ZA200303695B - Novel sulfamides and their use as endothelin receptor antagonists. - Google Patents
Novel sulfamides and their use as endothelin receptor antagonists. Download PDFInfo
- Publication number
- ZA200303695B ZA200303695B ZA200303695A ZA200303695A ZA200303695B ZA 200303695 B ZA200303695 B ZA 200303695B ZA 200303695 A ZA200303695 A ZA 200303695A ZA 200303695 A ZA200303695 A ZA 200303695A ZA 200303695 B ZA200303695 B ZA 200303695B
- Authority
- ZA
- South Africa
- Prior art keywords
- pyrimidin
- yloxy
- amide
- ethoxy
- phenyl
- Prior art date
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- 229940118365 Endothelin receptor antagonist Drugs 0.000 title description 7
- 239000002308 endothelin receptor antagonist Substances 0.000 title description 7
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 102
- 125000000217 alkyl group Chemical group 0.000 claims description 62
- 239000000203 mixture Substances 0.000 claims description 54
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 32
- 108050009340 Endothelin Proteins 0.000 claims description 32
- 102000002045 Endothelin Human genes 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 30
- 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 29
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- -1 mono-substituted phenyl Chemical group 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 22
- 239000000126 substance Substances 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 239000000460 chlorine Chemical group 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- SVEKJHBWJWHXKV-UHFFFAOYSA-N benzylsulfamic acid Chemical compound OS(=O)(=O)NCC1=CC=CC=C1 SVEKJHBWJWHXKV-UHFFFAOYSA-N 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 206010020772 Hypertension Diseases 0.000 claims description 8
- SIVVHUQWDOGLJN-UHFFFAOYSA-N ethylsulfamic acid Chemical compound CCNS(O)(=O)=O SIVVHUQWDOGLJN-UHFFFAOYSA-N 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 208000019695 Migraine disease Diseases 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 150000002431 hydrogen Chemical group 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 206010027599 migraine Diseases 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- KOTQMXOSUVRBGE-UHFFFAOYSA-N cyclopropylsulfamic acid Chemical compound OS(=O)(=O)NC1CC1 KOTQMXOSUVRBGE-UHFFFAOYSA-N 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- OUCYWJAACMAXQD-UHFFFAOYSA-N pyridin-2-ylcarbamic acid Chemical compound OC(=O)NC1=CC=CC=N1 OUCYWJAACMAXQD-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- GADXZXTXFHEOKH-UHFFFAOYSA-N 5-(4-bromophenyl)-n-(ethylsulfamoyl)-6-[2-(5-methylsulfanylpyrimidin-2-yl)oxyethoxy]pyrimidin-4-amine Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCC)=NC=NC=1OCCOC1=NC=C(SC)C=N1 GADXZXTXFHEOKH-UHFFFAOYSA-N 0.000 claims description 2
- LMOTTXPPAHPOIW-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]pyrimidin-4-amine Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC=NC(N)=C1C1=CC=C(Cl)C=C1 LMOTTXPPAHPOIW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000001769 aryl amino group Chemical group 0.000 claims description 2
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 2
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 2
- 239000011737 fluorine Chemical group 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 2
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 2
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
- 125000004468 heterocyclylthio group Chemical group 0.000 claims description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims 25
