IL122464A - Derivatives of N-pyrazine-pyridinesulfonamide, their preparation process and pharmaceutical mixtures containing them - Google Patents

Derivatives of N-pyrazine-pyridinesulfonamide, their preparation process and pharmaceutical mixtures containing them

Info

Publication number: IL122464A
Authority: IL; Israel
Prior art keywords: alkyl; alkoxy; methoxy; phenyl; carboxy
Prior art date: 1995-06-07

Application number

IL12246496A

Other languages

English (en)

Hebrew (he)

Other versions

IL122464A0 (en

Original Assignee

Zeneca Ltd

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.)

1995-06-07

Filing date

1996-06-03

Publication date

2002-05-23

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26307176&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IL122464(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1995-06-07 Priority claimed from GBGB9511507.7A external-priority patent/GB9511507D0/en

1995-09-27 Priority claimed from GBGB9519666.3A external-priority patent/GB9519666D0/en

1996-06-03 Application filed by Zeneca Ltd filed Critical Zeneca Ltd

1998-09-15 Publication of IL122464A0 publication Critical patent/IL122464A0/xx

2002-05-23 Publication of IL122464A publication Critical patent/IL122464A/en

Links

238000000034 method Methods 0.000 title claims description 123
230000008569 process Effects 0.000 title claims description 8
239000008194 pharmaceutical composition Substances 0.000 title claims description 7
238000002360 preparation method Methods 0.000 title description 6
-1 tribromomethyl Chemical group 0.000 claims abstract description 408
125000000217 alkyl group Chemical group 0.000 claims abstract description 194
150000001875 compounds Chemical class 0.000 claims abstract description 137
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 122
125000003545 alkoxy group Chemical group 0.000 claims abstract description 100
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 52
125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 42
150000003839 salts Chemical class 0.000 claims abstract description 41
125000001424 substituent group Chemical group 0.000 claims abstract description 40
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 36
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 36
125000005843 halogen group Chemical group 0.000 claims abstract description 33
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 30
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 25
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 19
239000001257 hydrogen Substances 0.000 claims abstract description 18
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
125000003342 alkenyl group Chemical group 0.000 claims abstract description 17
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 17
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 13
239000005864 Sulphur Chemical group 0.000 claims abstract description 12
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 12
125000005842 heteroatom Chemical group 0.000 claims abstract description 12
239000001301 oxygen Chemical group 0.000 claims abstract description 12
229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
150000001204 N-oxides Chemical class 0.000 claims abstract description 11
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 11
125000003302 alkenyloxy group Chemical group 0.000 claims abstract description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 11
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 11
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 11
125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 10
125000000304 alkynyl group Chemical group 0.000 claims abstract description 10
125000001589 carboacyl group Chemical group 0.000 claims abstract description 10
229940002612 prodrug Drugs 0.000 claims abstract description 10
239000000651 prodrug Substances 0.000 claims abstract description 10
125000004076 pyridyl group Chemical group 0.000 claims abstract description 10
125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 9
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract description 7
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 7
229910003827 NRaRb Inorganic materials 0.000 claims abstract description 6
125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 6
229910052799 carbon Inorganic materials 0.000 claims abstract description 6
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 6
229910052705 radium Inorganic materials 0.000 claims abstract description 6
229910052701 rubidium Inorganic materials 0.000 claims abstract description 6
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 6
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims abstract description 5
125000005281 alkyl ureido group Chemical group 0.000 claims abstract description 5
125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 4
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 4
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims abstract description 4
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 3
125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims abstract description 3
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
125000005505 thiomorpholino group Chemical group 0.000 claims abstract description 3
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims abstract description 3
125000004432 carbon atom Chemical group C* 0.000 claims abstract 3
229940124530 sulfonamide Drugs 0.000 claims description 109
239000007858 starting material Substances 0.000 claims description 63
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 33
238000006243 chemical reaction Methods 0.000 claims description 22
125000006239 protecting group Chemical group 0.000 claims description 15
150000001412 amines Chemical class 0.000 claims description 14
