FI113535B - Förfarande för framställning av terapeutiskt användbara D-vitaminanaloger - Google Patents
Förfarande för framställning av terapeutiskt användbara D-vitaminanaloger Download PDFInfo
- Publication number
- FI113535B FI113535B FI960303A FI960303A FI113535B FI 113535 B FI113535 B FI 113535B FI 960303 A FI960303 A FI 960303A FI 960303 A FI960303 A FI 960303A FI 113535 B FI113535 B FI 113535B
- Authority
- FI
- Finland
- Prior art keywords
- secopregna
- dihydroxy
- triazol
- triene
- ylmethyl
- Prior art date
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- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products 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-XFEUOLMDSA-N 0.000 title claims abstract description 19
- 150000003710 vitamin D derivatives Chemical class 0.000 title claims abstract description 17
- 239000011710 vitamin D Substances 0.000 title claims abstract description 16
- 229940046008 vitamin d Drugs 0.000 title claims abstract description 16
- 229930003316 Vitamin D Natural products 0.000 title claims abstract description 15
- 235000019166 vitamin D Nutrition 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims description 39
- 238000002360 preparation method Methods 0.000 title claims description 26
- 230000008569 process Effects 0.000 title claims description 21
- 150000001875 compounds Chemical class 0.000 claims abstract description 172
- -1 cyclohexylidene moiety Chemical group 0.000 claims abstract description 141
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 39
- 125000001425 triazolyl group Chemical group 0.000 claims abstract description 11
- 150000001540 azides Chemical class 0.000 claims abstract description 10
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 17
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 238000006317 isomerization reaction Methods 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 7
- 150000005671 trienes Chemical class 0.000 claims description 7
- 239000002243 precursor Substances 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
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- 125000005842 heteroatom Chemical group 0.000 claims description 3
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- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052717 sulfur Chemical group 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 3
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- 238000005886 esterification reaction Methods 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 2
- 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 claims 2
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
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- 230000000694 effects Effects 0.000 abstract description 33
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- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 abstract description 2
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- 230000001747 exhibiting effect Effects 0.000 abstract 1
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- 238000004587 chromatography analysis Methods 0.000 description 38
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 26
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 26
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- 150000003852 triazoles Chemical group 0.000 description 23
- 150000001412 amines Chemical class 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 19
- 238000011282 treatment Methods 0.000 description 15
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 14
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 14
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 13
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- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
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- GMRQFYUYWCNGIN-UHFFFAOYSA-N 1,25-Dihydroxy-vitamin D3' Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CC(O)C1=C GMRQFYUYWCNGIN-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Claims (18)
1. Förfarande för framställning av terapeutiskt användbara föreningar med den allmänna formeln (I) 5 R y-w. x ? - A där Rl betecknar en metylgrupp med en a- eller β-konfigu-ration eller en dimetyl-, metylen- eller spirocyklopropyl-gruppering; 10. betecknar en valensbindning eller en Cl-5- alkylengrupp; X betecknar azid eller en eventuellt substituerad triazolgrupp; och A= betecknar en cyklohexylidengrupp som är karak-15 teristisk för A-ringen för en la-hydroxylerad D-vitamin : eller analog därav, ^ kännetecknatav att förfarandet omfat- ,, \ tar ett eller flera av följande steg, där man: A) isomeriserar en 5,6-trans-isomer med den all- ’’··* 20 manna formeln (I) tili en motsvarande 5,6-cis-isomer, va- refter, vid behov och/eller om sä önskas, vilka som heist ,· · O-skyddsgrupper avlägsnas; B) hydroxylerar en l-osubstituerad-5,6-trans-ana- *:* log av en förening med den allmänna formeln (I) för att 25 framställa en 5,6-trans-isomer med den allmänna formeln . (I) , varefter, vid behov och/eller om sä önskas, vilken » * ♦ som heist O-skyddsgrupp isomeriseras och/eller avlägsnas; * » C) bringar en förening, som innehäller en prekur-sor tili den önskade 17-position-sidokedjan, att reagera i ·...: 30 ett eller flera steg och med en eller flera reaktanter vilka bildar den önskade sidokedjan, varefter, vid behov 73 11353E och/eller om sä önskas, vilka som heist O-skyddsgrupper isomeriseras och/eller avlägsnas; och D) bringar en förening med formeln (I) att reage-ra, varvid man modifierar substitueringsmönstret omkring 5 A= gruppen, varefter, vid behov och/eller om sä önskas, skyddsgrupper isomeriseras och/eller avlägsnas.
