NO328699B1 - Nye forbindelser, sammensetninger inneholdende nevnte forbindelser, samt anvendelse derav som inhibitorer av katekol-O-metyltransferase (COMT) enzymet - Google Patents

Nye forbindelser, sammensetninger inneholdende nevnte forbindelser, samt anvendelse derav som inhibitorer av katekol-O-metyltransferase (COMT) enzymet Download PDF

Info

Publication number: NO328699B1
Authority: NO; Norway
Prior art keywords: compounds; comt; arh; product; mhz
Prior art date: 2000-07-03

Application number

NO20026095A

Other languages

English (en)

Norwegian (no)

Other versions

NO20026095D0 (no

NO20026095L (no

Inventor

Jarmo Pystynen

Timo Lotta

Martti Ovaska

Jukka Vidgren

Marjo Yliperttula-Ikonen

Original Assignee

Orion Corp

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.)

2000-07-03

Filing date

2002-12-18

Publication date

2010-04-26

2002-12-18 Application filed by Orion Corp filed Critical Orion Corp

2002-12-18 Publication of NO20026095D0 publication Critical patent/NO20026095D0/no

2003-03-03 Publication of NO20026095L publication Critical patent/NO20026095L/no

2010-04-26 Publication of NO328699B1 publication Critical patent/NO328699B1/no

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 59
108020002739 Catechol O-methyltransferase Proteins 0.000 title abstract description 17
239000000203 mixture Substances 0.000 title description 18
102000006378 Catechol O-methyltransferase Human genes 0.000 title description 16
102000004190 Enzymes Human genes 0.000 title description 4
108090000790 Enzymes Proteins 0.000 title description 4
239000003112 inhibitor Substances 0.000 title description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
125000001424 substituent group Chemical group 0.000 claims abstract description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 10
150000002148 esters Chemical class 0.000 claims description 9
238000000034 method Methods 0.000 claims description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
238000001727 in vivo Methods 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 6
208000018737 Parkinson disease Diseases 0.000 claims description 5
-1 5-tetrazolyl Chemical group 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
241001465754 Metazoa Species 0.000 claims description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
229940079593 drug Drugs 0.000 claims description 2
125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
238000001356 surgical procedure Methods 0.000 claims 1
230000001225 therapeutic effect Effects 0.000 claims 1
239000003543 catechol methyltransferase inhibitor Substances 0.000 abstract description 8
230000002401 inhibitory effect Effects 0.000 abstract description 6
239000000047 product Substances 0.000 description 34
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
238000005481 NMR spectroscopy Methods 0.000 description 24
239000000243 solution Substances 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 12
238000002844 melting Methods 0.000 description 12
230000008018 melting Effects 0.000 description 12
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 10
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
239000005457 ice water Substances 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
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ZZTFJNNLOBLOPU-UHFFFAOYSA-N 2-hydroxy-3,4-dimethoxy-5-nitrobenzaldehyde Chemical compound COC1=C(O)C(C=O)=CC([N+]([O-])=O)=C1OC ZZTFJNNLOBLOPU-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 6
