ZA200105279B - 4-(heterocyclylsulfonamido)-5-methoxy-6-(2-methoxyphenoxy)-2-phenyl- of pyridylpyrimidines as endothelin receptor antagonists. - Google Patents

4-(heterocyclylsulfonamido)-5-methoxy-6-(2-methoxyphenoxy)-2-phenyl- of pyridylpyrimidines as endothelin receptor antagonists. Download PDF

Info

Publication number: ZA200105279B
Authority: ZA; South Africa
Prior art keywords: methoxy; pyridine; phenoxy; pyrimidin; methyl
Prior art date: 1999-01-18

Application number

ZA200105279A

Other languages

English (en)

Inventor

Volker Breu

Rolf Huber

Henri Ramuz

Hans Peter Wessel

Philippe Coassolo

Werner Neidhart

Sebastien Roux

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.)

1999-01-18

Filing date

2001-06-26

Publication date

2002-10-07

2001-06-26 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2002-10-07 Publication of ZA200105279B publication Critical patent/ZA200105279B/en

Links

229940118365 Endothelin receptor antagonist Drugs 0.000 title description 4
239000002308 endothelin receptor antagonist Substances 0.000 title description 4
125000000217 alkyl group Chemical group 0.000 claims description 108
-1 amidino, hydroxyamidino Chemical group 0.000 claims description 106
150000001875 compounds Chemical class 0.000 claims description 93
238000006243 chemical reaction Methods 0.000 claims description 25
238000000034 method Methods 0.000 claims description 25
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 24
239000001257 hydrogen Substances 0.000 claims description 22
229910052739 hydrogen Inorganic materials 0.000 claims description 22
238000011282 treatment Methods 0.000 claims description 20
125000000623 heterocyclic group Chemical group 0.000 claims description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
125000003342 alkenyl group Chemical group 0.000 claims description 15
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
125000004093 cyano group Chemical group *C#N 0.000 claims description 15
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
150000002431 hydrogen Chemical class 0.000 claims description 12
150000003839 salts Chemical class 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
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 11
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
239000000203 mixture Substances 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
230000008569 process Effects 0.000 claims description 8
229940124530 sulfonamide Drugs 0.000 claims description 8
125000000335 thiazolyl group Chemical group 0.000 claims description 8
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
PWSQPYYJRFUQNY-UHFFFAOYSA-N 4-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-methylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]pyridine-2-carboxylic acid Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C(O)=O)OC)=C1NS(=O)(=O)C1=CC=C(C)C=N1 PWSQPYYJRFUQNY-UHFFFAOYSA-N 0.000 claims description 7
125000005236 alkanoylamino group Chemical group 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000001589 carboacyl group Chemical group 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
239000003153 chemical reaction reagent Substances 0.000 claims description 7
125000004076 pyridyl group Chemical group 0.000 claims description 7
BDDSPURWPWLXQX-UHFFFAOYSA-N 1-acetyloxyethyl 4-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-methylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]pyridine-2-carboxylate Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C(=O)OC(C)OC(C)=O)OC)=C1NS(=O)(=O)C1=CC=C(C)C=N1 BDDSPURWPWLXQX-UHFFFAOYSA-N 0.000 claims description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
206010048554 Endothelial dysfunction Diseases 0.000 claims description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
230000002159 abnormal effect Effects 0.000 claims description 6
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
230000008694 endothelial dysfunction Effects 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical group 0.000 claims description 6
USAZCYCMURFAHN-UHFFFAOYSA-N n-[2-(3-hydroxyphenyl)-6-methoxy-5-(2-methoxyphenoxy)pyrimidin-4-yl]-5-methylpyridine-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(O)C=CC=2)OC)=C1NS(=O)(=O)C1=CC=C(C)C=N1 USAZCYCMURFAHN-UHFFFAOYSA-N 0.000 claims description 6
230000006442 vascular tone Effects 0.000 claims description 6
DSPWOBHBGWPXJE-UHFFFAOYSA-N 4-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-propan-2-ylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]pyridine-2-carboxylic acid Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C(O)=O)OC)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=N1 DSPWOBHBGWPXJE-UHFFFAOYSA-N 0.000 claims description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
208000035475 disorder Diseases 0.000 claims description 5
150000002148 esters Chemical class 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 5
150000003456 sulfonamides Chemical class 0.000 claims description 5
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 4
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 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
125000002971 oxazolyl group Chemical group 0.000 claims description 4
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
239000002904 solvent Substances 0.000 claims description 4
JBMOXASJKXMRQK-UHFFFAOYSA-N methyl 4-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-methylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OC)=CC(C=2N=C(OC)C(OC=3C(=CC=CC=3)OC)=C(NS(=O)(=O)C=3N=CC(C)=CC=3)N=2)=C1 JBMOXASJKXMRQK-UHFFFAOYSA-N 0.000 claims description 3
LXNTVTQZKZHOQG-UHFFFAOYSA-N methyl 4-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-propan-2-ylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OC)=CC(C=2N=C(OC)C(OC=3C(=CC=CC=3)OC)=C(NS(=O)(=O)C=3N=CC(=CC=3)C(C)C)N=2)=C1 LXNTVTQZKZHOQG-UHFFFAOYSA-N 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
238000011321 prophylaxis Methods 0.000 claims description 3
125000000168 pyrrolyl group Chemical group 0.000 claims description 3
