JPH0730042B2 - スルホンアミド類および薬物としてのそれらの使用 - Google Patents
スルホンアミド類および薬物としてのそれらの使用Info
- Publication number
- JPH0730042B2 JPH0730042B2 JP4174993A JP17499392A JPH0730042B2 JP H0730042 B2 JPH0730042 B2 JP H0730042B2 JP 4174993 A JP4174993 A JP 4174993A JP 17499392 A JP17499392 A JP 17499392A JP H0730042 B2 JPH0730042 B2 JP H0730042B2
- Authority
- JP
- Japan
- Prior art keywords
- methoxy
- phenoxy
- benzenesulfonamide
- butyl
- pyrimidin
- 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 11
- 150000003456 sulfonamides Chemical class 0.000 title abstract description 10
- 239000003814 drug Substances 0.000 title description 6
- 229940079593 drug Drugs 0.000 title description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- -1 methylenedioxy, ethylenedioxy Chemical group 0.000 claims description 245
- 150000001875 compounds Chemical class 0.000 claims description 96
- 125000000217 alkyl group Chemical group 0.000 claims description 64
- 239000001257 hydrogen Substances 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 150000002431 hydrogen Chemical class 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- 125000004414 alkyl thio group Chemical group 0.000 claims description 18
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 239000004615 ingredient Substances 0.000 claims description 5
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
- 125000005110 aryl thio group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 claims description 4
- 102000010180 Endothelin receptor Human genes 0.000 claims description 3
- 108050001739 Endothelin receptor Proteins 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 3
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 3
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 claims description 3
- OLQQNLDLUWGUOC-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-2-ethyl-6-(2-methylsulfinylethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound C=1C(OC)=CC=C(Cl)C=1OC=1C(OCCS(C)=O)=NC(CC)=NC=1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 OLQQNLDLUWGUOC-UHFFFAOYSA-N 0.000 claims description 2
- DRIHNVYRUGBDHI-QFIPXVFZSA-N 4-tert-butyl-n-[6-[(2s)-2,3-dihydroxypropoxy]-5-(2-methoxyphenoxy)-2-(4-methoxyphenyl)pyrimidin-4-yl]benzenesulfonamide Chemical compound C1=CC(OC)=CC=C1C(N=C1OC[C@@H](O)CO)=NC(NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1OC1=CC=CC=C1OC DRIHNVYRUGBDHI-QFIPXVFZSA-N 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract description 23
- 238000011282 treatment Methods 0.000 abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- 229910052727 yttrium Inorganic materials 0.000 abstract description 8
- 206010020772 Hypertension Diseases 0.000 abstract description 4
- 208000028867 ischemia Diseases 0.000 abstract description 4
- 206010002383 Angina Pectoris Diseases 0.000 abstract description 3
- 208000035475 disorder Diseases 0.000 abstract description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 167
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 128
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 239000011734 sodium Substances 0.000 description 53
- 239000000243 solution Substances 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 31
- 239000007858 starting material Substances 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 239000006260 foam Substances 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 19
- 239000007787 solid Substances 0.000 description 18
- 239000000203 mixture Substances 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 239000000725 suspension Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- KCZIRQGMWBGPRP-UHFFFAOYSA-N 2-(2-hydroxyacetyl)oxyethyl 2-hydroxyacetate Chemical compound OCC(=O)OCCOC(=O)CO KCZIRQGMWBGPRP-UHFFFAOYSA-N 0.000 description 10
- 102000002045 Endothelin Human genes 0.000 description 10
- 108050009340 Endothelin Proteins 0.000 description 10
- 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 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- FNJVDWXUKLTFFL-UHFFFAOYSA-N diethyl 2-bromopropanedioate Chemical compound CCOC(=O)C(Br)C(=O)OCC FNJVDWXUKLTFFL-UHFFFAOYSA-N 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WVOWEROKBOQYLJ-UHFFFAOYSA-N 4-propan-2-ylbenzenesulfonamide Chemical compound CC(C)C1=CC=C(S(N)(=O)=O)C=C1 WVOWEROKBOQYLJ-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 159000000000 sodium salts Chemical class 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 5
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 5
- UDJSKOBLGUNZNB-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)pyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=CN=C1Cl UDJSKOBLGUNZNB-UHFFFAOYSA-N 0.000 description 5
- KYDZEZNYRFJCSA-UHFFFAOYSA-N 4-tert-butylbenzenesulfonamide Chemical compound CC(C)(C)C1=CC=C(S(N)(=O)=O)C=C1 KYDZEZNYRFJCSA-UHFFFAOYSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 4
- XLTPRHUAGINFTI-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-thiophen-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C2=CSC=C2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 XLTPRHUAGINFTI-UHFFFAOYSA-N 0.000 description 4
- LYVFJACLADTRFC-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(5-fluoro-2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(F)C=C1OC1=C(Cl)N=CN=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 LYVFJACLADTRFC-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- SBUXKADXTZOBJV-UHFFFAOYSA-N dimethyl 2-(2-methoxyphenoxy)propanedioate Chemical compound COC(=O)C(C(=O)OC)OC1=CC=CC=C1OC SBUXKADXTZOBJV-UHFFFAOYSA-N 0.000 description 4
- LNBQBURECUEBKZ-UHFFFAOYSA-N dimethyl 2-chloropropanedioate Chemical compound COC(=O)C(Cl)C(=O)OC LNBQBURECUEBKZ-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- SKUMVOCQAXQIIT-UHFFFAOYSA-N 4,6-dichloro-5-(2,4,6-trichlorophenoxy)pyrimidine Chemical compound ClC1=CC(Cl)=CC(Cl)=C1OC1=C(Cl)N=CN=C1Cl SKUMVOCQAXQIIT-UHFFFAOYSA-N 0.000 description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 3
- CSHBWFOWZFSIDZ-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyridin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 CSHBWFOWZFSIDZ-UHFFFAOYSA-N 0.000 description 3
- DQGJBNBZQJTIHE-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-thiophen-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2SC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 DQGJBNBZQJTIHE-UHFFFAOYSA-N 0.000 description 3
- HDAQENIICKBGGO-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-thiophen-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2SC=CC=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HDAQENIICKBGGO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 241000872931 Myoporum sandwicense Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 3
- PLUUELDPPMQAOI-NUBCRITNSA-N [(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol;sodium Chemical compound [Na].CC1(C)OC[C@@H](CO)O1 PLUUELDPPMQAOI-NUBCRITNSA-N 0.000 description 3
- PLUUELDPPMQAOI-JEDNCBNOSA-N [(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol;sodium Chemical compound [Na].CC1(C)OC[C@H](CO)O1 PLUUELDPPMQAOI-JEDNCBNOSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 3
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 2
- HFAYWAUCHUMJMH-UHFFFAOYSA-N 1h-pyrimidine-4,6-dione Chemical compound O=C1CC(=O)N=CN1 HFAYWAUCHUMJMH-UHFFFAOYSA-N 0.000 description 2
- LXUNZSDDXMPKLP-UHFFFAOYSA-N 2-Methylbenzenethiol Chemical compound CC1=CC=CC=C1S LXUNZSDDXMPKLP-UHFFFAOYSA-N 0.000 description 2
- WIVYBAGKNQGJEB-UHFFFAOYSA-N 2-[6-(2,3-dihydroxypropoxy)-2-(furan-3-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound O1C=C(C=C1)C1=NC(=C(C(=N1)C1=C(C=CC=C1)S(=O)(=O)N)OC1=C(C=CC=C1)OC)OCC(CO)O WIVYBAGKNQGJEB-UHFFFAOYSA-N 0.000 description 2
- NMBWXBWFDHVLGS-UHFFFAOYSA-N 2-ethylbenzenesulfonamide Chemical compound CCC1=CC=CC=C1S(N)(=O)=O NMBWXBWFDHVLGS-UHFFFAOYSA-N 0.000 description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
- YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 description 2
- 125000005979 2-naphthyloxy group Chemical group 0.000 description 2
- HVQAHNBSEFQMPZ-UHFFFAOYSA-N 2-phenoxypropanedioic acid Chemical compound OC(=O)C(C(O)=O)OC1=CC=CC=C1 HVQAHNBSEFQMPZ-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- IHCCAYCGZOLTEU-UHFFFAOYSA-N 3-furoic acid Chemical compound OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 description 2
- HXIYCKAAQPHZBM-UHFFFAOYSA-N 3-methyl-1,2-oxazole-5-carboxylic acid Chemical compound CC=1C=C(C(O)=O)ON=1 HXIYCKAAQPHZBM-UHFFFAOYSA-N 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- RYTRWDVNPIYXCQ-UHFFFAOYSA-N 4,6-dichloro-5-(2-chloro-5-methoxyphenoxy)pyrimidine Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2Cl)Cl)=C1 RYTRWDVNPIYXCQ-UHFFFAOYSA-N 0.000 description 2
- MHIKSEXSQZQYPM-UHFFFAOYSA-N 4,6-dichloro-5-(2-chlorophenoxy)pyrimidine Chemical compound ClC1=CC=CC=C1OC1=C(Cl)N=CN=C1Cl MHIKSEXSQZQYPM-UHFFFAOYSA-N 0.000 description 2
- HQUXULQWCSCZSC-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-(trifluoromethyl)pyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C(F)(F)F)N=C1Cl HQUXULQWCSCZSC-UHFFFAOYSA-N 0.000 description 2
- QVRAUZVKWGOABD-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-propylpyrimidine Chemical compound ClC1=NC(CCC)=NC(Cl)=C1OC1=CC=CC=C1OC QVRAUZVKWGOABD-UHFFFAOYSA-N 0.000 description 2
- KCJVIGGXQNPXHK-UHFFFAOYSA-N 4,6-dichloro-5-(5-fluoro-2-methoxyphenoxy)pyrimidine Chemical compound COC1=CC=C(F)C=C1OC1=C(Cl)N=CN=C1Cl KCJVIGGXQNPXHK-UHFFFAOYSA-N 0.000 description 2
- CZQSVEUNAYHXHG-UHFFFAOYSA-N 4,6-dichloro-5-naphthalen-2-yloxypyrimidine Chemical compound ClC1=NC=NC(Cl)=C1OC1=CC=C(C=CC=C2)C2=C1 CZQSVEUNAYHXHG-UHFFFAOYSA-N 0.000 description 2
- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 2
- OGBPBUDKFTTZPL-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-2-ethyl-6-(2-methylsulfanylethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound C=1C(OC)=CC=C(Cl)C=1OC=1C(OCCSC)=NC(CC)=NC=1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 OGBPBUDKFTTZPL-UHFFFAOYSA-N 0.000 description 2
