JP2004517855A5 - - Google Patents
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- Publication number
- JP2004517855A5 JP2004517855A5 JP2002554676A JP2002554676A JP2004517855A5 JP 2004517855 A5 JP2004517855 A5 JP 2004517855A5 JP 2002554676 A JP2002554676 A JP 2002554676A JP 2002554676 A JP2002554676 A JP 2002554676A JP 2004517855 A5 JP2004517855 A5 JP 2004517855A5
- Authority
- JP
- Japan
- Prior art keywords
- pyrimidin
- yloxy
- amide
- ethoxy
- phenyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
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- 150000001875 compounds Chemical class 0.000 description 30
- 125000000217 alkyl group Chemical group 0.000 description 24
- -1 mono-substituted phenyl Chemical group 0.000 description 15
- 201000010099 disease Diseases 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 11
- 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 description 10
- 125000003545 alkoxy group Chemical group 0.000 description 10
- 102000002045 Endothelin Human genes 0.000 description 9
- 108050009340 Endothelin Proteins 0.000 description 9
- 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 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 125000003282 alkyl amino group Chemical group 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 125000001072 heteroaryl group Chemical group 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 0 **c1c(NS(N(*)*)(=O)=O)nc(*)nc1O* Chemical compound **c1c(NS(N(*)*)(=O)=O)nc(*)nc1O* 0.000 description 5
- 125000004414 alkyl thio group Chemical group 0.000 description 5
- SVEKJHBWJWHXKV-UHFFFAOYSA-N benzylsulfamic acid Chemical compound OS(=O)(=O)NCC1=CC=CC=C1 SVEKJHBWJWHXKV-UHFFFAOYSA-N 0.000 description 5
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 description 4
- 206010002383 Angina Pectoris Diseases 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 206010047163 Vasospasm Diseases 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 206010027599 migraine Diseases 0.000 description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- AIOGYCKREZXJJZ-UHFFFAOYSA-N 4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-chlorophenyl)-6-[[methyl(pyridin-2-yl)sulfamoyl]amino]pyrimidine Chemical compound N=1C=NC(OCCOC=2N=CC(Br)=CN=2)=C(C=2C=CC(Cl)=CC=2)C=1NS(=O)(=O)N(C)C1=CC=CC=N1 AIOGYCKREZXJJZ-UHFFFAOYSA-N 0.000 description 2
- PIJUSICWAKBTEZ-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-n-(ethylsulfamoyl)pyrimidin-4-amine Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 PIJUSICWAKBTEZ-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 150000002431 hydrogen Chemical group 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- OUCYWJAACMAXQD-UHFFFAOYSA-N pyridin-2-ylcarbamic acid Chemical compound OC(=O)NC1=CC=CC=N1 OUCYWJAACMAXQD-UHFFFAOYSA-N 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- CDYRIYSNNRFTJE-UHFFFAOYSA-N 4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-chlorophenyl)-6-[[furan-2-yl(methyl)sulfamoyl]amino]pyrimidine Chemical compound N=1C=NC(OCCOC=2N=CC(Br)=CN=2)=C(C=2C=CC(Cl)=CC=2)C=1NS(=O)(=O)N(C)C1=CC=CO1 CDYRIYSNNRFTJE-UHFFFAOYSA-N 0.000 description 1
- WDQPEDYBKDHJLW-UHFFFAOYSA-N 4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-chlorophenyl)-6-[[methyl(pyridin-3-yl)sulfamoyl]amino]pyrimidine Chemical compound N=1C=NC(OCCOC=2N=CC(Br)=CN=2)=C(C=2C=CC(Cl)=CC=2)C=1NS(=O)(=O)N(C)C1=CC=CN=C1 WDQPEDYBKDHJLW-UHFFFAOYSA-N 0.000 description 1
