JP4718449B2 - コルヒチン類似体 - Google Patents
コルヒチン類似体 Download PDFInfo
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- JP4718449B2 JP4718449B2 JP2006508205A JP2006508205A JP4718449B2 JP 4718449 B2 JP4718449 B2 JP 4718449B2 JP 2006508205 A JP2006508205 A JP 2006508205A JP 2006508205 A JP2006508205 A JP 2006508205A JP 4718449 B2 JP4718449 B2 JP 4718449B2
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- demethylthiocolchicine
- xylopyranosyl
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- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical class C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
- 239000001301 oxygen Substances 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 229910052717 sulfur Chemical group 0.000 claims abstract description 5
- 239000011593 sulfur Chemical group 0.000 claims abstract description 5
- 229960002708 antigout preparations Drugs 0.000 claims abstract description 3
- 239000003158 myorelaxant agent Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- 150000003904 phospholipids Chemical class 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000000699 topical effect Effects 0.000 claims 1
- PKYOHQGXPPVIGD-HNNXBMFYSA-N n-[(7s)-3-hydroxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5h-benzo[a]heptalen-7-yl]acetamide Chemical compound O=C1C(SC)=CC=C2C3=C(OC)C(OC)=C(O)C=C3CC[C@H](NC(C)=O)C2=C1 PKYOHQGXPPVIGD-HNNXBMFYSA-N 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 5
- JRRUSQGIRBEMRN-HNNXBMFYSA-N n-[(7s)-3-hydroxy-1,2,10-trimethoxy-9-oxo-6,7-dihydro-5h-benzo[a]heptalen-7-yl]acetamide Chemical group O=C1C(OC)=CC=C2C3=C(OC)C(OC)=C(O)C=C3CC[C@H](NC(C)=O)C2=C1 JRRUSQGIRBEMRN-HNNXBMFYSA-N 0.000 abstract description 5
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 3
- 229940045695 antineooplastic colchicine derivative Drugs 0.000 abstract description 3
- 210000003205 muscle Anatomy 0.000 abstract description 2
- 230000002040 relaxant effect Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- LEQAKWQJCITZNK-AXHKHJLKSA-N N-[(7S)-1,2-dimethoxy-10-(methylthio)-9-oxo-3-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide Chemical compound C1([C@@H](NC(C)=O)CCC2=C3)=CC(=O)C(SC)=CC=C1C2=C(OC)C(OC)=C3O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O LEQAKWQJCITZNK-AXHKHJLKSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- WHVNYMMWPUHYES-CZBDKTQLSA-N (3s,4r,5s)-2-fluorooxane-3,4,5-triol Chemical compound O[C@H]1COC(F)[C@@H](O)[C@@H]1O WHVNYMMWPUHYES-CZBDKTQLSA-N 0.000 description 2