125000002769 thiazolinyl group Chemical group 0.000 claims description 3
BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical class C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 2
UUTWKTXQFABFKR-UHFFFAOYSA-N 5-methyl-1,3-thiazole-2-sulfonic acid Chemical compound CC1=CN=C(S(O)(=O)=O)S1 UUTWKTXQFABFKR-UHFFFAOYSA-N 0.000 claims description 2
241001465754 Metazoa Species 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
IHKAXUYWYVTCEJ-UHFFFAOYSA-N ethyl 2-[3-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-methylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=CC(C=2N=C(OC)C(OC=3C(=CC=CC=3)OC)=C(NS(=O)(=O)C=3N=CC(C)=CC=3)N=2)=C1 IHKAXUYWYVTCEJ-UHFFFAOYSA-N 0.000 claims description 2
FFIICJXAEMQRPV-UHFFFAOYSA-N ethyl 4-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-propan-2-ylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OCC)=CC(C=2N=C(OC)C(OC=3C(=CC=CC=3)OC)=C(NS(=O)(=O)C=3N=CC(=CC=3)C(C)C)N=2)=C1 FFIICJXAEMQRPV-UHFFFAOYSA-N 0.000 claims description 2
MGOPRDLMTJAUDR-UHFFFAOYSA-N n-[2-[3-(2-hydroxyethoxy)phenyl]-6-methoxy-5-(2-methoxyphenoxy)pyrimidin-4-yl]-5-methylpyridine-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(OCCO)C=CC=2)OC)=C1NS(=O)(=O)C1=CC=C(C)C=N1 MGOPRDLMTJAUDR-UHFFFAOYSA-N 0.000 claims description 2
LEPZHONWBRDTIQ-UHFFFAOYSA-N n-[6-methoxy-5-(2-methoxyphenoxy)-2-(2-oxo-1h-pyridin-4-yl)pyrimidin-4-yl]-5-methylpyridine-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(O)N=CC=2)OC)=C1NS(=O)(=O)C1=CC=C(C)C=N1 LEPZHONWBRDTIQ-UHFFFAOYSA-N 0.000 claims description 2
238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
125000005270 trialkylamine group Chemical group 0.000 claims description 2
239000000126 substance Substances 0.000 claims 5
FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims 2
102100032157 Adenylate cyclase type 10 Human genes 0.000 claims 1
206010002383 Angina Pectoris Diseases 0.000 claims 1
101000775498 Homo sapiens Adenylate cyclase type 10 Proteins 0.000 claims 1
DTVHASKEQAUBMN-UHFFFAOYSA-N N'-hydroxy-4-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-propan-2-ylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]pyridine-2-carboximidamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C(=N)NO)OC)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=N1 DTVHASKEQAUBMN-UHFFFAOYSA-N 0.000 claims 1
ZDLIYCVDCFABIY-UHFFFAOYSA-N [3-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-methylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]phenyl] acetate Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(OC(C)=O)C=CC=2)OC)=C1NS(=O)(=O)C1=CC=C(C)C=N1 ZDLIYCVDCFABIY-UHFFFAOYSA-N 0.000 claims 1
230000003288 anthiarrhythmic effect Effects 0.000 claims 1
230000002785 anti-thrombosis Effects 0.000 claims 1
239000003416 antiarrhythmic agent Substances 0.000 claims 1
239000003146 anticoagulant agent Substances 0.000 claims 1
239000002220 antihypertensive agent Substances 0.000 claims 1
229940127088 antihypertensive drug Drugs 0.000 claims 1
239000003524 antilipemic agent Substances 0.000 claims 1
239000003963 antioxidant agent Substances 0.000 claims 1
201000010099 disease Diseases 0.000 claims 1
JBOAZACHEBUCCG-UHFFFAOYSA-N ethyl 4-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-methylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OCC)=CC(C=2N=C(OC)C(OC=3C(=CC=CC=3)OC)=C(NS(=O)(=O)C=3N=CC(C)=CC=3)N=2)=C1 JBOAZACHEBUCCG-UHFFFAOYSA-N 0.000 claims 1
ZAPIXIFQZPXOQX-UHFFFAOYSA-N n-[6-methoxy-5-(2-methoxyphenoxy)-2-[2-(5-methyl-1,2,4-oxadiazol-3-yl)pyridin-4-yl]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=2N=C(C)ON=2)OC)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=N1 ZAPIXIFQZPXOQX-UHFFFAOYSA-N 0.000 claims 1
ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 claims 1
OCZRIJKYGLCQGB-UHFFFAOYSA-N propan-2-yl 4-[4-methoxy-5-(2-methoxyphenoxy)-6-[(5-propan-2-ylpyridin-2-yl)sulfonylamino]pyrimidin-2-yl]pyridine-2-carboxylate Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C(=O)OC(C)C)OC)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=N1 OCZRIJKYGLCQGB-UHFFFAOYSA-N 0.000 claims 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 25
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
125000001424 substituent group Chemical group 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 7
241000700159 Rattus Species 0.000 description 7
239000002585 base Substances 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 6
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
108050009340 Endothelin Proteins 0.000 description 5
102000002045 Endothelin Human genes 0.000 description 5
101800004490 Endothelin-1 Proteins 0.000 description 5
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 5
230000027455 binding Effects 0.000 description 5
230000008878 coupling Effects 0.000 description 5
238000010168 coupling process Methods 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
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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 description 5
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229910052708 sodium Inorganic materials 0.000 description 5
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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 4
125000004432 carbon atom Chemical group C* 0.000 description 4
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BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
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OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
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102400000686 Endothelin-1 Human genes 0.000 description 2
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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
- C07D401/12—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
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ZA200105279A 1999-01-18 2001-06-26 4-(heterocyclylsulfonamido)-5-methoxy-6-(2-methoxyphenoxy)-2-phenyl- of pyridylpyrimidines as endothelin receptor antagonists. ZA200105279B (en)

