AU717238B2 - Calcitriol derivatives and their uses - Google Patents

Calcitriol derivatives and their uses Download PDF

Info

Publication number: AU717238B2
Authority: AU; Australia
Prior art keywords: group; hydrogen; vitamin; represent; compound
Prior art date: 1995-09-21
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Ceased

Application number

AU72426/96A

Other languages

English (en)

Other versions

AU7242696A (en

Inventor

Zu Yun Cai

Hector F. Deluca

Mary E. Phelps

Heinrich K. Schnoes

Connie M. Smith

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Wisconsin Alumni Research Foundation

Original Assignee

Wisconsin Alumni Research Foundation

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-09-21

Filing date

1996-09-20

Publication date

2000-03-23

1995-09-21 Priority claimed from US08/531,403 external-priority patent/US5952317A/en

1996-09-20 Application filed by Wisconsin Alumni Research Foundation filed Critical Wisconsin Alumni Research Foundation

1997-04-09 Publication of AU7242696A publication Critical patent/AU7242696A/en

2000-03-23 Application granted granted Critical

2000-03-23 Publication of AU717238B2 publication Critical patent/AU717238B2/en

2016-09-20 Anticipated expiration legal-status Critical

Status Ceased legal-status Critical Current

Links

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GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 claims description 31
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229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
208000032349 type 2B vitamin D-dependent rickets Diseases 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical class C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C401/00—Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Physical Education & Sports Medicine (AREA)
Hematology (AREA)
Diabetes (AREA)
Obesity (AREA)
Nutrition Science (AREA)
Orthopedic Medicine & Surgery (AREA)
Rheumatology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

AU72426/96A 1995-09-21 1996-09-20 Calcitriol derivatives and their uses Ceased AU717238B2 (en)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US53186795A	1995-09-21	1995-09-21
US08/531867		1995-09-21
US08/531,403 US5952317A (en)	1995-09-21	1995-09-21	Calcitriol derivatives and their uses
US08/531403		1995-09-21
PCT/US1996/015184 WO1997011053A1 (fr)	1995-09-21	1996-09-20	Derives de calcitriol et leurs utilisations

Publications (2)

Publication Number	Publication Date
AU7242696A AU7242696A (en)	1997-04-09
AU717238B2 true AU717238B2 (en)	2000-03-23

Family

ID=27063537

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU72426/96A Ceased AU717238B2 (en)	1995-09-21	1996-09-20	Calcitriol derivatives and their uses

Country Status (9)