125000001309 chloro group Chemical group Cl* 0.000 claims description 13
FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 12
230000000694 effects Effects 0.000 claims description 12
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
125000003282 alkyl amino group Chemical group 0.000 claims description 11
241000282414 Homo sapiens Species 0.000 claims description 10
125000001246 bromo group Chemical group Br* 0.000 claims description 10
125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 9
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
241001465754 Metazoa Species 0.000 claims description 8
239000002585 base Substances 0.000 claims description 8
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 7
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
102000002045 Endothelin Human genes 0.000 claims description 6
108050009340 Endothelin Proteins 0.000 claims description 6
229910052783 alkali metal Inorganic materials 0.000 claims description 6
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 description 6
125000001153 fluoro group Chemical group F* 0.000 claims description 6
125000002346 iodo group Chemical group I* 0.000 claims description 6
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
125000000524 functional group Chemical group 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
206010020772 Hypertension Diseases 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
230000015572 biosynthetic process Effects 0.000 claims description 4
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
DMEKUKDWAIXWSL-UHFFFAOYSA-N n,n-dimethyl-7-nitro-9h-fluoren-2-amine Chemical compound [O-][N+](=O)C1=CC=C2C3=CC=C(N(C)C)C=C3CC2=C1 DMEKUKDWAIXWSL-UHFFFAOYSA-N 0.000 claims description 4
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
208000002815 pulmonary hypertension Diseases 0.000 claims description 4
125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 3
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
208000009304 Acute Kidney Injury Diseases 0.000 claims description 3
201000001320 Atherosclerosis Diseases 0.000 claims description 3
206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
206010019280 Heart failures Diseases 0.000 claims description 3
208000033626 Renal failure acute Diseases 0.000 claims description 3
230000001154 acute effect Effects 0.000 claims description 3
201000011040 acute kidney failure Diseases 0.000 claims description 3
208000012998 acute renal failure Diseases 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
150000001768 cations Chemical class 0.000 claims description 3
208000020832 chronic kidney disease Diseases 0.000 claims description 3
208000022831 chronic renal failure syndrome Diseases 0.000 claims description 3
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 3
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 claims description 2
ILROLYQPRYHHFG-UHFFFAOYSA-N 1-$l^{1}-oxidanylprop-2-en-1-one Chemical group [O]C(=O)C=C ILROLYQPRYHHFG-UHFFFAOYSA-N 0.000 claims description 2
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 2
IQNHBUQSOSYAJU-UHFFFAOYSA-N 2,2,2-trifluoro-n-methylacetamide Chemical compound CNC(=O)C(F)(F)F IQNHBUQSOSYAJU-UHFFFAOYSA-N 0.000 claims description 2
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 2
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 2
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 2
208000032928 Dyslipidaemia Diseases 0.000 claims description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
150000007513 acids Chemical class 0.000 claims description 2
125000005336 allyloxy group Chemical group 0.000 claims description 2
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
150000001450 anions Chemical class 0.000 claims description 2
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 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
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
230000002950 deficient Effects 0.000 claims description 2
125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 claims description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
125000003838 furazanyl group Chemical group 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
150000002391 heterocyclic compounds Chemical class 0.000 claims description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000001786 isothiazolyl group Chemical group 0.000 claims description 2
125000000842 isoxazolyl group Chemical group 0.000 claims description 2
125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 2
125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 2
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
125000002098 pyridazinyl group Chemical group 0.000 claims description 2
208000037803 restenosis Diseases 0.000 claims description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000004306 triazinyl group Chemical group 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
101100443238 Caenorhabditis elegans dif-1 gene Proteins 0.000 claims 1
208000032843 Hemorrhage Diseases 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 claims 1
150000002500 ions Chemical class 0.000 claims 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 1
125000000168 pyrrolyl group Chemical group 0.000 claims 1
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 22
239000002308 endothelin receptor antagonist Substances 0.000 abstract description 9
229940118365 Endothelin receptor antagonist Drugs 0.000 abstract description 8
125000004448 alkyl carbonyl group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 381
239000000243 solution Substances 0.000 description 215
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 182
238000001819 mass spectrum Methods 0.000 description 134
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 129
238000005481 NMR spectroscopy Methods 0.000 description 125