- UDJIQNVFLWLRET-UHFFFAOYSA-N 4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-chlorophenyl)-6-[[methyl(pyridin-4-yl)sulfamoyl]amino]pyrimidine Chemical compound N=1C=NC(OCCOC=2N=CC(Br)=CN=2)=C(C=2C=CC(Cl)=CC=2)C=1NS(=O)(=O)N(C)C1=CC=NC=C1 UDJIQNVFLWLRET-UHFFFAOYSA-N 0.000 description 1
- DCNYMZHJYGMUAP-UHFFFAOYSA-N 4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-chlorophenyl)-6-[[methyl(thiophen-2-yl)sulfamoyl]amino]pyrimidine Chemical compound N=1C=NC(OCCOC=2N=CC(Br)=CN=2)=C(C=2C=CC(Cl)=CC=2)C=1NS(=O)(=O)N(C)C1=CC=CS1 DCNYMZHJYGMUAP-UHFFFAOYSA-N 0.000 description 1
- LGFUPYWNJPMKKF-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-[[furan-2-yl(methyl)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=CO1 LGFUPYWNJPMKKF-UHFFFAOYSA-N 0.000 description 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 description 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 description 1
- OHDJBKMKVMFQIY-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-[[methyl(pyridin-4-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=NC=C1 OHDJBKMKVMFQIY-UHFFFAOYSA-N 0.000 description 1
- ZLDJCOJFGRLYDN-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-6-[[methyl(thiophen-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=CS1 ZLDJCOJFGRLYDN-UHFFFAOYSA-N 0.000 description 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 description 1
- GRMNNBBUDDGUJW-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]-6-[[methyl(thiophen-2-yl)sulfamoyl]amino]pyrimidine Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)N(C)C=2SC=CC=2)=C1C1=CC=C(Br)C=C1 GRMNNBBUDDGUJW-UHFFFAOYSA-N 0.000 description 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 description 1
- XYCFQJYVDREZPE-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[[furan-2-yl(methyl)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=2OC=CC=2)=C1C1=CC=C(Br)C=C1 XYCFQJYVDREZPE-UHFFFAOYSA-N 0.000 description 1
- HVSRHDAIPVEISZ-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[[methyl(pyridin-2-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=2N=CC=CC=2)=C1C1=CC=C(Br)C=C1 HVSRHDAIPVEISZ-UHFFFAOYSA-N 0.000 description 1
- WTEIMXRBTNAONF-UHFFFAOYSA-N 5-(4-bromophenyl)-4-[[methyl(pyridin-3-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=NC=CC=2)=C1C1=CC=C(Br)C=C1 WTEIMXRBTNAONF-UHFFFAOYSA-N 0.000 description 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 description 1
- FWDCVKXLJHFYKJ-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-n-(cyclopentylsulfamoyl)pyrimidin-4-amine Chemical compound C1=CC(Br)=CC=C1C(C(=NC=N1)OCCOC=2N=CC(Br)=CN=2)=C1NS(=O)(=O)NC1CCCC1 FWDCVKXLJHFYKJ-UHFFFAOYSA-N 0.000 description 1
- LKOLDYBWXOYQMQ-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-n-(cyclopropylsulfamoyl)pyrimidin-4-amine Chemical compound C1=CC(Br)=CC=C1C(C(=NC=N1)OCCOC=2N=CC(Br)=CN=2)=C1NS(=O)(=O)NC1CC1 LKOLDYBWXOYQMQ-UHFFFAOYSA-N 0.000 description 1
- BRSITRUZDCGGKH-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-n-(methylsulfamoyl)pyrimidin-4-amine Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 BRSITRUZDCGGKH-UHFFFAOYSA-N 0.000 description 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 description 1