- FUYIWALKTPDJRC-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(C)=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCO)=C1 FUYIWALKTPDJRC-UHFFFAOYSA-N 0.000 description 2
- OKHMERPFPZODRR-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-2-(2-methoxyethyl)-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound C=1C=CC(OC)=CC=1OC=1C(OCCO)=NC(CCOC)=NC=1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 OKHMERPFPZODRR-UHFFFAOYSA-N 0.000 description 2
- WEUUDVAKLXYINL-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(1-oxidopyridin-1-ium-4-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C[N+]([O-])=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 WEUUDVAKLXYINL-UHFFFAOYSA-N 0.000 description 2
- JANQEUYONJBENB-HXUWFJFHSA-N 4-tert-butyl-n-[6-[(2r)-2,3-dihydroxypropoxy]-5-(2-methoxyphenoxy)-2-thiophen-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=CSC=C2)OC[C@H](O)CO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 JANQEUYONJBENB-HXUWFJFHSA-N 0.000 description 2
- BDFRYTNUXQDOHF-IBGZPJMESA-N 4-tert-butyl-n-[6-[(2s)-2,3-dihydroxypropoxy]-5-(2-methoxyphenoxy)-2-thiophen-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2SC=CC=2)OC[C@@H](O)CO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 BDFRYTNUXQDOHF-IBGZPJMESA-N 0.000 description 2
- JANQEUYONJBENB-FQEVSTJZSA-N 4-tert-butyl-n-[6-[(2s)-2,3-dihydroxypropoxy]-5-(2-methoxyphenoxy)-2-thiophen-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=CSC=C2)OC[C@@H](O)CO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 JANQEUYONJBENB-FQEVSTJZSA-N 0.000 description 2
- FOQVKYGAEBGWJE-LJQANCHMSA-N 4-tert-butyl-n-[6-[[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]-5-(5-fluoro-2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(F)C=C1OC(C(=NC=N1)OC[C@H]2OC(C)(C)OC2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 FOQVKYGAEBGWJE-LJQANCHMSA-N 0.000 description 2
- OHBCVWCMZRCROU-HXUWFJFHSA-N 4-tert-butyl-n-[6-[[(4s)-1,3-dioxolan-4-yl]methoxy]-5-(2-methoxyphenoxy)-2-thiophen-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2SC=CC=2)OC[C@@H]2OCOC2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 OHBCVWCMZRCROU-HXUWFJFHSA-N 0.000 description 2
- COFDKDVVWFKKOL-FQEVSTJZSA-N 4-tert-butyl-n-[6-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]-5-(2-methoxyphenoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(C)=N1)OC[C@@H]2OC(C)(C)OC2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 COFDKDVVWFKKOL-FQEVSTJZSA-N 0.000 description 2
- FOQVKYGAEBGWJE-IBGZPJMESA-N 4-tert-butyl-n-[6-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]-5-(5-fluoro-2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(F)C=C1OC(C(=NC=N1)OC[C@@H]2OC(C)(C)OC2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 FOQVKYGAEBGWJE-IBGZPJMESA-N 0.000 description 2
- UNTAHNCRGJDPRU-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-2-(furan-2-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2OC=CC=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 UNTAHNCRGJDPRU-UHFFFAOYSA-N 0.000 description 2
- YUKBCVHAUXSWLT-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-(1-oxidopyridin-1-ium-2-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2[N+](=CC=CC=2)[O-])N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 YUKBCVHAUXSWLT-UHFFFAOYSA-N 0.000 description 2
- FGLBIGUYLXZNDM-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-pyridin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2N=CC=CC=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 FGLBIGUYLXZNDM-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 102100033902 Endothelin-1 Human genes 0.000 description 2
- 101800004490 Endothelin-1 Proteins 0.000 description 2
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 206010063897 Renal ischaemia Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 206010047139 Vasoconstriction Diseases 0.000 description 2
- 206010047163 Vasospasm Diseases 0.000 description 2
- 238000007239 Wittig reaction Methods 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- BILVOROKFPUARW-UHFFFAOYSA-N dimethyl 2-(2-chloro-5-methoxyphenoxy)propanedioate Chemical compound COC(=O)C(C(=O)OC)OC1=CC(OC)=CC=C1Cl BILVOROKFPUARW-UHFFFAOYSA-N 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical group Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- BTQGDMLCRXCBGR-UHFFFAOYSA-N furan-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC=CO1 BTQGDMLCRXCBGR-UHFFFAOYSA-N 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 2
- CIQSELJNJWOORS-UHFFFAOYSA-N n-[5-(2-chlorophenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound C1=CC(C(C)C)=CC=C1S(=O)(=O)NC1=NC=NC(OCCO)=C1OC1=CC=CC=C1Cl CIQSELJNJWOORS-UHFFFAOYSA-N 0.000 description 2
- MADUPCFUTOKGEM-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2,4,6-trichlorophenoxy)pyrimidin-4-yl]-2,4-dimethylbenzenesulfonamide Chemical compound CC1=CC(C)=CC=C1S(=O)(=O)NC1=NC=NC(OCCO)=C1OC1=C(Cl)C=C(Cl)C=C1Cl MADUPCFUTOKGEM-UHFFFAOYSA-N 0.000 description 2
- HCLUVEKHLYUWMQ-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2,4,6-trichlorophenoxy)pyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound C1=CC(C(C)C)=CC=C1S(=O)(=O)NC1=NC=NC(OCCO)=C1OC1=C(Cl)C=C(Cl)C=C1Cl HCLUVEKHLYUWMQ-UHFFFAOYSA-N 0.000 description 2
- HJQRNFPSYLHLAX-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-propylpyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound C=1C=CC=C(OC)C=1OC=1C(OCCO)=NC(CCC)=NC=1NS(=O)(=O)C1=CC=C(C(C)C)C=C1 HJQRNFPSYLHLAX-UHFFFAOYSA-N 0.000 description 2
- PRRHUCPGHAFRQS-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]-2-methoxybenzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC=N1)OCCO)=C1NS(=O)(=O)C1=CC=CC=C1OC PRRHUCPGHAFRQS-UHFFFAOYSA-N 0.000 description 2
- SGHSFQCRHPPDOT-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=C1 SGHSFQCRHPPDOT-UHFFFAOYSA-N 0.000 description 2
- HOADLZGXXKFLFR-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-phenylethyl)pyrimidin-4-yl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=NC=NC(OCCO)=C1CCC1=CC=CC=C1 HOADLZGXXKFLFR-UHFFFAOYSA-N 0.000 description 2
- PIOSTCVPPXIUET-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-naphthalen-2-yloxypyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound C1=CC(C(C)C)=CC=C1S(=O)(=O)NC1=NC=NC(OCCO)=C1OC1=CC=C(C=CC=C2)C2=C1 PIOSTCVPPXIUET-UHFFFAOYSA-N 0.000 description 2
- BOQHKRHIFYIHNL-UHFFFAOYSA-N n-[6-chloro-5-(5-fluoro-2-methoxyphenoxy)pyrimidin-4-yl]-4-(trifluoromethyl)benzenesulfonamide Chemical compound COC1=CC=C(F)C=C1OC1=C(Cl)N=CN=C1NS(=O)(=O)C1=CC=C(C(F)(F)F)C=C1 BOQHKRHIFYIHNL-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012285 osmium tetroxide Substances 0.000 description 2
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 210000005152 placental membrane Anatomy 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- GLVRRISIYQRARB-UHFFFAOYSA-N potassium;4-propan-2-ylbenzenesulfonamide Chemical compound [K].CC(C)C1=CC=C(S(N)(=O)=O)C=C1 GLVRRISIYQRARB-UHFFFAOYSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 210000002254 renal artery Anatomy 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- 230000025033 vasoconstriction Effects 0.000 description 2
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- PLUUELDPPMQAOI-UHFFFAOYSA-N (2,2-dimethyl-1,3-dioxolan-4-yl)methanol;sodium Chemical compound [Na].CC1(C)OCC(CO)O1 PLUUELDPPMQAOI-UHFFFAOYSA-N 0.000 description 1
- RBACIKXCRWGCBB-UHFFFAOYSA-N 1,2-Epoxybutane Chemical compound CCC1CO1 RBACIKXCRWGCBB-UHFFFAOYSA-N 0.000 description 1
- JHTLPSNDZNHQDZ-UHFFFAOYSA-N 1,3-benzodioxole-5-sulfonamide Chemical compound NS(=O)(=O)C1=CC=C2OCOC2=C1 JHTLPSNDZNHQDZ-UHFFFAOYSA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- ZOZNCAMOIPYYIK-UHFFFAOYSA-N 1-aminoethylideneazanium;acetate Chemical compound CC(N)=N.CC(O)=O ZOZNCAMOIPYYIK-UHFFFAOYSA-N 0.000 description 1
- LINPIYWFGCPVIE-UHFFFAOYSA-N 2,4,6-trichlorophenol Chemical compound OC1=C(Cl)C=C(Cl)C=C1Cl LINPIYWFGCPVIE-UHFFFAOYSA-N 0.000 description 1
- RCZQAFFLGUHJRM-UHFFFAOYSA-N 2-(2-chloro-5-methoxyphenoxy)-4-hydroxy-1h-pyrimidin-6-one Chemical compound COC1=CC=C(Cl)C(OC=2NC(=O)C=C(O)N=2)=C1 RCZQAFFLGUHJRM-UHFFFAOYSA-N 0.000 description 1
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
- LHFJECURYYNCDO-UHFFFAOYSA-N 2-[6-[(4-tert-butylphenyl)sulfonylamino]-5-(2-chloro-5-methoxyphenoxy)-2-methylpyrimidin-4-yl]oxyethyl furan-3-carboxylate Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(C)=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCOC(=O)C2=COC=C2)=C1 LHFJECURYYNCDO-UHFFFAOYSA-N 0.000 description 1
- LOJXRQOEWBJNLR-UHFFFAOYSA-N 2-[6-amino-5-(2-methoxyphenoxy)pyrimidin-4-yl]ethanol Chemical compound COC1=CC=CC=C1OC1=C(N)N=CN=C1CCO LOJXRQOEWBJNLR-UHFFFAOYSA-N 0.000 description 1
- FTBJKXHKOMVWHN-UHFFFAOYSA-N 2-[6-chloro-5-(2-methoxyphenoxy)-2-propan-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound ClC1=C(C(=NC(=N1)C(C)C)C1=C(C=CC=C1)S(=O)(=O)N)OC1=C(C=CC=C1)OC FTBJKXHKOMVWHN-UHFFFAOYSA-N 0.000 description 1
- KIYGHUKZLSPKRE-UHFFFAOYSA-N 2-[6-chloro-5-(2-methoxyphenoxy)-2-pyridin-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound ClC1=C(C(=NC(=N1)C=1C=NC=CC=1)C1=C(C=CC=C1)S(=O)(=O)N)OC1=C(C=CC=C1)OC KIYGHUKZLSPKRE-UHFFFAOYSA-N 0.000 description 1
- XIZNSFKZKZTGNG-UHFFFAOYSA-N 2-butylbenzenesulfonamide Chemical compound CCCCC1=CC=CC=C1S(N)(=O)=O XIZNSFKZKZTGNG-UHFFFAOYSA-N 0.000 description 1
- KULSVCANYQIOFD-UHFFFAOYSA-N 2-chloro-5-methoxyphenol Chemical compound COC1=CC=C(Cl)C(O)=C1 KULSVCANYQIOFD-UHFFFAOYSA-N 0.000 description 1
- XDHGYEVKIDLDJY-UHFFFAOYSA-N 2-cyclopropyl-5-(2-methoxyphenoxy)-1h-pyrimidine-4,6-dione Chemical compound COC1=CC=CC=C1OC1C(=O)N=C(C2CC2)NC1=O XDHGYEVKIDLDJY-UHFFFAOYSA-N 0.000 description 1
- MKQNYQGIPARLKO-UHFFFAOYSA-N 2-methoxybenzenesulfonamide Chemical compound COC1=CC=CC=C1S(N)(=O)=O MKQNYQGIPARLKO-UHFFFAOYSA-N 0.000 description 1
- FEKXIZVLPGDIHB-UHFFFAOYSA-N 2-methoxypropanimidamide;hydrochloride Chemical compound Cl.COC(C)C(N)=N FEKXIZVLPGDIHB-UHFFFAOYSA-N 0.000 description 1
- LNJMHEJAYSYZKK-UHFFFAOYSA-N 2-methylpyrimidine Chemical compound CC1=NC=CC=N1 LNJMHEJAYSYZKK-UHFFFAOYSA-N 0.000 description 1
