NO841439L - Fremgangsmaate for fremstilling av terapeutisk aktive triazin-derivater - Google Patents
Fremgangsmaate for fremstilling av terapeutisk aktive triazin-derivaterInfo
- Publication number
- NO841439L NO841439L NO841439A NO841439A NO841439L NO 841439 L NO841439 L NO 841439L NO 841439 A NO841439 A NO 841439A NO 841439 A NO841439 A NO 841439A NO 841439 L NO841439 L NO 841439L
- Authority
- NO
- Norway
- Prior art keywords
- compound
- general formula
- salt
- defined above
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 57
- 238000002360 preparation method Methods 0.000 title description 6
- IMHBYKMAHXWHRP-UHFFFAOYSA-N anilazine Chemical class ClC1=CC=CC=C1NC1=NC(Cl)=NC(Cl)=N1 IMHBYKMAHXWHRP-UHFFFAOYSA-N 0.000 title 1
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 147
- -1 amino, carboxy, hydroxy, ureido Chemical group 0.000 claims description 122
- 150000003839 salts Chemical class 0.000 claims description 111
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- 125000003282 alkyl amino group Chemical group 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000004076 pyridyl group Chemical group 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 239000002585 base Substances 0.000 claims description 17
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 125000002541 furyl group Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000004193 piperazinyl group Chemical group 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 9
- 125000001589 carboacyl group Chemical group 0.000 claims description 9
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
- 125000005544 phthalimido group Chemical group 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 230000002829 reductive effect Effects 0.000 claims description 8
- HCXJFMDOHDNDCC-UHFFFAOYSA-N 5-$l^{1}-oxidanyl-3,4-dihydropyrrol-2-one Chemical group O=C1CCC(=O)[N]1 HCXJFMDOHDNDCC-UHFFFAOYSA-N 0.000 claims description 7
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 7
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 7
- 125000006319 alkynyl amino group Chemical group 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910017604 nitric acid Inorganic materials 0.000 claims description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 6
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 6
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000005504 styryl group Chemical group 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- PEVNNZLSNNLVCI-UHFFFAOYSA-N 2-hydroxy-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]propanamide Chemical compound C1=CC(NC(=O)C(O)C)=CC=C1C1=NNC(=O)NC1C PEVNNZLSNNLVCI-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 claims description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 3
- 238000003379 elimination reaction Methods 0.000 claims description 3
- 239000012312 sodium hydride Substances 0.000 claims description 3
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 3
- 150000003973 alkyl amines Chemical group 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- SCSVAFVWECLKQF-UHFFFAOYSA-N 2-amino-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]acetamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)CN)C=C1 SCSVAFVWECLKQF-UHFFFAOYSA-N 0.000 claims 1
- 230000008030 elimination Effects 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 148
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 139
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
- 238000002844 melting Methods 0.000 description 112
- 230000008018 melting Effects 0.000 description 112
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- 238000002329 infrared spectrum Methods 0.000 description 56
- 239000000203 mixture Substances 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 50
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 238000004458 analytical method Methods 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 40