- JBMDWSYCKXKSIX-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]-n-(methylsulfamoyl)pyrimidin-4-amine Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NC)=NC=NC=1OCCOC1=NC=C(OC)C=N1 JBMDWSYCKXKSIX-UHFFFAOYSA-N 0.000 description 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 description 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 description 1
- IYYXUAMBMQMWBL-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-methylsulfanylpyrimidin-2-yl)oxyethoxy]pyrimidin-4-amine Chemical compound N1=CC(SC)=CN=C1OCCOC1=NC=NC(N)=C1C1=CC=C(Br)C=C1 IYYXUAMBMQMWBL-UHFFFAOYSA-N 0.000 description 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 description 1
- XYKNJZNFEGDDIP-UHFFFAOYSA-N 5-(4-bromophenyl)-n-(butylsulfamoyl)-6-[2-(5-methylsulfanylpyrimidin-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(SC)C=N1 XYKNJZNFEGDDIP-UHFFFAOYSA-N 0.000 description 1
- ASLHUBXUHZDUMZ-UHFFFAOYSA-N 5-(4-bromophenyl)-n-(cyclopentylsulfamoyl)-6-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]pyrimidin-4-amine Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)NC2CCCC2)=C1C1=CC=C(Br)C=C1 ASLHUBXUHZDUMZ-UHFFFAOYSA-N 0.000 description 1
- PZGKTNMDYCZDGX-UHFFFAOYSA-N 5-(4-bromophenyl)-n-(cyclopropylsulfamoyl)-6-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]pyrimidin-4-amine Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)NC2CC2)=C1C1=CC=C(Br)C=C1 PZGKTNMDYCZDGX-UHFFFAOYSA-N 0.000 description 1
- HLAWSLTYQNVRNY-UHFFFAOYSA-N 5-(4-bromophenyl)-n-(ethylsulfamoyl)-6-[2-(5-methoxypyrimidin-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(OC)C=N1 HLAWSLTYQNVRNY-UHFFFAOYSA-N 0.000 description 1
- KSGHGYRWLMKYNA-UHFFFAOYSA-N 5-(4-bromophenyl)-n-(methylsulfamoyl)-6-[2-(5-methylsulfanylpyrimidin-2-yl)oxyethoxy]pyrimidin-4-amine Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NC)=NC=NC=1OCCOC1=NC=C(SC)C=N1 KSGHGYRWLMKYNA-UHFFFAOYSA-N 0.000 description 1
- XEAZERSGWNZAOI-UHFFFAOYSA-N 5-(4-bromophenyl)-n-[(4-fluorophenyl)methylsulfamoyl]-6-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]pyrimidin-4-amine Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)NCC=2C=CC(F)=CC=2)=C1C1=CC=C(Br)C=C1 XEAZERSGWNZAOI-UHFFFAOYSA-N 0.000 description 1
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- XZUKUAMPTAUGHG-UHFFFAOYSA-N 5-(4-chlorophenyl)-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(Cl)C=C1 XZUKUAMPTAUGHG-UHFFFAOYSA-N 0.000 description 1
- PJAURNROAJAHTL-UHFFFAOYSA-N 5-(4-chlorophenyl)-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(Cl)C=C1 PJAURNROAJAHTL-UHFFFAOYSA-N 0.000 description 1
- OJXQHXIZRWTCPD-UHFFFAOYSA-N 5-(4-chlorophenyl)-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(Cl)C=C1 OJXQHXIZRWTCPD-UHFFFAOYSA-N 0.000 description 1
- XRXGMFHYOVYOAC-UHFFFAOYSA-N 5-(4-chlorophenyl)-4-[2-(5-methylsulfanylpyrimidin-2-yl)oxyethoxy]-6-[[methyl(thiophen-2-yl)sulfamoyl]amino]pyrimidine Chemical compound N1=CC(SC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)N(C)C=2SC=CC=2)=C1C1=CC=C(Cl)C=C1 XRXGMFHYOVYOAC-UHFFFAOYSA-N 0.000 description 1
- LUXYTYCSCLVIRP-UHFFFAOYSA-N 5-(4-chlorophenyl)-4-[[furan-2-yl(methyl)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=2OC=CC=2)=C1C1=CC=C(Cl)C=C1 LUXYTYCSCLVIRP-UHFFFAOYSA-N 0.000 description 1
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| PL2254570T3 (pl) * | 2008-02-20 | 2014-05-30 | Actelion Pharmaceuticals Ltd | Połączenie zawierające paklitaksel do leczenia raka jajnika |
| RS57132B1 (sr) * | 2008-07-08 | 2018-07-31 | Incyte Holdings Corp | 1,2,5-oksadiazoli kao inhibitori indolamin 2,3-dioksigenaze |
| WO2010018549A2 (en) * | 2008-08-13 | 2010-02-18 | Actelion Pharmaceuticals Ltd | Therapeutic compositions containing 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 |
| HRP20150890T1 (hr) | 2009-08-10 | 2015-09-25 | Board Of Regents, The University Of Texas System | Lijeäśenje metastaza na mozgu s inhibitorima receptora endotelina u kombinaciji s citotoksiäśnim kemoterapijskim sredstvom |
| EP3205647B1 (en) | 2009-08-17 | 2020-05-13 | 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 |
| WO2012104822A1 (en) | 2011-02-04 | 2012-08-09 | Actelion Pharmaceuticals Ltd | Combinations comprising macitentan for the treatment of glioblastoma 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 |
| CN105693624B (zh) * | 2013-06-14 | 2018-05-18 | 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 |
| EP3143013B1 (en) | 2014-05-13 | 2019-12-18 | Memorial Sloan Kettering Cancer Center | Hsp70 modulators and methods for making and using the same |
| US20170158645A1 (en) * | 2014-07-15 | 2017-06-08 | 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 |
| ZA201605808B (en) | 2015-08-26 | 2017-08-30 | Cipla Ltd | Process for preparing an endothelin receptor antagonist |
| CN105388244B (zh) * | 2015-12-10 | 2017-03-08 | 合肥久诺医药科技有限公司 | 一种马西替坦有关物质的高效液相色谱分析方法 |
| CN105461639B (zh) * | 2015-12-10 | 2018-03-09 | 合肥久诺医药科技有限公司 | 一种高纯度马西替坦的精制方法 |
| WO2017191565A1 (en) * | 2016-05-04 | 2017-11-09 | Shilpa Medicare Limited | Process for preparation of macitentan |
| CN107868055B (zh) * | 2016-09-28 | 2020-02-07 | 普济生物科技（台州）有限公司 | 一种马西替坦的制备方法 |
| CN106478520B (zh) * | 2016-10-11 | 2018-09-11 | 合肥久诺医药科技有限公司 | 一种马西替坦杂质标准品的合成方法 |
| CN106478522A (zh) * | 2016-10-11 | 2017-03-08 | 合肥久诺医药科技有限公司 | 一种马西替坦杂质标准品的制备方法 |
| LT3658140T (lt) | 2017-02-27 | 2025-08-25 | Idorsia Pharmaceuticals Ltd | Aprocitentano ir kitų veikliųjų sudedamųjų dalių deriniai, skirti atsparios hipertenzijos gydymui |
| US20210101874A1 (en) | 2017-04-03 | 2021-04-08 | Syngenta Participations Ag | Microbiocidal oxadiazole derivatives |
| CN107141238A (zh) * | 2017-06-16 | 2017-09-08 | 吴宁怡 | 一种马西替坦中间体的制备方法 |
| HRP20230318T1 (hr) * | 2017-11-21 | 2023-05-12 | Wuxi Biocity Biopharmaceutics Co., Ltd. | Derivat pirimidin sulfamida, postupak pripreme i njegova medicinska primjena |
| PL3716979T3 (pl) | 2017-11-30 | 2025-08-04 | Idorsia Pharmaceuticals Ltd | Połączenie pochodnej 4-pirymidynosulfamidu z inhibitorem sglt-2 do leczenia chorób związanych w endoteliną |
| CN108653292B (zh) * | 2018-07-03 | 2019-05-24 | 中国人民解放军总医院 | 一种化合物在治疗或预防高原病中的用途 |
| CN108997223B (zh) * | 2018-08-09 | 2020-06-30 | 浙江先锋科技股份有限公司 | 5-(4-溴苯基)-4，6-二氯嘧啶的制备方法 |
| CN109232546B (zh) | 2018-09-25 | 2020-09-04 | 中国人民解放军总医院 | 一种嘧啶磺酰胺类衍生物的医药用途 |
| MA54522B1 (fr) | 2018-12-21 | 2024-07-31 | Actelion Pharmaceuticals Ltd | Macitentan pour le traitement de l'hypertension artérielle pulmonaire |
| TW202042818A (zh) | 2019-01-25 | 2020-12-01 | 瑞士商艾克泰聯製藥有限公司 | 用於治療慢性血栓性肺高血壓之醫藥組成物 |
| TW202103703A (zh) | 2019-04-05 | 2021-02-01 | 瑞士商艾克泰聯製藥有限公司 | 用於治療門脈肺高血壓之方法 |
| EP3974421B1 (en) | 2019-05-22 | 2024-09-11 | Wuxi Biocity Biopharmaceutics Co., Ltd. | Crystal form of pyrimidine sulfonamide compound and preparation method therefor |
| WO2021005478A1 (en) | 2019-07-05 | 2021-01-14 | TECNIMEDE - Sociedade Técnico-medicinal, SA | Compressed macitentan compositions, methods and uses thereof |
| KR20220106974A (ko) | 2019-11-29 | 2022-08-01 | 액테리온 파마슈티칼 리미티드 | 폐동맥 고혈압을 치료하는 방법 |
| TW202317119A (zh) | 2021-06-11 | 2023-05-01 | 瑞士商艾克泰聯製藥有限公司 | 用於口服投予之分散錠 |
| EP4154873A1 (en) | 2021-09-22 | 2023-03-29 | Sanovel Ilac Sanayi Ve Ticaret A.S. | The tablet comprising macitentan |
| WO2023227490A1 (en) | 2022-05-22 | 2023-11-30 | Idorsia Pharmaceuticals Ltd | Aprocitentan for the treatment of hypertension |
| CA3251318A1 (en) | 2022-05-25 | 2023-11-30 | Idorsia Pharmaceuticals Ltd | CRYSTALLINE FORMS OF (5-(4-BROMOPHENYL)-6-(2-((5-BROMOPYRIMIDIN-2-YL)OXY)ETHOXY)PYRIMIDIN-4-YL)(SULFAMOYL) SODIUM AMIDE |
| WO2024099953A1 (en) | 2022-11-07 | 2024-05-16 | Actelion Pharmaceuticals Ltd | Combination of macitentan and tadalafil for the treatment of pulmonary arterial hypertension |
| WO2025102245A1 (zh) * | 2023-11-14 | 2025-05-22 | 浙江天宇药业股份有限公司 | 一种双重内皮素受体拮抗剂阿普昔腾坦的合成方法 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2801584A1 (de) | 1978-01-14 | 1979-07-19 | Bayer Ag | Halogensubstituierte pyrimidin (2)yl-thiono-thiol-phosphor(phosphon)- saeureester, verfahren zu ihrer herstellung und ihre verwendung als insektizide und akarizide |
| US5132373A (en) * | 1990-08-13 | 1992-07-21 | General Electric Company | Ortho ester-capped polyphenylene ethers and copolymers prepared therefrom |
| RU2086544C1 (ru) | 1991-06-13 | 1997-08-10 | Хоффманн-Ля Рош АГ | Бензолсульфонамидные производные пиримидина или их соли, фармацевтическая композиция для лечения заболеваний, связанных с активностью эндотелина |
| US5324796A (en) * | 1992-12-02 | 1994-06-28 | General Electric Company | Polyarylene sulfide and epoxy-functionalized siloxane blends |
| TW394761B (en) | 1993-06-28 | 2000-06-21 | Hoffmann La Roche | Novel Sulfonylamino Pyrimidines |
| US5523204A (en) | 1993-12-10 | 1996-06-04 | Becton Dickinson And Company | Detection of nucleic acids in cells by strand displacement amplification |
| WO1996016963A1 (de) | 1994-11-25 | 1996-06-06 | F. Hoffmann-La Roche Ag | Sulfonamide und deren verwendung als heilmittel |
| TW313568B (enExample) * | 1994-12-20 | 1997-08-21 | Hoffmann La Roche | |
| US5739333A (en) * | 1995-05-16 | 1998-04-14 | Tanabe Seiyaku Co., Ltd. | Sulfonamide derivative and process for preparing the same |
| RU2172735C2 (ru) | 1995-12-20 | 2001-08-27 | Яманоути Фармасьютикал Ко., Лтд. | Арилэтенсульфонамидные производные и фармацевтическая композиция |
| TWI284642B (en) * | 1999-01-18 | 2007-08-01 | Hoffmann La Roche | Novel heterocyclic sulfonamides |
| EP1137642B1 (en) | 1999-09-03 | 2007-12-05 | Actelion Pharmaceuticals Ltd. | Bis-sulfonamides |
| MXPA02006250A (es) | 1999-12-22 | 2004-09-06 | Actelion Pharmaceuticals Ltd | Derivados de butino diol. |
| WO2001081335A1 (en) * | 2000-04-20 | 2001-11-01 | Actelion Pharmaceuticals Ltd | Pyrimidine-sulfonamides having endothelin-antagonist activity |
| WO2001081338A1 (en) * | 2000-04-25 | 2001-11-01 | Actelion Pharmaceuticals Ltd | Substituted sulfonylaminopyrimidines |
| BRPI0116237B8 (pt) * | 2000-12-18 | 2021-05-25 | Actelion Pharmaceuticals Ltd | "composto de sulfamida, composição farmacêutica contendo o mesmo e seu uso como medicamento antagonista de receptor de endotelina". |
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