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
230000000694 effects Effects 0.000 description 5
229910000042 hydrogen bromide Inorganic materials 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
WNCNWLVQSHZVKV-UHFFFAOYSA-N 2,4,5-trihydroxybenzaldehyde Chemical compound OC1=CC(O)=C(C=O)C=C1O WNCNWLVQSHZVKV-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
201000010099 disease Diseases 0.000 description 4
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
229910017604 nitric acid Inorganic materials 0.000 description 4
239000004323 potassium nitrate Substances 0.000 description 4
235000010333 potassium nitrate Nutrition 0.000 description 4
239000002904 solvent Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
239000002253 acid Substances 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
150000004775 coumarins Chemical class 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
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238000000926 separation method Methods 0.000 description 3
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VOLGAXAGEUPBDM-UHFFFAOYSA-N $l^{1}-oxidanylethane Chemical compound CC[O] VOLGAXAGEUPBDM-UHFFFAOYSA-N 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
SVXDAGYNZSMVBE-UHFFFAOYSA-N 3-ethoxycarbonyl-4-(2,4,5-trimethoxyphenyl)but-3-enoic acid Chemical compound CCOC(=O)C(CC(O)=O)=CC1=CC(OC)=C(OC)C=C1OC SVXDAGYNZSMVBE-UHFFFAOYSA-N 0.000 description 2
CVAKRGWBLNNJJI-UHFFFAOYSA-N 5-(2-aminoethyl)-1-methylcyclohexa-2,4-diene-1,2-diol Chemical compound CC1(O)CC(CCN)=CC=C1O CVAKRGWBLNNJJI-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
GGNQRNBDZQJCCN-UHFFFAOYSA-N benzene-1,2,4-triol Chemical compound OC1=CC=C(O)C(O)=C1 GGNQRNBDZQJCCN-UHFFFAOYSA-N 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
239000000460 chlorine Chemical group 0.000 description 2
229960003638 dopamine Drugs 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
BHWOTMCVUUPCPP-UHFFFAOYSA-N ethyl 2-(6,7-dihydroxy-4-methyl-2-oxochromen-3-yl)acetate Chemical compound OC1=C(O)C=C2OC(=O)C(CC(=O)OCC)=C(C)C2=C1 BHWOTMCVUUPCPP-UHFFFAOYSA-N 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
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235000011149 sulphuric acid Nutrition 0.000 description 2
CWWADBFDUPRVIN-UHFFFAOYSA-N (3-acetyloxy-6-oxo-7,8,9,10-tetrahydrobenzo[c]chromen-2-yl) acetate Chemical compound C1CCCC2=C1C(=O)OC1=C2C=C(OC(C)=O)C(OC(=O)C)=C1 CWWADBFDUPRVIN-UHFFFAOYSA-N 0.000 description 1
YBADLXQNJCMBKR-UHFFFAOYSA-N (4-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C=C1 YBADLXQNJCMBKR-UHFFFAOYSA-N 0.000 description 1
125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
150000005206 1,2-dihydroxybenzenes Chemical class 0.000 description 1
IAJBQAYHSQIQRE-UHFFFAOYSA-N 2,4,5-trimethoxybenzaldehyde Chemical compound COC1=CC(OC)=C(C=O)C=C1OC IAJBQAYHSQIQRE-UHFFFAOYSA-N 0.000 description 1
ZFZAFNQYRZGWNK-UHFFFAOYSA-N 2,4-dihydroxy-5-methoxybenzaldehyde Chemical compound COC1=CC(C=O)=C(O)C=C1O ZFZAFNQYRZGWNK-UHFFFAOYSA-N 0.000 description 1
RZWGTXHSYZGXKF-UHFFFAOYSA-N 2-(2-methylphenyl)acetic acid Chemical compound CC1=CC=CC=C1CC(O)=O RZWGTXHSYZGXKF-UHFFFAOYSA-N 0.000 description 1
BGFWNEQCWRXRFO-UHFFFAOYSA-N 2-(6,7-dihydroxy-2-oxochromen-3-yl)acetic acid Chemical compound OC1=C(O)C=C2OC(=O)C(CC(=O)O)=CC2=C1 BGFWNEQCWRXRFO-UHFFFAOYSA-N 0.000 description 1