- WBBPRCNXBQTYLF-UHFFFAOYSA-N 2-methylthioethanol Chemical compound CSCCO WBBPRCNXBQTYLF-UHFFFAOYSA-N 0.000 description 1
- MJGJMQGRZOEPJD-UHFFFAOYSA-N 2-propan-2-ylbenzenesulfonamide Chemical compound CC(C)C1=CC=CC=C1S(N)(=O)=O MJGJMQGRZOEPJD-UHFFFAOYSA-N 0.000 description 1
- ROZONHXKGSVJFN-UHFFFAOYSA-N 2-thiophen-2-ylpyrimidine Chemical compound C1=CSC(C=2N=CC=CN=2)=C1 ROZONHXKGSVJFN-UHFFFAOYSA-N 0.000 description 1
- 125000001137 3-hydroxypropoxy group Chemical group [H]OC([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- TTYBHKNBZUDMAL-UHFFFAOYSA-N 4,6-dichloro-2-(2-methylphenoxy)pyrimidine Chemical compound CC1=CC=CC=C1OC1=NC(Cl)=CC(Cl)=N1 TTYBHKNBZUDMAL-UHFFFAOYSA-N 0.000 description 1
- ZFLVERMCPKZWPG-UHFFFAOYSA-N 4,6-dichloro-2-(furan-3-yl)-5-(2-methoxyphenoxy)pyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C2=COC=C2)N=C1Cl ZFLVERMCPKZWPG-UHFFFAOYSA-N 0.000 description 1
- JVYKFTSRHBWVPQ-UHFFFAOYSA-N 4,6-dichloro-2-cyclopropyl-5-(2-methoxyphenoxy)pyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C2CC2)N=C1Cl JVYKFTSRHBWVPQ-UHFFFAOYSA-N 0.000 description 1
- CFYYPFJNLFVMEC-UHFFFAOYSA-N 4,6-dichloro-2-ethyl-5-(2-methoxyphenoxy)pyrimidine Chemical compound ClC1=NC(CC)=NC(Cl)=C1OC1=CC=CC=C1OC CFYYPFJNLFVMEC-UHFFFAOYSA-N 0.000 description 1
- POFRSRHDZWJCOA-UHFFFAOYSA-N 4,6-dichloro-5-(2-chloro-5-methoxyphenoxy)-2-ethylpyrimidine Chemical compound ClC1=NC(CC)=NC(Cl)=C1OC1=CC(OC)=CC=C1Cl POFRSRHDZWJCOA-UHFFFAOYSA-N 0.000 description 1
- RXRLLJAKHMTLRR-UHFFFAOYSA-N 4,6-dichloro-5-(2-chloro-5-methoxyphenoxy)-2-methylpyrimidine Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(C)=NC=2Cl)Cl)=C1 RXRLLJAKHMTLRR-UHFFFAOYSA-N 0.000 description 1
- LVZOOMGXAOYNMP-UHFFFAOYSA-N 4,6-dichloro-5-(2-fluoro-6-methoxyphenoxy)pyrimidine Chemical compound COC1=CC=CC(F)=C1OC1=C(Cl)N=CN=C1Cl LVZOOMGXAOYNMP-UHFFFAOYSA-N 0.000 description 1
- BPXMOQLQXOLWKQ-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-phenylpyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2C=CC=CC=2)N=C1Cl BPXMOQLQXOLWKQ-UHFFFAOYSA-N 0.000 description 1
- FTAQUOFSNGWGSY-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-propan-2-ylpyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C(C)C)N=C1Cl FTAQUOFSNGWGSY-UHFFFAOYSA-N 0.000 description 1
- SPHFHJVMMAVLBM-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-pyridin-2-ylpyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2N=CC=CC=2)N=C1Cl SPHFHJVMMAVLBM-UHFFFAOYSA-N 0.000 description 1
- YMSYHLFNZWCYDW-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-pyridin-3-ylpyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2C=NC=CC=2)N=C1Cl YMSYHLFNZWCYDW-UHFFFAOYSA-N 0.000 description 1
- IZGOBGVYADHVKH-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2N=CC=CN=2)N=C1Cl IZGOBGVYADHVKH-UHFFFAOYSA-N 0.000 description 1
- SPIOZALFLMMQIG-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)-2-thiophen-2-ylpyrimidine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2SC=CC=2)N=C1Cl SPIOZALFLMMQIG-UHFFFAOYSA-N 0.000 description 1
- FOWWZSFNFFSERO-UHFFFAOYSA-N 4,6-dichloro-5-(2-methoxyphenoxy)pyrimidin-2-amine Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(N)N=C1Cl FOWWZSFNFFSERO-UHFFFAOYSA-N 0.000 description 1
- SSUDNTYHVDOBHO-UHFFFAOYSA-N 4,6-dichloro-5-(3-methoxyphenoxy)-2-methylpyrimidine Chemical compound COC1=CC=CC(OC=2C(=NC(C)=NC=2Cl)Cl)=C1 SSUDNTYHVDOBHO-UHFFFAOYSA-N 0.000 description 1
- IJJRCVNZBFSVMC-UHFFFAOYSA-N 4,6-dichloro-5-(3-methoxyphenoxy)-2-thiophen-2-ylpyrimidine Chemical compound COC1=CC=CC(OC=2C(=NC(=NC=2Cl)C=2SC=CC=2)Cl)=C1 IJJRCVNZBFSVMC-UHFFFAOYSA-N 0.000 description 1
- TWYRHWWVMQAIAE-UHFFFAOYSA-N 4,6-dichloro-5-(3-methoxyphenoxy)pyrimidine Chemical compound COC1=CC=CC(OC=2C(=NC=NC=2Cl)Cl)=C1 TWYRHWWVMQAIAE-UHFFFAOYSA-N 0.000 description 1
- PKCFAPSJYPKHKT-UHFFFAOYSA-N 4,6-dichloro-5-(4-fluoro-2-methoxyphenoxy)-2-methylpyrimidine Chemical compound COC1=CC(F)=CC=C1OC1=C(Cl)N=C(C)N=C1Cl PKCFAPSJYPKHKT-UHFFFAOYSA-N 0.000 description 1
- ZJPHSULPXWWPAH-UHFFFAOYSA-N 4,6-dichloro-5-phenoxypyrimidine Chemical compound ClC1=NC=NC(Cl)=C1OC1=CC=CC=C1 ZJPHSULPXWWPAH-UHFFFAOYSA-N 0.000 description 1
- JHOGTDTUILPHQC-UHFFFAOYSA-N 4-(2,2-dimethylpropyl)benzenesulfonyl chloride Chemical compound CC(C)(C)CC1=CC=C(S(Cl)(=O)=O)C=C1 JHOGTDTUILPHQC-UHFFFAOYSA-N 0.000 description 1
- RGOJCHYYBKMRLL-UHFFFAOYSA-N 4-(trifluoromethoxy)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(OC(F)(F)F)C=C1 RGOJCHYYBKMRLL-UHFFFAOYSA-N 0.000 description 1
- TVHXQQJDMHKGGK-UHFFFAOYSA-N 4-(trifluoromethyl)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(C(F)(F)F)C=C1 TVHXQQJDMHKGGK-UHFFFAOYSA-N 0.000 description 1
- ZUCLXTCEWIIPHJ-UHFFFAOYSA-N 4-chloro-n-[3-(5-fluoro-2-methoxyphenoxy)-6-(2-hydroxyethoxy)-2h-pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(F)C=C1ON1C(NS(=O)(=O)C=2C=CC(Cl)=CC=2)=CC(OCCO)=NC1 ZUCLXTCEWIIPHJ-UHFFFAOYSA-N 0.000 description 1
- IPVYXMXFTUASKG-UHFFFAOYSA-N 4-chloro-n-[6-chloro-5-(5-fluoro-2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(F)C=C1OC1=C(Cl)N=CN=C1NS(=O)(=O)C1=CC=C(Cl)C=C1 IPVYXMXFTUASKG-UHFFFAOYSA-N 0.000 description 1
- HHHDJHHNEURCNV-UHFFFAOYSA-N 4-chlorobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(Cl)C=C1 HHHDJHHNEURCNV-UHFFFAOYSA-N 0.000 description 1
- KYJMYKDNPYLJLR-UHFFFAOYSA-N 4-hydroxy-2-pyridin-2-yl-1h-pyrimidin-6-one Chemical compound OC1=CC(=O)NC(C=2N=CC=CC=2)=N1 KYJMYKDNPYLJLR-UHFFFAOYSA-N 0.000 description 1
- YEQCQVIXATYOQT-UHFFFAOYSA-N 4-hydroxy-5-(2-methoxyphenoxy)-1h-pyrimidin-6-one Chemical compound COC1=CC=CC=C1OC1=C(O)N=CNC1=O YEQCQVIXATYOQT-UHFFFAOYSA-N 0.000 description 1
- AFVWOEIXJJCKJT-UHFFFAOYSA-N 4-hydroxy-5-(2-methoxyphenoxy)-2-pyridin-4-yl-1h-pyrimidin-6-one Chemical compound COC1=CC=CC=C1OC1=C(O)N=C(C=2C=CN=CC=2)N=C1O AFVWOEIXJJCKJT-UHFFFAOYSA-N 0.000 description 1
- OOLSRCOHLIRPLE-UHFFFAOYSA-N 4-hydroxy-5-(2-methoxyphenoxy)-2-thiophen-2-yl-1h-pyrimidin-6-one Chemical compound COC1=CC=CC=C1OC1=C(O)N=C(C=2SC=CC=2)N=C1O OOLSRCOHLIRPLE-UHFFFAOYSA-N 0.000 description 1
- SZYPOIFGKLVAPD-UHFFFAOYSA-N 4-hydroxy-5-(2-methylphenoxy)-1h-pyrimidin-6-one Chemical compound CC1=CC=CC=C1OC1=C(O)N=CNC1=O SZYPOIFGKLVAPD-UHFFFAOYSA-N 0.000 description 1
- CHIHRRCRPHMPEQ-UHFFFAOYSA-N 4-hydroxy-5-(3-methoxyphenoxy)-1h-pyrimidin-6-one Chemical compound COC1=CC=CC(OC=2C(NC=NC=2O)=O)=C1 CHIHRRCRPHMPEQ-UHFFFAOYSA-N 0.000 description 1
- WTMZBNRWVRZFOX-UHFFFAOYSA-N 4-hydroxy-5-(3-methoxyphenoxy)-2-methyl-1h-pyrimidin-6-one Chemical compound COC1=CC=CC(OC=2C(NC(C)=NC=2O)=O)=C1 WTMZBNRWVRZFOX-UHFFFAOYSA-N 0.000 description 1
- AJOSDIDPIBJFAI-UHFFFAOYSA-N 4-methoxybenzenecarboximidamide;hydrochloride Chemical compound Cl.COC1=CC=C(C(N)=N)C=C1 AJOSDIDPIBJFAI-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- FWTVSQPVQPVZAA-UHFFFAOYSA-N 4-tert-butyl-N-[5-(2-chloro-5-methoxyphenoxy)-6-(2-methylsulfinylethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound CC(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC2=C(C(=NC=N2)OCCS(=O)C)OC3=C(C=CC(=C3)OC)Cl FWTVSQPVQPVZAA-UHFFFAOYSA-N 0.000 description 1
- SRAIMGJIFOFERO-UHFFFAOYSA-N 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-propylpyrimidin-4-yl]-4-propan-2-ylcyclohexa-1,5-diene-1-sulfonamide Chemical compound CCCC1=NC(=C(C(=N1)OCCO)OC2=CC=CC=C2OC)NS(=O)(=O)C3=CCC(C=C3)(C(C)C)C(C)(C)C SRAIMGJIFOFERO-UHFFFAOYSA-N 0.000 description 1
- GCSXVVQKKDLQGF-OAQYLSRUSA-N 4-tert-butyl-N-[6-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]-5-(2-methoxyphenoxy)-2-thiophen-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC(=NC(=C1OC1=C(C=CC=C1)OC)OC[C@H]1OC(OC1)(C)C)C=1SC=CC=1 GCSXVVQKKDLQGF-OAQYLSRUSA-N 0.000 description 1
- RQFPHOKNMDKLRN-UHFFFAOYSA-N 4-tert-butyl-N-[6-chloro-2-(2-methoxyethyl)-2-(2-methoxyphenoxy)-1H-pyrimidin-4-yl]benzenesulfonamide Chemical compound CC(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC2=NC(NC(=C2)Cl)(CCOC)OC3=CC=CC=C3OC RQFPHOKNMDKLRN-UHFFFAOYSA-N 0.000 description 1
- RUPHLPQDQBORMJ-UHFFFAOYSA-N 4-tert-butyl-N-[6-chloro-2-ethyl-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound C=1C=C(C(C)(C)C)C=CC=1S(=O)(=O)NC1=NC(CC)=NC(Cl)=C1OC1=CC=CC=C1OC RUPHLPQDQBORMJ-UHFFFAOYSA-N 0.000 description 1
- HGCNVBFWQCYTTB-UHFFFAOYSA-N 4-tert-butyl-n-[2-(furan-2-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2OC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HGCNVBFWQCYTTB-UHFFFAOYSA-N 0.000 description 1
- XWEWXELBVQVFOR-UHFFFAOYSA-N 4-tert-butyl-n-[2-cyclopropyl-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2CC2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 XWEWXELBVQVFOR-UHFFFAOYSA-N 0.000 description 1
- QSZPTRRZTQCBNH-UHFFFAOYSA-N 4-tert-butyl-n-[2-ethyl-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound C=1C=CC=C(OC)C=1OC=1C(OCCO)=NC(CC)=NC=1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 QSZPTRRZTQCBNH-UHFFFAOYSA-N 0.000 description 1
- TXJQLDNVVFRPGL-UHFFFAOYSA-N 4-tert-butyl-n-[5-(4-fluoro-2-methoxyphenoxy)-6-(2-hydroxyethoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC(F)=CC=C1OC(C(=NC(C)=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 TXJQLDNVVFRPGL-UHFFFAOYSA-N 0.000 description 1
- KNFMAXWQURUHMD-UHFFFAOYSA-N 4-tert-butyl-n-[5-(4-fluoro-2-methoxyphenoxy)-6-(2-hydroxyethoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC(F)=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 KNFMAXWQURUHMD-UHFFFAOYSA-N 0.000 description 1
- ZDIPQVFJFSGFMS-UHFFFAOYSA-N 4-tert-butyl-n-[5-(5-fluoro-2-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(F)C=C1OC(C(=NC=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 ZDIPQVFJFSGFMS-UHFFFAOYSA-N 0.000 description 1
- YTBGKHFJEQITFY-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(1-oxidopyridin-1-ium-2-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2[N+](=CC=CC=2)[O-])OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 YTBGKHFJEQITFY-UHFFFAOYSA-N 0.000 description 1
- QOPGXVVGPBNZHE-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-propan-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C(C)C)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 QOPGXVVGPBNZHE-UHFFFAOYSA-N 0.000 description 1