2. Förfarande enligt patentkrav 1, kanne-tecknat av att en förening med den allmänna formeln (III) R . L Φ (111) A 10 där Rl, W och A är definierade säsom i patentkravet 1 och L betecknar en avgäende grupp, eller en prekursor därför bringas att reagera med en azidjonkälla.
3. Förfarande enligt patentkrav 1 eller 2, k ä n- .. 15 netecknat av att en förening med den allmänna ’ formeln (I), där X betecknar azid, eller en prekursor där för, bringas att reagera med ett acetylenderivat, varvid ’ * man erhäller en förening med den allmänna formeln (I), där • ..* X betecknar en substituerad triazolgrupp. / 20
4. Förfarande enligt patentkrav 1, k ä n n e- ; : : t e c k n a t av att man framställer en förening med den allmänna formeln (II) : Λ R]YW'^Y Z λ: ςτ> "* if ·; a » · där Rl, W och A är definierade säsom i patentkravet 1; Y 113535 74 betecknar en valensbindning eller en lägre alkylengrupp som är förenad med 4- eller 5-positionen av triazolringen; och Z betecknar antingen (i) en grupp -CO.NR2R3, där R2 och R3 kan vara lika eller olika och väljs bland väteato-5 mer, alifatiska, cykloalifatiska, aralfatiska och aryl-grupper, eller R2 och R3 bildar tillsammans med kväveato-men, med vilken de är förenade, en heterocyklisk grupp; eller (ii) en grupp —C (R4) (R5).0H, där R4 och R5 kan vara lika eller olika och väljs bland väteatomer, alifatiska, 10 cykloalifatiska, aralfatiska och arylgrupper, eller R2 och R3 bildar tillsammans med kolatomen, med vilken de är förenade, en C3-8-karbocyklisk ring.
5. Förfarande enligt patentkrav 4, k ä n n e- tecknat av att R2-R5 väljs bland väteatomer, Cl-6- 15 alkylgrupper, C3-8-cykloalkylgrupper, C6-12-aryl-Cl-4-al- kylgrupper och eventuellt substituerade C6-12-karbocyk-liska arylgrupper.
6. Förfarande enligt patentkrav 5, k ä n n e- tecknat av att Y förenas med 4-positionen av tria- 20 zolringen och R2-R5 väljs bland väteatomer, Cl-6- alkylgrupper och C3-8-cykloalkylgrupper.
: . ’ 7. Förfarande enligt patentkrav 4, k ä n n e- t I t ,,/ t e c k n a t av att R2-R5 väljs bland väteatomer, metyl- : ' : , etyl-, n-propyl-, isopropyl-, isobutyl-, cykopropyl- och 25. enylgrupper.
« '. 8. Förfarande enligt patentkrav 4, kanne- tecknat av att R2R3N- betecknar en heterocyklisk $ grupp som omfattar en eller flera 5- och/eller 6-ledade , ringar som eventuellt innehäller en eller flera til- 30 läggsheteroatomer valda bland syre, kväve och svavel.
9. Förfarande enligt patentkrav 8, k ä n. n e- ; t e c k n a t av att R2R3N- betecknar en piperidino- el- ler morfolinogrupp.
10. Förfarande enligt patentkrav 4, k ä n n e-’35 tecknat av att -C(R4) (R5)— betecknar en cyklohexy- lidengrupp. 113535 75
11. Förfarande enligt nägot av patentkraven 4-10, kännetecknat av att Y betecknar en valensbind-ning eller en metylen-, etylen- eller trimetylengrupp.
12. Förfarande enligt nägot av de föregäende pa-5 tentkraven, kännetecknat av att W betecknar en valensbindning eller en metylen-, etylen- eller trimetylengrupp .
13. Förfarande enligt nägot av de föregäende patentkraven, kännetecknat av att A= betecknar 10 en av grupperna Af Λ r'o'^or' rW\or‘ (A - 2) ‘A-31 Λτ Λ r6o^or7 r7o^ors ( A - 4 ) ( A - S ) s A ... r'o/v'or7 r’o^or6 . ‘ "· . ( A - 6 ) ( A - 7 ) v · och 15 ν’ r'o^OR6 : .: i a -1) där R6 och R7, som kan vara lika eller olika, vardera be- tecknar en väteatom eller en O-skyddsgrupp.