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Application Number	Priority Date	Filing Date	Title
EP99100784		1999-01-18

Publications (1)

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ZA200105279B true ZA200105279B (en)	2002-10-07

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ZA200105279A ZA200105279B (en)	1999-01-18	2001-06-26	4-(heterocyclylsulfonamido)-5-methoxy-6-(2-methoxyphenoxy)-2-phenyl- of pyridylpyrimidines as endothelin receptor antagonists.

Country Status (31)

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US (1)	US6242601B1 (es)
EP (1)	EP1149091B1 (es)
JP (1)	JP3983477B2 (es)
KR (1)	KR100478797B1 (es)
CN (1)	CN1340049A (es)
AR (1)	AR029879A1 (es)
AT (1)	ATE389648T1 (es)
AU (1)	AU763112B2 (es)
BR (1)	BR0007595A (es)
CA (1)	CA2359363C (es)
CO (1)	CO5150187A1 (es)
CZ (1)	CZ20012546A3 (es)
DE (1)	DE60038365D1 (es)
ES (1)	ES2301476T3 (es)
GC (1)	GC0000248A (es)
HR (1)	HRP20010515A2 (es)
HU (1)	HUP0200021A3 (es)
IL (2)	IL144055A0 (es)
MA (1)	MA27124A1 (es)
MY (1)	MY121136A (es)
NO (1)	NO322800B1 (es)
NZ (1)	NZ512662A (es)
PE (1)	PE20001421A1 (es)
PL (1)	PL350093A1 (es)
RU (1)	RU2224757C2 (es)
TR (1)	TR200102071T2 (es)
TW (1)	TWI284642B (es)
UY (1)	UY25904A1 (es)
WO (1)	WO2000042035A1 (es)
YU (1)	YU50001A (es)
ZA (1)	ZA200105279B (es)