- ICGLTOLBTVCGPB-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyridin-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=NC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 ICGLTOLBTVCGPB-UHFFFAOYSA-N 0.000 description 1
- HEBWMVUSTSZAMZ-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyridin-4-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=CN=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HEBWMVUSTSZAMZ-UHFFFAOYSA-N 0.000 description 1
- NFEWKJNARXIISE-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-thiophen-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=CSC=C2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 NFEWKJNARXIISE-UHFFFAOYSA-N 0.000 description 1
- BOUYHPQCWYVAAS-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(3-methoxyphenoxy)-2-thiophen-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC(OC=2C(=NC(=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)C=2SC=CC=2)OCCO)=C1 BOUYHPQCWYVAAS-UHFFFAOYSA-N 0.000 description 1
- BDFRYTNUXQDOHF-LJQANCHMSA-N 4-tert-butyl-n-[6-[(2r)-2,3-dihydroxypropoxy]-5-(2-methoxyphenoxy)-2-thiophen-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2SC=CC=2)OC[C@H](O)CO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 BDFRYTNUXQDOHF-LJQANCHMSA-N 0.000 description 1
- HCAJUXSCGLHBQN-FQEVSTJZSA-N 4-tert-butyl-n-[6-[(2s)-2,3-dihydroxypropoxy]-2-(furan-3-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=COC=C2)OC[C@@H](O)CO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HCAJUXSCGLHBQN-FQEVSTJZSA-N 0.000 description 1
- MDKGUKJBSQLBAO-JOCHJYFZSA-N 4-tert-butyl-n-[6-[[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]-2-(furan-3-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=COC=C2)OC[C@H]2OC(C)(C)OC2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 MDKGUKJBSQLBAO-JOCHJYFZSA-N 0.000 description 1
- MDKGUKJBSQLBAO-QFIPXVFZSA-N 4-tert-butyl-n-[6-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]-2-(furan-3-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=COC=C2)OC[C@@H]2OC(C)(C)OC2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 MDKGUKJBSQLBAO-QFIPXVFZSA-N 0.000 description 1
- GVKLKQRGAVOPQY-QFIPXVFZSA-N 4-tert-butyl-n-[6-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]-5-(2-methoxyphenoxy)-2-thiophen-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=CSC=C2)OC[C@@H]2OC(C)(C)OC2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GVKLKQRGAVOPQY-QFIPXVFZSA-N 0.000 description 1
- OFJSNCHEINAMKP-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-2-(2-methoxyethyl)-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound C=1C=C(C(C)(C)C)C=CC=1S(=O)(=O)NC1=NC(CCOC)=NC(Cl)=C1OC1=CC=CC(OC)=C1 OFJSNCHEINAMKP-UHFFFAOYSA-N 0.000 description 1
- DWPIHINHYHWOMM-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-2-(furan-3-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C2=COC=C2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 DWPIHINHYHWOMM-UHFFFAOYSA-N 0.000 description 1
- SLFKCUCRRGTATR-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-2-cyclopropyl-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C2CC2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 SLFKCUCRRGTATR-UHFFFAOYSA-N 0.000 description 1
- AJGVFEHMHMEWTH-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-fluoro-6-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC(F)=C1OC1=C(Cl)N=CN=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 AJGVFEHMHMEWTH-UHFFFAOYSA-N 0.000 description 1
- JVIAENLKEPCIKM-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-(1-oxidopyridin-1-ium-4-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2C=C[N+]([O-])=CC=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 JVIAENLKEPCIKM-UHFFFAOYSA-N 0.000 description 1
- UWYDHRUDKAOSKH-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-propan-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C(C)C)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 UWYDHRUDKAOSKH-UHFFFAOYSA-N 0.000 description 1
- QKKYYRXPRRPHQI-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-pyridin-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2C=NC=CC=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 QKKYYRXPRRPHQI-UHFFFAOYSA-N 0.000 description 1
- YAGNJEMBLUXKOZ-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-pyridin-4-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2C=CN=CC=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 YAGNJEMBLUXKOZ-UHFFFAOYSA-N 0.000 description 1
- LZHJWSYFGZNMIM-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-pyridin-4-ylpyrimidin-4-yl]benzenesulfonamide;potassium Chemical compound [K].COC1=CC=CC=C1OC1=C(Cl)N=C(C=2C=CN=CC=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 LZHJWSYFGZNMIM-UHFFFAOYSA-N 0.000 description 1
- XKISWHVJIZSPSC-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC1=C(Cl)N=C(C=2N=CC=CN=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 XKISWHVJIZSPSC-UHFFFAOYSA-N 0.000 description 1
- QANRJCJPLPJJFP-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(3-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC(OC=2C(=NC(=NC=2Cl)C=2N=CC=CN=2)NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1 QANRJCJPLPJJFP-UHFFFAOYSA-N 0.000 description 1
- FFQRNDNXANRQOL-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(3-methoxyphenoxy)-2-thiophen-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC(OC=2C(=NC(=NC=2Cl)C=2SC=CC=2)NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1 FFQRNDNXANRQOL-UHFFFAOYSA-N 0.000 description 1
- NKPDNZUYUTXHBJ-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(4-fluoro-2-methoxyphenoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC(F)=CC=C1OC1=C(Cl)N=C(C)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 NKPDNZUYUTXHBJ-UHFFFAOYSA-N 0.000 description 1
- UQYLTZGCINUQCB-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(4-fluoro-2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC(F)=CC=C1OC1=C(Cl)N=C(C=2N=CC=CN=2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 UQYLTZGCINUQCB-UHFFFAOYSA-N 0.000 description 1
- XJPQZVGWMAUNDS-UHFFFAOYSA-N 4-tert-butyl-n-[6-chloro-5-(4-fluoro-2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC(F)=CC=C1OC1=C(Cl)N=CN=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 XJPQZVGWMAUNDS-UHFFFAOYSA-N 0.000 description 1
- GDJXFXLLABUMGV-UHFFFAOYSA-N 5-(1,3-benzodioxol-5-yloxy)-4,6-dichloropyrimidine Chemical compound ClC1=NC=NC(Cl)=C1OC1=CC=C(OCO2)C2=C1 GDJXFXLLABUMGV-UHFFFAOYSA-N 0.000 description 1
- IDEFCSXLXWMYOU-UHFFFAOYSA-N 5-(2-chloro-5-methoxyphenoxy)-2-ethyl-4-hydroxy-1h-pyrimidin-6-one Chemical compound O=C1NC(CC)=NC(O)=C1OC1=CC(OC)=CC=C1Cl IDEFCSXLXWMYOU-UHFFFAOYSA-N 0.000 description 1
- JOQWZAWKUFABPE-UHFFFAOYSA-N 5-(2-chlorophenoxy)-4-hydroxy-1h-pyrimidin-6-one Chemical compound N1=CNC(=O)C(OC=2C(=CC=CC=2)Cl)=C1O JOQWZAWKUFABPE-UHFFFAOYSA-N 0.000 description 1
- CECGHDGLUTYDBW-UHFFFAOYSA-N 5-(2-ethoxyphenoxy)-4-hydroxy-1h-pyrimidin-6-one Chemical compound CCOC1=CC=CC=C1OC1=C(O)N=CNC1=O CECGHDGLUTYDBW-UHFFFAOYSA-N 0.000 description 1
- TYTLXDABSNFQFA-UHFFFAOYSA-N 5-(3-methoxyphenoxy)-1H-pyrimidine-4,6-dione Chemical compound COC1=CC=CC(OC2C(N=CNC2=O)=O)=C1 TYTLXDABSNFQFA-UHFFFAOYSA-N 0.000 description 1
- BNDLYSPAJLLDEO-UHFFFAOYSA-N 5-(4-fluoro-2-methoxyphenoxy)-1h-pyrimidine-4,6-dione Chemical compound COC1=CC(F)=CC=C1OC1C(=O)N=CNC1=O BNDLYSPAJLLDEO-UHFFFAOYSA-N 0.000 description 1
- DJYRJPUSXUVOTC-UHFFFAOYSA-N 5-(4-fluoro-2-methoxyphenoxy)-2-methyl-1h-pyrimidine-4,6-dione Chemical compound COC1=CC(F)=CC=C1OC1C(=O)N=C(C)NC1=O DJYRJPUSXUVOTC-UHFFFAOYSA-N 0.000 description 1
- SGLPRIIINMCHCW-UHFFFAOYSA-N 5h-pyrimidine-2,4-dione Chemical compound O=C1CC=NC(=O)N1 SGLPRIIINMCHCW-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- RPVGBNBTSHZAGG-UHFFFAOYSA-N 6-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-5-(2-methoxyphenoxy)pyrimidin-4-amine Chemical compound CC(C)(C)[Si](C)(C)OCCC1=C(C(=NC=N1)N)OC2=CC=CC=C2OC RPVGBNBTSHZAGG-UHFFFAOYSA-N 0.000 description 1
- AAMLJUYFMWWQJI-UHFFFAOYSA-N 6-chloro-5-(2-methoxyphenoxy)pyrimidin-4-amine Chemical compound COC1=CC=CC=C1OC1=C(N)N=CN=C1Cl AAMLJUYFMWWQJI-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OXWCOKWZTGROQP-UHFFFAOYSA-N CC(C)(C)C(C=C1)=CC=C1S(NC(C=C(N1)OCCO)=NC1(CCOCCO)OC(C=CC=C1)=C1OC)(=O)=O Chemical compound CC(C)(C)C(C=C1)=CC=C1S(NC(C=C(N1)OCCO)=NC1(CCOCCO)OC(C=CC=C1)=C1OC)(=O)=O OXWCOKWZTGROQP-UHFFFAOYSA-N 0.000 description 1
- DMHUBBSBJHUPEB-SANMLTNESA-N CC(C)(C)C(C=C1)=CC=C1S(NC1=NC(C2=CSC=C2)(C2=CSC=C2)NC(OC[C@@H]2OC(C)(C)OC2)=C1OC(C=CC=C1)=C1OC)(=O)=O Chemical compound CC(C)(C)C(C=C1)=CC=C1S(NC1=NC(C2=CSC=C2)(C2=CSC=C2)NC(OC[C@@H]2OC(C)(C)OC2)=C1OC(C=CC=C1)=C1OC)(=O)=O DMHUBBSBJHUPEB-SANMLTNESA-N 0.000 description 1
- IDQNADSDOVRNJJ-UHFFFAOYSA-N CCC(N=C1C(C=CC=C2)=C2S(N)(=O)=O)=NC(Cl)=C1OC(C=CC=C1)=C1OC Chemical compound CCC(N=C1C(C=CC=C2)=C2S(N)(=O)=O)=NC(Cl)=C1OC(C=CC=C1)=C1OC IDQNADSDOVRNJJ-UHFFFAOYSA-N 0.000 description 1
- BPHVYYBSNBLPKM-UHFFFAOYSA-N COC1=CC=CC(ON(C(C2)=O)C(C3=CC=CS3)=NC2=O)=C1 Chemical compound COC1=CC=CC(ON(C(C2)=O)C(C3=CC=CS3)=NC2=O)=C1 BPHVYYBSNBLPKM-UHFFFAOYSA-N 0.000 description 1
- OHBCVWCMZRCROU-FQEVSTJZSA-N COC1=CC=CC=C1OC(C(=NC(=N1)C=2SC=CC=2)OC[C@H]2OCOC2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2SC=CC=2)OC[C@H]2OCOC2)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 OHBCVWCMZRCROU-FQEVSTJZSA-N 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- PIVXLJVNGCMHLR-UHFFFAOYSA-N ClC1=CC(=NC(=N1)OC1=C(C=CC=C1)OC)C1=C(C=CC=C1)S(=O)(=O)N Chemical compound ClC1=CC(=NC(=N1)OC1=C(C=CC=C1)OC)C1=C(C=CC=C1)S(=O)(=O)N PIVXLJVNGCMHLR-UHFFFAOYSA-N 0.000 description 1
- AWUOCXBSACVSPI-UHFFFAOYSA-N ClCCC1=NC=C(C=N1)OC1=CC(=CC=C1)OC Chemical compound ClCCC1=NC=C(C=N1)OC1=CC(=CC=C1)OC AWUOCXBSACVSPI-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical class C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000005230 Leg Ulcer Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- OINJJBPRHCSDMS-UHFFFAOYSA-N N-[6-(2-hydroxyethoxy)-5-(2,4,6-trichlorophenoxy)pyrimidin-4-yl]-2-methylbenzenesulfonamide Chemical compound OCCOC1=C(C(=NC=N1)NS(=O)(=O)C=1C(C)=CC=CC1)OC1=C(C=C(C=C1Cl)Cl)Cl OINJJBPRHCSDMS-UHFFFAOYSA-N 0.000 description 1