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010021118 Hypotonia Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 208000006111 contracture Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000036640 muscle relaxation Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 2
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229960000287 thiocolchicoside Drugs 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- -1 3-demethyl-thiocolchicine glucoside Chemical class 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000011714 Glycine Receptors Human genes 0.000 description 1
- 108010076533 Glycine Receptors Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- 206010062575 Muscle contracture Diseases 0.000 description 1
- XIQNPZJUNWWQCN-RCWTZXSCSA-N [(3R,4S,5S,6R)-4,5-diacetyl-6-fluoro-4,5-dihydroxyoxan-3-yl] acetate Chemical compound C(C)(=O)[C@@]1([C@H](OC[C@H]([C@@]1(O)C(C)=O)OC(C)=O)F)O XIQNPZJUNWWQCN-RCWTZXSCSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 238000010825 rotarod performance test Methods 0.000 description 1
- 210000003699 striated muscle Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C07H15/248—Colchicine radicals, e.g. colchicosides
-
- 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
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biochemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
実験の部
融点をBuchi 510装置により測定した。NMRスペクトルをBruker AC200を用いて記録した。
3−O−(2’,3’4’−O−トリアセチル−β−D−キシロピラノシル)−3−O−デメチルチオコルヒチン
3−O−デメチルチオコルヒチン(IIb)(0.5mmol)および2,3,4−O−トリアセチル−α−D−キシロピラノシルフルオリド(0.75mmol)(Hayashiら、Chemistry Lett.1984,1747に従って調製)を、窒素の下で攪拌して、室温で乾燥アセトニトリル(10ml)中に懸濁させた。1,1,3,3−テトラメチルグアニジン(1.5mmol)を加えると、懸濁液は透明な赤色に変わった。三フッ化ホウ素・エーテル錯塩(4mmol)を加えると、その後、溶液は無色に変わった。TLC(CH2Cl2:MeOH 9:1)により反応をモニターした。出発調製物が認められなくなった後(30分)、飽和炭酸水素ナトリウム溶液(10ml)を加えることにより、反応を止めた。相分離させて、水性相を酢酸エチルで抽出した(3×10ml)。有機層を合わせて硫酸水素カリウム飽和溶液(15ml)、塩水(brine)(15ml)で洗い、硫酸マグネシウムで乾燥した。溶剤を蒸発させた後、反応生成物をシリカゲルでのクロマトグラフィーにより分離した。あるいは、粗生成物をそのまま脱保護した。
1H−NMR(CDCl3)−δ(ppm)7.06(NH,d,7.4Hz)、7.06(H12,d,10.3Hz)、7.27(H11.d,10.3Hz)、7.33(H8,s)、6.71(H4,s)、4.71〜4.55(H7,m)、2.60〜1.90(H5−H6,m)、3.90(2−OMe,s)、3.66(1−OMe,s)、2.44(SMe,s)、2.00(アセトアミド)、5.28〜5.18、5.08〜4.98(H1’,H2’,H3’,H4’,m)、4.30(H5’a,ddd,4.3,7.0,12.1Hz)、3.58(H5’b,ddd 4.3,7.0,12.1Hz)、2.12(OAc)、2.11(OAc)、2.10(OAc)。
3−O−(2’,3’,4’−O−トリアセチル−β−L−キシロピラノシル)−3−O−デメチルチオコルヒチン
3−O−デメチルチオコルヒチン(IIb)(0.5mmol)および2,3,4−O−トリアセチル−α−L−キシロピラノシルフルオリド(0.75mmol)(Takanashiら、Liebigs Ann.Chem.1997,1081に従って調製)を、窒素の下で攪拌して、室温で乾燥アセトニトリル(10ml)中に懸濁させた。次に、1,1,3,3−テトラメチルグアニジン(1.5mmol)を加えると、懸濁液は透明な赤色に変わった。三フッ化ホウ素・エーテル錯塩(4mmol)を加えると、その後、溶液は無色に変わった。TLC(CH2Cl2:MeOH 9:1)により反応をモニターした。出発物質が認めらなくなった後(2時間)、飽和炭酸水素ナトリウム溶液(10ml)を加えることにより、反応を止めた。相分離させて、水性相を酢酸エチルで抽出した(3×10ml)。有機層を合わせて硫酸水素カリウム飽和溶液(15ml)、塩水(15ml)で洗い、硫酸マグネシウムで乾燥した。溶剤を蒸発させた後、反応生成物をシリカゲルでのクロマトグラフィーにより分離した。あるいは、粗生成物をそのまま脱保護した。