DKELHZLAKMOKAR-UHFFFAOYSA-N 2-(6,7-dihydroxy-4-methyl-2-oxochromen-3-yl)acetic acid Chemical compound C1=C(O)C(O)=CC2=C1OC(=O)C(CC(O)=O)=C2C DKELHZLAKMOKAR-UHFFFAOYSA-N 0.000 description 1
UIOMNPYQUBMBOJ-UHFFFAOYSA-N 2-hydroxy-3,4-dimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(O)=C1OC UIOMNPYQUBMBOJ-UHFFFAOYSA-N 0.000 description 1
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical class C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
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CDPKJZJVTHSESZ-UHFFFAOYSA-N 4-chlorophenylacetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1 CDPKJZJVTHSESZ-UHFFFAOYSA-N 0.000 description 1
NBUKMJKGRAGSET-UHFFFAOYSA-N 6,7-dihydroxy-8-nitro-2-oxochromene-3-carboxylic acid Chemical compound OC1=C(O)C([N+]([O-])=O)=C2OC(=O)C(C(=O)O)=CC2=C1 NBUKMJKGRAGSET-UHFFFAOYSA-N 0.000 description 1
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PNZYJXLIUODGDB-UHFFFAOYSA-N 7,8-dihydroxy-3-(2-methylphenyl)-6-nitrochromen-2-one Chemical compound CC1=CC=CC=C1C1=CC2=CC([N+]([O-])=O)=C(O)C(O)=C2OC1=O PNZYJXLIUODGDB-UHFFFAOYSA-N 0.000 description 1
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238000011978 dissolution method Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
NAOHMNNTUFFTBF-UHFFFAOYSA-N ethyl 2-(2h-tetrazol-5-yl)acetate Chemical compound CCOC(=O)CC=1N=NNN=1 NAOHMNNTUFFTBF-UHFFFAOYSA-N 0.000 description 1
ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
CMWAWVMXRVRPFX-UHFFFAOYSA-N ethyl 6,7-dihydroxy-2-iminochromene-3-carboxylate Chemical compound OC1=C(O)C=C2OC(=N)C(C(=O)OCC)=CC2=C1 CMWAWVMXRVRPFX-UHFFFAOYSA-N 0.000 description 1
JXAIAZYGEYXKGM-UHFFFAOYSA-N ethyl 7,8-dimethoxy-6-nitro-2-oxochromene-3-carboxylate Chemical compound [O-][N+](=O)C1=C(OC)C(OC)=C2OC(=O)C(C(=O)OCC)=CC2=C1 JXAIAZYGEYXKGM-UHFFFAOYSA-N 0.000 description 1
LFPNYZFIEJHSMC-UHFFFAOYSA-N ethyl 7-hydroxy-6-methoxy-2-oxochromene-3-carboxylate Chemical compound COC1=C(O)C=C2OC(=O)C(C(=O)OCC)=CC2=C1 LFPNYZFIEJHSMC-UHFFFAOYSA-N 0.000 description 1
NSEBATSRASFYRC-UHFFFAOYSA-N ethyl 7-hydroxy-6-methoxy-8-nitro-2-oxochromene-3-carboxylate Chemical compound COC1=C(O)C([N+]([O-])=O)=C2OC(=O)C(C(=O)OCC)=CC2=C1 NSEBATSRASFYRC-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
208000021822 hypotensive Diseases 0.000 description 1
230000001077 hypotensive effect Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
229910001506 inorganic fluoride Inorganic materials 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
239000011630 iodine Chemical group 0.000 description 1
229910052740 iodine Chemical group 0.000 description 1
CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 1
150000002515 isoflavone derivatives Chemical class 0.000 description 1
235000008696 isoflavones Nutrition 0.000 description 1
229960004502 levodopa Drugs 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000002048 spasmolytic effect Effects 0.000 description 1
241000894007 species Species 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
230000006492 vascular dysfunction Effects 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- 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
- A61P25/06—Antimigraine agents
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Neurosurgery (AREA)
Engineering & Computer Science (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pain & Pain Management (AREA)
Psychology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrane Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Plant Substances (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)

NO20026095A 2000-07-03 2002-12-18 Nye forbindelser, sammensetninger inneholdende nevnte forbindelser, samt anvendelse derav som inhibitorer av katekol-O-metyltransferase (COMT) enzymet NO328699B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FI20001593A FI20001593A (fi)	2000-07-03	2000-07-03	Comt-entsyymiõ inhiboivaa aktiivisuutta omaavia kumariinijohdannaisia
PCT/FI2001/000613 WO2002002548A1 (en)	2000-07-03	2001-06-28	Coumarin derivatives with comt inhibiting activity

Publications (3)

Publication Number	Publication Date
NO20026095D0 NO20026095D0 (no)	2002-12-18
NO20026095L NO20026095L (no)	2003-03-03
NO328699B1 true NO328699B1 (no)	2010-04-26

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ID=8558717

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Application Number	Title	Priority Date	Filing Date
NO20026095A NO328699B1 (no)	2000-07-03	2002-12-18	Nye forbindelser, sammensetninger inneholdende nevnte forbindelser, samt anvendelse derav som inhibitorer av katekol-O-metyltransferase (COMT) enzymet

Country Status (27)

Country	Link
US (1)	US6951870B2 (de)
EP (1)	EP1301503B1 (de)
JP (1)	JP4851051B2 (de)
KR (1)	KR20030040225A (de)
CN (1)	CN1199963C (de)
AT (1)	ATE260268T1 (de)
AU (2)	AU7259701A (de)
BG (1)	BG107513A (de)
BR (1)	BR0111969A (de)
CA (1)	CA2414787C (de)
DE (1)	DE60102161T2 (de)
DK (1)	DK1301503T3 (de)
EE (1)	EE200300008A (de)
ES (1)	ES2215919T3 (de)
FI (1)	FI20001593A (de)
HU (1)	HUP0301706A3 (de)
IL (2)	IL153352A0 (de)
MX (1)	MXPA02012657A (de)
NO (1)	NO328699B1 (de)
NZ (1)	NZ523121A (de)
PL (1)	PL359068A1 (de)
PT (1)	PT1301503E (de)
RU (1)	RU2282627C2 (de)
SK (1)	SK18452002A3 (de)
TR (1)	TR200400802T4 (de)
WO (1)	WO2002002548A1 (de)
ZA (1)	ZA200210161B (de)

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AUPR846401A0 (en) *	2001-10-25	2001-11-15	Novogen Research Pty Ltd	6-Hydroxy isoflavones, derivatives and medicaments involving same
AU2002951833A0 (en)	2002-10-02	2002-10-24	Novogen Research Pty Ltd	Compositions and therapeutic methods invloving platinum complexes
AU2003265737B2 (en) *	2002-10-02	2008-10-16	Novogen Research Pty Ltd	Combination chemotherapy compositions and methods
CN1506359A (zh) *	2002-12-05	2004-06-23	�й�ҽѧ��ѧԺҩ��о��	新的香豆素酰胺衍生物及其制法和其药物组合物与用途
CN101056868B (zh)	2004-09-21	2012-05-02	马休爱德华兹股份有限公司	取代的苯并二氢吡喃衍生物、药物及其在治疗中的应用
US8080675B2 (en)	2004-09-21	2011-12-20	Marshall Edwards, Inc.	Chroman derivatives, medicaments and use in therapy
MY148644A (en) *	2005-07-18	2013-05-15	Orion Corp	New pharmaceutical compounds
US8686002B2 (en)	2005-08-21	2014-04-01	AbbVie Deutschland GmbH & Co. KG	Heterocyclic compounds and their use as binding partners for 5-HT5 receptors
WO2007124617A1 (fr) *	2006-04-28	2007-11-08	Institute Of Mataria Medica, Chinese Academy Of Medical Sciences	Dérivés de coumarine, leurs procédés de préparation, compositions pharmaceutiques et utilisations
ES2343347B2 (es) *	2009-01-27	2011-12-07	Universidade De Santiago De Compostela	Uso de derivados de 3-fenilcumarinas 6-sustituidas y preparacion de nuevos derivados.
CA2816319C (en)	2010-11-01	2020-06-30	Marshall Edwards, Inc.	Isoflavonoid compounds and methods for the treatment of cancer
TWI638802B (zh)	2012-05-24	2018-10-21	芬蘭商奧利安公司	兒茶酚ｏ－甲基轉移酶活性抑制化合物
HUE054998T2 (hu)	2015-02-02	2021-10-28	Mei Pharma Inc	Kombinációs terápiák emlõrák kezelésében való alkalmazásra
EP3390351A1 (de) *	2015-12-18	2018-10-24	Koester, Hubert	Neuartige bicyclische verbindungen zur verwendung als medikament, insbesondere zur behandlung von morbus parkinson
CN107868069A (zh) *	2017-10-31	2018-04-03	山东新华制药股份有限公司	7‑羟基‑8‑甲基‑6‑硝基‑2‑氧‑2h‑苯并吡喃‑3‑羧酸的制备工艺

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US3973608A (en)	1973-08-01	1976-08-10	Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai	Microbial production of certain isoflavones
JPS5035393A (de) *	1973-08-01	1975-04-04
US5236952A (en) *	1986-03-11	1993-08-17	Hoffmann-La Roche Inc.	Catechol derivatives
US5283352A (en) *	1986-11-28	1994-02-01	Orion-Yhtyma Oy	Pharmacologically active compounds, methods for the preparation thereof and compositions containing the same
GB8816519D0 (en)	1987-07-23	1988-08-17	Ici Plc	Antibiotic compounds
HUT63843A (en)	1992-02-13	1993-10-28	Biosignal Kutato Fejlesztoe Kf	Process for producing new kumarin derivatives and their analogs inhibiting mammal cell proliferation and tumour growth, as well as pharmaceutical comkpositions comprising such compounds
JP3166094B2 (ja) *	1993-09-08	2001-05-14	森永乳業株式会社	クマリン誘導体及びそれらの用途
JPH0892157A (ja)	1994-05-02	1996-04-09	F Hoffmann La Roche Ag	プルプロガリン誘導体
GB9626472D0 (en)	1996-12-20	1997-02-05	Aperia Anita C	New use of comt inhibitors

2000
- 2000-07-03 FI FI20001593A patent/FI20001593A/fi unknown
2001
- 2001-06-28 CA CA2414787A patent/CA2414787C/en not_active Expired - Fee Related
- 2001-06-28 EP EP01951741A patent/EP1301503B1/de not_active Expired - Lifetime
- 2001-06-28 AU AU7259701A patent/AU7259701A/xx active Pending
- 2001-06-28 SK SK1845-2002A patent/SK18452002A3/sk unknown
- 2001-06-28 BR BR0111969-9A patent/BR0111969A/pt not_active IP Right Cessation
- 2001-06-28 EE EEP200300008A patent/EE200300008A/xx unknown
- 2001-06-28 ES ES01951741T patent/ES2215919T3/es not_active Expired - Lifetime
- 2001-06-28 RU RU2003102894/04A patent/RU2282627C2/ru not_active IP Right Cessation
- 2001-06-28 KR KR1020027017767A patent/KR20030040225A/ko not_active Application Discontinuation
- 2001-06-28 HU HU0301706A patent/HUP0301706A3/hu unknown
- 2001-06-28 IL IL15335201A patent/IL153352A0/xx unknown
- 2001-06-28 CN CNB018121934A patent/CN1199963C/zh not_active Expired - Fee Related
- 2001-06-28 AU AU2001272597A patent/AU2001272597B9/en not_active Ceased
- 2001-06-28 TR TR2004/00802T patent/TR200400802T4/xx unknown
- 2001-06-28 JP JP2002507800A patent/JP4851051B2/ja not_active Expired - Fee Related
- 2001-06-28 PL PL01359068A patent/PL359068A1/xx not_active Application Discontinuation
- 2001-06-28 DE DE60102161T patent/DE60102161T2/de not_active Expired - Lifetime
- 2001-06-28 US US10/312,817 patent/US6951870B2/en not_active Expired - Fee Related
- 2001-06-28 AT AT01951741T patent/ATE260268T1/de active
- 2001-06-28 PT PT01951741T patent/PT1301503E/pt unknown
- 2001-06-28 WO PCT/FI2001/000613 patent/WO2002002548A1/en active IP Right Grant
- 2001-06-28 NZ NZ523121A patent/NZ523121A/en not_active IP Right Cessation
- 2001-06-28 MX MXPA02012657A patent/MXPA02012657A/es active IP Right Grant
- 2001-06-28 DK DK01951741T patent/DK1301503T3/da active
2002
- 2002-12-10 IL IL153352A patent/IL153352A/en not_active IP Right Cessation
- 2002-12-13 ZA ZA200210161A patent/ZA200210161B/en unknown
- 2002-12-18 NO NO20026095A patent/NO328699B1/no not_active IP Right Cessation
2003
- 2003-01-31 BG BG107513A patent/BG107513A/bg unknown

Also Published As

Publication number	Publication date
HUP0301706A2 (hu)	2003-09-29
TR200400802T4 (tr)	2004-07-21
DE60102161T2 (de)	2004-09-16
RU2282627C2 (ru)	2006-08-27
EE200300008A (et)	2004-08-16
ES2215919T3 (es)	2004-10-16
JP2004502684A (ja)	2004-01-29
FI20001593A0 (fi)	2000-07-03
EP1301503A1 (de)	2003-04-16
HUP0301706A3 (en)	2005-12-28
ZA200210161B (en)	2004-03-15
CA2414787C (en)	2010-12-14
AU2001272597B2 (en)	2005-07-21
WO2002002548A1 (en)	2002-01-10
US20030186975A1 (en)	2003-10-02
EP1301503B1 (de)	2004-02-25
CN1440399A (zh)	2003-09-03
BG107513A (bg)	2003-06-30
ATE260268T1 (de)	2004-03-15
SK18452002A3 (sk)	2004-04-06
CN1199963C (zh)	2005-05-04
NO20026095D0 (no)	2002-12-18
NO20026095L (no)	2003-03-03
DK1301503T3 (da)	2004-06-28
AU7259701A (en)	2002-01-14
DE60102161D1 (de)	2004-04-01
FI20001593A (fi)	2002-01-04
IL153352A (en)	2009-05-04
NZ523121A (en)	2004-08-27
BR0111969A (pt)	2003-07-01
US20040110750A9 (en)	2004-06-10
IL153352A0 (en)	2003-07-06
PT1301503E (pt)	2004-06-30
CA2414787A1 (en)	2002-01-10
US6951870B2 (en)	2005-10-04
KR20030040225A (ko)	2003-05-22
AU2001272597B9 (en)	2005-08-11
PL359068A1 (en)	2004-08-23
MXPA02012657A (es)	2003-05-14
JP4851051B2 (ja)	2012-01-11

Legal Events

Date	Code	Title	Description
2013-02-04	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO328699B1 (no)	2010-04-26	Nye forbindelser, sammensetninger inneholdende nevnte forbindelser, samt anvendelse derav som inhibitorer av katekol-O-metyltransferase (COMT) enzymet
JP3107829B2 (ja)	2000-11-13	シクロプロピルアセチレンの改良型合成法
KR20200131249A (ko)	2020-11-23	항-염증제, 면역조절제 및 항-증식제로서의 신규한 칼슘 염 다형체
AU2001272597A1 (en)	2002-04-11	Coumarin derivatives with COMT inhibiting activity
US4224342A (en)	1980-09-23	Guanidinobenzoic acid compounds and process for preparing the same
EP1317411A1 (de)	2003-06-11	Naphthalinderivate mit comt-inhibierender wirkung
EP0283761A1 (de)	1988-09-28	Chromon-derivate
JP2931986B2 (ja)	1999-08-09	アラルキルアミン誘導体
JPH02124884A (ja)	1990-05-14	Ｎ―置換アミド誘導体
KR100431789B1 (ko)	2004-08-30	신규한벤조티아졸유도체
JP2725378B2 (ja)	1998-03-11	カルバミド酸エステル誘導体
CN115175913B (zh)	2023-11-28	取代的双三环化合物及其药物组合物和用途
CN108794517A (zh)	2018-11-13	一种精氨酸酶抑制剂及其制备方法与用途
US4797498A (en)	1989-01-10	Flavonoxypropanolamines and esters of flavonoxypropanolamines as antiarrhythmic agents
EP0005091B1 (de)	1981-11-25	Monosubstituierte Piperazine, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate
JP2861274B2 (ja)	1999-02-24	アミノケトン誘導体
WO2017170859A1 (ja)	2017-10-05	ビスアリール誘導体及びその医薬用途
HU215387B (hu)	1998-12-28	Vizelet-visszatartási képtelenség kezelésére alkalmas kinolonszármazék, eljárás előállítására, és a vegyület alkalmazása gyógyszerkészítmények előállítására
US6706732B1 (en)	2004-03-16	Nasal preparation of guanidinoimino quinoline derivatives
HU194193B (en)	1988-01-28	Process for preparing new 4-/amino-methylidene/-3-aryl-5/4h/-isoxazolinone derivatives and pharmaceutical compositions containing such compounds as active ingredients
JPH08113574A (ja)	1996-05-07	ピリダジノインドール誘導体
JPH04282370A (ja)	1992-10-07	ジヒドロキノリン誘導体
HU195179B (en)	1988-04-28	Process for producing benzoic acid derivatives and pharmaceutical preparations comprising these compounds as active substance
JPH07173061A (ja)	1995-07-11	β−ケト酸誘導体およびそれを有効成分とするエラスターゼ阻害剤