239000000203 mixture Substances 0.000 description 121
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 108
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 82
239000007787 solid Substances 0.000 description 79
238000001704 evaporation Methods 0.000 description 78
230000008020 evaporation Effects 0.000 description 78
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
239000000463 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
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 51
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 50
101150041968 CDC13 gene Proteins 0.000 description 49
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
239000011541 reaction mixture Substances 0.000 description 42
238000010992 reflux Methods 0.000 description 41
239000000741 silica gel Substances 0.000 description 41
229910002027 silica gel Inorganic materials 0.000 description 41
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
239000002904 solvent Substances 0.000 description 33
239000003921 oil Substances 0.000 description 31
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 28
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 25
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
238000004587 chromatography analysis Methods 0.000 description 23
238000010828 elution Methods 0.000 description 23
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 22
239000012074 organic phase Substances 0.000 description 22
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 22
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 19
238000012360 testing method Methods 0.000 description 19
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
229920006395 saturated elastomer Polymers 0.000 description 17
238000003756 stirring Methods 0.000 description 17
238000004452 microanalysis Methods 0.000 description 16
239000012044 organic layer Substances 0.000 description 16
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DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
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 description 1
PMOOWBBVXMSTCD-UHFFFAOYSA-N n-(5-chloro-3-methoxypyrazin-2-yl)-2-[4-(dimethylamino)phenyl]pyridine-3-sulfonamide Chemical compound COC1=NC(Cl)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(N(C)C)C=C1 PMOOWBBVXMSTCD-UHFFFAOYSA-N 0.000 description 1
DQBHQCKZHBJKGN-UHFFFAOYSA-N n-[4-[3-[(3-methoxy-5-methylpyrazin-2-yl)sulfamoyl]pyridin-2-yl]phenyl]acetamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(NC(C)=O)C=C1 DQBHQCKZHBJKGN-UHFFFAOYSA-N 0.000 description 1
HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 1
239000004090 neuroprotective agent Substances 0.000 description 1
210000000607 neurosecretory system Anatomy 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
KFBKRCXOTTUAFS-UHFFFAOYSA-N nickel;triphenylphosphane Chemical compound [Ni].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 KFBKRCXOTTUAFS-UHFFFAOYSA-N 0.000 description 1
UYLRKRLDQUXYKB-UHFFFAOYSA-N nickel;triphenylphosphane Chemical compound [Ni].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 UYLRKRLDQUXYKB-UHFFFAOYSA-N 0.000 description 1
HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
229960001597 nifedipine Drugs 0.000 description 1
239000002840 nitric oxide donor Substances 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000001991 pathophysiological effect Effects 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
BWSDNRQVTFZQQD-AYVHNPTNSA-N phosphoramidon Chemical compound O([P@@](O)(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC=1[C]2C=CC=CC2=NC=1)C(O)=O)[C@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@@H]1O BWSDNRQVTFZQQD-AYVHNPTNSA-N 0.000 description 1
108010072906 phosphoramidon Proteins 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
229920000166 polytrimethylene carbonate Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000000063 preceeding effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000011165 process development Methods 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000001294 propane Substances 0.000 description 1
RVYNIIJBIAINNT-UHFFFAOYSA-N propane-1,3-diol;hydrochloride Chemical compound Cl.OCCCO RVYNIIJBIAINNT-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
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 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
NKFLEFWUYAUDJV-UHFFFAOYSA-N pyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CN=C1 NKFLEFWUYAUDJV-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000005057 refrigeration Methods 0.000 description 1
210000004994 reproductive system Anatomy 0.000 description 1
238000011160 research Methods 0.000 description 1
201000004193 respiratory failure Diseases 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000452 restraining effect Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000004289 sodium hydrogen sulphite Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L sodium sulphate Substances [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
230000035882 stress Effects 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000004291 sulphur dioxide Substances 0.000 description 1
235000010269 sulphur dioxide Nutrition 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
229960000103 thrombolytic agent Drugs 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
GYUURHMITDQTRU-UHFFFAOYSA-N tributyl(pyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=N1 GYUURHMITDQTRU-UHFFFAOYSA-N 0.000 description 1
NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
239000002753 trypsin inhibitor Substances 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
239000002550 vasoactive agent Substances 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
239000013598 vector Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1