1H−NMR(CDCl3)−δ(ppm)7.34(NH,d,7.9Hz)、7.07(H12,d,10.7Hz)、7.30(H11,d,10.7Hz)、7.37(H8,s)、6.71(H4,s)、4.71〜4.55(H7,m)、2.60〜1.80(H5−H6,m)、3.88(2−OMe,s)、3.64(1−OMe,s)、2.44(SMe,s)、2.00(アセトアミド)、5.28〜5.18 e 5.10〜4.90(H1’,H2’,H3’,H4’m)、4.25(H5’a,ddd,4.3,4.4,12.1Hz)、3.58(H5’b,ddd 4.3,4.4,12.1Hz)、2.14(OAc)、2.11(OAc)、2.10(OAc)。
エタノール中での脱保護の一般的方法
実施例1または2による粗生成物(0.5理論mmol)を、エタノール(4ml)および1N NaOH(2ml)に室温で溶解した。反応をTLCでチェックした。出発物が認められなくなった後、溶剤を蒸発させて除き、残留物をシリカゲルでのクロマトグラフィーにかけた。生成物をメタノール/イソプロパノールからさらに結晶化させることができる。
アセトン中での脱保護の一般的方法
実施例1または2(1理論mmol)からの粗生成物を、炭酸カリウムと共に、アセトン(30ml)および水(10ml)中に懸濁させた。混合物を出発物が認められなくなるまで還流した。溶剤を蒸発させて除き、生成物をクロマトグラフィーにより回収した。生成物をメタノールおよびジイソプロピルエーテルからさらに結晶化させることができる。
3−O−β−D−キシロピラノシル−3−O−デメチルチオコルヒチン
生成物を、実施例3または4の脱保護の方法に従って、CH2Cl2/MeOHグラジエントで溶出するシリカゲルでのクロマトグラフィー後、45%の収率で得た。
m.p. 193℃;[α]D 22 −201(c1, MeOH);
1H−NMR(CDCl3):ppm 8.64(NH,d,7.6Hz)、7.15(H12,d,10.6Hz)、7.28(H11,d,10.6Hz)、7.03(H8,s)、6.85(H4,s)4.37〜4.25(H7,m)、2.60〜1.80(H5−H6,m)、3.84(2−OMe,s)、3.55(1−OMe,s)、2.42(SMe,s)、1.86(アセトアミド)、4.97(Hl’,6.6Hz)、3.20〜3.90(H2’,H3’,H4’,H5’,m)、4.40〜5.60(OH)。
3−O−β−L−キシロピラノシル−3−O−デメチルチオコルヒチン
生成物を、実施例3または4の脱保護の方法に従って、CH2Cl2/MeOHのグラジエントで溶出するシリカゲルでのクロマトグラフィー後、45%の収率で得た。
m.p. 220℃;[α]D 22 −176(c1, MeOH);
1H−NMR(CDCl3):ppm 8.64(NH,d,7.3Hz)、7.17(H12,d,10.2Hz)、7.29(H11,d,10.2Hz)、7.03(H8,s)、6.87(H4,s)4.23〜4.41(H7,m)、2.70〜1.90(H5−H6,m)、3.84(2−OMe,s)、3.55(1−OMe,s)、2.42(SMe,s)、1.86(アセトアミド)、5.02(Hl’,6.9Hz)、3.20〜3.90(H2’,H3’,H4’,H5’,m)、4.90〜5.60(OH)。
Claims (12)
- Xが酸素である請求項1に記載の化合物。
- Xが硫黄である請求項1に記載の化合物。
- 3―O−β−D―キシロピラノシル―3―O―デメチルチオコルヒチンおよび
3―O−β−L―キシロピラノシル―3―O―デメチルチオコルヒチン
から選択される化合物。 - 薬剤としての、請求項1から4のいずれか一項に記載の化合物。
- 筋弛緩薬を調製するための、請求項1から4のいずれか一項に記載の化合物の使用。
- 抗炎症薬を調製するための、請求項1から4のいずれか一項に記載の化合物の使用。
- 抗痛風薬を調製するための、請求項1から4のいずれか一項に記載の化合物の使用。
- 適切な賦形剤および/または担体との混合物に、請求項1から4のいずれか一項に記載の化合物を含む薬剤組成物。
- 局所使用のための、請求項9に記載の薬剤組成物。
- 非経口的使用のための、請求項9に記載の薬剤組成物。
- 前記賦形剤が天然および合成リン脂質から選択される、請求項10または11に記載の薬剤組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT001144A ITMI20031144A1 (it) | 2003-06-06 | 2003-06-06 | Analoghi del colchicoside. |
ITMI2003A001144 | 2003-06-06 | ||
PCT/EP2004/005645 WO2004111068A1 (en) | 2003-06-06 | 2004-05-26 | Colchicoside analogues |
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JP2006527173A JP2006527173A (ja) | 2006-11-30 |
JP4718449B2 true JP4718449B2 (ja) | 2011-07-06 |
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JP2006508205A Expired - Fee Related JP4718449B2 (ja) | 2003-06-06 | 2004-05-26 | コルヒチン類似体 |