- 238000003756 stirring Methods 0.000 description 38
- 238000001914 filtration Methods 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 239000002244 precipitate Substances 0.000 description 28
- 239000002904 solvent Substances 0.000 description 25
- 238000001816 cooling Methods 0.000 description 24
- RFIKVHSAMRFXOM-UHFFFAOYSA-N 6-(4-aminophenyl)-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N)C=C1 RFIKVHSAMRFXOM-UHFFFAOYSA-N 0.000 description 21
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000010438 heat treatment Methods 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 239000012954 diazonium Substances 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 150000001989 diazonium salts Chemical class 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 235000010288 sodium nitrite Nutrition 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 208000025865 Ulcer Diseases 0.000 description 5
- 239000002168 alkylating agent Substances 0.000 description 5
- 229940100198 alkylating agent Drugs 0.000 description 5
- 230000003276 anti-hypertensive effect Effects 0.000 description 5
- 239000003849 aromatic solvent Substances 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000012047 saturated solution Substances 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 239000012258 stirred mixture Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000000767 anti-ulcer Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- GXGRTBMAGICDBN-UHFFFAOYSA-N 6-(4-hydrazinylphenyl)-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one;hydrochloride Chemical compound Cl.CC1NC(=O)NN=C1C1=CC=C(NN)C=C1 GXGRTBMAGICDBN-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 239000002220 antihypertensive agent Substances 0.000 description 3
- 239000003699 antiulcer agent Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 210000004623 platelet-rich plasma Anatomy 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- 238000003797 solvolysis reaction Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- JZAAAYYVBBYTNE-WVQRXBFSSA-N (2R)-2-hydroxy-N-[4-(5-methyl-3-oxo-4,5-dihydro-2H-1,2,4-triazin-6-yl)phenyl]-2-phenylacetamide Chemical compound C([C@H](O)C1=CC=CC=C1)(=O)NC1=CC=C(C=C1)C=1C(NC(NN=1)=O)C JZAAAYYVBBYTNE-WVQRXBFSSA-N 0.000 description 2
- BRMGXYCPPGIPML-UHFFFAOYSA-N 1-methyl-6-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)-3,4-dihydroquinolin-2-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N(C)C(=O)CC2)C2=C1 BRMGXYCPPGIPML-UHFFFAOYSA-N 0.000 description 2
- OYIKUTJFENZXIR-UHFFFAOYSA-N 2-[(1-methyl-2-oxo-3,4-dihydroquinolin-8-yl)oxy]-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]acetamide Chemical compound CC1NC(=O)NN=C1C(C=C1)=CC=C1NC(=O)COC1=CC=CC2=C1N(C)C(=O)CC2 OYIKUTJFENZXIR-UHFFFAOYSA-N 0.000 description 2
- IWSAYFHYFDJKJR-UHFFFAOYSA-N 2-chloro-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]propanamide Chemical compound C1=CC(NC(=O)C(Cl)C)=CC=C1C1=NNC(=O)NC1C IWSAYFHYFDJKJR-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- AEUDROKRWXZQJP-UHFFFAOYSA-N 5-methyl-3-methylsulfanyl-6-(4-phenylmethoxyphenyl)-1,2,4-triazine Chemical compound CC1=NC(SC)=NN=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 AEUDROKRWXZQJP-UHFFFAOYSA-N 0.000 description 2
- UCPPCWADFQBJRE-UHFFFAOYSA-N 5-methyl-6-(4-morpholin-4-ylphenyl)-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N2CCOCC2)C=C1 UCPPCWADFQBJRE-UHFFFAOYSA-N 0.000 description 2
- CMWQXLDKRVZJDC-UHFFFAOYSA-N 5-methyl-6-(4-pyrrolidin-1-ylphenyl)-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N2CCCC2)C=C1 CMWQXLDKRVZJDC-UHFFFAOYSA-N 0.000 description 2
- WALYIQKSMYAQDP-UHFFFAOYSA-N 5-methyl-6-[4-(2-oxopyrrolidin-1-yl)phenyl]-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N2C(CCC2)=O)C=C1 WALYIQKSMYAQDP-UHFFFAOYSA-N 0.000 description 2