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
- C07D401/12—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
- 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
- A61K31/495—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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- A61P9/10—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
- 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
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Urology & Nephrology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Reproductive Health (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Endocrinology (AREA)
Vascular Medicine (AREA)
Pulmonology (AREA)
Physical Education & Sports Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyridine Compounds (AREA)
Hydrogenated Pyridines (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

IL12246496A 1995-06-07 1996-06-03 Derivatives of N-pyrazine-pyridinesulfonamide, their preparation process and pharmaceutical mixtures containing them IL122464A (en)

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 (2)

Publication Number	Publication Date
IL122464A0 IL122464A0 (en)	1998-09-15
IL122464A true IL122464A (en)	2002-05-23

Family

ID=26307176

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL12246496A IL122464A (en)	1995-06-07	1996-06-03	Derivatives of N-pyrazine-pyridinesulfonamide, their preparation process and pharmaceutical mixtures containing them

Country Status (31)

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US (3)	US5866568A (pl)
EP (1)	EP0832082B1 (pl)
JP (1)	JP3193058B2 (pl)
KR (1)	KR100451523B1 (pl)
CN (1)	CN1097051C (pl)
AR (1)	AR003132A1 (pl)
AT (1)	ATE209200T1 (pl)
AU (1)	AU715041B2 (pl)
BR (1)	BR9608611A (pl)
CA (1)	CA2219742C (pl)
CZ (1)	CZ289387B6 (pl)
DE (1)	DE69617236T2 (pl)
DK (1)	DK0832082T3 (pl)
EG (1)	EG25227A (pl)
ES (1)	ES2168487T3 (pl)
GE (1)	GEP20053470B (pl)
HR (1)	HRP960272B1 (pl)
HU (1)	HUP9802300A3 (pl)
IL (1)	IL122464A (pl)
MX (1)	MX9709521A (pl)
MY (1)	MY114926A (pl)
NO (1)	NO314503B1 (pl)
NZ (1)	NZ308619A (pl)
PL (1)	PL187897B1 (pl)
PT (1)	PT832082E (pl)
RU (1)	RU2172738C2 (pl)
SK (1)	SK282338B6 (pl)
TR (1)	TR199701502T1 (pl)
TW (1)	TW340845B (pl)
UA (1)	UA58494C2 (pl)
WO (1)	WO1996040681A1 (pl)

