CA2423351C - Novel arylalkane-sulfonamides - Google Patents
Novel arylalkane-sulfonamides Download PDFInfo
- Publication number
- CA2423351C CA2423351C CA2423351A CA2423351A CA2423351C CA 2423351 C CA2423351 C CA 2423351C CA 2423351 A CA2423351 A CA 2423351A CA 2423351 A CA2423351 A CA 2423351A CA 2423351 C CA2423351 C CA 2423351C
- Authority
- CA
- Canada
- Prior art keywords
- lower alkyl
- compound
- amino
- phenyl
- general formula
- 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.)
- Expired - Fee Related
Links
- 229940124530 sulfonamide Drugs 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 108
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- -1 tri-substituted phenyl Chemical group 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
- 208000035475 disorder Diseases 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 239000001301 oxygen Substances 0.000 claims description 24
- 108050009340 Endothelin Proteins 0.000 claims description 23
- 102000002045 Endothelin Human genes 0.000 claims description 23
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 23
- 125000003282 alkyl amino group Chemical group 0.000 claims description 22
- 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 21
- 125000004414 alkyl thio group Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000001589 carboacyl group Chemical group 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 206010020772 Hypertension Diseases 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 208000019695 Migraine disease Diseases 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 208000006673 asthma Diseases 0.000 claims description 7
- 206010027599 migraine Diseases 0.000 claims description 7
- 239000011593 sulfur Chemical group 0.000 claims description 7
- 206010002383 Angina Pectoris Diseases 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 206010047163 Vasospasm Diseases 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 230000000903 blocking effect Effects 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 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
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 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
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 2
- 125000005149 cycloalkylsulfinyl group Chemical group 0.000 claims description 2
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 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
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
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- DAZOXLCENQFWSQ-UHFFFAOYSA-N n-[5-(2-methoxyphenoxy)-6-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]-2-pyrimidin-2-ylpyrimidin-4-yl]-2-phenylethanesulfonamide Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC(C=2N=CC=CN=2)=NC(NS(=O)(=O)CCC=2C=CC=CC=2)=C1OC1=CC=CC=C1OC DAZOXLCENQFWSQ-UHFFFAOYSA-N 0.000 claims description 2
- KDBRYGUPPHTMQK-UHFFFAOYSA-N n-[6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-chlorophenyl)pyrimidin-4-yl]-2-thiophen-2-ylethanesulfonamide Chemical compound C1=CC(Cl)=CC=C1C(C(=NC=N1)OCCOC=2N=CC(Br)=CN=2)=C1NS(=O)(=O)CCC1=CC=CS1 KDBRYGUPPHTMQK-UHFFFAOYSA-N 0.000 claims description 2
- XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 230000002062 proliferating effect Effects 0.000 claims 8
- 208000027866 inflammatory disease Diseases 0.000 claims 4
- 208000028867 ischemia Diseases 0.000 claims 4
- 102000017914 EDNRA Human genes 0.000 claims 2
- 101150062404 EDNRA gene Proteins 0.000 claims 2
- 102000017930 EDNRB Human genes 0.000 claims 2
- 101150001833 EDNRB gene Proteins 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 1
- NXGRSEAXZLFVEA-UHFFFAOYSA-N n-[5-(4-chlorophenyl)-6-[2-(5-methoxypyrimidin-2-yl)oxyethoxy]pyrimidin-4-yl]-2-thiophen-2-ylethanesulfonamide Chemical compound N1=CC(OC)=CN=C1OCCOC1=NC=NC(NS(=O)(=O)CCC=2SC=CC=2)=C1C1=CC=C(Cl)C=C1 NXGRSEAXZLFVEA-UHFFFAOYSA-N 0.000 claims 1
- ULMBSZNPLCEURN-UHFFFAOYSA-N n-[6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(2-methoxyphenoxy)-2-pyridin-4-ylpyrimidin-4-yl]-2-pyridin-2-ylethanesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=CN=CC=2)OCCOC=2N=CC(Br)=CN=2)=C1NS(=O)(=O)CCC1=CC=CC=N1 ULMBSZNPLCEURN-UHFFFAOYSA-N 0.000 claims 1
- HZBZCDADERXTNS-UHFFFAOYSA-N n-[6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-methylphenyl)-2-pyrimidin-2-ylpyrimidin-4-yl]-2-phenylethanesulfonamide Chemical compound C1=CC(C)=CC=C1C(C(=NC(=N1)C=2N=CC=CN=2)OCCOC=2N=CC(Br)=CN=2)=C1NS(=O)(=O)CCC1=CC=CC=C1 HZBZCDADERXTNS-UHFFFAOYSA-N 0.000 claims 1
- YRFFAZUVONSXEE-UHFFFAOYSA-N n-[6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-methylphenyl)pyrimidin-4-yl]-2-phenylethanesulfonamide Chemical compound C1=CC(C)=CC=C1C(C(=NC=N1)OCCOC=2N=CC(Br)=CN=2)=C1NS(=O)(=O)CCC1=CC=CC=C1 YRFFAZUVONSXEE-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 39
- 238000002360 preparation method Methods 0.000 abstract description 11
- 229940118365 Endothelin receptor antagonist Drugs 0.000 abstract description 5
- 239000002308 endothelin receptor antagonist Substances 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 99
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 51
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
- 229960004132 diethyl ether Drugs 0.000 description 33
- 239000000725 suspension Substances 0.000 description 28
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 27
- 239000000843 powder Substances 0.000 description 23
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
- 229910000104 sodium hydride Inorganic materials 0.000 description 18
- 238000003756 stirring Methods 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- ZTJLYUVAFAMUKO-UHFFFAOYSA-N 2-phenylethanesulfonic acid Chemical compound OS(=O)(=O)CCC1=CC=CC=C1 ZTJLYUVAFAMUKO-UHFFFAOYSA-N 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 102100040611 Endothelin receptor type B Human genes 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- 102400000686 Endothelin-1 Human genes 0.000 description 11
- 101800004490 Endothelin-1 Proteins 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 239000002480 mineral oil Substances 0.000 description 10
- 235000010446 mineral oil Nutrition 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- OPOKZCARZIRCKT-UHFFFAOYSA-N 2-phenylethanesulfonamide;potassium Chemical compound [K].NS(=O)(=O)CCC1=CC=CC=C1 OPOKZCARZIRCKT-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- VMKJEDPZABLCPW-UHFFFAOYSA-N potassium;2-thiophen-2-ylethanesulfonamide Chemical compound [K].NS(=O)(=O)CCC1=CC=CS1 VMKJEDPZABLCPW-UHFFFAOYSA-N 0.000 description 6
- 239000011343 solid material Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- KDMGVAJFSJTDIN-UHFFFAOYSA-N 3-phenylpropane-1-sulfonamide;potassium Chemical compound [K].NS(=O)(=O)CCCC1=CC=CC=C1 KDMGVAJFSJTDIN-UHFFFAOYSA-N 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- XPGIBDJXEVAVTO-UHFFFAOYSA-N 5-bromo-2-chloropyrimidine Chemical compound ClC1=NC=C(Br)C=N1 XPGIBDJXEVAVTO-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 4
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- 206010061218 Inflammation Diseases 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 208000001647 Renal Insufficiency Diseases 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- NMVVJCLUYUWBSZ-UHFFFAOYSA-N aminomethylideneazanium;chloride Chemical compound Cl.NC=N NMVVJCLUYUWBSZ-UHFFFAOYSA-N 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
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- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- AKJATHXVXXAURO-UHFFFAOYSA-N potassium benzylsulfonylazanide Chemical compound [K+].[NH-]S(=O)(=O)Cc1ccccc1 AKJATHXVXXAURO-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 210000003437 trachea Anatomy 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- SDFQMDWIFGNAGM-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-pyridin-4-ylpyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2C=CN=CC=2)N=C1Cl SDFQMDWIFGNAGM-UHFFFAOYSA-N 0.000 description 3
- LHHADLIWXDJPLB-UHFFFAOYSA-N 4-hydroxy-5-(4-methylphenyl)-1h-pyrimidin-6-one Chemical compound C1=CC(C)=CC=C1C1=C(O)N=CN=C1O LHHADLIWXDJPLB-UHFFFAOYSA-N 0.000 description 3
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- 201000001320 Atherosclerosis Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- IONKMFGAXKCLMI-UHFFFAOYSA-N [amino(pyridin-4-yl)methylidene]azanium;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=NC=C1 IONKMFGAXKCLMI-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
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- 239000000706 filtrate Substances 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- 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
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
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- 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
- C07D401/02—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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
-
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP0009327 | 2000-09-25 | ||
| EPPCT/EP00/09327 | 2000-09-25 | ||
| PCT/EP2001/009894 WO2002024665A1 (en) | 2000-09-25 | 2001-08-28 | Arylalkane-sulfonamides having endothelin-antagonist activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2423351A1 CA2423351A1 (en) | 2002-03-28 |
| CA2423351C true CA2423351C (en) | 2010-12-21 |
Family
ID=8164105
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2423351A Expired - Fee Related CA2423351C (en) | 2000-09-25 | 2001-08-28 | Novel arylalkane-sulfonamides |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US7091201B2 (enExample) |
| JP (1) | JP2004509874A (enExample) |
| KR (1) | KR100835770B1 (enExample) |
| CN (1) | CN1326841C (enExample) |
| AR (1) | AR032896A1 (enExample) |
| AT (1) | ATE446289T1 (enExample) |
| AU (2) | AU2002212171B2 (enExample) |
| BR (1) | BR0114082A (enExample) |
| CA (1) | CA2423351C (enExample) |
| DE (1) | DE60140263D1 (enExample) |
| ES (1) | ES2333409T3 (enExample) |
| HU (1) | HUP0303364A3 (enExample) |
| IL (1) | IL154364A0 (enExample) |
| MX (1) | MXPA03001991A (enExample) |
| NO (1) | NO20031332L (enExample) |
| NZ (1) | NZ524172A (enExample) |
| WO (1) | WO2002024665A1 (enExample) |
| ZA (1) | ZA200302292B (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0217431D0 (en) | 2002-07-27 | 2002-09-04 | Astrazeneca Ab | Novel compounds |
| DE60318219T2 (de) | 2002-08-24 | 2009-01-15 | Astrazeneca Ab | PYRIMIDINDERIVATE ALS MODULATOREN DER AKTIVITuT VON CHEMOKINREZEPTOREN |
| SE0301654D0 (sv) * | 2003-06-05 | 2003-06-05 | Astrazeneca Ab | Novel compounds |
| SE0301653D0 (sv) * | 2003-06-05 | 2003-06-05 | Astrazeneca Ab | Novel compounds |
| CA2557372C (en) | 2004-03-05 | 2013-01-08 | F. Hoffmann-La Roche Ag | Diaminopyrimidines as p2x3 and p2x2/3 antagonists |
| BRPI0514735B8 (pt) | 2004-08-28 | 2021-05-25 | Astrazeneca Ab | derivados de pirimidino sulfonamida como moduladores do receptor de quimiocina. |
| WO2007025899A1 (en) | 2005-09-01 | 2007-03-08 | F. Hoffmann-La Roche Ag | Diaminopyrimidines as p2x3 and p2x2/3 modulators |
| MX2008002731A (es) | 2005-09-01 | 2008-03-26 | Hoffmann La Roche | Diaminopirimidinas como moduladores de p2x3 y p3x2/3. |
| CA2620129C (en) | 2005-09-01 | 2014-12-23 | F. Hoffmann-La Roche Ag | Diaminopyrimidines as p2x3 and p2x2/3 modulators |
| US9181231B2 (en) * | 2011-05-03 | 2015-11-10 | Agios Pharmaceuticals, Inc | Pyruvate kinase activators for use for increasing lifetime of the red blood cells and treating anemia |
| CN103864701B (zh) * | 2014-03-10 | 2016-08-24 | 常熟市金申医化制品有限责任公司 | 4-磺胺-5-甲氧基-6-氯嘧啶的制备方法 |
| SMT202300090T1 (it) | 2018-10-23 | 2023-05-12 | Step Pharma S A S | Derivati di amminopirimidina/pirazina come inibitori di ctps1 |
| US20230086703A1 (en) * | 2019-06-04 | 2023-03-23 | Step Pharma S.A.S. | N-(4-(5-chloropyridin-3-yl)phenyl)-2-(2-(cyclopropanesulfonamido)pyrimidin-4-yl) butanamide derivatives and related compounds as human CTPS1 inhibitors for the treatment of proliferative diseases |
| FI3980411T3 (fi) * | 2019-06-04 | 2025-10-28 | Step Pharma S A S | N-(5-(6-etoksipyratsin-2-yyli)pyridin-2-yyli)-4-(2-(etyylisulfonamido)pyrimidin-4-yyli)tetrahydro-2h-pyran-4-karboksamidi ihmisen ctps1:n estäjänä proliferatiivisten sairauksien hoitoon |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1549494A (enExample) | 1967-10-31 | 1968-12-13 | ||
| TW394761B (en) | 1993-06-28 | 2000-06-21 | Hoffmann La Roche | Novel Sulfonylamino Pyrimidines |
| JP2790065B2 (ja) * | 1993-12-17 | 1998-08-27 | 田辺製薬株式会社 | ベンゼンスルホンアミド誘導体及びその製法 |
| US5837708A (en) * | 1994-11-25 | 1998-11-17 | Hoffmann-La Roche Inc. | Sulphonamides |
| US5739333A (en) * | 1995-05-16 | 1998-04-14 | Tanabe Seiyaku Co., Ltd. | Sulfonamide derivative and process for preparing the same |
| JP3013752B2 (ja) * | 1995-05-16 | 2000-02-28 | 田辺製薬株式会社 | スルホンアミド誘導体 |
| JP3067131B2 (ja) * | 1995-06-16 | 2000-07-17 | 田辺製薬株式会社 | 医薬組成物 |
| ATE201202T1 (de) * | 1995-12-20 | 2001-06-15 | Yamanouchi Pharma Co Ltd | Arylethensulfonamid-derivate und diese enthaltende medikamente |
| JP3116347B2 (ja) * | 1996-11-13 | 2000-12-11 | 田辺製薬株式会社 | 医薬組成物 |
| WO1998057938A1 (en) * | 1997-06-19 | 1998-12-23 | Yamanouchi Pharmaceutical Co., Ltd. | Substituted lower alkanesulfonamide derivatives and pharmaceutical composition containing the same |
| JPH11343239A (ja) * | 1998-03-31 | 1999-12-14 | Tanabe Seiyaku Co Ltd | 排尿障害の予防・治療剤 |
-
2001
- 2001-08-28 NZ NZ524172A patent/NZ524172A/en unknown
- 2001-08-28 WO PCT/EP2001/009894 patent/WO2002024665A1/en not_active Ceased
- 2001-08-28 US US10/381,568 patent/US7091201B2/en not_active Expired - Fee Related
- 2001-08-28 HU HU0303364A patent/HUP0303364A3/hu unknown
- 2001-08-28 BR BR0114082-5A patent/BR0114082A/pt not_active Application Discontinuation
- 2001-08-28 ES ES01980288T patent/ES2333409T3/es not_active Expired - Lifetime
- 2001-08-28 MX MXPA03001991A patent/MXPA03001991A/es active IP Right Grant
- 2001-08-28 KR KR1020037003599A patent/KR100835770B1/ko not_active Expired - Fee Related
- 2001-08-28 DE DE60140263T patent/DE60140263D1/de not_active Expired - Lifetime
- 2001-08-28 AU AU2002212171A patent/AU2002212171B2/en not_active Ceased
- 2001-08-28 IL IL15436401A patent/IL154364A0/xx unknown
- 2001-08-28 CA CA2423351A patent/CA2423351C/en not_active Expired - Fee Related
- 2001-08-28 JP JP2002529075A patent/JP2004509874A/ja not_active Ceased
- 2001-08-28 CN CNB01815896XA patent/CN1326841C/zh not_active Expired - Fee Related
- 2001-08-28 AU AU1217102A patent/AU1217102A/xx active Pending
- 2001-08-28 AT AT01980288T patent/ATE446289T1/de active
- 2001-09-24 AR ARP010104490A patent/AR032896A1/es not_active Application Discontinuation
-
2003
- 2003-03-24 ZA ZA200302292A patent/ZA200302292B/en unknown
- 2003-03-24 NO NO20031332A patent/NO20031332L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002212171B2 (en) | 2006-12-14 |
| ATE446289T1 (de) | 2009-11-15 |
| ES2333409T3 (es) | 2010-02-22 |
| KR20030029979A (ko) | 2003-04-16 |
| IL154364A0 (en) | 2003-09-17 |
| CN1326841C (zh) | 2007-07-18 |
| ZA200302292B (en) | 2004-06-30 |
| WO2002024665A8 (en) | 2002-06-06 |
| NZ524172A (en) | 2004-09-24 |
| HUP0303364A2 (hu) | 2004-03-01 |
| DE60140263D1 (de) | 2009-12-03 |
| NO20031332D0 (no) | 2003-03-24 |
| AR032896A1 (es) | 2003-12-03 |
| AU1217102A (en) | 2002-04-02 |
| US7091201B2 (en) | 2006-08-15 |
| JP2004509874A (ja) | 2004-04-02 |
| BR0114082A (pt) | 2003-07-22 |
| US20040102464A1 (en) | 2004-05-27 |
| KR100835770B1 (ko) | 2008-06-09 |
| NO20031332L (no) | 2003-03-24 |
| CA2423351A1 (en) | 2002-03-28 |
| WO2002024665A1 (en) | 2002-03-28 |
| HUP0303364A3 (en) | 2004-04-28 |
| CN1633418A (zh) | 2005-06-29 |
| MXPA03001991A (es) | 2003-06-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130828 |