- PINGYOMODVQOSC-UHFFFAOYSA-N N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC1=NC(=NC(=C1OC1=C(C=CC=C1)OC)OCCO)C PINGYOMODVQOSC-UHFFFAOYSA-N 0.000 description 1
- RONXOIFOHHRMKV-UHFFFAOYSA-N N-[6-(2-hydroxyethoxy)-5-(3-methoxyphenoxy)-2-methylpyrimidin-4-yl]-4,4-di(propan-2-yl)cyclohexa-1,5-diene-1-sulfonamide Chemical compound CC1=NC(=C(C(=N1)OCCO)OC2=CC=CC(=C2)OC)NS(=O)(=O)C3=CCC(C=C3)(C(C)C)C(C)C RONXOIFOHHRMKV-UHFFFAOYSA-N 0.000 description 1
- DTBRNHGVDLUHBA-UHFFFAOYSA-N N-[6-chloro-5-(3-methoxyphenoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC1=NC(=NC(=C1OC1=CC(=CC=C1)OC)Cl)C DTBRNHGVDLUHBA-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- LPOZTOACDKSWLI-UHFFFAOYSA-N O=C(C1)NC(OC(C(Cl)=CC(Cl)=C2)=C2Cl)=NC1=O Chemical compound O=C(C1)NC(OC(C(Cl)=CC(Cl)=C2)=C2Cl)=NC1=O LPOZTOACDKSWLI-UHFFFAOYSA-N 0.000 description 1
- 206010038419 Renal colic Diseases 0.000 description 1
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- RNVYQYLELCKWAN-RXMQYKEDSA-N [(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol Chemical compound CC1(C)OC[C@@H](CO)O1 RNVYQYLELCKWAN-RXMQYKEDSA-N 0.000 description 1
- RNVYQYLELCKWAN-YFKPBYRVSA-N [(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol Chemical compound CC1(C)OC[C@H](CO)O1 RNVYQYLELCKWAN-YFKPBYRVSA-N 0.000 description 1
- MKJPBOVLAZADQJ-UHFFFAOYSA-N [amino(pyridin-3-yl)methylidene]azanium;chloride Chemical compound Cl.NC(=N)C1=CC=CN=C1 MKJPBOVLAZADQJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
- AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- YDPWVAMKZSUTGO-UHFFFAOYSA-N benzenesulfonamide;sodium Chemical compound [Na].NS(=O)(=O)C1=CC=CC=C1 YDPWVAMKZSUTGO-UHFFFAOYSA-N 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 1
- USFRYJRPHFMVBZ-UHFFFAOYSA-M benzyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CC1=CC=CC=C1 USFRYJRPHFMVBZ-UHFFFAOYSA-M 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000006630 butoxycarbonylamino group Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- JRYOZJIRAVZGMV-UHFFFAOYSA-N cyclopropanecarboximidamide;hydron;chloride Chemical group Cl.NC(=N)C1CC1 JRYOZJIRAVZGMV-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- STORWMDPIHOSMF-UHFFFAOYSA-N decanoic acid;octanoic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCC(O)=O.CCCCCCCCCC(O)=O STORWMDPIHOSMF-UHFFFAOYSA-N 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- RYFCSKVXWRJEOB-UHFFFAOYSA-N dibenzyl propanedioate Chemical compound C=1C=CC=CC=1COC(=O)CC(=O)OCC1=CC=CC=C1 RYFCSKVXWRJEOB-UHFFFAOYSA-N 0.000 description 1
- BHXCZZVCSWSJJV-UHFFFAOYSA-N diethyl 2-(3-methoxyphenoxy)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)OC1=CC=CC(OC)=C1 BHXCZZVCSWSJJV-UHFFFAOYSA-N 0.000 description 1
- WLWCQKMQYZFTDR-UHFFFAOYSA-N diethyl 2-chloropropanedioate Chemical compound CCOC(=O)C(Cl)C(=O)OCC WLWCQKMQYZFTDR-UHFFFAOYSA-N 0.000 description 1
- ZQNYBTKCSIVYBX-UHFFFAOYSA-N diethyl 2-phenoxypropanedioate Chemical compound CCOC(=O)C(C(=O)OCC)OC1=CC=CC=C1 ZQNYBTKCSIVYBX-UHFFFAOYSA-N 0.000 description 1
- GDWAYKGILJJNBB-UHFFFAOYSA-N diethyl 2-prop-2-enylpropanedioate Chemical compound CCOC(=O)C(CC=C)C(=O)OCC GDWAYKGILJJNBB-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- RXQFSKAWABBDNG-UHFFFAOYSA-N disodium;ethane-1,2-diolate Chemical compound [Na+].[Na+].[O-]CC[O-] RXQFSKAWABBDNG-UHFFFAOYSA-N 0.000 description 1
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- NWJKPSLXLQLUTC-UHFFFAOYSA-N ethane-1,2-diol;sodium Chemical compound [Na].OCCO NWJKPSLXLQLUTC-UHFFFAOYSA-N 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- PUVPFBUAXGEEAD-UHFFFAOYSA-N ethyl 2-(5-chlorosulfonyl-2-methoxyphenoxy)acetate Chemical compound CCOC(=O)COC1=CC(S(Cl)(=O)=O)=CC=C1OC PUVPFBUAXGEEAD-UHFFFAOYSA-N 0.000 description 1
- BRGKCGDHUGFABB-UHFFFAOYSA-N ethyl 2-[4-[[6-[2-[tert-butyl(dimethyl)silyl]oxyethoxy]-5-(2-methoxyphenoxy)pyrimidin-4-yl]sulfamoyl]-2-methoxyphenoxy]acetate Chemical compound CCOC(=O)COC1=C(C=C(C=C1)S(=O)(=O)NC2=C(C(=NC=N2)OCCO[Si](C)(C)C(C)(C)C)OC3=CC=CC=C3OC)OC BRGKCGDHUGFABB-UHFFFAOYSA-N 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- RBBOWEDMXHTEPA-UHFFFAOYSA-N hexane;toluene Chemical compound CCCCCC.CC1=CC=CC=C1 RBBOWEDMXHTEPA-UHFFFAOYSA-N 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- RKAJLULSWQQOJB-UHFFFAOYSA-N n-[4-(2-hydroxyethoxy)-4-(2,4,6-trichlorophenoxy)-1h-pyrimidin-6-yl]-2-methylbenzenesulfonamide Chemical compound CC1=CC=CC=C1S(=O)(=O)NC1=CC(OC=2C(=CC(Cl)=CC=2Cl)Cl)(OCCO)NC=N1 RKAJLULSWQQOJB-UHFFFAOYSA-N 0.000 description 1
- MPFBYDMHEVLWRI-UHFFFAOYSA-N n-[5-(1,3-benzodioxol-5-yloxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound C1=CC(C(C)C)=CC=C1S(=O)(=O)NC1=NC=NC(OCCO)=C1OC1=CC=C(OCO2)C2=C1 MPFBYDMHEVLWRI-UHFFFAOYSA-N 0.000 description 1
- GHGLMUURJGHLNZ-UHFFFAOYSA-N n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-methylsulfinylethoxy)pyrimidin-4-yl]-1,3-benzodioxole-5-sulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=C3OCOC3=CC=2)OCCS(C)=O)=C1 GHGLMUURJGHLNZ-UHFFFAOYSA-N 0.000 description 1
- DWZMFXBHYHDCKV-UHFFFAOYSA-N n-[5-(5-fluoro-2-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-4-(trifluoromethyl)benzenesulfonamide Chemical compound COC1=CC=C(F)C=C1OC(C(=NC=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(F)(F)F)C=C1 DWZMFXBHYHDCKV-UHFFFAOYSA-N 0.000 description 1
- HNTMFYNZVGOMBK-UHFFFAOYSA-N n-[5-(5-fluoro-2-methoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound COC1=CC=C(F)C=C1OC(C(=NC=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=C1 HNTMFYNZVGOMBK-UHFFFAOYSA-N 0.000 description 1
- PRTPSXRUUNCJGZ-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-methylpyrimidin-4-yl]naphthalene-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(C)=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 PRTPSXRUUNCJGZ-UHFFFAOYSA-N 0.000 description 1
- ZHYADMKRGVVLCQ-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=CC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=C1 ZHYADMKRGVVLCQ-UHFFFAOYSA-N 0.000 description 1
- WOLZYFGUBLXWIM-UHFFFAOYSA-N n-[6-chloro-5-(2-chloro-5-methoxyphenoxy)pyrimidin-4-yl]-1,3-benzodioxole-5-sulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2Cl)NS(=O)(=O)C=2C=C3OCOC3=CC=2)=C1 WOLZYFGUBLXWIM-UHFFFAOYSA-N 0.000 description 1
- XVKVRWPIWJDPJH-UHFFFAOYSA-N n-[6-chloro-5-(2-chlorophenoxy)pyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound C1=CC(C(C)C)=CC=C1S(=O)(=O)NC1=NC=NC(Cl)=C1OC1=CC=CC=C1Cl XVKVRWPIWJDPJH-UHFFFAOYSA-N 0.000 description 1
- SWBLLSQMOMPTMC-UHFFFAOYSA-N naphthalene-2-sulfonamide Chemical compound C1=CC=CC2=CC(S(=O)(=O)N)=CC=C21 SWBLLSQMOMPTMC-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- QWOCNQFGAYCFIZ-UHFFFAOYSA-N potassium;2-propan-2-ylbenzenesulfonamide Chemical compound [K].CC(C)C1=CC=CC=C1S(N)(=O)=O QWOCNQFGAYCFIZ-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- XYKIUTSFQGXHOW-UHFFFAOYSA-N propan-2-one;toluene Chemical compound CC(C)=O.CC1=CC=CC=C1 XYKIUTSFQGXHOW-UHFFFAOYSA-N 0.000 description 1
- DFWRZHZPJJAJMX-UHFFFAOYSA-N propanimidamide;hydrochloride Chemical compound Cl.CCC(N)=N DFWRZHZPJJAJMX-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- GMHCEDDZKAYPLB-UHFFFAOYSA-N pyridine-2-carboximidamide;hydrochloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=N1 GMHCEDDZKAYPLB-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- LZIYBABLVXXFGZ-UHFFFAOYSA-N pyrimidine-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=NC=CC=N1 LZIYBABLVXXFGZ-UHFFFAOYSA-N 0.000 description 1
- 150000008512 pyrimidinediones Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229940023144 sodium glycolate Drugs 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 1
- NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 1
- GQFIWFPBDXSASA-UHFFFAOYSA-M sodium;2-chlorophenolate Chemical compound [Na+].[O-]C1=CC=CC=C1Cl GQFIWFPBDXSASA-UHFFFAOYSA-M 0.000 description 1
- ONFAAMBUOAGWSG-UHFFFAOYSA-M sodium;2-methylphenolate Chemical compound [Na+].CC1=CC=CC=C1[O-] ONFAAMBUOAGWSG-UHFFFAOYSA-M 0.000 description 1
- IIHZUISTNNNXQQ-UHFFFAOYSA-M sodium;3-methoxyphenolate Chemical compound [Na+].COC1=CC=CC([O-])=C1 IIHZUISTNNNXQQ-UHFFFAOYSA-M 0.000 description 1
- MYMOTVMHKLYQCM-UHFFFAOYSA-M sodium;4-methoxyphenolate Chemical compound [Na+].COC1=CC=C([O-])C=C1 MYMOTVMHKLYQCM-UHFFFAOYSA-M 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 101150035983 str1 gene Proteins 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 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 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- QGVNJRROSLYGKF-UHFFFAOYSA-N thiobarbital Chemical compound CCC1(CC)C(=O)NC(=S)NC1=O QGVNJRROSLYGKF-UHFFFAOYSA-N 0.000 description 1
- CAUZIIYPBLBRFI-UHFFFAOYSA-N thiophene-3-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C=1C=CSC=1 CAUZIIYPBLBRFI-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
-
- 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
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- 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
- C07D239/69—Benzenesulfonamido-pyrimidines
-
- 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
- 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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
-
- 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
- C07D409/04—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 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
- C07D409/14—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Lubricants (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Glass Compositions (AREA)
- Bipolar Transistors (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH176091 | 1991-06-13 | ||
CH01760/91-0 | 1992-05-12 | ||
CH151692 | 1992-05-12 | ||
CH01516/92-6 | 1992-05-12 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH05222003A JPH05222003A (ja) | 1993-08-31 |
JPH0730042B2 true JPH0730042B2 (ja) | 1995-04-05 |
