114317A (en) * | 1998-05-21 | 2000-09-05 | Wisconsin Alumni Research Foundation | Method of locking 1α-OH of vitamin D compounds in axial orientation |
| EP1745787B1 (en) | 1999-04-01 | 2016-11-09 | Johns Hopkins University | NON-CALCEMIC, ANTIPROLIFERATIVE, TRANSCRIPTIONALLY ACTIVE SULFUR-CONTAINING ANALOGS OF 1-alpha 25-DIHYDROXY VITAMIN D3 |
| US6806262B2 (en) * | 2000-05-31 | 2004-10-19 | Wisconsin Alumni Research Foundation | 2-ethyl and 2-ethylidene-19-nor-vitamin D compounds |
| WO2002005823A2 (en) * | 2000-07-14 | 2002-01-24 | Wisconsin Alumni Research Foundation | USE OF 2-METHYLENE-19-NOR-20(S)-1α,25-DIHYDROXYVITAMIN D3 TO INCREASE BONE STRENGTH |
| US6384087B1 (en) * | 2000-09-01 | 2002-05-07 | University Of Tennesseee Research Corporation, Inc. | Materials and methods for the treatment or prevention of obesity |
| WO2002020021A1 (en) * | 2000-09-08 | 2002-03-14 | Wisconsin Alumni Research Foundation | 1alpha-hydroxy-2-methylene-19-nor-homopregnacalciferol and its therapeutic applications |
| US6835723B2 (en) * | 2001-12-13 | 2004-12-28 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-20(S)-1α-hydroxy-bis-homo-pregnacalciferol in crystalline form |
| 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 |
| BR0307896A (pt) * | 2002-03-29 | 2004-12-07 | Wisconsin Alumni Res Found | Método de produção de 1(alfa)-hidroxi-2-metileno-19-nor-homopregnacalcif erol |
| 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 |
| US20080249068A1 (en) | 2002-09-05 | 2008-10-09 | Deluca Hector F | Method of Extending the Dose Range of Vitamin D Compounds |
| US6894037B2 (en) * | 2003-07-03 | 2005-05-17 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-20(S)-25-methyl-1α-hydroxycalciferol and its uses |
| AU2004266706B2 (en) * | 2003-08-20 | 2009-07-30 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-vitamin D2 compounds |
| WO2005027913A1 (en) | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and a growth hormone secretagogue |
| KR20060058133A (ko) | 2003-09-19 | 2006-05-29 | 화이자 프로덕츠 인코포레이티드 | 2-알킬리덴-19-노르-비타민 ｄ 유도체 및 부갑상선호르몬의 조합을 포함하는 약학 조성물 및 방법 |
| WO2005027929A1 (en) | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and an estrogen |
| CA2539361A1 (en) * | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and an estrogen agonist/antagonist |
| WO2005027931A1 (en) * | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and an ep2 or ep4 selective agonist |
| US7214670B2 (en) * | 2003-09-24 | 2007-05-08 | Wisconsin Alumni Research Foundation | Use of 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3 to increase the life expectancy of human beings |
| US7704980B2 (en) * | 2003-10-08 | 2010-04-27 | Wisconsin Alumni Research Foundation | Treatment of inflammatory bowel disease with 2-methylene-19-nor-vitamin D compounds |
| CA2544502A1 (en) * | 2003-11-25 | 2005-06-09 | Wisconsin Alumni Research Foundation | Vitamin d analogs for obesity prevention and treatment |
| US7053075B2 (en) * | 2003-11-25 | 2006-05-30 | Deluca Hector F | Methods for reducing body fat using vitamin D compounds |
| US7915242B2 (en) * | 2004-02-17 | 2011-03-29 | Wisconsin Alumni Research Foundation | Vitamin D receptor antagonists and their use in treating asthma |
| US7214671B2 (en) * | 2004-02-19 | 2007-05-08 | Wisconsin Alumni Research Foundation | Use of 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3 for the prophylaxis of bone diseases |
| US7713951B2 (en) * | 2004-04-09 | 2010-05-11 | Wisconsin Alumni Research Foundation | 2-alkylidene-18,19-dinor-vitamin D compounds |
| JP2008520689A (ja) * | 2004-11-22 | 2008-06-19 | ウィスコンシン・アルムニ・リサーチ・ファウンデーション | １９，２６，２７−トリノル−（２０Ｓ）−１α−ヒドロキシビタミンＤ３の２α−メチルおよび２β−メチル類似体およびそれらの使用 |
| ATE467614T1 (de) * | 2004-11-22 | 2010-05-15 | Wisconsin Alumni Res Found | 2-methylen-19,26,27-trinor-(20s)-1-alpha- hydroxyvitamin d3 and dessen verwendungen |
| US7238681B2 (en) * | 2004-11-22 | 2007-07-03 | Wisconsin Alumni Research Foundation | 2-Methylene-18,19-dinor-1α-hydroxy-homopregnacalciferol and its uses |
| US7541348B2 (en) * | 2004-11-22 | 2009-06-02 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-(20S)-1α-hydroxy-trishomopregnacalciferol |