Country	Link
EP (1)	EP1021401A1 (fr)
JP (1)	JP3372259B2 (fr)
KR (1)	KR100327922B1 (fr)
AU (1)	AU717238B2 (fr)
CA (1)	CA2229316C (fr)
HU (1)	HUP9802303A3 (fr)
NO (1)	NO981282L (fr)
NZ (2)	NZ501318A (fr)
WO (1)	WO1997011053A1 (fr)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5795909A (en)	1996-05-22	1998-08-18	Neuromedica, Inc.	DHA-pharmaceutical agent conjugates of taxanes
WO2001011986A1 (fr) *	1999-08-17	2001-02-22	Wisconsin Alumni Research Foundation	Aliments pour animaux contenant des derives de calcitriol hydrolysables
KR100317935B1 (ko) *	1999-10-20	2001-12-22	유승필	대사성 골질환 치료용 약제조성물 및 이의 제조방법
WO2001040177A2 (fr)	1999-12-02	2001-06-07	Women And Infants Hospital	Esters de vitamine d3 et utilisation de ces ceux-ci
US20030195175A1 (en) *	2002-03-25	2003-10-16	Deluca Hector F.	Use of carbon-2-modified-vitamin D analogs to induce the formation of new bone
AU2005216651A1 (en)	2004-03-01	2005-09-09	Bioxell Spa	Treatment of interstitial cystitis with vitamin D compounds
EP1812011A1 (fr)	2004-11-12	2007-08-01	Bioxell S.p.a.	Emploi combiné de dérivés de vitamine d et d'agents antiproliférants pour le traitement de cancers de la vessie
US8426391B2 (en)	2006-02-03	2013-04-23	Proventiv Therapeutics, Llc	Treating vitamin D insufficiency and deficiency with 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3
SI2679228T1 (en)	2006-06-21	2018-06-29	Opko Ireland Global Holdings, Ltd.	THERAPY WITH THE USE OF VITAMIN D ADDITIONAL FIBER AND HORMON RESISTANCE OF VITAMIN D
PT2148684E (pt)	2007-04-25	2013-04-19	Cytochroma Inc	Método de tratamento para a insuficiência e deficiência de vitamina d
ES3047207T3 (en)	2007-04-25	2025-12-03	Opko Renal Llc	Method of safely and effectively treating and preventing secondary hyperparathyroidism in chronic kidney disease
KR20190028822A (ko)	2007-04-25	2019-03-19	사이토크로마 인코포레이티드	비타민 ｄ 화합물과 밀랍성 담체를 포함하는 경구 조절성 방출 조성물
US8592401B2 (en)	2007-04-25	2013-11-26	Proventiv Therapeutics, Llc	Methods and compounds for vitamin D therapy
CA2714996C (fr)	2008-04-02	2020-04-07	Cytochroma Inc.	Procedes, compositions, utilisations, et kits utiles pour la carence en vitamine d et des troubles associes
RS60087B1 (sr)	2010-03-29	2020-05-29	Opko Ireland Global Holdings Ltd	Postupci i kompozicije za snižavanje nivoa paratireoidnog hormona
KR101847947B1 (ko)	2013-03-15	2018-05-28	옵코 아이피 홀딩스 Ⅱ 인코포레이티드	안정화되고 변형된 비타민 ｄ 방출 제형
US10220047B2 (en)	2014-08-07	2019-03-05	Opko Ireland Global Holdings, Ltd.	Adjunctive therapy with 25-hydroxyvitamin D and articles therefor
SG11201808227YA (en)	2016-03-28	2018-10-30	Opko Ireland Global Holdings Limited	Methods of vitamin d treatment
KR101983654B1 (ko) *	2018-07-24	2019-05-29	한국과학기술원	Cfc 증후군 환자의 발달 저해를 완화할 수 있는 치료용 조성물
CN114681467B (zh) *	2022-03-30	2024-03-12	南通华山药业有限公司	一种阿法骨化醇杂环酯类衍生物在制备抗肿瘤药物中的应用
CN114656413B (zh) *	2022-03-30	2024-04-09	南通华山药业有限公司	一种阿法骨化醇杂环酯类衍生物及其制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB2026494A (en) *	1978-07-26	1980-02-06	Wisconsin Alumni Res Found	Fluorinated compounds of the vitamin d structure
US4195027A (en) *	1978-01-16	1980-03-25	Wisconsin Alumni Research Foundation	Process for preparing 1α-hydroxylated compounds

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4206131A (en) *	1978-06-19	1980-06-03	The Upjohn Company	Compounds and process
JPS5846508A (ja) *	1981-09-14	1983-03-18	日本石油化学株式会社	導電性材料の製法
IT1163846B (it) *	1982-07-26	1987-04-08	Wisconsin Alumni Res Found	Analoghi della vitamina d
JPH0825993B2 (ja) *	1990-08-20	1996-03-13	大同ほくさん株式会社	ビタミンｄ２およびｄ３又は活性型ビタミンｄ２およびｄ３の製造方法，並びにその中間体
JPH05339230A (ja) *	1992-03-12	1993-12-21	Nisshin Flour Milling Co Ltd	活性型ビタミンｄ２及びその誘導体の製造法
JP3182215B2 (ja) *	1992-06-26	2001-07-03	日清製粉株式会社	１−アシルオキシビタミンｄ誘導体