Family
ID=25687870
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP4174993A Expired - Fee Related JPH0730042B2 (ja) | 1991-06-13 | 1992-06-10 | スルホンアミド類および薬物としてのそれらの使用 |
Country Status (34)
Families Citing this family (191)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5591761A (en) * | 1993-05-20 | 1997-01-07 | Texas Biotechnology Corporation | Thiophenyl-, furyl-and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin |
US5571821A (en) * | 1993-05-20 | 1996-11-05 | Texas Biotechnology Corporation | Sulfonamides and derivatives thereof that modulate the activity of endothelin |
US5594021A (en) * | 1993-05-20 | 1997-01-14 | Texas Biotechnology Corporation | Thienyl-, furyl- and pyrrolyl sulfonamides and derivatives thereof that modulate the activity of endothelin |
US5962490A (en) | 1987-09-25 | 1999-10-05 | Texas Biotechnology Corporation | Thienyl-, furyl- and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin |
US5514691A (en) * | 1993-05-20 | 1996-05-07 | Immunopharmaceutics, Inc. | N-(4-halo-isoxazolyl)-sulfonamides and derivatives thereof that modulate the activity of endothelin |
RU2080158C1 (ru) * | 1989-08-30 | 1997-05-27 | Фокс Ирвин | Способ получения носителя из минерала монтмориллонита |
US5736509A (en) * | 1990-12-14 | 1998-04-07 | Texas Biotechnology Corporation | Cyclic peptide surface feature mimics of endothelin |
TW224462B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1992-02-24 | 1994-06-01 | Squibb & Sons Inc | |
US5378715A (en) * | 1992-02-24 | 1995-01-03 | Bristol-Myers Squibb Co. | Sulfonamide endothelin antagonists |
NZ247440A (en) * | 1992-05-06 | 1995-04-27 | Squibb & Sons Inc | Phenyl sulphonamide derivatives, preparation and pharmaceutical compositions thereof |
US5514696A (en) * | 1992-05-06 | 1996-05-07 | Bristol-Myers Squibb Co. | Phenyl sulfonamide endothelin antagonists |
US5420123A (en) * | 1992-12-21 | 1995-05-30 | Bristol-Myers Squibb Company | Dibenzodiazepine endothelin antagonists |
US5352800A (en) * | 1993-03-11 | 1994-10-04 | Merck & Co., Inc. | Process for the production of a novel endothelin antagonist |
US5374638A (en) * | 1993-03-19 | 1994-12-20 | Merck & Co., Inc. | Six membered ring fused imidazoles substituted with phenoxyphenylacetic acid derivatives used to treat asthma |
US5401745A (en) * | 1993-03-19 | 1995-03-28 | Merck & Co., Inc. | Quinazolinones substituted with phenoxyphenylacetic acid derivatives |
US5420133A (en) * | 1993-03-19 | 1995-05-30 | Merck & Co., Inc. | Quinazolinones substituted with phenoxyphenylacetic acid derivatives |
US5767310A (en) * | 1993-03-19 | 1998-06-16 | Merck & Co., Inc. | Phenoxyphenylacetic acid derivatives |
US5334598A (en) * | 1993-03-19 | 1994-08-02 | Merck & Co., Inc. | Six-membered ring fused imidazoles substituted with phenoxyphenylacetic acid derivatives |
CA2121724A1 (en) | 1993-04-21 | 1994-10-22 | Toshifumi Watanabe | Methods and compositions for the prophylactic and/or therapeutic treatment of organ hypofunction |
US6541498B2 (en) | 1993-05-20 | 2003-04-01 | Texas Biotechnology | Benzenesulfonamides and the use thereof to modulate the activity of endothelin |
US6376523B1 (en) | 1994-05-20 | 2002-04-23 | Texas Biotechnology Corporation | Benzenesulfonamides and the use thereof to modulate the activity of endothelin |
US6613804B2 (en) | 1993-05-20 | 2003-09-02 | Encysive Pharmaceuticals, Inc. | Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin |
US6030991A (en) * | 1993-05-20 | 2000-02-29 | Texas Biotechnology Corp. | Benzenesulfonamides and the use thereof to modulate the activity of endothelin |
US6342610B2 (en) | 1993-05-20 | 2002-01-29 | Texas Biotechnology Corp. | N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin |
US6087324A (en) | 1993-06-24 | 2000-07-11 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
TW394761B (en) * | 1993-06-28 | 2000-06-21 | Hoffmann La Roche | Novel Sulfonylamino Pyrimidines |
ES2154277T3 (es) * | 1993-07-15 | 2001-04-01 | Hoffmann La Roche | Combinacion farmaceutica que contiene un inhibidor del sistema renina-angiotensina y un antagonista de endotelina. |
US5686478A (en) * | 1993-07-20 | 1997-11-11 | Merck & Co. Inc. | Endothelin antagonists |
US6140325A (en) * | 1993-08-19 | 2000-10-31 | Takeda Chemical Industries, Ltd. | Thienopyrimidine derivatives, their production and use |
US5965732A (en) * | 1993-08-30 | 1999-10-12 | Bristol-Myers Squibb Co. | Sulfonamide endothelin antagonists |
RU2126418C1 (ru) * | 1993-11-01 | 1999-02-20 | Циба-Гейги Джапан Димитед | Антагонисты рецепторов эндотелина |
IL111959A (en) * | 1993-12-17 | 2000-07-16 | Tanabe Seiyaku Co | N-(polysubstituted pyrimidin-4-yl) benzenesulfonamide derivatives their preparation and pharmaceutical compositions containing them |
GB9504854D0 (en) * | 1994-03-31 | 1995-04-26 | Zeneca Ltd | Nitrogen derivatives |
GB9409618D0 (en) * | 1994-05-13 | 1994-07-06 | Zeneca Ltd | Pyridine derivatives |
US5612359A (en) * | 1994-08-26 | 1997-03-18 | Bristol-Myers Squibb Company | Substituted biphenyl isoxazole sulfonamides |
US5559135A (en) * | 1994-09-14 | 1996-09-24 | Merck & Co., Inc. | Endothelin antagonists bearing pyridyl amides |
US5538991A (en) * | 1994-09-14 | 1996-07-23 | Merck & Co., Inc. | Endothelin antagonists bearing 5-membered heterocyclic amides |
US6268369B1 (en) | 1994-11-16 | 2001-07-31 | Synaptic Pharmaceutical Corporation | 5-(heterocyclic alkyl)-6-aryl-dihydropyrimidines |
EP0790826A4 (en) | 1994-11-16 | 1998-11-11 | Synaptic Pharma Corp | DIHYDROPYRIMIDINES AND THEIR USES |
WO1996016963A1 (de) * | 1994-11-25 | 1996-06-06 | F. Hoffmann-La Roche Ag | Sulfonamide und deren verwendung als heilmittel |
CA2162630C (en) * | 1994-11-25 | 2007-05-01 | Volker Breu | Sulfonamides |
US5837708A (en) * | 1994-11-25 | 1998-11-17 | Hoffmann-La Roche Inc. | Sulphonamides |
CN1064965C (zh) * | 1994-11-25 | 2001-04-25 | 弗·哈夫曼-拉罗切有限公司 | 新的磺酰胺类化合物及其作为药物的用途 |
RU2151767C1 (ru) * | 1994-12-20 | 2000-06-27 | Ф.Хоффманн-Ля Рош Аг | Сульфонамиды и фармацевтическая композиция |
TW313568B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1994-12-20 | 1997-08-21 | Hoffmann La Roche | |
NZ297774A (en) * | 1994-12-20 | 1998-10-28 | Hoffmann La Roche | Aryl and heteroaryl sulphonamide derivatives; preparation and medicaments |
ES2196090T3 (es) * | 1994-12-28 | 2003-12-16 | Kowa Co | Derivados pirimidinicos. |
US5780473A (en) * | 1995-02-06 | 1998-07-14 | Bristol-Myers Squibb Company | Substituted biphenyl sulfonamide endothelin antagonists |
US5760038A (en) * | 1995-02-06 | 1998-06-02 | Bristol-Myers Squibb Company | Substituted biphenyl sulfonamide endothelin antagonists |
US5573762A (en) | 1995-04-24 | 1996-11-12 | Genentech, Inc. | Use of leukemia inhibitory factor specific antibodies and endothelin antagonists for treatment of cardiac hypertrophy |
US5739333A (en) * | 1995-05-16 | 1998-04-14 | Tanabe Seiyaku Co., Ltd. | Sulfonamide derivative and process for preparing the same |
UA58494C2 (uk) * | 1995-06-07 | 2003-08-15 | Зенека Лімітед | Похідні n-гетероарилпіридинсульфонаміду, фармацевтична композиція, спосіб одержання та спосіб протидії впливам ендотеліну |
GB9512697D0 (en) * | 1995-06-22 | 1995-08-23 | Zeneca Ltd | Heterocyclic compounds |
DE19527568A1 (de) * | 1995-07-28 | 1997-01-30 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
US5846990A (en) * | 1995-07-24 | 1998-12-08 | Bristol-Myers Squibb Co. | Substituted biphenyl isoxazole sulfonamides |
DE19528418A1 (de) * | 1995-08-02 | 1997-02-06 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
DE19530032A1 (de) * | 1995-08-16 | 1997-02-20 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
EP0852226B1 (en) * | 1995-09-06 | 2003-11-19 | Kowa Co. Ltd. | Pyrimidine derivatives |
JPH09124620A (ja) | 1995-10-11 | 1997-05-13 | Bristol Myers Squibb Co | 置換ビフェニルスルホンアミドエンドセリン拮抗剤 |
CZ260596A3 (en) * | 1995-10-12 | 1997-12-17 | Hoffmann La Roche | Sulfonamide derivative, process of its preparation and pharmaceutical composition containing thereof |
US6228861B1 (en) | 1995-11-16 | 2001-05-08 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
AU703386B2 (en) * | 1995-12-20 | 1999-03-25 | Astellas Pharma Inc. | Arylethenesulfonamide derivatives and drug composition containing the same |
US5977117A (en) * | 1996-01-05 | 1999-11-02 | Texas Biotechnology Corporation | Substituted phenyl compounds and derivatives thereof that modulate the activity of endothelin |
JP2001523218A (ja) | 1996-02-20 | 2001-11-20 | ブリストル―マイヤーズ・スクイブ・カンパニー | ビフェニルイソキサゾール・スルホンアミドの製造法 |
US5856507A (en) * | 1997-01-21 | 1999-01-05 | Bristol-Myers Squibb Co. | Methods for the preparation of biphenyl isoxazole sulfonamides |
US5958905A (en) * | 1996-03-26 | 1999-09-28 | Texas Biotechnology Corporation | Phosphoramidates, phosphinic amides and related compounds and the use thereof to modulate the activity of endothelin |
US5939446A (en) * | 1996-04-09 | 1999-08-17 | Bristol-Myers Squibb Co. | Heteroaryl substituted phenyl isoxazole sulfonamide endothelin antagonists |
US5804585A (en) | 1996-04-15 | 1998-09-08 | Texas Biotechnology Corporation | Thieno-pyridine sulfonamides derivatives thereof and related compounds that modulate the activity of endothelin |
US6172066B1 (en) | 1996-05-16 | 2001-01-09 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
US6245773B1 (en) | 1996-05-16 | 2001-06-12 | Synaptic Pharmaceutical Corporation | 5-(heterocyclic alkyl)-6-aryl-dihydropyrimidines |
WO1998006700A1 (en) * | 1996-08-09 | 1998-02-19 | Merck & Co., Inc. | Stereoselective deoxygenation reaction |
WO1998011913A1 (en) * | 1996-09-16 | 1998-03-26 | Dalhousie University | Use of igf-i for the treatment of polycystic kidney disease and related indications |
US5883254A (en) * | 1996-11-08 | 1999-03-16 | Hoffmann-La Roche Inc. | Process for making pyrimidine derivatives |
DE19653024A1 (de) * | 1996-12-19 | 1998-06-25 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
US5998625A (en) * | 1997-01-14 | 1999-12-07 | Merck & Co., Inc. | Asymmetric conjugate addition reaction using a chiral additive |
