CA1329589C - Composes seco-sterol capables d'induire la differenciation cellulaire - Google Patents

Composes seco-sterol capables d'induire la differenciation cellulaire

Info

Publication number: CA1329589C
Authority: CA; Canada
Prior art keywords: group; compound; alkyl; carbon atoms; ethyl
Prior art date: 1985-04-23
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.): Expired - Fee Related

Application number

CA000603774A

Other languages

English (en)

Inventor

Hector F. De Luca

Heinrich K. Schnoes

Wan Fang Lau

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.)

1985-04-23

Filing date

1989-06-23

Publication date

1994-05-17

1989-06-23 Application filed by Wisconsin Alumni Research Foundation filed Critical Wisconsin Alumni Research Foundation

1994-05-17 Application granted granted Critical

1994-05-17 Publication of CA1329589C publication Critical patent/CA1329589C/fr

2011-05-17 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

230000024245 cell differentiation Effects 0.000 title claims abstract description 9
DIFSFFZHWQSHBX-CLECVEASSA-N (1ar,3s,4as,7s,8as)-3-[(1s,2r,3r)-3-[(2r,5s)-5,6-dimethylheptan-2-yl]-2-(2-hydroxyethyl)-2-methylcyclopentyl]-7-hydroxy-4a-methyl-2,3,5,6,7,8-hexahydro-1ah-naphtho[4,4a-b]oxiren-4-one Chemical class OCC[C@]1(C)[C@@H]([C@H](C)CC[C@H](C)C(C)C)CC[C@H]1[C@H]1C(=O)[C@@]2(C)CC[C@H](O)C[C@@]32O[C@@H]3C1 DIFSFFZHWQSHBX-CLECVEASSA-N 0.000 title abstract description 16
230000001939 inductive effect Effects 0.000 title abstract description 7
239000000203 mixture Substances 0.000 claims abstract description 41
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 38
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 27
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 20
230000004069 differentiation Effects 0.000 claims abstract description 17
-1 vitamin D compounds Chemical class 0.000 claims abstract description 16
239000001257 hydrogen Substances 0.000 claims abstract description 15
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
239000008194 pharmaceutical composition Substances 0.000 claims abstract 6
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 3
150000001875 compounds Chemical class 0.000 claims description 49
125000002252 acyl group Chemical group 0.000 claims description 29
125000003435 aroyl group Chemical group 0.000 claims description 17
125000000217 alkyl group Chemical group 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
125000001475 halogen functional group Chemical group 0.000 claims description 9
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
125000003651 hexanedioyl group Chemical group C(CCCCC(=O)*)(=O)* 0.000 claims description 5
125000003431 oxalo group Chemical group 0.000 claims description 5
150000002431 hydrogen Chemical group 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims 13
125000006331 halo benzoyl group Chemical group 0.000 claims 4
125000000346 malonyl group Chemical group C(CC(=O)*)(=O)* 0.000 claims 4
239000003937 drug carrier Substances 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 20
239000011575 calcium Substances 0.000 abstract description 20
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238000001727 in vivo Methods 0.000 abstract description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
229910052799 carbon Inorganic materials 0.000 abstract 1
230000002939 deleterious effect Effects 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 40
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 37
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
229910052757 nitrogen Inorganic materials 0.000 description 22
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 21
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 21
238000000034 method Methods 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
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238000003556 assay Methods 0.000 description 16
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235000017557 sodium bicarbonate Nutrition 0.000 description 14
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UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
239000000047 product Substances 0.000 description 12
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238000005481 NMR spectroscopy Methods 0.000 description 11
229940125904 compound 1 Drugs 0.000 description 11
239000011780 sodium chloride Substances 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
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150000004678 hydrides Chemical class 0.000 description 8
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238000002360 preparation method Methods 0.000 description 8
238000012746 preparative thin layer chromatography Methods 0.000 description 8
230000008569 process Effects 0.000 description 8
239000002904 solvent Substances 0.000 description 8
239000003795 chemical substances by application Substances 0.000 description 7
JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
239000007858 starting material Substances 0.000 description 7
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
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230000000968 intestinal effect Effects 0.000 description 6
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229960000583 acetic acid Drugs 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000012259 ether extract Substances 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
238000000746 purification Methods 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
238000010992 reflux Methods 0.000 description 5
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 5
239000000725 suspension Substances 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
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DAKIDYQCFJQMDF-UHFFFAOYSA-N dichloromethane;pyridine Chemical compound ClCCl.C1=CC=NC=C1 DAKIDYQCFJQMDF-UHFFFAOYSA-N 0.000 description 4
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
239000000284 extract Substances 0.000 description 4
QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 4
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000603774A 1985-04-23 1989-06-23 Composes seco-sterol capables d'induire la differenciation cellulaire Expired - Fee Related CA1329589C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date
US72649685A	1985-04-23	1985-04-23
US28324488A	1988-12-12	1988-12-12
US07/283,244		1988-12-12

Publications (1)

Publication Number	Publication Date
CA1329589C true CA1329589C (fr)	1994-05-17

Family

ID=26961937

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000603774A Expired - Fee Related CA1329589C (fr)	1985-04-23	1989-06-23	Composes seco-sterol capables d'induire la differenciation cellulaire

Country Status (1)

Country	Link
CA (1)	CA1329589C (fr)

1989
- 1989-06-23 CA CA000603774A patent/CA1329589C/fr not_active Expired - Fee Related

Legal Events

Date	Code	Title	Description
2004-05-17	MKLA	Lapsed
2023-05-26	MKLA	Lapsed	Effective date: 20040517

Publication	Publication Date	Title
US4800198A (en)	1989-01-24	Method of inducing the differentiation of malignant cells with secosterol
US5585369A (en)	1996-12-17	Method of treating low bone turnover osteoporosis with (205) vitamin D compounds
EP0637299B1 (fr)	1996-05-22	Derives de vitamine d a substitution 20-methyle
US4260549A (en)	1981-04-07	Process for preparing 1α-hydroxylated compounds
US5532391A (en)	1996-07-02	Homologated vitamin D2 compounds and the corresponding 1α-hydroxylated derivatives
KR100294600B1 (ko)	2001-09-17	비타민d계열의25-카르복실산유도체,그의제조방법,그제조방법의중간생성물,그들유도체를함유하는제약조성물및약제의제조를위한그들의용도
US5250523A (en)	1993-10-05	Side chain unsaturated 1α-hydroxyvitanim D homologs
JPH04505468A (ja)	1992-09-24	同族化されたビタミンＤ↓２化合物および対応する１α―ヒドロキシル化誘導体
WO1985003298A1 (fr)	1985-08-01	Isomeres de l'hydroxyvitamine d2
US4940700A (en)	1990-07-10	Seco-sterol compounds effective in inducing cell differentiation
AU629831B2 (en)	1992-10-15	Side chain unsaturated 1 alpha-hydroxyvitamin d homologs for the treatment of leukemia
US5380720A (en)	1995-01-10	Iodo vitamin D3 compounds and method for preparing same
EP0218714B1 (fr)	1991-08-07	Composes de seco-sterol efficaces dans l'induction de la differentiation de cellules malignes
EP1226155A2 (fr)	2002-07-31	18-nor-steroides utilises comme oestrogenes a effet selectif
US5354744A (en)	1994-10-11	Side chain unsaturated 1 alpha-hydroxyvitamin D analogs
DE69732369T2 (de)	2006-05-11	Vitamin d3-derivate
EP0157781B1 (fr)	1988-05-11	Composes de 1,23-dihydroxyvitamine d
DE3590021C2 (de)	1992-09-10	1alpha-Hydroxyvitamin D-Derivat und dieses enthaltendes Arzneimittel
Ohyama et al.	1999	Biosynthesis of 20-hydroxyecdysone in Ajuga hairy roots: Fate of 6α-and 6β-hydrogens of lathosterol
AU584071B2 (en)	1989-05-18	1a-hydroxyvitamin d2 analogs and process for preparing same
JPH05238937A (ja)	1993-09-17	細胞分化誘発薬剤
JPH0686421B2 (ja)	1994-11-02	セコステロール類似体
DE4445045A1 (de)	1996-06-13	20-Fluor-substituierte Vitamin D-Derivate, Verfahren zu deren Herstellung, deren Verwendung zur Herstellung von Arzneimitteln und Zwischenprodukte zur Darstellung der Verbindungen
NO180537B (no)	1997-01-27	Fremgangsmåte for fremstilling av vitamin D2-forbindelser og de tilsvarende -hydroksylerte derivater