- 230000000903 blocking effect Effects 0.000 claims 9
- 238000004519 manufacturing process Methods 0.000 claims 7
- GBEWVFVMUXHESI-UHFFFAOYSA-N cyclopentylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCC1 GBEWVFVMUXHESI-UHFFFAOYSA-N 0.000 claims 5
- 206010002383 Angina Pectoris Diseases 0.000 claims 4
- 206010047163 Vasospasm Diseases 0.000 claims 4
- 208000027866 inflammatory disease Diseases 0.000 claims 4
- 208000028867 ischemia Diseases 0.000 claims 4
- 230000002062 proliferating effect Effects 0.000 claims 4
- FECFIIXKXJBOSU-UHFFFAOYSA-N butylsulfamic acid Chemical compound CCCCNS(O)(=O)=O FECFIIXKXJBOSU-UHFFFAOYSA-N 0.000 claims 3
- HEFVEPWESGAVMJ-UHFFFAOYSA-N cyclopropylmethylsulfamic acid Chemical compound OS(=O)(=O)NCC1CC1 HEFVEPWESGAVMJ-UHFFFAOYSA-N 0.000 claims 3
- NKRKVBHEFWMSCD-UHFFFAOYSA-N methyl(pyridin-2-yl)sulfamic acid Chemical compound OS(=O)(=O)N(C)C1=CC=CC=N1 NKRKVBHEFWMSCD-UHFFFAOYSA-N 0.000 claims 3
- MYMDOKBFMTVEGE-UHFFFAOYSA-N methylsulfamic acid Chemical compound CNS(O)(=O)=O MYMDOKBFMTVEGE-UHFFFAOYSA-N 0.000 claims 3
- GUNQKELHNQVFCA-UHFFFAOYSA-N 2-phenylethylsulfamic acid Chemical compound OS(=O)(=O)NCCC1=CC=CC=C1 GUNQKELHNQVFCA-UHFFFAOYSA-N 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 239000012876 carrier material Substances 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- HLIBNTOXKQCYMV-UHFFFAOYSA-N propylsulfamic acid Chemical compound CCCNS(O)(=O)=O HLIBNTOXKQCYMV-UHFFFAOYSA-N 0.000 claims 2
- RKKGZPSHYLXVHK-UHFFFAOYSA-N (4-fluorophenyl)methylsulfamic acid Chemical compound OS(=O)(=O)NCC1=CC=C(F)C=C1 RKKGZPSHYLXVHK-UHFFFAOYSA-N 0.000 claims 1
- HQTCWMOCUPICJI-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-[[methyl(pyridin-2-yl)sulfamoyl]amino]pyrimidine Chemical compound N=1C=NC(OCCOC=2N=CC(Br)=CN=2)=C(C=2C=CC(Br)=CC=2)C=1NS(=O)(=O)N(C)C1=CC=CC=N1 HQTCWMOCUPICJI-UHFFFAOYSA-N 0.000 claims 1
- ISJQPCOMTBDAMT-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-[[methyl(pyridin-3-yl)sulfamoyl]amino]pyrimidine Chemical compound N=1C=NC(OCCOC=2N=CC(Br)=CN=2)=C(C=2C=CC(Br)=CC=2)C=1NS(=O)(=O)N(C)C1=CC=CN=C1 ISJQPCOMTBDAMT-UHFFFAOYSA-N 0.000 claims 1
- GWOUVHUMXSOJQE-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]-6-[[methyl(pyridin-2-yl)sulfamoyl]amino]pyrimidine Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)N(C)C=2N=CC=CC=2)=C1C1=CC=C(Br)C=C1 GWOUVHUMXSOJQE-UHFFFAOYSA-N 0.000 claims 1
- RZMHAFWDYQRCCM-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]-6-[[methyl(pyridin-3-yl)sulfamoyl]amino]pyrimidine Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)N(C)C=2C=NC=CC=2)=C1C1=CC=C(Br)C=C1 RZMHAFWDYQRCCM-UHFFFAOYSA-N 0.000 claims 1
- DKWDMCCNUCWCKU-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]-6-[[methyl(pyridin-4-yl)sulfamoyl]amino]pyrimidine Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)N(C)C=2C=CN=CC=2)=C1C1=CC=C(Br)C=C1 DKWDMCCNUCWCKU-UHFFFAOYSA-N 0.000 claims 1
- SCCMBDIZRNGJIJ-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[[furan-2-yl(methyl)sulfamoyl]amino]-6-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]pyrimidine Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)N(C)C=2OC=CC=2)=C1C1=CC=C(Br)C=C1 SCCMBDIZRNGJIJ-UHFFFAOYSA-N 0.000 claims 1
- FAYAMAAFPRXGJT-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-n-(butylsulfamoyl)pyrimidin-4-amine Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCCCC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 FAYAMAAFPRXGJT-UHFFFAOYSA-N 0.000 claims 1
