NO314503B1 - N-Heteroarylpyridinsulfonamidderivater, anvendelse og fremstilling derav samt farmasöytisk preparat - Google Patents
N-Heteroarylpyridinsulfonamidderivater, anvendelse og fremstilling derav samt farmasöytisk preparat Download PDFInfo
- Publication number
- NO314503B1 NO314503B1 NO19975700A NO975700A NO314503B1 NO 314503 B1 NO314503 B1 NO 314503B1 NO 19975700 A NO19975700 A NO 19975700A NO 975700 A NO975700 A NO 975700A NO 314503 B1 NO314503 B1 NO 314503B1
- Authority
- NO
- Norway
- Prior art keywords
- methoxy
- sulfonamide
- alkyl
- pyridine
- phenyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 11
- DWJMBQYORXLGAE-UHFFFAOYSA-N pyridine-2-sulfonamide Chemical class NS(=O)(=O)C1=CC=CC=N1 DWJMBQYORXLGAE-UHFFFAOYSA-N 0.000 title claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 142
- 238000000034 method Methods 0.000 claims description 120
- 125000000217 alkyl group Chemical group 0.000 claims description 87
- -1 3-hydroxy-2-methyl-propyl Chemical group 0.000 claims description 84
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 57
- 150000003839 salts Chemical class 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 38
- NKFLEFWUYAUDJV-UHFFFAOYSA-N pyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CN=C1 NKFLEFWUYAUDJV-UHFFFAOYSA-N 0.000 claims description 29
- 229940124530 sulfonamide Drugs 0.000 claims description 29
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
- 239000000460 chlorine Substances 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
- 150000003461 sulfonyl halides Chemical class 0.000 claims description 8
- 229910052783 alkali metal Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 229910003827 NRaRb Inorganic materials 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000000524 functional group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 5
- 150000001450 anions Chemical class 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 5
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 208000032382 Ischaemic stroke Diseases 0.000 claims description 4
- 208000033626 Renal failure acute Diseases 0.000 claims description 4
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 4
- 201000011040 acute kidney failure Diseases 0.000 claims description 4
- 208000012998 acute renal failure Diseases 0.000 claims description 4
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 208000020832 chronic kidney disease Diseases 0.000 claims description 4
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- QDLQHGLUNGMAKG-UHFFFAOYSA-N n-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-pyridin-2-ylphenyl)pyridine-3-sulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C=2N=CC=CC=2)C=C1 QDLQHGLUNGMAKG-UHFFFAOYSA-N 0.000 claims description 4
- 229910052705 radium Inorganic materials 0.000 claims description 4
- 229910052701 rubidium Inorganic materials 0.000 claims description 4
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 3
- WMEJLSWILDWHNN-UHFFFAOYSA-N 2-[4-(1-hydroxyethyl)phenyl]-n-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C(C)O)C=C1 WMEJLSWILDWHNN-UHFFFAOYSA-N 0.000 claims description 3
- MHWPGYSKTFVVDQ-UHFFFAOYSA-N 2-[4-[3-[(3-methoxy-5-methylpyrazin-2-yl)sulfamoyl]pyridin-2-yl]phenoxy]propanoic acid Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(OC(C)C(O)=O)C=C1 MHWPGYSKTFVVDQ-UHFFFAOYSA-N 0.000 claims description 3
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 3
- 206010022562 Intermittent claudication Diseases 0.000 claims description 3
- 206010053159 Organ failure Diseases 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 230000002950 deficient Effects 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