- IDAHVMGGUVADIJ-UHFFFAOYSA-N 5-methyl-6-[4-(3-methyl-5-oxo-4h-pyrazol-1-yl)phenyl]-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N2C(CC(C)=N2)=O)C=C1 IDAHVMGGUVADIJ-UHFFFAOYSA-N 0.000 description 2
- ZFVAOEQGGQOENP-UHFFFAOYSA-N 5-methyl-6-[4-(methylamino)phenyl]-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound C1=CC(NC)=CC=C1C1=NNC(=O)NC1C ZFVAOEQGGQOENP-UHFFFAOYSA-N 0.000 description 2
- RYUKAGCWZWOOEP-UHFFFAOYSA-N 6-(4-amino-3-chlorophenyl)-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N)C(Cl)=C1 RYUKAGCWZWOOEP-UHFFFAOYSA-N 0.000 description 2
- FEQYEYLORAJPER-UHFFFAOYSA-N 6-(4-hydrazinylphenyl)-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(NN)C=C1 FEQYEYLORAJPER-UHFFFAOYSA-N 0.000 description 2
- GMQOWCAJJLQSDP-UHFFFAOYSA-N 6-[3-chloro-4-(dimethylamino)phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N(C)C)C(Cl)=C1 GMQOWCAJJLQSDP-UHFFFAOYSA-N 0.000 description 2
- FXQGHBRVMNWVJY-UHFFFAOYSA-N 6-[4-(2-hydroxyethylamino)phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(NCCO)C=C1 FXQGHBRVMNWVJY-UHFFFAOYSA-N 0.000 description 2
- QOWLAULGQWLTMF-UHFFFAOYSA-N 6-[4-(2-methoxyethylamino)phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound C1=CC(NCCOC)=CC=C1C1=NNC(=O)NC1C QOWLAULGQWLTMF-UHFFFAOYSA-N 0.000 description 2
- CWUVETSCYBRJMI-UHFFFAOYSA-N 6-[4-(benzylamino)phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C(C=C1)=CC=C1NCC1=CC=CC=C1 CWUVETSCYBRJMI-UHFFFAOYSA-N 0.000 description 2
- HSDKQKVETSZMMW-UHFFFAOYSA-N 6-[4-(butylamino)phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound C1=CC(NCCCC)=CC=C1C1=NNC(=O)NC1C HSDKQKVETSZMMW-UHFFFAOYSA-N 0.000 description 2
- XYPOPAYFVUVRSG-UHFFFAOYSA-N 6-[4-(dimethylamino)phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N(C)C)C=C1 XYPOPAYFVUVRSG-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- VORNEKHCIKCQLF-UHFFFAOYSA-N [2-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)anilino]-2-oxoethyl] acetate Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)COC(C)=O)C=C1 VORNEKHCIKCQLF-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 238000007098 aminolysis reaction Methods 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 2
- YEUFQUBWCSGTOI-UHFFFAOYSA-N diethyl 1-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]triazole-4,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C(=O)OCC)N=NN1C1=CC=C(C=2C(NC(=O)NN=2)C)C=C1 YEUFQUBWCSGTOI-UHFFFAOYSA-N 0.000 description 2
- 150000002085 enols Chemical group 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- PRFBBSPMRMTDDN-UHFFFAOYSA-N n-[2-chloro-4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]-2-oxopropanamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)C(C)=O)C(Cl)=C1 PRFBBSPMRMTDDN-UHFFFAOYSA-N 0.000 description 2
- WKNHPEMSALYLIE-UHFFFAOYSA-N n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]pyridine-3-carboxamide Chemical compound CC1NC(=O)NN=C1C(C=C1)=CC=C1NC(=O)C1=CC=CN=C1 WKNHPEMSALYLIE-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229960002317 succinimide Drugs 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 150000003918 triazines Chemical class 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- ALHZEIINTQJLOT-UHFFFAOYSA-N (1-chloro-1-oxopropan-2-yl) acetate Chemical compound ClC(=O)C(C)OC(C)=O ALHZEIINTQJLOT-UHFFFAOYSA-N 0.000 description 1
- PEVNNZLSNNLVCI-BRFYHDHCSA-N (2R)-2-hydroxy-N-[4-(5-methyl-3-oxo-4,5-dihydro-2H-1,2,4-triazin-6-yl)phenyl]propanamide Chemical compound C([C@H](O)C)(=O)NC1=CC=C(C=C1)C=1C(NC(NN=1)=O)C PEVNNZLSNNLVCI-BRFYHDHCSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- XZAWSITUGNWYAO-UHFFFAOYSA-N 1-methyl-6-(5-methyl-3-methylsulfanyl-1,2,4-triazin-6-yl)-3,4-dihydroquinolin-2-one Chemical compound CC1=NC(SC)=NN=C1C1=CC=C(N(C)C(=O)CC2)C2=C1 XZAWSITUGNWYAO-UHFFFAOYSA-N 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 1