- TYCTWXNHVWBKAM-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-n-[(4-fluorophenyl)methylsulfamoyl]pyrimidin-4-amine Chemical compound C1=CC(F)=CC=C1CNS(=O)(=O)NC1=NC=NC(OCCOC=2N=CC(Br)=CN=2)=C1C1=CC=C(Br)C=C1 TYCTWXNHVWBKAM-UHFFFAOYSA-N 0.000 claims 1
- IDRSXRPOEONBKT-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]-n-(propylsulfamoyl)pyrimidin-4-amine Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCCC)=NC=NC=1OCCOC1=NC=C(OC)C=N1 IDRSXRPOEONBKT-UHFFFAOYSA-N 0.000 claims 1
- LDYLIYKANSSERK-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-methylsulfanylpyrimidin-2-yl)oxyethoxy]-n-(propylsulfamoyl)pyrimidin-4-amine Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCCC)=NC=NC=1OCCOC1=NC=C(SC)C=N1 LDYLIYKANSSERK-UHFFFAOYSA-N 0.000 claims 1
- ZWTAXWXITAZUQP-UHFFFAOYSA-N 5-(4-bromophenyl)-n-(butylsulfamoyl)-6-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]pyrimidin-4-amine Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCCCC)=NC=NC=1OCCOC1=NC=C(OC)C=N1 ZWTAXWXITAZUQP-UHFFFAOYSA-N 0.000 claims 1
- IEWNTHNOQNSSEF-UHFFFAOYSA-N 5-(4-bromophenyl)-n-(cyclopentylsulfamoyl)-6-[2-(5-methylsulfanylpyrimidin-2-yl)oxyethoxy]pyrimidin-4-amine Chemical compound N1=CC(SC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)NC2CCCC2)=C1C1=CC=C(Br)C=C1 IEWNTHNOQNSSEF-UHFFFAOYSA-N 0.000 claims 1
- HQGIDDDJEHWECC-UHFFFAOYSA-N 5-(4-chlorophenyl)-4-[[methyl(pyridin-4-yl)sulfamoyl]amino]-6-[2-(5-methylsulfanylpyrimidin-2-yl)oxyethoxy]pyrimidine Chemical compound N1=CC(SC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)N(C)C=2C=CN=CC=2)=C1C1=CC=C(Cl)C=C1 HQGIDDDJEHWECC-UHFFFAOYSA-N 0.000 claims 1
- UIQQWMKWMPXRKH-UHFFFAOYSA-N 6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-amine Chemical compound COC1=CC=CC=C1OC1=C(N)N=C(C=2N=CC=CN=2)N=C1OCCOC1=NC=C(Br)C=N1 UIQQWMKWMPXRKH-UHFFFAOYSA-N 0.000 claims 1
- JPXXLPSYKLAUKC-UHFFFAOYSA-N 6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-chlorophenyl)-n-(methylsulfamoyl)pyrimidin-4-amine Chemical compound C=1C=C(Cl)C=CC=1C=1C(NS(=O)(=O)NC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 JPXXLPSYKLAUKC-UHFFFAOYSA-N 0.000 claims 1
- OXHAHXSAOMBNOX-UHFFFAOYSA-N 6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-chlorophenyl)-n-(propylsulfamoyl)pyrimidin-4-amine Chemical compound C=1C=C(Cl)C=CC=1C=1C(NS(=O)(=O)NCCC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 OXHAHXSAOMBNOX-UHFFFAOYSA-N 0.000 claims 1
- MTASHOUPPXXWDT-UHFFFAOYSA-N 6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-chlorophenyl)-n-[(4-fluorophenyl)methylsulfamoyl]pyrimidin-4-amine Chemical compound C1=CC(F)=CC=C1CNS(=O)(=O)NC1=NC=NC(OCCOC=2N=CC(Br)=CN=2)=C1C1=CC=C(Cl)C=C1 MTASHOUPPXXWDT-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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PT1345920E (pt) * | 2000-12-18 | 2006-08-31 | Actelion Pharmaceuticals Ltd | Novas sulfonamidas e sua utilizacao como antagonistas dos receptores de endotelina |
CA2469316A1 (en) * | 2001-12-07 | 2003-06-19 | Vertex Pharmaceuticals, Inc. | Pyrimidine-based compounds useful as gsk-3 inhibitors |
EP1569914B1 (en) * | 2002-12-02 | 2009-02-18 | Actelion Pharmaceuticals Ltd. | Pyrimidine-sulfamides and their use as endothelian receptor antagonist |
BRPI0508461B8 (pt) | 2004-03-05 | 2021-05-25 | Hoffmann La Roche | diaminopirimidinas, seus usos, e composição farmacêutica |
UA90269C2 (ru) | 2004-04-02 | 2010-04-26 | Мицубиси Танабе Фарма Корпорейшн | Тетрагидрохинолиновые производные и способ их получения |
TW200628467A (en) | 2004-11-11 | 2006-08-16 | Actelion Pharmaceuticals Ltd | Novel sulfamides |
ATE524475T1 (de) | 2005-07-29 | 2011-09-15 | Tibotec Pharm Ltd | Makrocyclische inhibitoren des hepatitis-c-virus |
RU2436787C2 (ru) | 2005-07-29 | 2011-12-20 | Тиботек Фармасьютикалз Лтд. | Макроциклические ингибиторы вируса гепатита с |
WO2007025901A1 (en) | 2005-09-01 | 2007-03-08 | F. Hoffmann-La Roche Ag | Diaminopyrimidines as p2x3 and p2x2/3 modulators |
CN101296907B (zh) | 2005-09-01 | 2013-03-27 | 弗·哈夫曼-拉罗切有限公司 | 作为p2x3和p2x2/3调节剂的二氨基嘧啶类 |
BRPI0615613A2 (pt) | 2005-09-01 | 2009-05-19 | Hoffmann La Roche | diaminopirimidinas como moduladores de p2x3 e p3x2/3 |
JP4955685B2 (ja) * | 2005-09-12 | 2012-06-20 | アクテリオン ファーマシューティカルズ リミテッド | ピリミジン−スルファミドを含む安定な医薬組成物 |
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. |
US20100222347A1 (en) | 2007-09-27 | 2010-09-02 | Kowa Company, Ltd. | Prophylactic and/or therapeutic agent for anemia, comprising tetrahydroquinoline compound as active ingredient |
DK2254570T3 (da) * | 2008-02-20 | 2014-02-03 | Actelion Pharmaceuticals Ltd | Kombination omfattende paclitaxel til behandling af ovariecancer |
SI2315587T1 (en) * | 2008-08-13 | 2018-04-30 | Actelion Pharmaceuticals Ltd | A therapeutic composition comprising macitentan |
EP2415764A4 (en) | 2009-03-31 | 2012-08-08 | Kowa Co | PROPHYLACTIC AND / OR THERAPEUTIC AGENT AGAINST ANEMIA WITH A TETRAHYDROCHINOLINE COMPOUND AS AN ACTIVE SUBSTANCE |
KR20120088665A (ko) | 2009-08-10 | 2012-08-08 | 보드 오브 리전츠 더 유니버시티 오브 텍사스 시스템 | 세포독성 화학요법제와 조합한 엔도텔린 수용체의 억제제를 이용한 뇌 전이 치료 |
EP2467142B1 (en) | 2009-08-17 | 2016-09-21 | Memorial Sloan-Kettering Cancer Center | 2-(Pyrimidin-5-yl)-thiopyrimidine derivatives as Hsp70 and Hsc70 modulators for the treatment of proliferative disorders |
WO2011078143A1 (ja) * | 2009-12-22 | 2011-06-30 | 塩野義製薬株式会社 | ピリミジン誘導体およびそれらを含有する医薬組成物 |
MA34952B1 (fr) * | 2011-02-04 | 2014-03-01 | Actelion Pharmaceuticals Ltd | Combinaisons comprenant du macitentan pour le traitement d'un glioblastome multiforme |
JP2016510781A (ja) * | 2013-03-15 | 2016-04-11 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | RORcモジュレーターとしてのアリールスルファミド及びスルファミン酸誘導体 |
AR095727A1 (es) * | 2013-03-27 | 2015-11-04 | Actelion Pharmaceuticals Ltd | Preparación de intermediarios de pirimidina |
DE14721256T1 (de) | 2013-04-22 | 2017-03-16 | Sandoz Ag | Pharmazeutische zusammensetzungen mit kristallinem macitentan |
WO2014198178A1 (zh) * | 2013-06-14 | 2014-12-18 | 杭州普晒医药科技有限公司 | 马西替坦晶体及其制备方法、其药物组合物和用途 |
AR096865A1 (es) * | 2013-07-12 | 2016-02-03 | Actelion Pharmaceuticals Ltd | Proceso para la preparación de un intermediario de pirimidina |
CN103724281A (zh) * | 2013-12-03 | 2014-04-16 | 镇江圣安医药有限公司 | N-[5-(4-溴苯基)-6-[2-[(5-溴-2-嘧啶基)氧基]乙氧基]-4-嘧啶基]-n′-丙基磺酰胺的新型衍生物及其应用 |
EP2907811A1 (en) * | 2014-02-14 | 2015-08-19 | Actelion Pharmaceuticals Ltd. | Process for manufacturing pyrimidine sulfamide derivatives |
CN103819411A (zh) * | 2014-03-14 | 2014-05-28 | 成都克莱蒙医药科技有限公司 | 一种马西替坦中间体新的制备方法 |
AU2015259173B2 (en) | 2014-05-13 | 2019-09-05 | Memorial Sloan Kettering Cancer Center | Hsp70 modulators and methods for making and using the same |
EP3169669A1 (en) * | 2014-07-15 | 2017-05-24 | OLON S.p.A. | Amorphous form and new crystalline forms of macitentan |
CN104447572A (zh) * | 2014-12-15 | 2015-03-25 | 南京艾德凯腾生物医药有限责任公司 | 一种马西替坦的制备方法 |
WO2016203489A1 (en) | 2015-06-15 | 2016-12-22 | Megafine Pharma (P) Ltd. | Process for the preparation of macitentan and intermediates thereof |
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