- ZWLRFKXOUHKNLI-UHFFFAOYSA-N n-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-pyridin-3-ylphenyl)pyridine-3-sulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C=2C=NC=CC=2)C=C1 ZWLRFKXOUHKNLI-UHFFFAOYSA-N 0.000 claims description 3
- OWRXTBUPEKJMPQ-UHFFFAOYSA-N n-(5-chloro-3-methoxypyrazin-2-yl)-2-[4-(2-methylpropyl)phenyl]pyridine-3-sulfonamide Chemical compound COC1=NC(Cl)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(CC(C)C)C=C1 OWRXTBUPEKJMPQ-UHFFFAOYSA-N 0.000 claims description 3
- MWSDMYZTAMBGKE-UHFFFAOYSA-N propyl 3-[4-[3-[(3-methoxy-5-methylpyrazin-2-yl)sulfamoyl]pyridin-2-yl]phenyl]-2,2-dimethylpropanoate Chemical compound C1=CC(CC(C)(C)C(=O)OCCC)=CC=C1C1=NC=CC=C1S(=O)(=O)NC1=NC=C(C)N=C1OC MWSDMYZTAMBGKE-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 3
- 238000002054 transplantation Methods 0.000 claims description 3
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 2
- WOIGGUHJFVDVEY-UHFFFAOYSA-N 2-(4-ethylphenyl)-n-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulfonamide Chemical compound C1=CC(CC)=CC=C1C1=NC=CC=C1S(=O)(=O)NC1=NC=C(C)N=C1OC WOIGGUHJFVDVEY-UHFFFAOYSA-N 0.000 claims description 2
- NVMWIBZFTMDUHO-UHFFFAOYSA-N 2-[4-(2-hydroxyethoxy)phenyl]-n-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(OCCO)C=C1 NVMWIBZFTMDUHO-UHFFFAOYSA-N 0.000 claims description 2
- FUZRZKMHKFCQRI-UHFFFAOYSA-N 2-[4-(cyclopropylmethyl)phenyl]-n-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C(C=C1)=CC=C1CC1CC1 FUZRZKMHKFCQRI-UHFFFAOYSA-N 0.000 claims description 2
- FJHHZXWJVIEFGJ-UHFFFAOYSA-N N-(3-methoxy-5-methyl-2-pyrazinyl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]-3-pyridinesulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C=2OC=NN=2)C=C1 FJHHZXWJVIEFGJ-UHFFFAOYSA-N 0.000 claims description 2
- 206010034576 Peripheral ischaemia Diseases 0.000 claims description 2
- ZSJDZWHBWHUZAA-UHFFFAOYSA-N [3-[4-[3-[(3-methoxy-5-methylpyrazin-2-yl)sulfamoyl]pyridin-2-yl]phenyl]-2-methylpropyl] acetate Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(CC(C)COC(C)=O)C=C1 ZSJDZWHBWHUZAA-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- MAQAIMQRQPBRPD-UHFFFAOYSA-N n-(3-methoxy-5-methylpyrazin-2-yl)-2-[4-(1,2,4-oxadiazol-3-yl)phenyl]pyridine-3-sulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C2=NOC=N2)C=C1 MAQAIMQRQPBRPD-UHFFFAOYSA-N 0.000 claims description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 10
- GRPBLCVLKWBMRV-UHFFFAOYSA-N 2-[4-(2-hydroxyethoxymethyl)phenyl]-n-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(COCCO)C=C1 GRPBLCVLKWBMRV-UHFFFAOYSA-N 0.000 claims 1
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
- USPRGUCKBIXGIG-UHFFFAOYSA-N n-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-pyrimidin-2-ylphenyl)pyridine-3-sulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C=2N=CC=CN=2)C=C1 USPRGUCKBIXGIG-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 408
- 239000000243 solution Substances 0.000 description 218
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 215
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 172
- 238000001819 mass spectrum Methods 0.000 description 136
- 239000000203 mixture Substances 0.000 description 130
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 122
- 238000005481 NMR spectroscopy Methods 0.000 description 115
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 110
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 86
- 235000019341 magnesium sulphate Nutrition 0.000 description 86
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 79
- 238000001704 evaporation Methods 0.000 description 79