,.,.: 14. Förfarande enligt patentkrav 13, k ä n n e- » · 20 tecknat av att R6 och R7 betecknar företrande si- 113535 76 lylgrupper.
15. Förfarande enligt patentkrav 13, k ä n n e-tecknat av att R6 och R7 väljs bland väteatomer och metaboliskt labila företrings- och förestringsgrupper. 5
16. Förfarande enligt nägot av patentkraven 1-12, kännetecknat av att A= betecknar en av grup-perna & H0,,-\^0H ho/\Aoh (A‘2a> ( A - 3 a } och 10
17. Förfarande enligt nägot av de föregäende pat entkraven, kännetecknat av att man fram-ställer: 20a-(3-azidopropyl)-la,35-dihydroxi-9,10-sekopreg-na-5(Z),7,10(19)-trien; 15 20a-azido-la,3fi-dihydroxi-9,10-sekopregna-5(Z),7, 10(19)-trien; la,3ft-dihydroxi-20a-[4-(2-hydroxiprop-2-yl)-1,2,3-;· , triazol-l-yl]-9,10-sekopregna-5(Z),7,10(19)-trien; la,3h-dihydroxi-20a-[4-(3-hydroxipent-3-yl)-1,2,3- 20 triazol-l-yl]-9,10-sekopregna-5(Z),7,10(19)-trien; la,35-dihydroxi-20a-[4-(2-hydroxiprop-2-yl)-l,2,3~ triazol-1-ylmetyl]-9,10-sekopregna-5(Z),7,10(19)-trien; ' la,3ft-dihydroxi-20fi>-[4-(3-hydroxipent-3-yl)-1,2,3- V : triazol-1-ylmetyl]-9,10-sekopregna-5 (Z) , 7,10 (19) -trien; 25 la,3B-dihydroxi-20a-[4-(3-hydroxipent-3-yl)-1,2,3- *· triazol-1-ylmetyl]-9,10-sekopregna-5(Z),7,10(19)-trien; . la,3B-dihydroxi-20a-[4-(N,N-pentametylenkarbamo- / t yl)-1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z) , 7,10- ’* '· (19) -trien; • I > ’...· 30 la,3fi-dihydroxi-20a-[4-(Ν,Ν-dietylkarbamoyl)-1,2, •/’h 3-triazol-l-ylmetyl] -9,10-sekopregna-5 (Z) , 7,10 (19) -trien; la, 3fi-dihydroxi-20a- [4- (N-cyklopropylkarbamoyl) - 113535 77 1.2.3- triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,10(19)-trien; la, 35-dihydroxi-20a-[4-(N,N-3-oxapentametylenkar-bamoyl)-1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7, 5 10(19)-trien; la,35-dihydroxi-20a-(4-(N,N-di-isopropylkarbamo-yl)-1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,10-(19)-trien; la,3β-dihydroxi-20β-[4-(N,N-pentametylenkarbamo-10 yl)-1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,10-(19)-trien; la,3β-dihydroxi-20β-[4-(N,N-dietylkarbamoyl) - 1.2.3- triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,10(19)-trien; 15 la,35-dihydroxi-205-[4-(N-cyklopropylkarbamoyl) - 1.2.3- triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,10(19)-trien; la,35-dihydroxi-205-[4-(N,N-3-oxapentametylenkar-bamoyl)-1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7, 20 10(19)-trien; la,3β-dihydroxi-20β-[4-(N,N-di-isopropylkarbamo-* yl)-1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,ΙΟΙ* (19)-trien; la,35-dihydroxi-20a-{2-[4-(N,N-pentametylenkarba-.* 25 moyl)-1,2,3-triazol-l-yl]etyl}-9,10-sekopregna-5(Z),7,10- ..