1996
- 1996-09-20 AU AU72426/96A patent/AU717238B2/en not_active Ceased
- 1996-09-20 HU HU9802303A patent/HUP9802303A3/hu unknown
- 1996-09-20 WO PCT/US1996/015184 patent/WO1997011053A1/fr not_active Ceased
- 1996-09-20 CA CA002229316A patent/CA2229316C/fr not_active Expired - Fee Related
- 1996-09-20 NZ NZ501318A patent/NZ501318A/en unknown
- 1996-09-20 EP EP96933853A patent/EP1021401A1/fr not_active Withdrawn
- 1996-09-20 KR KR1019980702077A patent/KR100327922B1/ko not_active Expired - Fee Related
- 1996-09-20 NZ NZ319819A patent/NZ319819A/en unknown
- 1996-09-20 JP JP51294597A patent/JP3372259B2/ja not_active Expired - Fee Related
1998
- 1998-03-20 NO NO981282A patent/NO981282L/no not_active Application Discontinuation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4195027A (en) *	1978-01-16	1980-03-25	Wisconsin Alumni Research Foundation	Process for preparing 1α-hydroxylated compounds
GB2026494A (en) *	1978-07-26	1980-02-06	Wisconsin Alumni Res Found	Fluorinated compounds of the vitamin d structure

Also Published As

Publication number	Publication date
CA2229316A1 (fr)	1997-03-27
NO981282L (no)	1998-05-22
KR100327922B1 (ko)	2002-05-09
WO1997011053A1 (fr)	1997-03-27
HUP9802303A3 (en)	1999-05-28
MX9801943A (es)	1998-08-30
AU7242696A (en)	1997-04-09
CA2229316C (fr)	2005-04-12
NO981282D0 (no)	1998-03-20
HUP9802303A2 (hu)	1999-02-01
NZ501318A (en)	2001-07-27
NZ319819A (en)	2000-02-28
JP3372259B2 (ja)	2003-01-27
JPH11511475A (ja)	1999-10-05
KR19990063628A (ko)	1999-07-26
EP1021401A1 (fr)	2000-07-26

Publication	Publication Date	Title
AU717238B2 (en)	2000-03-23	Calcitriol derivatives and their uses
US5976784A (en)	1999-11-02	Calcitriol derivatives and their uses
US5952317A (en)	1999-09-14	Calcitriol derivatives and their uses
US5561123A (en)	1996-10-01	Method of treating proliferative skin disorders with 19-nor-vitamin D compounds
US5552392A (en)	1996-09-03	Method of treating hypoparathyroidism with (20S) vitamin D compounds
KR100321414B1 (ko)	2002-12-05	비타민d아미드유도체
US7531527B2 (en)	2009-05-12	2-Propylidene-19-nor-vitamin D compounds
KR100271461B1 (ko)	2000-11-15	비타민 d 아미드 유도체
EP0971888A1 (fr)	2000-01-19	Derives 2-alkyle-19-nor- de la vitamine d
US5373004A (en)	1994-12-13	26,28-methylene-1α, 25-dihydroxyvitamin D2 compounds
JP2002506429A (ja)	2002-02-26	３−エピビタミンｄ２化合物及びその使用法
CA2562535C (fr)	2012-07-10	Composes de vitamine d 2-alkylidene-18,19-dinor
AU2005309747A1 (en)	2006-06-01	2-methylene-18,19-dinor-1alpha-hydroxy-homopregnacalciferol and its uses
NZ571773A (en)	2011-11-25	2-Methylene-1alpha,25-dihydroxy-18,19,21-trinorvitamin D3 and uses thereof
US5036061A (en)	1991-07-30	Process for the preparation of 1 alpha,25-dihydroxylated vitamin D2 and related compounds
AU5117198A (en)	1998-06-29	Vitamin d3 derivatives
EP0793648A1 (fr)	1997-09-10	Composes du type 18-nor-vitamine d
MXPA98001943A (en)	1998-11-12	Derivatives of calcitriol and its u
AU2007306292A1 (en)	2008-04-17	Novel method of treatment of male sub-fertility

Legal Events

Date	Code	Title	Description
2000-07-20	FGA	Letters patent sealed or granted (standard patent)
2004-04-22	MK14	Patent ceased section 143(a) (annual fees not paid) or expired