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US6541498B2 (en)	1993-05-20	2003-04-01	Texas Biotechnology	Benzenesulfonamides and the use thereof to modulate the activity of endothelin
US6613804B2 (en)	1993-05-20	2003-09-02	Encysive Pharmaceuticals, Inc.	Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
US6342610B2 (en)	1993-05-20	2002-01-29	Texas Biotechnology Corp.	N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
US6376523B1 (en)	1994-05-20	2002-04-23	Texas Biotechnology Corporation	Benzenesulfonamides and the use thereof to modulate the activity of endothelin
US5612359A (en) *	1994-08-26	1997-03-18	Bristol-Myers Squibb Company	Substituted biphenyl isoxazole sulfonamides
US5780473A (en) *	1995-02-06	1998-07-14	Bristol-Myers Squibb Company	Substituted biphenyl sulfonamide endothelin antagonists
US5760038A (en) *	1995-02-06	1998-06-02	Bristol-Myers Squibb Company	Substituted biphenyl sulfonamide endothelin antagonists
US5846990A (en) *	1995-07-24	1998-12-08	Bristol-Myers Squibb Co.	Substituted biphenyl isoxazole sulfonamides
JPH09124620A (ja)	1995-10-11	1997-05-13	Bristol Myers Squibb Co	置換ビフェニルスルホンアミドエンドセリン拮抗剤
US5977117A (en)	1996-01-05	1999-11-02	Texas Biotechnology Corporation	Substituted phenyl compounds and derivatives thereof that modulate the activity of endothelin
US5856507A (en) *	1997-01-21	1999-01-05	Bristol-Myers Squibb Co.	Methods for the preparation of biphenyl isoxazole sulfonamides
PL328571A1 (en)	1996-02-20	1999-02-01	Bristol Myers Squibb Co	Methods of obtaining biphenylisoxazol sulphonamides
US5939446A (en) *	1996-04-09	1999-08-17	Bristol-Myers Squibb Co.	Heteroaryl substituted phenyl isoxazole sulfonamide endothelin antagonists
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
GB9614804D0 (en) *	1996-07-15	1996-09-04	Chiroscience Ltd	Resolution process
TW536540B (en) *	1997-01-30	2003-06-11	Bristol Myers Squibb Co	Endothelin antagonists: N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide and N-(4,5-dimethyl-3-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4'-(2-oxazolyl)[1,1'-biphe
AU6187898A (en) *	1997-01-30	1998-08-25	Bristol-Myers Squibb Company	Method for preventing or treating low renin hypertension by administering an endothelin antagonist
GB9704762D0 (en) *	1997-03-07	1997-04-23	Zeneca Ltd	Chemical process
US5783705A (en)	1997-04-28	1998-07-21	Texas Biotechnology Corporation	Process of preparing alkali metal salys of hydrophobic sulfonamides
US6432994B1 (en)	1997-04-28	2002-08-13	Texas Biotechnology Corporation	Sulfonamides for treatment of endothelin-mediated disorders
HK1039778A1 (zh)	1999-03-19	2002-05-10	Bristol-Myers Squibb Company	制造联苯异恶唑基磺胺的方法
US6448239B1 (en) *	1999-06-03	2002-09-10	Trustees Of Princeton University	Peroxynitrite decomposition catalysts and methods of use thereof
EP1244657B1 (en)	1999-12-31	2004-12-29	Encysive Pharmaceuticals Inc.	Sulfonamides and derivatives thereof that modulate the activity of endothelin
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1996
- 1996-03-06 UA UA98010043A patent/UA58494C2/uk unknown
- 1996-06-03 TR TR97/01502T patent/TR199701502T1/xx unknown
- 1996-06-03 KR KR1019970708807A patent/KR100451523B1/ko not_active Expired - Fee Related
- 1996-06-03 BR BR9608611A patent/BR9608611A/pt not_active IP Right Cessation
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- 1996-06-03 AU AU58403/96A patent/AU715041B2/en not_active Ceased
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- 1996-06-03 DE DE69617236T patent/DE69617236T2/de not_active Expired - Lifetime
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- 1996-06-03 RU RU98100054/04A patent/RU2172738C2/ru not_active IP Right Cessation
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- 1996-06-03 WO PCT/GB1996/001295 patent/WO1996040681A1/en not_active Ceased
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- 1996-06-04 AR ARP960102899A patent/AR003132A1/es active IP Right Grant
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- 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
- 1998-12-14 US US09/211,483 patent/US6060475A/en not_active Expired - Lifetime
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Publication number	Publication date
US6060475A (en)	2000-05-09
RU2172738C2 (ru)	2001-08-27
NO975700L (no)	1997-12-05
SK282338B6 (sk)	2002-01-07
BR9608611A (pt)	1999-05-11
CN1097051C (zh)	2002-12-25
HRP960272B1 (en)	2006-06-30
CZ289387B6 (cs)	2002-01-16
UA58494C2 (uk)	2003-08-15
HK1005801A1 (en)	1999-01-29
DE69617236D1 (de)	2002-01-03
TW340845B (en)	1998-09-21
EP0832082A1 (en)	1998-04-01
MX9709521A (es)	1998-03-31
ATE209200T1 (de)	2001-12-15
SK168097A3 (en)	1998-05-06
CA2219742C (en)	2007-01-16
AU715041B2 (en)	2000-01-13
PL324660A1 (en)	1998-06-08
US5866568A (en)	1999-02-02
NZ308619A (en)	2000-01-28
MY114926A (en)	2003-02-28
NO314503B1 (no)	2003-03-31
TR199701502T1 (xx)	1998-03-21
WO1996040681A1 (en)	1996-12-19
HUP9802300A2 (hu)	1999-10-28
AU5840396A (en)	1996-12-30
CN1192739A (zh)	1998-09-09
CZ388797A3 (cs)	1998-03-18
HUP9802300A3 (en)	2002-02-28
US6258817B1 (en)	2001-07-10
KR19990022327A (ko)	1999-03-25
PT832082E (pt)	2002-04-29
DE69617236T2 (de)	2002-07-11
HRP960272A2 (en)	1997-08-31
ES2168487T3 (es)	2002-06-16
EP0832082B1 (en)	2001-11-21
CA2219742A1 (en)	1996-12-19
GEP20053470B (en)	2005-02-25
AR003132A1 (es)	1998-07-08
JP3193058B2 (ja)	2001-07-30
KR100451523B1 (ko)	2004-12-03
PL187897B1 (pl)	2004-10-29
JPH11509175A (ja)	1999-08-17
EG25227A (en)	2011-11-17
IL122464A0 (en)	1998-09-15
DK0832082T3 (da)	2002-05-21
NO975700D0 (no)	1997-12-05

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2002-11-10	KB	Patent renewed
2006-08-01	KB	Patent renewed
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