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WO2004050640A1 (en) *	2002-12-02	2004-06-17	Actelion Pharmaceuticals Ltd	Pyrimidine-sulfamides and their use as endothelian receptor antagonist
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US7557129B2 (en) *	2003-02-28	2009-07-07	Bayer Healthcare Llc	Cyanopyridine derivatives useful in the treatment of cancer and other disorders
PT1636585E (pt)	2003-05-20	2008-03-27	Bayer Pharmaceuticals Corp	Diarilureias com actividade inibidora de cinase
NZ544920A (en)	2003-07-23	2009-11-27	Bayer Healthcare Llc	4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide and metabolites for the treatment and prevention of diseases and conditions
EP1595880A1 (en) *	2004-05-13	2005-11-16	Speedel Pharma AG	Crystalline forms of a pyridinyl-sulfonamide and their use as endothelin receptor antagonists
CR9465A (es) *	2005-03-25	2008-06-19	Surface Logix Inc	Compuestos mejorados farmacocineticamente
WO2007119214A2 (en) *	2006-04-13	2007-10-25	Actelion Pharmaceuticals Ltd	Endothelin receptor antagonists for early stage idiopathic pulmonary fibrosis
CN101454283A (zh)	2006-05-29	2009-06-10	尼科克斯公司	作为内皮素受体拮抗剂的硝化的杂环化合物
AR062501A1 (es)	2006-08-29	2008-11-12	Actelion Pharmaceuticals Ltd	Composiciones terapeuticas
MX2010001837A (es)	2007-08-17	2010-03-10	Actelion Pharmaceuticals Ltd	Derivados de 4-pirimidinasulfamida.
US10287263B2 (en) *	2014-11-21	2019-05-14	Daikin Industries, Ltd.	Fluorinated unsaturated cyclic carbonate and process for producing same
CN109260164A (zh) *	2018-10-07	2019-01-25	威海贯标信息科技有限公司	一种阿伏生坦片剂组合物
CN112898208B (zh) *	2021-01-29	2023-06-20	中国医科大学	苯基嘧啶胺类抗肿瘤化合物及其制备方法和应用
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Also Published As

Publication number	Publication date
NO20013454L (no)	2001-07-12
TR200102071T2 (tr)	2002-03-21
HUP0200021A2 (hu)	2002-05-29
AR029879A1 (es)	2003-07-23
NO20013454D0 (no)	2001-07-12
IL144055A0 (en)	2002-04-21
US6242601B1 (en)	2001-06-05
CA2359363C (en)	2006-03-14
RU2224757C2 (ru)	2004-02-27
YU50001A (sh)	2004-03-12
TWI284642B (en)	2007-08-01
JP3983477B2 (ja)	2007-09-26
WO2000042035A1 (en)	2000-07-20
CZ20012546A3 (cs)	2001-12-12
ATE389648T1 (de)	2008-04-15
KR20010094746A (ko)	2001-11-01
HUP0200021A3 (en)	2003-01-28
CA2359363A1 (en)	2000-07-20
UY25904A1 (es)	2001-07-31
EP1149091B1 (en)	2008-03-19
ES2301476T3 (es)	2008-07-01
MA27124A1 (fr)	2005-01-03
PE20001421A1 (es)	2000-12-18
BR0007595A (pt)	2001-10-16
AU2663000A (en)	2000-08-01
IL144055A (en)	2007-07-24
AU763112B2 (en)	2003-07-10
CN1340049A (zh)	2002-03-13
NZ512662A (en)	2003-11-28
PL350093A1 (en)	2002-11-04
CO5150187A1 (es)	2002-04-29
HRP20010515A2 (en)	2003-06-30
MY121136A (en)	2005-12-30
DE60038365D1 (en)	2008-04-30
JP2002534518A (ja)	2002-10-15
EP1149091A1 (en)	2001-10-31
KR100478797B1 (ko)	2005-03-24
NO322800B1 (no)	2006-12-11
GC0000248A (en)	2006-11-01

Publication	Publication Date	Title
ZA200105279B (en)	2002-10-07	4-(heterocyclylsulfonamido)-5-methoxy-6-(2-methoxyphenoxy)-2-phenyl- of pyridylpyrimidines as endothelin receptor antagonists.
KR100443850B1 (ko)	2004-08-11	헤테로시클릭 화합물의 도파민-ｄ３ 리간드로서의 용도
CN102933559B (zh)	2016-01-27	光学活性二苄胺衍生物及其制备方法
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