| AU2005309804B9 (en) * | 2004-11-22 | 2011-12-08 | Wisconsin Alumni Research Foundation | 2alpha-methyl-19-nor-(20S)-1alpha-hydroxy-bishomopregnacalciferol and its uses |
| JP5161582B2 (ja) * | 2004-11-22 | 2013-03-13 | ウィスコンシン・アルムニ・リサーチ・ファウンデーション | １７，２０（ｚ）−デヒドロビタミンｄ類似体およびそれらの使用 |
| NZ561076A (en) * | 2005-02-11 | 2010-01-29 | Wisconsin Alumni Res Found | 2-methylene-19-nor-(20S-24EPI)-1alpha,25-dihydroxyvitamin-D2 |
| AU2006213727B2 (en) * | 2005-02-11 | 2011-08-18 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor- (20S-24S) - 1alpha, 25-dihydroxyvitamin-D2 |
| AU2006230296B2 (en) * | 2005-03-29 | 2011-07-07 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-(23s)-25-dehydro-1alpha-hydroxyvitamin D3-26,23-lactone and 2-methylene-19-nor-(23R)-25-dehydro-1alpha-hydroxyvitamin D3-26,23-lactone |
| CA2605727A1 (en) * | 2005-05-03 | 2006-11-09 | Wisconsin Alumni Research Foundation | 19,26,27-trinor-1.alpha.,25-dihydroxyvitamin d3 compounds |
| JP2009533483A (ja) * | 2006-04-06 | 2009-09-17 | ウイスコンシン アラムニ リサーチ ファンデーション | ２−メチレン−１α，２５−ジヒドロキシ−１８，１９，２１−トリノルビタミンＤ３およびその使用 |
| CA2646909A1 (en) * | 2006-04-06 | 2008-03-27 | Hector F. Deluca | 2-methylene-1alpha-hydroxy-19,21-dinorvitamin d3 analogs and uses thereof |
| US7648973B2 (en) * | 2006-04-06 | 2010-01-19 | Wisconsin Alumni Research Foundation | 2-methylene-1α,25-dihydroxy-19,21-dinorvitamin D3 analogs and uses thereof |
| MX2009003241A (es) * | 2006-09-28 | 2009-05-05 | Wisconsin Alumni Res Found | Analogos de 2-metilen-(20r,25s)-19,27-dinor-(22e)-vitamina d. |
| US8377913B2 (en) * | 2007-11-20 | 2013-02-19 | Abbvie Inc. | Vitamin D receptor activators and methods of making |
| US7718638B2 (en) * | 2007-12-28 | 2010-05-18 | Wisconsin Alumni Research Foundation | (20R)-23,23-difluoro-2-methylene-19-nor-bishomopregnacalciferol-vitamin D analogs |
| CA2710954C (en) * | 2007-12-28 | 2015-07-21 | Wisconsin Alumni Research Foundation | (20s)-23,23-difluoro-2-methylene-19-nor-bishomopregnacalciferol-vitamin d analogs |
| CA2710970A1 (en) * | 2007-12-28 | 2009-07-09 | Wisconsin Alumni Research Foundation | 2-methylene-(20s,25r)-19,26-dinor-vitamin d analogs |
| AU2009221717A1 (en) * | 2008-03-06 | 2009-09-11 | Wisconsin Alumni Research Foundation | Methods of increasing epidermal skin thickness by topical administration of A 19-nor containing vitamin D compound |
| WO2009114540A2 (en) * | 2008-03-10 | 2009-09-17 | Wisconsin Alumni Research Foundation | Vitamin d compounds and methods for reducing ocular hypertension (oht) |
| US8399439B2 (en) * | 2008-07-10 | 2013-03-19 | Wisconsin Alumni Research Foundation | 2-methylene-19,26-dinor-(20S,22E,25R)-vitamin D analogs |
| US7888339B2 (en) * | 2008-07-10 | 2011-02-15 | Wisconsin Alumni Research Foundation | 2-methylene-20(21)-dehydro-19-nor-vitamin D analogs |
| US7893043B2 (en) * | 2008-07-10 | 2011-02-22 | Wisconsin Alumni Research Foundation | 2-methylene-(17Z)-17(20)-dehydro-19,21-dinor-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 |
| US20110034426A1 (en) * | 2009-08-03 | 2011-02-10 | Wisconsin Alumni Research Foundation | Method of Preventing Renal Disease and Treating Symptoms Thereof |
| 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 |
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2011
- 2011-03-22 AU AU2011232633A patent/AU2011232633B2/en not_active Ceased
- 2011-03-22 EP EP11711237.5A patent/EP2556053B1/en not_active Not-in-force
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- 2011-03-22 WO PCT/US2011/029432 patent/WO2011119610A2/en not_active Ceased
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- 2011-03-22 ES ES11711237.5T patent/ES2545403T3/es active Active
- 2011-03-22 US US13/053,844 patent/US8604009B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2011232633B2 (en) | 2014-05-29 |
| WO2011119610A3 (en) | 2012-11-29 |
| JP2013522369A (ja) | 2013-06-13 |
| EP2556053A2 (en) | 2013-02-13 |
| EP2556053B1 (en) | 2015-07-29 |
| ES2545403T3 (es) | 2015-09-10 |
| JP5770261B2 (ja) | 2015-08-26 |
| AU2011232633A1 (en) | 2012-10-18 |
| US8604009B2 (en) | 2013-12-10 |
| CA2794006A1 (en) | 2011-09-29 |
| US20110237556A1 (en) | 2011-09-29 |
| WO2011119610A2 (en) | 2011-09-29 |
| AU2011232633A8 (en) | 2012-11-01 |
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