- 230000008020 evaporation Effects 0.000 description 79
- 239000007787 solid Substances 0.000 description 75
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 65
- 239000007858 starting material Substances 0.000 description 64
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 59
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 56
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 55
- 239000000284 extract Substances 0.000 description 54
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 50
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 45
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 42
- 239000000741 silica gel Substances 0.000 description 41
- 229910002027 silica gel Inorganic materials 0.000 description 41
- 239000003039 volatile agent Substances 0.000 description 38
- 238000004587 chromatography analysis Methods 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 34
- 239000002904 solvent Substances 0.000 description 33
- 239000003921 oil Substances 0.000 description 30
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 28
- 229910052786 argon Inorganic materials 0.000 description 25
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 25
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
- 238000010828 elution Methods 0.000 description 23
- 239000012074 organic phase Substances 0.000 description 23
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 22
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 238000012360 testing method Methods 0.000 description 20
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000004452 microanalysis Methods 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 229910000029 sodium carbonate Inorganic materials 0.000 description 14
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 239000012312 sodium hydride Substances 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- 102000002045 Endothelin Human genes 0.000 description 11
- 108050009340 Endothelin Proteins 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 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 10
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- CDVMCGIOTMQKOU-UHFFFAOYSA-N 2-methylpropyl n-(2-chloropyridin-3-yl)sulfonyl-n-(3-methoxy-5-methylpyrazin-2-yl)carbamate Chemical compound COC1=NC(C)=CN=C1N(C(=O)OCC(C)C)S(=O)(=O)C1=CC=CN=C1Cl CDVMCGIOTMQKOU-UHFFFAOYSA-N 0.000 description 8
- 101800004490 Endothelin-1 Proteins 0.000 description 8
- 102100033902 Endothelin-1 Human genes 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
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Classifications
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- 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
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- C07D401/12—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 linked by a chain containing hetero atoms as chain links
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- C—CHEMISTRY; METALLURGY
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (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)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9511507.7A GB9511507D0 (en) | 1995-06-07 | 1995-06-07 | Heterocyclic compounds |
GBGB9519666.3A GB9519666D0 (en) | 1995-09-27 | 1995-09-27 | Heterocyclic derivatives |
PCT/GB1996/001295 WO1996040681A1 (en) | 1995-06-07 | 1996-06-03 | N-heteroaryl-pyridinesulfonamide derivatives and their use as endothelin antagonists |
Publications (3)
Publication Number | Publication Date |
---|---|
NO975700L NO975700L (no) | 1997-12-05 |
NO975700D0 NO975700D0 (no) | 1997-12-05 |
NO314503B1 true NO314503B1 (no) | 2003-03-31 |