HRP980001A2 (en) * | 1997-01-14 | 1998-10-31 | Feng Xu | Asymmetric conjugate addition reaction using a chiral additive |
TW536540B (en) * | 1997-01-30 | 2003-06-11 | Bristol Myers Squibb Co | Endothelin antagonists: N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide and N-(4,5-dimethyl-3-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4'-(2-oxazolyl)[1,1'-biphe |
WO1998033781A1 (en) * | 1997-01-30 | 1998-08-06 | Bristol-Myers Squibb Company | Method for preventing or treating low renin hypertension by administering an endothelin antagonist |
PL197843B1 (pl) | 1997-04-28 | 2008-05-30 | Encysive Pharmaceuticals Inc | Farmaceutycznie dopuszczalne sole metali alkalicznych ze związkami sulfonoamidowymi, środek farmaceutyczny, zastosowanie farmaceutycznie dopuszczalnych soli metali alkalicznych ze związkami sulfonoamidowymi, sposób wytwarzania liofilizowanego proszku i sposób wytwarzania farmaceutycznie dopuszczalnych soli metali alkalicznych ze związkami sulfonoamidowymi |
US5783705A (en) | 1997-04-28 | 1998-07-21 | Texas Biotechnology Corporation | Process of preparing alkali metal salys of hydrophobic sulfonamides |
US6022972A (en) | 1997-08-08 | 2000-02-08 | Merck & Co., Inc. | Pyridine propanoic acid derivatives |
US6410554B1 (en) | 1998-03-23 | 2002-06-25 | Merck & Co., Inc. | Combination therapy for the treatment of benign prostatic hyperplasia |
US6136971A (en) * | 1998-07-17 | 2000-10-24 | Roche Colorado Corporation | Preparation of sulfonamides |
US6274585B1 (en) | 1998-12-23 | 2001-08-14 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
US6680323B2 (en) | 1998-12-23 | 2004-01-20 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
KR20020004974A (ko) | 1999-03-19 | 2002-01-16 | 스티븐 비. 데이비스 | 비페닐 이속사졸 술폰아미드의 제조방법 |
DE19916719A1 (de) * | 1999-04-13 | 2000-10-19 | Basf Ag | Neue ECE-Inhibitoren, ihre Herstellung und Verwendung |
US7566452B1 (en) | 1999-05-04 | 2009-07-28 | New York University | Cancer treatment with endothelin receptor antagonists |
IL149529A0 (en) * | 1999-12-22 | 2002-11-10 | Actelion Pharmaceuticals Ltd | Butyne diol derivatives |
US6720322B2 (en) * | 1999-12-22 | 2004-04-13 | Actelion Pharamceuticals Ltd. | Butyne diol derivatives |
NZ519717A (en) | 1999-12-31 | 2003-06-30 | Texas Biotechnology Corp | Sulfonamides and derivatives thereof that modulate the activity of endothelin |
CA2397258C (en) * | 2000-01-25 | 2007-07-03 | F. Hoffmann-La Roche Ag | Preparation of sulfonamides |
GB0001621D0 (en) * | 2000-01-26 | 2000-03-15 | Astrazeneca Ab | Pharmaceutical compositions |
US6521632B2 (en) | 2000-02-11 | 2003-02-18 | Oy Juvantia Pharma Ltd | Method for the treatment or prevention of a disease mediated by the alpha-2B-adrenoceptor |
CA2399421A1 (en) * | 2000-02-11 | 2001-08-16 | Siegfried Wurster | Compounds useful for the treatment or prevention of a disease mediated by the alpha-2b-adrenoceptor |
US6720324B2 (en) | 2000-07-05 | 2004-04-13 | Synaptic Pharmaceutical Corporation | Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof |
MY140724A (en) * | 2000-07-21 | 2010-01-15 | Actelion Pharmaceuticals Ltd | Novel arylethene-sulfonamides |
WO2003079972A2 (en) | 2002-02-22 | 2003-10-02 | New River Parmaceuticals Inc. | Active agent delivery systems and methods for protecting and administering active agents |
US6670362B2 (en) | 2000-09-20 | 2003-12-30 | Pfizer Inc. | Pyridazine endothelin antagonists |
US6639082B2 (en) | 2000-10-17 | 2003-10-28 | Bristol-Myers Squibb Company | Methods for the preparation of biphenyl isoxazole sulfonamides |
US8168616B1 (en) | 2000-11-17 | 2012-05-01 | Novartis Ag | Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension |
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". |
MXPA04000615A (es) * | 2001-07-20 | 2004-04-20 | Juvantia Pharma Ltd Oy | Compuestos utiles para el tratamiento o la prevencion de enfermedades mediadas por alfa-2b-adrenoceptor. |
FI116940B (fi) | 2001-07-20 | 2006-04-13 | Juvantia Pharma Ltd Oy | Alfa-2B-adrenoseptorivälitteisen sairauden hoitoon tai ehkäisyyn käyttökelpoiset yhdisteet |
FR2831446B1 (fr) * | 2001-10-26 | 2004-03-05 | Sanofi Synthelabo | Utilisation de l'irbesartan pour la preparation de medicaments utiles pour la prevention ou le traitement de l'hypertension pulmonaire |
CA2485681C (en) | 2002-05-24 | 2012-10-16 | Millennium Pharmaceuticals, Inc. | Ccr9 inhibitors and methods of use thereof |
GB0219660D0 (en) | 2002-08-23 | 2002-10-02 | Astrazeneca Ab | Therapeutic use |
US20040102361A1 (en) * | 2002-11-27 | 2004-05-27 | Frederic Bodin | Pharmaceutical composition for the treatment of pulmonary arterial hypertension |
EP1569914B1 (en) | 2002-12-02 | 2009-02-18 | Actelion Pharmaceuticals Ltd. | Pyrimidine-sulfamides and their use as endothelian receptor antagonist |
US20050101608A1 (en) * | 2003-09-24 | 2005-05-12 | Santel Donald J. | Iloprost in combination therapies for the treatment of pulmonary arterial hypertension |
GB0327839D0 (en) | 2003-12-01 | 2003-12-31 | Novartis Ag | Organic compounds |
GB0403744D0 (en) | 2004-02-20 | 2004-03-24 | Astrazeneca Ab | Chemical process |
RU2426532C2 (ru) | 2004-03-17 | 2011-08-20 | Новартис Аг | Применение органических соединений |
KR20070054644A (ko) * | 2004-07-26 | 2007-05-29 | 액테리온 파마슈티칼 리미티드 | 미립자 제형으로 흡입된 일로프로스트에 의한 폐고혈압의치료 |
TW200628467A (en) | 2004-11-11 | 2006-08-16 | Actelion Pharmaceuticals Ltd | Novel sulfamides |
WO2006123285A2 (en) * | 2005-05-17 | 2006-11-23 | Actelion Pharmaceuticals Ltd | Dispersible bosertan tablet |
GT200600381A (es) | 2005-08-25 | 2007-03-28 | Compuestos organicos | |
WO2007031933A2 (en) | 2005-09-12 | 2007-03-22 | Actelion Pharmaceuticals Ltd | Stable pharmaceutical composition comprising a pyrimidine-sulfamide |
WO2007050783A2 (en) * | 2005-10-26 | 2007-05-03 | Asahi Kasei Pharma Corporation | Fasudil in combination therapies for the treatment of pulmonary arterial hypertension |
EP2351569B1 (en) | 2005-10-26 | 2012-08-22 | Asahi Kasei Pharma Corporation | Fasudil in combination therapies for the treatment of pulmonary arterial hypertension |
MX2008011842A (es) * | 2006-03-13 | 2008-10-02 | Encysive Pharmaceuticals Inc | Procedimientos y composiciones para el tratamiento de insuficiencia cardiaca diastolica. |
CA2644784A1 (en) * | 2006-03-13 | 2007-09-20 | Jinling Chen | Formulations of sitaxsentan sodium |
JP2009533420A (ja) * | 2006-04-13 | 2009-09-17 | アクテリオン ファーマシューティカルズ リミテッド | 早期特発性肺線維症の治療 |
US20080026061A1 (en) * | 2006-06-22 | 2008-01-31 | Reichwein John F | Crystalline N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-methyl-4.5-(methylenedioxy)phenylacetyl]-thiophene-3-sulfonamide |
HRP20140183T1 (hr) | 2006-07-20 | 2014-04-11 | Novartis Ag | Derivati amino-piperidina kao cetp-inhibitori |
AR062501A1 (es) * | 2006-08-29 | 2008-11-12 | Actelion Pharmaceuticals Ltd | Composiciones terapeuticas |
US8071596B2 (en) | 2007-01-12 | 2011-12-06 | Concert Pharmaceuticals, Inc. | Endothelin receptor antagonists |
US8080549B2 (en) * | 2007-01-12 | 2011-12-20 | Concert Pharmaceuticals, Inc. | Endothelin receptor antagonists |
AU2008232425A1 (en) * | 2007-04-02 | 2008-10-09 | Auspex Pharmaceuticals, Inc. | Substituted pyrimidines |
AU2008247169B2 (en) * | 2007-05-08 | 2013-09-12 | Generics [Uk] Limited | Polymorphic forms of bosentan |
CA2694242C (en) | 2007-06-29 | 2013-10-01 | Generics [Uk] Limited | Process for introduction of hydroxyethoxy side chain in bosentan |
MX2010001837A (es) | 2007-08-17 | 2010-03-10 | Actelion Pharmaceuticals Ltd | Derivados de 4-pirimidinasulfamida. |
US20090069351A1 (en) * | 2007-09-09 | 2009-03-12 | Protia, Llc | Deuterium-enriched bosentan |
WO2009047637A1 (en) * | 2007-10-11 | 2009-04-16 | Actavis Group Ptc Ehf | Novel polymorphs of bosentan |
CA2703230A1 (en) * | 2007-10-24 | 2009-04-30 | Generics [Uk] Limited | Novel crystalline forms |
ES2381518T3 (es) | 2007-11-05 | 2012-05-29 | Novartis Ag | Derivados del 4-bencilamino-1-carboxi acil-piperidina como inhibidores de CETP útiles para el tratamiento de enfermedades tales como hiperlipidemia o arteroesclerosis |
PL2229356T3 (pl) | 2007-12-03 | 2012-03-30 | Novartis Ag | 1,2-Dipodstawione pochodne 4-benzyloamino-pirolidyny jako inhibitory CETP użyteczne do leczenia chorób, takich jak hiperlipidemia lub stwardnienie tętnic |
ATE530531T1 (de) * | 2007-12-18 | 2011-11-15 | Dipharma Francis Srl | Verfahren zur herstellung von bosentan |
EP2248805A3 (en) | 2008-01-01 | 2011-02-23 | Cipla Ltd. | Method of synthesis of bosentan, its polymorphic forms and its salts |
WO2009095933A2 (en) * | 2008-01-10 | 2009-08-06 | Msn Laboratories Limited | Improved and novel process for the preparation of bosentan |
US20110021547A1 (en) * | 2008-01-24 | 2011-01-27 | Actavis Group Ptc Ehf | Substantially Pure and a Stable Crystalline Form of Bosentan |
CA2712860C (en) | 2008-02-08 | 2014-11-18 | Abhay Gaitonde | Process for preparing bosentan |
CN101279948B (zh) * | 2008-03-14 | 2010-08-11 | 苏州博鸿化工技术有限公司 | 4,6-二氯-5-(2-甲氧基苯氧基)-2,2'-二嘧啶的合成方法 |
EP2294056A1 (en) * | 2008-05-23 | 2011-03-16 | Synthon B.V. | Bosentan salts |
CN102137669A (zh) * | 2008-06-03 | 2011-07-27 | 弗雷森纽斯医疗护理德国有限责任公司 | 包含γ分泌酶调节剂的药物组合物 |
WO2010012637A1 (en) * | 2008-08-01 | 2010-02-04 | Inke, S.A. | Process for the preparation of bosentan |
WO2010015623A1 (en) * | 2008-08-05 | 2010-02-11 | Farmaprojects, S. A. | Process for the preparation of endothelin receptor antagonists |
EP2331513A1 (en) * | 2008-08-12 | 2011-06-15 | Cadila Healthcare Limited | Process for preparation of bosentan |
CA2741928A1 (en) * | 2008-11-03 | 2010-06-03 | Generics [Uk] Limited | Hplc method for the analysis of bosentan and related substances and use of these substances as reference standards and markers |
IT1393136B1 (it) * | 2009-03-11 | 2012-04-11 | Sifa Vitor S R L | Procedimento per la preparazione del bosentan |
US20100256371A1 (en) * | 2009-04-02 | 2010-10-07 | Glenmark | Processes for the preparation of bosentan and its intermediates thereof |
WO2010118992A1 (en) | 2009-04-13 | 2010-10-21 | Sandoz Ag | Process for preparation of endothelial receptor antagonist (bosentan) |