· (19) -trien; la,35-dihydroxi-20a-{2-[4-(N,N-dietylkarbamoyl)- 1.2.3- triazol-l-yl]etyl}-9,10-sekopregna-5(Z),7,10(19)- .:. trien; , ·, 30 la,35-dihydroxi-20a-{2-[4-(N-cyklopropylkarbamo- >’ yl)-1,2,3-triazol-l-yl]etyl}-9,10-sekopregna-5(Z),7,10- (19) -trien; : la, 35-dihydroxi-20a-{2- [4- (N,N-3-oxapentametylen- karbamoyl)-1,2,3-triazol-l-yl]etyl]-9,10-sekopregna-5(Z), 35 7,10 (19)-trien; * ♦ la,35-dihydroxi-20a-{2-[4-(N,N-di-isopropylkarba- 113535 78 moyl)-1,2,3-triazol-l-yl]etyl}-9,10-sekopregna-5(Z),7,10-(19)-trien; la,3B-dihydroxi-20a-[4-(1-hydroxicyklohex-l-yl) - 1.2.3- triazol-l-ylmetyl]-9,10-sekopregna-5(Z) ,7,10(19)-5 trien; la,35-dihydroxi-20a-{2-[4-(3-hydroxipent-3-yl) - 1.2.3- triazol-l-yl]etyl}-9,10-sekopregna-5(Z) ,7,10(19)-trien; la,35-dihydroxi-205-{2-[4-(3-hydroxipent-3-yl) -10 1,2,3-triazol-l-yl]etyl}-9,10-sekopregna-5(Z),7,10(19)- trien; la,35-dihydroxi-20a-{3-[4-(3-hydroxipent-3-yl) - 1.2.3- triazol-l-yl]propyl}-9,10-sekopregna-5(Z) ,7,10(19)-trien; 15 la,35-dihydroxi-20a-{3-[4-(3-metyl-3-hydroxibut- yl)-1,2,3-triazol-l-yl]propyl}-9,10-sekopregna-5(Z) ,7,10-(19)-trien; la,35-dihydroxi-20a-{3-[4-(2-metyl-2-hydroxipen-tyl)-1,2,3-triazol-l-yl]propyl}-9,10-sekopregna-5(Z),7, 20 10 (19)-trien; la,35-dihydroxi-20a-{3-[4-(4-etyl-4-hydroxihexyl)- : 1,2,3-triazol-l-yl]propyl}-9,10-sekopregna-5(Z),7,10(19)- : trien; ; la,3fi-dihydroxi-20a-{3-[4-(2-hydroxibut-2-yl)- 25 1,2,3-triazol-l-yl]propyl}-9,10-sekopregna-5(Z) , 7,10(19)- trien; la,3B-dihydroxi-20a-{3-[4-(4-metyl-2-hydroxipent- 2-yl)-1,2,3-triazol-l-yl]propyl}-9,10-sekopregna-5(Z),7, 10(19)-trien; • 30 la,3fi-dihydroxi-20a-{3-[4-(2,4-dimetyl-3-hydroxi- \. pent-3-yl)-1,2,3-triazol-l-yl]propyl}-9,10-sekopregna- I 5 (Z) , 7,10 (19)-trien; ,* ·. la, 35-dihydroxi-20a- [4- (2-etyl-2-hydroxibutyl) - » » *' 1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z) ,7,10(19)- 35 trien; » » 113535 79 la,3fi-dihydroxi-20a-[5-(2-etyl-2-hydroxibutyl)- 1.2.3- triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,10(19)-trien; la,35-dihydroxi-20a-[4-(3-hydroxipent-3-yl)-1,2,3-5 triazol-l-ylmetyl]-9,10-sekopregna-5(E),7-dien; la,35-dihydroxi-20a-[4-(3-hydroxipent-3-yl)-1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7-dien; la,3B-dihydroxi-20a-[4-(3-hydroxipent-3-yl)-1,2,3-triazol-l-ylmetyl]-10-spirocyklopropyl-9,10-sekopregna-10 5(E),7-dien; la,3fi-dihydroxi-20a-[4-(3-hydroxipent-3-yl)-1,2,3-triazol-l-ylmetyl]-10-spirocyklopropyl-9,10-sekopregna-5(Z),7-dien; la,35-dihydroxi-205-[4-(3-hydroxipent-3-yl)-1,2,3-15 triazol-l-ylmetyl]-19-nor-9,10-sekopregna-5,7-dien; la,3B-dihydroxi-20a-[4-(3-metyl-3-hydroxibutyl)- 1.2.3- triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,10(19)— trien; la,35-dihydroxi-20a-[4-(2-metyl-2-hydroxipentyl)-20 1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,10(19)- trien; I la, 3ft-dihydroxi-20a- [4- (4-etyl-4-hydroxihexyl) - * 1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,10(19)- ,** trien; 25 la,3B-dihydroxi-20a-[4-(2-hydroxibut-2-yl)-1,2,3- .* triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7,10(19)-trien; • la, 3fi-dihydroxi-20a-[4-(4-metyl-2-hydroxipent-2-yl)-1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7, ·· 10 (19)-trien; ·. 30 la,3B-dihydroxi-20a-[4-(2,4-dimetyl-3-hydroxipent- # 3-yl)-1,2,3-triazol-l-ylmetyl]-9,10-sekopregna-5(Z),7, 10 (19)-trien; och ' la, 3B-dihydroxi-20a- [4- (2-hydroxifenet-2-yl) -1,2, 3-triazol-l-ylmetyl]-9,10-sekopregna-5 (Z) , 7,10 (19) -trien. * ·
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939315253A GB9315253D0 (en) | 1993-07-23 | 1993-07-23 | Chemical compounds |
| GB9315253 | 1993-07-23 | ||
| PCT/GB1994/001587 WO1995003273A1 (en) | 1993-07-23 | 1994-07-22 | Vitamin d analogues |
| GB9401587 | 1994-07-22 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI960303A0 FI960303A0 (sv) | 1996-01-22 |
| FI960303A FI960303A (sv) | 1996-03-22 |
| FI113535B true FI113535B (sv) | 2004-05-14 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI960303A FI113535B (sv) | 1993-07-23 | 1996-01-22 | Förfarande för framställning av terapeutiskt användbara D-vitaminanaloger |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US5872140A (sv) |
| EP (1) | EP0710227B1 (sv) |
| JP (1) | JPH09500637A (sv) |
| KR (1) | KR100321415B1 (sv) |
| CN (1) | CN1043883C (sv) |
| AT (1) | ATE172451T1 (sv) |
| AU (1) | AU690565B2 (sv) |
| CA (1) | CA2167837A1 (sv) |
| CZ (1) | CZ20796A3 (sv) |
| DE (1) | DE69414115T2 (sv) |
| DK (1) | DK0710227T3 (sv) |
| ES (1) | ES2125466T3 (sv) |
| FI (1) | FI113535B (sv) |
| GB (1) | GB9315253D0 (sv) |
| HU (1) | HU221597B (sv) |
| IL (1) | IL110415A (sv) |
| NO (1) | NO314453B1 (sv) |
| NZ (1) | NZ268659A (sv) |
| WO (1) | WO1995003273A1 (sv) |
| ZA (1) | ZA945427B (sv) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19619036A1 (de) * | 1996-04-30 | 1997-11-13 | Schering Ag | Neue Vitamin D-Derivate mit carbo- oder heterocyclischen Substituenten an C-25, Verfahren zu ihrer Herstellung und die Verwendung zur Herstellung von Arzneimitteln |
| DE19935771A1 (de) | 1999-07-23 | 2001-02-01 | Schering Ag | Neue Vitamin D-Derivate mit cyclischen Substrukturen in den Seitenketten, Verfahren und Zwischenprodukte zu ihrer Herstellung und die Verwendung zur Herstellung von Arzneimitteln |
| US6703380B2 (en) | 1999-09-29 | 2004-03-09 | Colotech A/S | Prevention of cancer |
| ES2240159T3 (es) | 1999-09-29 | 2005-10-16 | Colotech A/S | Prevencion del cancer colorrectal. |
| US6989377B2 (en) | 1999-12-21 | 2006-01-24 | Wisconsin Alumni Research Foundation | Treating vitamin D responsive diseases |
| US6358939B1 (en) | 1999-12-21 | 2002-03-19 | Northern Lights Pharmaceuticals, Llc | Use of biologically active vitamin D compounds for the prevention and treatment of inflammatory bowel disease |
| US6555573B2 (en) * | 2000-12-21 | 2003-04-29 | The Quigley Corporation | Method and composition for the topical treatment of diabetic neuropathy |
| US20030118536A1 (en) * | 2001-11-06 | 2003-06-26 | Rosenbloom Richard A. | Topical compositions and methods for treatment of adverse effects of ionizing radiation |
| US7435725B2 (en) * | 2001-11-06 | 2008-10-14 | The Quigly Corporation | Oral compositions and methods for prevention, reduction and treatment of radiation injury |
| US20030105027A1 (en) * | 2001-11-06 | 2003-06-05 | Rosenbloom Richard A. | Nutritional supplements and methods for prevention, reduction and treatment of radiation injury |
| US20030105031A1 (en) * | 2001-11-06 | 2003-06-05 | Rosenbloom Richard A. | Methods for the treatment of skin disorders |
| US6974592B2 (en) * | 2002-04-11 | 2005-12-13 | Ocean Nutrition Canada Limited | Encapsulated agglomeration of microcapsules and method for the preparation thereof |
| NZ539777A (en) * | 2002-11-04 | 2008-02-29 | Ocean Nutrition Canada Ltd | Microcapsules having multiple shells and method for the preparation thereof |
| US7083813B2 (en) * | 2002-11-06 | 2006-08-01 | The Quigley Corporation | Methods for the treatment of peripheral neural and vascular ailments |
| US8034450B2 (en) * | 2005-01-21 | 2011-10-11 | Ocean Nutrition Canada Limited | Microcapsules and emulsions containing low bloom gelatin and methods of making and using thereof |
| US20080206316A1 (en) * | 2005-01-27 | 2008-08-28 | Colin Barrow | Chromium-Fatty Acid Compounds and Methods of Making and Using Thereof |
| WO2006117675A1 (en) * | 2005-01-27 | 2006-11-09 | Ocean Nutrition Canada Ltd. | Fatty acid-benzenediol derivatives and methods of making and using thereof |
| US9968120B2 (en) * | 2006-05-17 | 2018-05-15 | Dsm Nutritional Products Ag | Homogenized formulations containing microcapsules and methods of making and using thereof |
| US20100055281A1 (en) * | 2006-04-07 | 2010-03-04 | Ocean Nutrition Canada Limited | Emulsions and Microcapsules With Substances Having Low Interfacial Tension, Methods of Making and Using Thereof |
| MX306461B (es) * | 2006-06-05 | 2013-01-07 | Ocean Nutrition Canada Ltd | Microcapsulas con cubiertas mejoradas |
| AU2008205325B2 (en) | 2007-01-10 | 2013-09-12 | Dsm Nutritional Products Ag | Vegetarian microcapsules |
| US20090018151A1 (en) * | 2007-02-23 | 2009-01-15 | Ezekiel Fink | Topical Treatment of Peripheral diabetic complications |
| MX339746B (es) | 2009-01-27 | 2016-06-08 | Berg Llc | Vitamina d3 y análogos de la misma para aliviar efectos secundarios asociados con la quimioterapia. |
| JP5978130B2 (ja) | 2009-08-14 | 2016-08-24 | バーグ エルエルシー | 脱毛症を治療するためのビタミンｄ３およびその類似体 |
| US8987235B2 (en) | 2011-05-17 | 2015-03-24 | Wisconsin Alumni Research Foundation | N-cyclopropyl-(20R)-2-methylene-19,26,27-trinor-25-aza-vitamin D analogs and their uses |
| WO2014194133A1 (en) | 2013-05-29 | 2014-12-04 | Berg Llc | Preventing or mitigating chemotherapy induced alopecia using vitamin d |
| CN104926739B (zh) * | 2015-06-09 | 2017-06-27 | 南京理工大学 | 基于氮杂环修饰的维生素d2衍生物、合成及应用 |
| US10548908B2 (en) * | 2016-09-15 | 2020-02-04 | Nostopharma, LLC | Compositions and methods for preventing and treating heterotopic ossification and pathologic calcification |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL67153A (en) * | 1981-11-02 | 1986-12-31 | Res Inst Medicine Chem | Intermediates in the production of vitamin d analogues and method for their production |
| DE4141746A1 (de) * | 1991-12-13 | 1993-06-17 | Schering Ag | 20-methyl-substituierte vitamin d-derivate |
| IL107185A (en) * | 1992-10-06 | 1998-02-22 | Schering Ag | History of 52-carboxylic acid, processes for their preparation and pharmaceutical preparations containing them |
| US5446635A (en) * | 1993-06-24 | 1995-08-29 | Quarton, Inc. | Laser assembly for marking a line on a workpiece for guiding a cutting tool |
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1993
- 1993-07-23 GB GB939315253A patent/GB9315253D0/en active Pending
-
1994
- 1994-07-22 KR KR1019960700344A patent/KR100321415B1/ko not_active IP Right Cessation
- 1994-07-22 AU AU71939/94A patent/AU690565B2/en not_active Ceased
- 1994-07-22 HU HU9600136A patent/HU221597B/hu not_active IP Right Cessation
- 1994-07-22 NZ NZ268659A patent/NZ268659A/en unknown
- 1994-07-22 ES ES94921070T patent/ES2125466T3/es not_active Expired - Lifetime
- 1994-07-22 DE DE69414115T patent/DE69414115T2/de not_active Expired - Fee Related
- 1994-07-22 ZA ZA945427A patent/ZA945427B/xx unknown
- 1994-07-22 US US08/537,869 patent/US5872140A/en not_active Expired - Fee Related
- 1994-07-22 CZ CZ96207A patent/CZ20796A3/cs unknown
- 1994-07-22 IL IL11041594A patent/IL110415A/xx not_active IP Right Cessation
- 1994-07-22 AT AT94921070T patent/ATE172451T1/de not_active IP Right Cessation
- 1994-07-22 CN CN94193108A patent/CN1043883C/zh not_active Expired - Fee Related
- 1994-07-22 DK DK94921070T patent/DK0710227T3/da active
- 1994-07-22 EP EP94921070A patent/EP0710227B1/en not_active Expired - Lifetime
- 1994-07-22 CA CA002167837A patent/CA2167837A1/en not_active Abandoned
- 1994-07-22 JP JP7505021A patent/JPH09500637A/ja not_active Ceased
- 1994-07-22 WO PCT/GB1994/001587 patent/WO1995003273A1/en not_active Application Discontinuation
-
1996
- 1996-01-22 FI FI960303A patent/FI113535B/sv not_active IP Right Cessation
- 1996-01-22 NO NO19960251A patent/NO314453B1/no not_active IP Right Cessation
-
1998
- 1998-10-20 US US09/175,311 patent/US6013814A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2167837A1 (en) | 1995-02-02 |
| DK0710227T3 (da) | 1999-06-28 |
| GB9315253D0 (en) | 1993-09-08 |
| CN1129441A (zh) | 1996-08-21 |
| AU690565B2 (en) | 1998-04-30 |
| ATE172451T1 (de) | 1998-11-15 |
| HU221597B (hu) | 2002-11-28 |
| NO314453B1 (no) | 2003-03-24 |
| ZA945427B (en) | 1995-08-24 |
| ES2125466T3 (es) | 1999-03-01 |
| CN1043883C (zh) | 1999-06-30 |
| NO960251D0 (no) | 1996-01-22 |
| JPH09500637A (ja) | 1997-01-21 |
| NZ268659A (en) | 1996-09-25 |
| HUT73846A (en) | 1996-09-30 |
| FI960303A0 (sv) | 1996-01-22 |
| CZ20796A3 (en) | 1996-10-16 |
| WO1995003273A1 (en) | 1995-02-02 |
| DE69414115D1 (de) | 1998-11-26 |
| DE69414115T2 (de) | 1999-04-08 |
| HU9600136D0 (en) | 1996-03-28 |
| NO960251L (no) | 1996-03-22 |
| US6013814A (en) | 2000-01-11 |
| US5872140A (en) | 1999-02-16 |
| AU7193994A (en) | 1995-02-20 |
| IL110415A0 (en) | 1996-03-31 |
| IL110415A (en) | 2000-01-31 |
| KR100321415B1 (ko) | 2002-11-13 |
| EP0710227A1 (en) | 1996-05-08 |
| FI960303A (sv) | 1996-03-22 |
| EP0710227B1 (en) | 1998-10-21 |
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| FI112361B (sv) | Förfarande för framställning av terapeutiskt användbara derivat av vitamin D | |
| EP0614455B1 (en) | Vitamin d amide derivatives | |
| EP0734376B1 (en) | Vitamin d amine and amide derivatives | |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |