JP2004509874A - 新規なアリールアルカン−スルフォンアミド類 - Google Patents
新規なアリールアルカン−スルフォンアミド類 Download PDFInfo
- Publication number
- JP2004509874A JP2004509874A JP2002529075A JP2002529075A JP2004509874A JP 2004509874 A JP2004509874 A JP 2004509874A JP 2002529075 A JP2002529075 A JP 2002529075A JP 2002529075 A JP2002529075 A JP 2002529075A JP 2004509874 A JP2004509874 A JP 2004509874A
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- Prior art keywords
- lower alkyl
- amino
- compound
- 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.)
- Ceased
Links
- 229940124530 sulfonamide Drugs 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 90
- 238000000034 method Methods 0.000 claims abstract description 38
- 108050009340 Endothelin Proteins 0.000 claims abstract description 24
- 102000002045 Endothelin Human genes 0.000 claims abstract description 24
- 201000010099 disease Diseases 0.000 claims abstract description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 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 abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 206010020772 Hypertension Diseases 0.000 claims abstract description 8
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims abstract description 7
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 6
- 201000011510 cancer Diseases 0.000 claims abstract description 6
- 206010002383 Angina Pectoris Diseases 0.000 claims abstract 4
- 206010047163 Vasospasm Diseases 0.000 claims abstract 4
- 208000028867 ischemia Diseases 0.000 claims abstract 4
- 230000002062 proliferating effect Effects 0.000 claims abstract 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract 3
- 239000002671 adjuvant Substances 0.000 claims abstract 2
- -1 Cyano, carboxyl Chemical group 0.000 claims description 79
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 47
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 125000003282 alkyl amino group Chemical group 0.000 claims description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- ZTJLYUVAFAMUKO-UHFFFAOYSA-N 2-phenylethanesulfonic acid Chemical compound OS(=O)(=O)CCC1=CC=CC=C1 ZTJLYUVAFAMUKO-UHFFFAOYSA-N 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 125000004414 alkyl thio group Chemical group 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 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 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000001589 carboacyl group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000011593 sulfur Chemical group 0.000 claims description 7
- 208000019695 Migraine disease Diseases 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 5
- 206010027599 migraine Diseases 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004644 alkyl 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
- 239000007795 chemical reaction product Substances 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
- 230000000694 effects Effects 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
- 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
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 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
- 230000000903 blocking effect Effects 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 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
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 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 3
- 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 63
- 239000000243 solution Substances 0.000 description 53
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 46
- 239000000725 suspension Substances 0.000 description 28
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 24
- 239000000843 powder Substances 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 17
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 102400000686 Endothelin-1 Human genes 0.000 description 11
- 101800004490 Endothelin-1 Proteins 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 239000002480 mineral oil Substances 0.000 description 10
- 235000010446 mineral oil Nutrition 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 7
- 229960004592 isopropanol Drugs 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 7
- AKJATHXVXXAURO-UHFFFAOYSA-N potassium benzylsulfonylazanide Chemical compound [K+].[NH-]S(=O)(=O)Cc1ccccc1 AKJATHXVXXAURO-UHFFFAOYSA-N 0.000 description 7
- VMKJEDPZABLCPW-UHFFFAOYSA-N potassium;2-thiophen-2-ylethanesulfonamide Chemical compound [K].NS(=O)(=O)CCC1=CC=CS1 VMKJEDPZABLCPW-UHFFFAOYSA-N 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical class [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-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
- 230000014509 gene expression Effects 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- MUVXKGKUECYBHJ-UHFFFAOYSA-N 2-thiophen-2-ylethanesulfonamide Chemical compound NS(=O)(=O)CCC1=CC=CS1 MUVXKGKUECYBHJ-UHFFFAOYSA-N 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 5
- 0 C*(C**)S(Nc1c(*)c(*C2CC(**)C2)nc(C)n1)(=O)=O Chemical compound C*(C**)S(Nc1c(*)c(*C2CC(**)C2)nc(C)n1)(=O)=O 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
- 230000015572 biosynthetic process Effects 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- LNBQBURECUEBKZ-UHFFFAOYSA-N dimethyl 2-chloropropanedioate Chemical compound COC(=O)C(Cl)C(=O)OC LNBQBURECUEBKZ-UHFFFAOYSA-N 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000011343 solid material Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- OPOKZCARZIRCKT-UHFFFAOYSA-N 2-phenylethanesulfonamide;potassium Chemical compound [K].NS(=O)(=O)CCC1=CC=CC=C1 OPOKZCARZIRCKT-UHFFFAOYSA-N 0.000 description 4
- XPGIBDJXEVAVTO-UHFFFAOYSA-N 5-bromo-2-chloropyrimidine Chemical compound ClC1=NC=C(Br)C=N1 XPGIBDJXEVAVTO-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 206010019280 Heart failures Diseases 0.000 description 4
- 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
- NMVVJCLUYUWBSZ-UHFFFAOYSA-N aminomethylideneazanium;chloride Chemical compound Cl.NC=N NMVVJCLUYUWBSZ-UHFFFAOYSA-N 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 201000006370 kidney failure Diseases 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- ROZCUVMFXOURIS-UHFFFAOYSA-N 2-phenylethanesulfonamide Chemical compound NS(=O)(=O)CCC1=CC=CC=C1 ROZCUVMFXOURIS-UHFFFAOYSA-N 0.000 description 3
- SWUBZLMHIZAJMC-UHFFFAOYSA-N 2-thiophen-2-ylethanesulfonic acid Chemical compound OS(=O)(=O)CCC1=CC=CS1 SWUBZLMHIZAJMC-UHFFFAOYSA-N 0.000 description 3
- KDMGVAJFSJTDIN-UHFFFAOYSA-N 3-phenylpropane-1-sulfonamide;potassium Chemical compound [K].NS(=O)(=O)CCCC1=CC=CC=C1 KDMGVAJFSJTDIN-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
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000032851 Subarachnoid Hemorrhage Diseases 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
- 150000001408 amides Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
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- 238000001704 evaporation Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
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- 230000001965 increasing effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- DFSVJAAXXPHQMN-UHFFFAOYSA-N potassium (4-methylphenyl)methylsulfonylazanide Chemical compound [K+].Cc1ccc(CS([NH-])(=O)=O)cc1 DFSVJAAXXPHQMN-UHFFFAOYSA-N 0.000 description 3
- 208000002815 pulmonary hypertension Diseases 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- LXPHPKVWHQLBBA-UHFFFAOYSA-N sarafotoxin s6c Chemical compound C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(C(C)CC)NC(=O)C(C(C)C)NC(=O)C(CC(O)=O)NC(=O)C(CCC(N)=O)NC(=O)C(NC(=O)C1NC(=O)C(CC=2C=CC=CC=2)NC(=O)C(CC(N)=O)NC(=O)C(CC(C)C)NC(=O)C2CSSCC(C(NC(CC(N)=O)C(=O)NC(CC(O)=O)C(=O)NC(CCSC)C(=O)NC(C(=O)NC(CC(O)=O)C(=O)NC(CCC(O)=O)C(=O)NC(CCC(O)=O)C(=O)N2)C(C)O)=O)NC(=O)C(C(C)O)NC(=O)C(N)CSSC1)CC1=CN=CN1 LXPHPKVWHQLBBA-UHFFFAOYSA-N 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 210000003437 trachea Anatomy 0.000 description 3
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 2
- LKFNLHZZPHHFEC-UHFFFAOYSA-N 2-phenylethanesulfonyl chloride Chemical compound ClS(=O)(=O)CCC1=CC=CC=C1 LKFNLHZZPHHFEC-UHFFFAOYSA-N 0.000 description 2
- GCYDUTOUEUWVAX-UHFFFAOYSA-N 2-pyridin-1-ium-2-ylethanesulfonyl chloride;chloride Chemical compound Cl.ClS(=O)(=O)CCC1=CC=CC=N1 GCYDUTOUEUWVAX-UHFFFAOYSA-N 0.000 description 2
- VRBVUAYEXFCDPE-UHFFFAOYSA-N 2-pyridin-2-ylethanesulfonic acid Chemical compound OS(=O)(=O)CCC1=CC=CC=N1 VRBVUAYEXFCDPE-UHFFFAOYSA-N 0.000 description 2
- NYTNMUXNWRMSDC-UHFFFAOYSA-N 2-thiophen-2-ylethanesulfonyl chloride Chemical compound ClS(=O)(=O)CCC1=CC=CS1 NYTNMUXNWRMSDC-UHFFFAOYSA-N 0.000 description 2
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- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 1
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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
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- 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]
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- 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
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- A61P9/12—Antihypertensives
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- 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
Landscapes
- 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)
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- 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP0009327 | 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 |
|---|---|
| JP2004509874A true JP2004509874A (ja) | 2004-04-02 |
| JP2004509874A5 JP2004509874A5 (enExample) | 2008-11-27 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002529075A Ceased JP2004509874A (ja) | 2000-09-25 | 2001-08-28 | 新規なアリールアルカン−スルフォンアミド類 |
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|---|---|
| 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 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0899961A (ja) * | 1993-12-17 | 1996-04-16 | Tanabe Seiyaku Co Ltd | ベンゼンスルホンアミド誘導体及びその製法 |
| JPH08311043A (ja) * | 1995-05-16 | 1996-11-26 | Tanabe Seiyaku Co Ltd | スルホンアミド誘導体 |
| JPH0959160A (ja) * | 1995-06-16 | 1997-03-04 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
| JPH10194972A (ja) * | 1996-11-13 | 1998-07-28 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
| US5837708A (en) * | 1994-11-25 | 1998-11-17 | Hoffmann-La Roche Inc. | Sulphonamides |
| 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 |
Family Cites Families (4)
| 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 |
| US5739333A (en) * | 1995-05-16 | 1998-04-14 | Tanabe Seiyaku Co., Ltd. | Sulfonamide derivative and process for preparing the same |
| ATE201202T1 (de) * | 1995-12-20 | 2001-06-15 | Yamanouchi Pharma Co Ltd | Arylethensulfonamid-derivate und diese enthaltende medikamente |
-
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
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0899961A (ja) * | 1993-12-17 | 1996-04-16 | Tanabe Seiyaku Co Ltd | 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 |
| JPH08311043A (ja) * | 1995-05-16 | 1996-11-26 | Tanabe Seiyaku Co Ltd | スルホンアミド誘導体 |
| JPH0959160A (ja) * | 1995-06-16 | 1997-03-04 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
| JPH10194972A (ja) * | 1996-11-13 | 1998-07-28 | Tanabe Seiyaku Co Ltd | 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2423351C (en) | 2010-12-21 |
| 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 |
| 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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