CA2761853A1 (en) | 2009-05-15 | 2010-11-18 | Novartis Ag | Benzoxazolone derivatives as aldosterone synthase inhibitors |
SI2429995T1 (sl) | 2009-05-15 | 2014-05-30 | Novartis Ag | Arilpiridini kot inhibitorji aldosteron sintaze |
KR101442897B1 (ko) | 2009-05-28 | 2014-09-23 | 노파르티스 아게 | 네프릴리신 억제제로서의 치환된 아미노프로피온산 유도체 |
EP2435402B1 (en) | 2009-05-28 | 2016-04-13 | Novartis AG | Substituted aminobutyric derivatives as neprilysin inhibitors |
WO2011024056A2 (en) | 2009-08-27 | 2011-03-03 | Aurobindo Pharma Limited | An improved process for the preparation of bosentan |
CA2781541A1 (en) | 2009-11-12 | 2011-05-19 | Ranbaxy Laboratories Limited | Crystalline forms of bosentan salt and processes for their preparation |
ES2551002T3 (es) | 2009-11-17 | 2015-11-13 | Novartis Ag | Derivados de aril-piridina como inhibidores de la aldosterona sintasa |
JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
ES2472446T3 (es) | 2009-11-30 | 2014-07-01 | Novartis Ag | Derivados de imidazol como inhibidores de aldosterona sintasa |
US20120283190A1 (en) | 2009-12-09 | 2012-11-08 | Institut National de la Santé et de la Recherche Medicale (INSERM) | Endothelin inhibitors for the treatment of rapidly progressive glomerulonephritis |
EP2368884A1 (en) | 2010-03-25 | 2011-09-28 | Laboratorios Lesvi, S.L. | Process for the preparation of bosentan |
JP5850576B2 (ja) * | 2010-07-06 | 2016-02-03 | 富士化学工業株式会社 | ボセンタン固体分散体 |
WO2012020421A1 (en) | 2010-08-11 | 2012-02-16 | Megafine Pharma (P) Ltd. | A novel process for preparation of bosentan |
WO2012041764A1 (en) * | 2010-10-01 | 2012-04-05 | Zach System S.P.A. | Process for preparing bosentan monohydrate and its intermediates |
WO2012056468A1 (en) | 2010-10-13 | 2012-05-03 | Matrix Laboratories Ltd | A process for the preparation of bosentan |
US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
US8877815B2 (en) | 2010-11-16 | 2014-11-04 | Novartis Ag | Substituted carbamoylcycloalkyl acetic acid derivatives as NEP |
US20130303762A1 (en) | 2010-12-03 | 2013-11-14 | Jayaraman Venkat Raman | Process for preparing bosentan |
ES2386173B1 (es) * | 2011-01-13 | 2013-06-25 | Urquima, S.A. | Proceso de preparación de un antagonista del receptor de la endotelina |
WO2012139736A1 (en) | 2011-04-11 | 2012-10-18 | Alfred E. Tiefenbacher (Gmbh & Co. Kg) | Pharmaceutical composition comprising bosentan |
WO2012159456A1 (zh) * | 2011-05-23 | 2012-11-29 | 昂科生物医学技术(苏州)有限公司 | 一种cdc42抑制剂及其应用 |
WO2013098577A1 (en) | 2011-12-31 | 2013-07-04 | Abdi Ibrahim Ilac Sanayi Ve Ticaret Anonim Sirketi | Pharmaceutical compositions of bosentan |
US20130245259A1 (en) | 2012-03-16 | 2013-09-19 | Natco Pharma Limited | Process for the preparation of bosentan monohydrate |
ITMI20120701A1 (it) | 2012-04-27 | 2013-10-28 | Dipharma Francis Srl | Procedimento per la purificazione di un composto benzensolfonammidico |
US20140377346A1 (en) | 2012-05-11 | 2014-12-25 | Hanall Biopharma Co., Ltd. | Bosentan controlled release oral preparation |
JP2015521594A (ja) | 2012-06-12 | 2015-07-30 | カディラ ファーマシューティカルズ リミテッド | ボセンタンの製造方法 |
US9296705B2 (en) | 2012-08-31 | 2016-03-29 | Davuluri Ramamohan Rao | 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2(2-pyrimidinyl)-pyrimidine-4-yl)-benzen esulfonamide sodium |
UY35144A (es) | 2012-11-20 | 2014-06-30 | Novartis Ag | Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca |
KR102004422B1 (ko) | 2012-12-20 | 2019-07-26 | 제일약품주식회사 | 보센탄 일수화물의 제조방법, 이에 사용되는 신규 중간체 및 이의 제조방법 |
BR112015019369A2 (pt) | 2013-02-14 | 2017-07-18 | Novartis Ag | derivados de ácido bisfenil butanóico substituídos como inibidores de nep (endopeptidase neutra) |
PE20160878A1 (es) | 2013-07-25 | 2016-09-08 | Novartis Ag | Polipeptidos ciclicos para el tratamiento de la insuficiencia cardiaca |
TW201518323A (zh) | 2013-07-25 | 2015-05-16 | Novartis Ag | 合成apelin多肽之生物結合物 |
CN103554037B (zh) * | 2013-11-08 | 2015-03-18 | 南京靖龙药物研发有限公司 | 一种波生坦代谢物羟基波生坦的制备方法 |
WO2016116842A1 (en) | 2015-01-23 | 2016-07-28 | Novartis Ag | Synthetic apelin fatty acid conjugates with improved half-life |
ES2584534B1 (es) | 2015-03-27 | 2017-03-13 | Retinset, S.L. | Formulación tópica oftálmica de bosentan |
KR20220123727A (ko) | 2016-06-10 | 2022-09-08 | 비타이 파마슈티컬즈, 엘엘씨 | 메닌-mll 상호 작용의 억제제 |
WO2018185516A1 (en) | 2017-04-05 | 2018-10-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for treating cardiovascular toxicity induced by anti-cancer therapy |
UY38072A (es) | 2018-02-07 | 2019-10-01 | Novartis Ag | Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos |
WO2023078463A1 (zh) * | 2021-11-08 | 2023-05-11 | 正大天晴药业集团股份有限公司 | 氮杂联苯类化合物及其应用 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1545944A1 (de) * | 1964-06-19 | 1969-12-11 | Hoffmann La Roche | Verfahren zur Herstellung von neuen Sulfonamiden der Pyrimidinreihe |
AU6623690A (en) * | 1990-10-29 | 1992-05-26 | Ibrahim Raouf Shimi | Novel sulfamide derivatives, a method for obtaining them and their use as a drug |
-
1992
- 1992-01-31 RU SU925011139A patent/RU2086544C1/ru active Protection Beyond IP Right Term
- 1992-06-04 EP EP92109431A patent/EP0526708B1/de not_active Expired - Lifetime
- 1992-06-04 DK DK92109431T patent/DK0526708T3/da not_active Application Discontinuation
- 1992-06-04 DE DE59209872T patent/DE59209872D1/de not_active Expired - Lifetime
- 1992-06-04 DE DE10299047C patent/DE10299047I2/de active Active
- 1992-06-04 PT PT92109431T patent/PT526708E/pt unknown
- 1992-06-04 AT AT92109431T patent/ATE197044T1/de active
- 1992-06-04 ES ES92109431T patent/ES2152222T4/es not_active Expired - Lifetime
- 1992-06-04 SG SG1996004376A patent/SG54209A1/en unknown
- 1992-06-05 ZA ZA924126A patent/ZA924126B/xx unknown
- 1992-06-09 MX MX9202747A patent/MX9202747A/es active IP Right Grant
- 1992-06-09 IL IL10213892A patent/IL102138A/en active Protection Beyond IP Right Term
- 1992-06-09 NZ NZ243074A patent/NZ243074A/en not_active IP Right Cessation
- 1992-06-09 US US07/896,015 patent/US5292740A/en not_active Expired - Lifetime
- 1992-06-09 AU AU18121/92A patent/AU653604B2/en not_active Expired
- 1992-06-10 JP JP4174993A patent/JPH0730042B2/ja not_active Expired - Fee Related
- 1992-06-10 HU HU9201930A patent/HU221203B1/hu active Protection Beyond IP Right Term
- 1992-06-10 DZ DZ920066A patent/DZ1587A1/fr active
- 1992-06-11 RO RO92-0780A patent/RO111268B/ro unknown
- 1992-06-12 NO NO922323A patent/NO303826B1/no not_active IP Right Cessation
- 1992-06-12 IS IS3877A patent/IS2054B/is unknown
- 1992-06-12 KR KR1019920010205A patent/KR100235507B1/ko not_active Expired - Lifetime
- 1992-06-12 FI FI922746A patent/FI112216B/fi active Protection Beyond IP Right Term
- 1992-06-12 SK SK1804-92A patent/SK279006B6/sk not_active IP Right Cessation
- 1992-06-12 CA CA002071193A patent/CA2071193C/en not_active Expired - Lifetime
- 1992-06-12 CZ CS921804A patent/CZ281434B6/cs not_active IP Right Cessation
- 1992-06-15 BR BR929202219A patent/BR9202219A/pt not_active Application Discontinuation
- 1992-07-01 IE IE192092A patent/IE921920A1/en active Protection Beyond IP Right Term
- 1992-11-18 TW TW081109235A patent/TW222625B/zh not_active IP Right Cessation
-
1994
- 1994-02-28 BG BG098607A patent/BG60831B2/bg unknown
- 1994-11-23 EE EE9400322A patent/EE03028B1/xx unknown
-
1995
- 1995-06-20 HU HU95P/P00261P patent/HU211683A9/hu unknown
-
2000
- 2000-12-28 GR GR20000402849T patent/GR3035162T3/el unknown
-
2001
- 2001-11-01 CY CY0100036A patent/CY2306B1/xx unknown
-
2002
- 2002-09-02 NL NL300097C patent/NL300097I1/nl unknown
- 2002-10-16 LU LU90976C patent/LU90976I2/fr unknown
- 2002-10-16 LU LU90975C patent/LU90975I2/fr unknown
- 2002-10-29 NO NO2002012C patent/NO2002012I2/no unknown
-
2004
- 2004-10-27 CY CY2004005C patent/CY2004005I2/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPH0730042B2 (ja) | スルホンアミド類および薬物としてのそれらの使用 | |
KR100238366B1 (ko) | 설폰아미드 및 이를 함유하는 약제학적 제제 | |
EP0959072B1 (en) | Sulfonamide derivative and process for preparing the same | |
US5420129A (en) | Phenylsulfonylamide pyrimidine | |
RU2162084C2 (ru) | Сульфонамиды и фармацевтический препарат | |
JP2004509874A (ja) | 新規なアリールアルカン−スルフォンアミド類 | |
JP3067131B2 (ja) | 医薬組成物 | |
RU2083567C1 (ru) | Производные арилсульфонамида или их соли и фармацевтическая композиция, проявляющая ангиопротекторное, антигипертензивное и вазоспазмолитическое, в частности противоишемическое, действие | |
JPH10226649A (ja) | 医薬組成物 | |
JPH10194972A (ja) | 医薬組成物 | |
JPH08311043A (ja) | スルホンアミド誘導体 | |
SA92130049B1 (ar) | سلفوناميدات sulphonamides | |
SI9200268A (sl) | Uporaba sulfonamidov za pripravo zdravil in novi sulfonamidi |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S201 | Request for registration of exclusive licence |
Free format text: JAPANESE INTERMEDIATE CODE: R314201 |
|
S202 | Request for registration of non-exclusive licence |
Free format text: JAPANESE INTERMEDIATE CODE: R315201 |
|
R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
R371 | Transfer withdrawn |
Free format text: JAPANESE INTERMEDIATE CODE: R371 |
|
S202 | Request for registration of non-exclusive licence |
Free format text: JAPANESE INTERMEDIATE CODE: R315201 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R371 | Transfer withdrawn |
Free format text: JAPANESE INTERMEDIATE CODE: R371 |
|
S202 | Request for registration of non-exclusive licence |
Free format text: JAPANESE INTERMEDIATE CODE: R315201 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R153 | Grant of patent term extension |
Free format text: JAPANESE INTERMEDIATE CODE: R153 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20080405 Year of fee payment: 13 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090405 Year of fee payment: 14 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090405 Year of fee payment: 14 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100405 Year of fee payment: 15 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110405 Year of fee payment: 16 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130405 Year of fee payment: 18 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140405 Year of fee payment: 19 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |