FI120397B - Uudet sulfonamidit - Google Patents

Uudet sulfonamidit Download PDF

Info

Publication number: FI120397B
Authority: FI; Finland
Prior art keywords: methoxy; phenoxy; pyridin; pyrimidin; tetrazol
Prior art date: 1994-12-20

Application number

FI972628A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI972628L (fi

FI972628A0 (fi

Inventor

Werner Neidhart

Henri Ramuz

Volker Breu

Jean-Marie Cassal

Martine Clozel

Georges Hirth

Bernd-Michael Loeffler

Marcel Mueller

Kaspar Burri

Original Assignee

Hoffmann La Roche

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.)

1994-12-20

Filing date

1997-06-18

Publication date

2009-10-15

1997-06-18 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1997-06-18 Publication of FI972628L publication Critical patent/FI972628L/fi

1997-06-18 Publication of FI972628A0 publication Critical patent/FI972628A0/fi

2009-10-15 Application granted granted Critical

2009-10-15 Publication of FI120397B publication Critical patent/FI120397B/fi

Links

229940124530 sulfonamide Drugs 0.000 title claims description 6
150000003456 sulfonamides Chemical class 0.000 title claims description 5
150000001875 compounds Chemical class 0.000 claims abstract description 61
102000002045 Endothelin Human genes 0.000 claims abstract description 12
108050009340 Endothelin Proteins 0.000 claims abstract description 12
ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims abstract description 12
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
206010020772 Hypertension Diseases 0.000 claims abstract description 6
-1 cyano, carboxy Chemical group 0.000 claims description 449
239000001257 hydrogen Substances 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 13
WOZCSRYOBKSMBL-UHFFFAOYSA-N 1,3-benzodioxole-5-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C2OCOC2=C1 WOZCSRYOBKSMBL-UHFFFAOYSA-N 0.000 claims description 12
XYDHSCZUHCZWHJ-UHFFFAOYSA-N 5-methylpyridine-2-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)N=C1 XYDHSCZUHCZWHJ-UHFFFAOYSA-N 0.000 claims description 11
HXAZFIXWZPERHB-UHFFFAOYSA-N 5-propan-2-ylpyridine-2-sulfonic acid Chemical compound CC(C)C1=CC=C(S(O)(=O)=O)N=C1 HXAZFIXWZPERHB-UHFFFAOYSA-N 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 11
229910052757 nitrogen Inorganic materials 0.000 claims description 10
125000004076 pyridyl group Chemical group 0.000 claims description 10
125000003831 tetrazolyl group Chemical group 0.000 claims description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
230000000694 effects Effects 0.000 claims description 9
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 8
208000035475 disorder Diseases 0.000 claims description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
DVECLMOWYVDJRM-UHFFFAOYSA-N pyridine-3-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CN=C1 DVECLMOWYVDJRM-UHFFFAOYSA-N 0.000 claims description 7
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 6
125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims description 5
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
125000000623 heterocyclic group Chemical group 0.000 claims description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
JIBMEFUIGPATLZ-UHFFFAOYSA-N 1,3-benzodioxole-4-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC2=C1OCO2 JIBMEFUIGPATLZ-UHFFFAOYSA-N 0.000 claims description 3
LXVABXINMPXSBT-UHFFFAOYSA-N 2-(2H-tetrazol-5-yl)-3H-pyridin-4-one Chemical compound N1N=NN=C1C1=NC=CC(C1)=O LXVABXINMPXSBT-UHFFFAOYSA-N 0.000 claims description 3
206010002383 Angina Pectoris Diseases 0.000 claims description 3
125000000815 N-oxide group Chemical group 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
206010047163 Vasospasm Diseases 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
208000028867 ischemia Diseases 0.000 claims description 3
125000002950 monocyclic group Chemical group 0.000 claims description 3
IFDFZXKDKJLNSU-UHFFFAOYSA-N n-[2-(2-cyanopyridin-4-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C#N)OCCO)=C1NS(=O)(=O)C1=CC=CC=C1 IFDFZXKDKJLNSU-UHFFFAOYSA-N 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
239000011593 sulfur Substances 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
WSNKHKVQQXYVTI-UHFFFAOYSA-N 4-tert-butyl-n-[2-(2-cyanopyridin-4-yl)-5-(2-methoxyphenoxy)-6-(2-phenylmethoxyethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C#N)OCCOCC=2C=CC=CC=2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 WSNKHKVQQXYVTI-UHFFFAOYSA-N 0.000 claims description 2
DQWVRLQQDDEQAS-UHFFFAOYSA-N 4-tert-butyl-n-[2-(3-cyanophenyl)-5-(2-methoxyphenoxy)-6-(2-phenylmethoxyethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(C=CC=2)C#N)OCCOCC=2C=CC=CC=2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 DQWVRLQQDDEQAS-UHFFFAOYSA-N 0.000 claims description 2
OWRNHBUDZZRGAL-UHFFFAOYSA-N 4-tert-butyl-n-[2-(6-cyanopyridin-2-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=C(C=CC=2)C#N)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 OWRNHBUDZZRGAL-UHFFFAOYSA-N 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
GYZKCMRPFJRTKQ-UHFFFAOYSA-N n-[2-(2-cyanopyridin-4-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]-3,4-dimethoxybenzenesulfonamide Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)NC1=NC(C=2C=C(N=CC=2)C#N)=NC(OCCO)=C1OC1=CC=CC=C1OC GYZKCMRPFJRTKQ-UHFFFAOYSA-N 0.000 claims description 2
HDEQVSSOIDIBRF-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-4-methoxybenzenesulfonamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)NC1=NC(C=2C=C(N=CC=2)C=2NN=NN=2)=NC(OCCO)=C1OC1=CC=CC=C1OC HDEQVSSOIDIBRF-UHFFFAOYSA-N 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims 2
DRTQHJPVMGBUCF-UCVXFZOQSA-N 1-[(2s,3s,4s,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@H]1[C@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UCVXFZOQSA-N 0.000 claims 1
FFFHZZFNHCYBNX-UHFFFAOYSA-N 2-methylsulfanylbenzenesulfonamide Chemical compound CSC1=CC=CC=C1S(N)(=O)=O FFFHZZFNHCYBNX-UHFFFAOYSA-N 0.000 claims 1
XDXVBIVCXGUWMX-UHFFFAOYSA-N 3-propan-2-ylpyridine-2-sulfonic acid Chemical compound C(C)(C)C=1C(=NC=CC1)S(=O)(=O)O XDXVBIVCXGUWMX-UHFFFAOYSA-N 0.000 claims 1
RWIVKELYZQOGEK-UHFFFAOYSA-N 4-tert-butyl-n-[2-(3-cyanophenyl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(C=CC=2)C#N)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 RWIVKELYZQOGEK-UHFFFAOYSA-N 0.000 claims 1
HJKZCTLLFAYXSU-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[6-(2h-tetrazol-5-yl)pyridin-2-yl]pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=C(C=CC=2)C=2NN=NN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HJKZCTLLFAYXSU-UHFFFAOYSA-N 0.000 claims 1
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
VIUSCZUQFSTOSQ-UHFFFAOYSA-N ethyl 4-[4-[(4-tert-butylphenyl)sulfonylamino]-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-2-yl]pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OCC)=CC(C=2N=C(OCCO)C(OC=3C(=CC=CC=3)OC)=C(NS(=O)(=O)C=3C=CC(=CC=3)C(C)(C)C)N=2)=C1 VIUSCZUQFSTOSQ-UHFFFAOYSA-N 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
QNRLTJAYWJYZHK-UHFFFAOYSA-N n-[2-(2-cyanopyridin-4-yl)-5-(2-methoxyphenoxy)-6-(2-phenylmethoxyethoxy)pyrimidin-4-yl]-5-propan-2-ylpyridine-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C#N)OCCOCC=2C=CC=CC=2)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=N1 QNRLTJAYWJYZHK-UHFFFAOYSA-N 0.000 claims 1
UMIYJHCDVVUVTQ-UHFFFAOYSA-N n-[2-(2-cyanopyridin-4-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]-2,5-dimethoxybenzenesulfonamide Chemical compound COC1=CC=C(OC)C(S(=O)(=O)NC=2C(=C(OCCO)N=C(N=2)C=2C=C(N=CC=2)C#N)OC=2C(=CC=CC=2)OC)=C1 UMIYJHCDVVUVTQ-UHFFFAOYSA-N 0.000 claims 1
FNMAQJQQWOBFAW-UHFFFAOYSA-N n-[2-(2-cyanopyridin-4-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]-4-methylbenzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C#N)OCCO)=C1NS(=O)(=O)C1=CC=C(C)C=C1 FNMAQJQQWOBFAW-UHFFFAOYSA-N 0.000 claims 1
ZTWJEDKVMNINTP-UHFFFAOYSA-N n-[2-(2-cyanopyridin-4-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]-4-methylsulfanylbenzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C#N)OCCO)=C1NS(=O)(=O)C1=CC=C(SC)C=C1 ZTWJEDKVMNINTP-UHFFFAOYSA-N 0.000 claims 1
VDFSDWITBOJTED-UHFFFAOYSA-N n-[2-(2-cyanopyridin-4-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]-5-methylpyridine-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C#N)OCCO)=C1NS(=O)(=O)C1=CC=C(C)C=N1 VDFSDWITBOJTED-UHFFFAOYSA-N 0.000 claims 1
SRSMCKYFLXOFOM-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-2-(2-cyanopyridin-4-yl)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-1,3-benzodioxole-5-sulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(=NC=2NS(=O)(=O)C=2C=C3OCOC3=CC=2)C=2C=C(N=CC=2)C#N)OCCO)=C1 SRSMCKYFLXOFOM-UHFFFAOYSA-N 0.000 claims 1
ORSUOOCBOGMNKA-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-propan-2-ylpyridine-2-sulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(=NC=2NS(=O)(=O)C=2N=CC(=CC=2)C(C)C)C=2C=C(N=CC=2)C=2NN=NN=2)OCCO)=C1 ORSUOOCBOGMNKA-UHFFFAOYSA-N 0.000 claims 1
UUIRIJJVXNTIBK-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-1,3-benzodioxole-5-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C=2NN=NN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(OCO2)C2=C1 UUIRIJJVXNTIBK-UHFFFAOYSA-N 0.000 claims 1
UKDSUPWSXLYLQP-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-4-methylbenzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C=2NN=NN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C)C=C1 UKDSUPWSXLYLQP-UHFFFAOYSA-N 0.000 claims 1
239000000825 pharmaceutical preparation Substances 0.000 claims 1
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims 1
239000003112 inhibitor Substances 0.000 abstract description 2
201000010099 disease Diseases 0.000 abstract 1
239000008194 pharmaceutical composition Substances 0.000 abstract 1
238000003786 synthesis reaction Methods 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 59
239000000243 solution Substances 0.000 description 41
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
235000019439 ethyl acetate Nutrition 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
239000007787 solid Substances 0.000 description 17
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
238000000034 method Methods 0.000 description 15
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 14
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
239000000725 suspension Substances 0.000 description 14
239000000203 mixture Substances 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 12
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
239000000460 chlorine Substances 0.000 description 10
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
235000019270 ammonium chloride Nutrition 0.000 description 9
125000004093 cyano group Chemical group *C#N 0.000 description 9
239000011734 sodium Substances 0.000 description 9
238000003756 stirring Methods 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
RUEMLKUMKKDJTF-UHFFFAOYSA-N (2z)-n-diazoniopyridine-2-carboximidate Chemical compound [N-]=[N+]=NC(=O)C1=CC=CC=N1 RUEMLKUMKKDJTF-UHFFFAOYSA-N 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
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 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
239000007858 starting material Substances 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
239000013078 crystal Substances 0.000 description 5
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SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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
- 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
- A61P9/08—Vasodilators for multiple indications
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/69—Benzenesulfonamido-pyrimidines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Cardiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Bipolar Transistors (AREA)
Lubricants (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Surgical Instruments (AREA)
Steroid Compounds (AREA)

FI972628A 1994-12-20 1997-06-18 Uudet sulfonamidit FI120397B (fi)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
CH383794		1994-12-20
CH383794		1994-12-20
CH241995		1995-08-24
CH241995		1995-08-24
PCT/EP1995/004843 WO1996019459A1 (en)	1994-12-20	1995-12-08	Novel sulfonamides
EP9504843		1995-12-08

Publications (3)

Publication Number	Publication Date
FI972628L FI972628L (fi)	1997-06-18
FI972628A0 FI972628A0 (fi)	1997-06-18
FI120397B true FI120397B (fi)	2009-10-15

Family

ID=25690401

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI972628A FI120397B (fi)	1994-12-20	1997-06-18	Uudet sulfonamidit

Country Status (26)

Country	Link
US (1)	US6004965A (xx)
EP (1)	EP0799209B1 (xx)
JP (1)	JP2989014B2 (xx)
KR (1)	KR100445085B1 (xx)
CN (1)	CN1098254C (xx)
AT (1)	ATE246681T1 (xx)
AU (1)	AU701767B2 (xx)
BR (1)	BR9510104A (xx)
CA (1)	CA2208018C (xx)
CY (1)	CY2495B1 (xx)
CZ (1)	CZ287916B6 (xx)
DE (1)	DE69531457T2 (xx)
DK (1)	DK0799209T3 (xx)
ES (1)	ES2203649T3 (xx)
FI (1)	FI120397B (xx)
HK (1)	HK1001973A1 (xx)
HU (1)	HU228619B1 (xx)
IL (1)	IL116385A (xx)
MA (1)	MA23744A1 (xx)
MY (1)	MY131126A (xx)
NO (1)	NO316645B1 (xx)
NZ (1)	NZ297797A (xx)
PT (1)	PT799209E (xx)
SA (1)	SA95160421B1 (xx)
TW (1)	TW313568B (xx)
WO (1)	WO1996019459A1 (xx)

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EP0897914B1 (en) *	1997-08-19	2004-05-26	F. Hoffmann-La Roche Ag	Process for the preparation of 2,5-disubstitued pyridines
US7329670B1 (en)	1997-12-22	2008-02-12	Bayer Pharmaceuticals Corporation	Inhibition of RAF kinase using aryl and heteroaryl substituted heterocyclic ureas
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ATE311382T1 (de) *	1998-08-10	2005-12-15		Verfahren zur herstellung von 2-carbamoyl- pyridinen
US6660843B1 (en)	1998-10-23	2003-12-09	Amgen Inc.	Modified peptides as therapeutic agents
WO2000042012A1 (en)	1999-01-13	2000-07-20	Bayer Corporation	φ-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS
RU2319693C9 (ru)	1999-01-13	2008-08-20	Байер Копэрейшн	Производные мочевины (варианты), фармацевтическая композиция (варианты) и способ лечения заболевания, связанного с ростом раковых клеток (варианты)
US7928239B2 (en)	1999-01-13	2011-04-19	Bayer Healthcare Llc	Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas
JP2002534468A (ja) *	1999-01-13	2002-10-15	バイエルコーポレイション	ｐ３８キナーゼ阻害剤としてのω−カルボキシアリール置換ジフェニル尿素
US8124630B2 (en)	1999-01-13	2012-02-28	Bayer Healthcare Llc	ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
TWI284642B (en) *	1999-01-18	2007-08-01	Hoffmann La Roche	Novel heterocyclic sulfonamides
US6417360B1 (en) *	1999-03-03	2002-07-09	Hoffmann-La Roche Inc.	Heterocyclic sulfonamides
AU747596B2 (en) *	1999-05-22	2002-05-16	Actelion Pharmaceuticals Ltd	Aqueous pharmaceutical composition
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CN100424079C (zh)	1999-09-03	2008-10-08	埃科特莱茵药品有限公司	双磺胺
AU3536701A (en) *	1999-12-22	2001-07-03	Actelion Pharmaceuticals Ltd	Butyne diol derivatives
WO2001081338A1 (en) *	2000-04-25	2001-11-01	Actelion Pharmaceuticals Ltd	Substituted sulfonylaminopyrimidines
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US6670362B2 (en)	2000-09-20	2003-12-30	Pfizer Inc.	Pyridazine endothelin antagonists
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JP4245130B2 (ja) *	2000-12-18	2009-03-25	アクテリオンファーマシューティカルズリミテッド	新規なスルファミド類
US7235576B1 (en)	2001-01-12	2007-06-26	Bayer Pharmaceuticals Corporation	Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
WO2002083650A1 (en) *	2001-04-11	2002-10-24	Actelion Pharmaceuticals Ltd	Novel sulfonylamino-pyrimidines
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- 1995-11-29 SA SA95160421A patent/SA95160421B1/ar unknown
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Also Published As

Publication number	Publication date
IL116385A (en)	2000-07-16
DE69531457T2 (de)	2004-06-24
BR9510104A (pt)	1997-11-25
DE69531457D1 (en)	2003-09-11
FI972628L (fi)	1997-06-18
NO316645B1 (no)	2004-03-22
MA23744A1 (fr)	1996-07-01
CZ287916B6 (cs)	2001-03-14
HU228619B1 (en)	2013-04-29
WO1996019459A1 (en)	1996-06-27
IL116385A0 (en)	1996-03-31
CA2208018C (en)	2007-03-27
JP2989014B2 (ja)	1999-12-13
AU4304196A (en)	1996-07-10
NZ297797A (en)	1999-10-28
US6004965A (en)	1999-12-21
PT799209E (pt)	2003-12-31
CY2495B1 (en)	2005-09-02
NO972538D0 (no)	1997-06-04
MY131126A (en)	2007-07-31
MX9704587A (es)	1998-07-31
CA2208018A1 (en)	1996-06-27
DK0799209T3 (da)	2003-11-24
ES2203649T3 (es)	2004-04-16
EP0799209A1 (en)	1997-10-08
HUT77884A (hu)	1998-09-28
NO972538L (no)	1997-06-04
KR100445085B1 (ko)	2004-10-14
CN1170407A (zh)	1998-01-14
CZ187497A3 (en)	1997-10-15
SA95160421B1 (ar)	2006-05-01
TW313568B (xx)	1997-08-21
CN1098254C (zh)	2003-01-08
AU701767B2 (en)	1999-02-04
ATE246681T1 (de)	2003-08-15
FI972628A0 (fi)	1997-06-18
EP0799209B1 (en)	2003-08-06
HK1001973A1 (en)	1998-07-24
JPH10509182A (ja)	1998-09-08

Publication	Publication Date	Title
FI120397B (fi)	2009-10-15	Uudet sulfonamidit
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KR100478797B1 (ko)	2005-03-24	엔도텔린 수용체 길항제로서의 4-(헤테로사이클릴설폰아미도)-6-메톡시-5-(2-메톡시페녹시)-2-페닐- 또는 -피리딜-피리미딘
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EP1137642A1 (en)	2001-10-04	Bis-sulfonamides
US7091201B2 (en)	2006-08-15	Arylalkane-sulfonamides having endothelin-antagonist activity
AU2002212171A1 (en)	2002-06-20	Arylalkane-sulfonamides having endothelin-antagonist activity
CZ289920B6 (cs)	2002-04-17	Derivát sulfonamidu, způsob jeho přípravy, farmaceutický prostředek, který ho obsahuje a meziprodukt pro jeho přípravu
WO2001081335A1 (en)	2001-11-01	Pyrimidine-sulfonamides having endothelin-antagonist activity
JPH09110840A (ja)	1997-04-28	新規なスルホニルアミノピリミジン類
RU2151767C1 (ru)	2000-06-27	Сульфонамиды и фармацевтическая композиция
WO2002083650A1 (en)	2002-10-24	Novel sulfonylamino-pyrimidines
NO327220B1 (no)	2009-05-18	Alkansulfonamider, fremgangsmate for fremstilling av slike, disse forbindelsene for anvendelse som medikamenter for behandling av lidelser samt anvendelse for fremstilling av medikamenter for behandling av lidelser
MXPA97004587A (es)	1998-11-09	Sulfonamidas novedosas
PL185692B1 (pl)	2003-07-31	Nowe sulfonamidy, sposób ich wytwarzania oraz zawierające je preparaty farmaceutyczne
EP1322624B1 (en)	2009-10-21	Arylalkane-sulfonamides having endothelin-antagonist activity

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