Family
ID=26307176
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19975700A NO314503B1 (no) | 1995-06-07 | 1997-12-05 | N-Heteroarylpyridinsulfonamidderivater, anvendelse og fremstilling derav samt farmasöytisk preparat |
Country Status (32)
Country | Link |
---|---|
US (3) | US5866568A (xx) |
EP (1) | EP0832082B1 (xx) |
JP (1) | JP3193058B2 (xx) |
KR (1) | KR100451523B1 (xx) |
CN (1) | CN1097051C (xx) |
AR (1) | AR003132A1 (xx) |
AT (1) | ATE209200T1 (xx) |
AU (1) | AU715041B2 (xx) |
BR (1) | BR9608611A (xx) |
CA (1) | CA2219742C (xx) |
CZ (1) | CZ289387B6 (xx) |
DE (1) | DE69617236T2 (xx) |
DK (1) | DK0832082T3 (xx) |
EG (1) | EG25227A (xx) |
ES (1) | ES2168487T3 (xx) |
GE (1) | GEP20053470B (xx) |
HK (1) | HK1005801A1 (xx) |
HR (1) | HRP960272B1 (xx) |
HU (1) | HUP9802300A3 (xx) |
IL (1) | IL122464A (xx) |
MX (1) | MX9709521A (xx) |
MY (1) | MY114926A (xx) |
NO (1) | NO314503B1 (xx) |
NZ (1) | NZ308619A (xx) |
PL (1) | PL187897B1 (xx) |
PT (1) | PT832082E (xx) |
RU (1) | RU2172738C2 (xx) |
SK (1) | SK282338B6 (xx) |
TR (1) | TR199701502T1 (xx) |
TW (1) | TW340845B (xx) |
UA (1) | UA58494C2 (xx) |
WO (1) | WO1996040681A1 (xx) |
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US6376523B1 (en) | 1994-05-20 | 2002-04-23 | Texas Biotechnology Corporation | Benzenesulfonamides and the use thereof to modulate the activity of endothelin |
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US5804585A (en) | 1996-04-15 | 1998-09-08 | Texas Biotechnology Corporation | Thieno-pyridine sulfonamides derivatives thereof and related compounds that modulate the activity of endothelin |
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US5783705A (en) | 1997-04-28 | 1998-07-21 | Texas Biotechnology Corporation | Process of preparing alkali metal salys of hydrophobic sulfonamides |
JP2002540088A (ja) | 1999-03-19 | 2002-11-26 | ブリストル−マイヤーズ スクイブ カンパニー | ビフェニルイソキサゾール・スルホンアミド化合物の製造法 |
US6448239B1 (en) * | 1999-06-03 | 2002-09-10 | Trustees Of Princeton University | Peroxynitrite decomposition catalysts and methods of use thereof |
DK1533311T3 (da) | 1999-12-31 | 2007-09-17 | Encysive Pharmaceuticals Inc | Sulfonamider og derivater deraf, der modulerer aktiviteten af endothelin |
US6639082B2 (en) | 2000-10-17 | 2003-10-28 | Bristol-Myers Squibb Company | Methods for the preparation of biphenyl isoxazole sulfonamides |
US6858592B2 (en) | 2001-06-29 | 2005-02-22 | Genzyme Corporation | Aryl boronic acids for treating obesity |
US7041280B2 (en) * | 2001-06-29 | 2006-05-09 | Genzyme Corporation | Aryl boronate functionalized polymers for treating obesity |
GB0219660D0 (en) * | 2002-08-23 | 2002-10-02 | Astrazeneca Ab | Therapeutic use |
GB0223854D0 (en) * | 2002-10-12 | 2002-11-20 | Astrazeneca Ab | Therapeutic treatment |
US7169805B2 (en) * | 2003-05-28 | 2007-01-30 | Nicox S.A. | Captopril derivatives |
GB0320806D0 (en) * | 2003-09-05 | 2003-10-08 | Astrazeneca Ab | Therapeutic treatment |
GB0403744D0 (en) * | 2004-02-20 | 2004-03-24 | Astrazeneca Ab | Chemical process |
KR100839512B1 (ko) * | 2004-07-02 | 2008-06-19 | 주식회사 코오롱 | 설파제를 디아조화체로 하는 산성 항균 염료 및 그를이용한 항균 섬유 |
WO2006053250A2 (en) | 2004-11-12 | 2006-05-18 | Trustees Of Tufts College | Lipase inhibitors |
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KR20080111137A (ko) * | 2006-04-13 | 2008-12-22 | 액테리온 파마슈티칼 리미티드 | 초기 단계 특발성 폐 섬유증을 위한 엔도텔린 수용체 대항제 |
EP2094663B1 (en) * | 2006-09-21 | 2011-01-26 | Piramal Life Sciences Limited | Pyridine derivatives for the treatment of metabolic disorders related to insulin resistance or hyperglycemia |
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NZ581606A (en) | 2007-05-03 | 2012-06-29 | Intermune Inc | Novel macrocyclic inhibitors of hepatitis c virus replication |
ATE536893T1 (de) | 2007-10-12 | 2011-12-15 | Astrazeneca Ab | Zibotentan zusammensetzung mit mannitol und mikrokristalliner zellulose |
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PL2394999T3 (pl) * | 2009-02-06 | 2014-06-30 | Nippon Shinyaku Co Ltd | Pochodna aminopirazyny i lek |
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US20230227477A1 (en) * | 2020-06-25 | 2023-07-20 | Wake Forest University Health Sciences | Compounds for sensing reactive oxygen species and methods for using the same |
KR20230038234A (ko) | 2020-07-10 | 2023-03-17 | 아스트라제네카 아베 | 만성 신장 질환 치료를 위한 지보텐탄 및 다파글리플로진의 조합 |
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US20240058331A1 (en) | 2022-08-12 | 2024-02-22 | Astrazeneca Ab | Combination therapies for treatment of cirrhosis with portal hypertension |
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DE4426346A1 (de) * | 1994-07-25 | 1996-02-01 | Basf Ag | Herbizide Pyrazinderivate |
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-
1996
- 1996-03-06 UA UA98010043A patent/UA58494C2/uk unknown
- 1996-06-03 CN CN96196149A patent/CN1097051C/zh not_active Expired - Fee Related
- 1996-06-03 KR KR1019970708807A patent/KR100451523B1/ko not_active IP Right Cessation
- 1996-06-03 PL PL96324660A patent/PL187897B1/pl not_active IP Right Cessation
- 1996-06-03 EP EP96919941A patent/EP0832082B1/en not_active Expired - Lifetime
- 1996-06-03 WO PCT/GB1996/001295 patent/WO1996040681A1/en active IP Right Grant
- 1996-06-03 AU AU58403/96A patent/AU715041B2/en not_active Ceased
- 1996-06-03 CZ CZ19973887A patent/CZ289387B6/cs not_active IP Right Cessation
- 1996-06-03 IL IL12246496A patent/IL122464A/en not_active IP Right Cessation
- 1996-06-03 ES ES96919941T patent/ES2168487T3/es not_active Expired - Lifetime
- 1996-06-03 MX MX9709521A patent/MX9709521A/es unknown
- 1996-06-03 SK SK1680-97A patent/SK282338B6/sk not_active IP Right Cessation
- 1996-06-03 NZ NZ308619A patent/NZ308619A/xx not_active IP Right Cessation
- 1996-06-03 RU RU98100054/04A patent/RU2172738C2/ru not_active IP Right Cessation
- 1996-06-03 DK DK96919941T patent/DK0832082T3/da active
- 1996-06-03 AT AT96919941T patent/ATE209200T1/de active
- 1996-06-03 PT PT96919941T patent/PT832082E/pt unknown
- 1996-06-03 CA CA002219742A patent/CA2219742C/en not_active Expired - Fee Related
- 1996-06-03 DE DE69617236T patent/DE69617236T2/de not_active Expired - Lifetime
- 1996-06-03 BR BR9608611A patent/BR9608611A/pt not_active IP Right Cessation
- 1996-06-03 JP JP50020997A patent/JP3193058B2/ja not_active Expired - Fee Related
- 1996-06-03 HU HU9802300A patent/HUP9802300A3/hu unknown
- 1996-06-03 TR TR97/01502T patent/TR199701502T1/xx unknown
- 1996-06-04 AR ARP960102899A patent/AR003132A1/es active IP Right Grant
- 1996-06-04 TW TW085106632A patent/TW340845B/zh not_active IP Right Cessation
- 1996-06-04 US US08/658,969 patent/US5866568A/en not_active Expired - Lifetime
- 1996-06-04 MY MYPI96002166A patent/MY114926A/en unknown
- 1996-06-06 HR HR960272A patent/HRP960272B1/xx not_active IP Right Cessation
- 1996-06-06 EG EG50996A patent/EG25227A/xx active
-
1997
- 1997-12-05 NO NO19975700A patent/NO314503B1/no not_active IP Right Cessation
-
1998
- 1998-06-06 HK HK98105010A patent/HK1005801A1/xx not_active IP Right Cessation
- 1998-12-14 US US09/211,483 patent/US6060475A/en not_active Expired - Lifetime
-
2000
- 2000-02-15 US US09/504,364 patent/US6258817B1/en not_active Expired - Lifetime
-
2004
- 2004-07-19 GE GE5624A patent/GEP20053470B/en unknown
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