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US (1) | US7683163B2 (ja) |
EP (1) | EP1631574B1 (ja) |
JP (1) | JP4718449B2 (ja) |
KR (1) | KR101121374B1 (ja) |
CN (1) | CN100348605C (ja) |
AT (1) | ATE425174T1 (ja) |
AU (1) | AU2004247346B2 (ja) |
BR (1) | BRPI0411068B8 (ja) |
CA (1) | CA2528223C (ja) |
CY (1) | CY1109019T1 (ja) |
DE (1) | DE602004019914D1 (ja) |
DK (1) | DK1631574T3 (ja) |
ES (1) | ES2321838T3 (ja) |
HK (1) | HK1090062A1 (ja) |
IL (1) | IL172358A (ja) |
IT (1) | ITMI20031144A1 (ja) |
MX (1) | MXPA05013161A (ja) |
NO (1) | NO330964B1 (ja) |
NZ (1) | NZ543943A (ja) |
PL (1) | PL1631574T3 (ja) |
PT (1) | PT1631574E (ja) |
RU (1) | RU2343157C2 (ja) |
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Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
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ITMI20051418A1 (it) * | 2005-07-22 | 2007-01-23 | Indena Spa | Analoghi del tiocolchicoside ad attivita'miorilassante e antiinfiammatoria |
WO2008067039A2 (en) * | 2006-10-06 | 2008-06-05 | Wisconsin Alumni Research Foundation | Colchicine neoglycosides and methods for their synthesis and use |
EP2128170B1 (en) * | 2008-05-28 | 2010-12-22 | Indena S.p.A. | "Process for the glycosidation of colchicine and thiocolchicine" |
US8722205B2 (en) | 2009-03-23 | 2014-05-13 | Universal Display Corporation | Heteroleptic iridium complex |
US8497290B2 (en) * | 2009-05-27 | 2013-07-30 | Takeda Pharmaceuticals U.S.A., Inc. | Thiocolchicine derivatives, method of making and methods of use thereof |
EP2830606A4 (en) * | 2012-03-30 | 2015-08-12 | Takeda Pharmaceuticals Usa Inc | FORMULATIONS OF COLCHICINE; MANUFACTURING PROCESSES ; AND ASSOCIATED METHODS OF USE |
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WO1999061457A1 (fr) * | 1998-05-27 | 1999-12-02 | Sanofi-Synthelabo | Derive de thiocolchicoside, sa preparation et son application en therapeutique |
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AU634921B2 (en) * | 1990-12-25 | 1993-03-04 | Ohgen Research Laboratories Ltd. | Deacetylcolchicine derivatives |
CN1208003A (zh) * | 1997-08-08 | 1999-02-17 | 韩财元 | 摆翼式直升飞机 |
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JPH11501324A (ja) * | 1995-06-27 | 1999-02-02 | インデナ・ソチエタ・ペル・アチオニ | コルヒチン誘導体、それらの使用およびそれらを含有する製剤 |
JPH09309896A (ja) * | 1996-02-08 | 1997-12-02 | Indena Spa | コルヒチン誘導体をグリコシド化する方法、及びその生成物 |
WO1998015642A1 (en) * | 1996-10-07 | 1998-04-16 | Indena S.P.A. | A process for the biotransformation of colchicinoid compounds into the corresponding 3-glycosyl derivatives |
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