- WYGOSQGYYMYRSB-UHFFFAOYSA-N 2-(dimethylamino)-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]acetamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)CN(C)C)C=C1 WYGOSQGYYMYRSB-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- OBQGQPWSTFJBHY-UHFFFAOYSA-N 2-[[6-(4-acetamidophenyl)-5-methyl-1,2,4-triazin-3-yl]sulfanyl]acetic acid Chemical compound C1=CC(NC(=O)C)=CC=C1C1=NN=C(SCC(O)=O)N=C1C OBQGQPWSTFJBHY-UHFFFAOYSA-N 0.000 description 1
- KOWZETIWMNABMY-UHFFFAOYSA-N 2-[[6-[4-[acetyl(methyl)amino]phenyl]-5-methyl-1,2,4-triazin-3-yl]sulfanyl]acetic acid Chemical compound C1=CC(N(C(C)=O)C)=CC=C1C1=NN=C(SCC(O)=O)N=C1C KOWZETIWMNABMY-UHFFFAOYSA-N 0.000 description 1
- KRCSSGZXMRRTJK-UHFFFAOYSA-N 2-[di(propan-2-yl)amino]-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]acetamide Chemical compound C1=CC(NC(=O)CN(C(C)C)C(C)C)=CC=C1C1=NNC(=O)NC1C KRCSSGZXMRRTJK-UHFFFAOYSA-N 0.000 description 1
- CPWFUVAMEMQHEK-UHFFFAOYSA-N 2-amino-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]acetamide;hydrochloride Chemical compound Cl.CC1NC(=O)NN=C1C1=CC=C(NC(=O)CN)C=C1 CPWFUVAMEMQHEK-UHFFFAOYSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- MMJOVUJCJDFSGE-UHFFFAOYSA-N 2-chloro-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]acetamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)CCl)C=C1 MMJOVUJCJDFSGE-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- TZXJJSAQSRHKCZ-UHFFFAOYSA-N 2-methoxyethyl 4-methylbenzenesulfonate Chemical compound COCCOS(=O)(=O)C1=CC=C(C)C=C1 TZXJJSAQSRHKCZ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- HFBHPHBIBAUDNE-UHFFFAOYSA-N 2h-1,2,4-triazin-3-one Chemical class O=C1N=CC=NN1 HFBHPHBIBAUDNE-UHFFFAOYSA-N 0.000 description 1
- LQYWKCMPNXKGHT-UHFFFAOYSA-N 3-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)anilino]propylurea Chemical compound CC1NC(=O)NN=C1C1=CC=C(NCCCNC(N)=O)C=C1 LQYWKCMPNXKGHT-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- YVGWLFVGJSEUQH-UHFFFAOYSA-N 3-hydroxy-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]propanamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)CCO)C=C1 YVGWLFVGJSEUQH-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
- KBKHMSRGMRMXQD-UHFFFAOYSA-N 4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)benzenesulfonyl chloride Chemical compound CC1NC(=O)NN=C1C1=CC=C(S(Cl)(=O)=O)C=C1 KBKHMSRGMRMXQD-UHFFFAOYSA-N 0.000 description 1
- BYPXOBVQQPYSAL-UHFFFAOYSA-N 4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)benzonitrile Chemical compound CC1NC(=O)NN=C1C1=CC=C(C#N)C=C1 BYPXOBVQQPYSAL-UHFFFAOYSA-N 0.000 description 1
- QFBYXXGDUFLVJH-UHFFFAOYSA-N 4-chloro-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]butanamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)CCCCl)C=C1 QFBYXXGDUFLVJH-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
- SOUHXSHRRURVTN-UHFFFAOYSA-N 5-methyl-6-(4-phenylmethoxyphenyl)-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 SOUHXSHRRURVTN-UHFFFAOYSA-N 0.000 description 1
- LTHJUYVNAKDPSX-UHFFFAOYSA-N 5-methyl-6-[4-(2-oxo-1,3-diazinan-1-yl)phenyl]-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N2C(NCCC2)=O)C=C1 LTHJUYVNAKDPSX-UHFFFAOYSA-N 0.000 description 1
- GALQTSRPXPIVJP-UHFFFAOYSA-N 5-methyl-6-[4-(2h-tetrazol-5-yl)phenyl]-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(C=2NN=NN=2)C=C1 GALQTSRPXPIVJP-UHFFFAOYSA-N 0.000 description 1
- BNWJNXAEFNYMSN-UHFFFAOYSA-N 5-methyl-6-[4-(pyridin-2-ylamino)phenyl]-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C(C=C1)=CC=C1NC1=CC=CC=N1 BNWJNXAEFNYMSN-UHFFFAOYSA-N 0.000 description 1
- CEJWBKYULAPCRN-UHFFFAOYSA-N 5-phenyl-1,3-dioxolane-2,4-dione Chemical compound O=C1OC(=O)OC1C1=CC=CC=C1 CEJWBKYULAPCRN-UHFFFAOYSA-N 0.000 description 1
- YTZUEXHZSIAHBV-UHFFFAOYSA-N 6-(2-hydroxyiminopropanoyl)-1-methyl-3,4-dihydroquinolin-2-one Chemical compound ON=C(C)C(=O)C1=CC=C2N(C)C(=O)CCC2=C1 YTZUEXHZSIAHBV-UHFFFAOYSA-N 0.000 description 1
- MDTQBRNXXDCMMY-UHFFFAOYSA-N 6-(4-amino-3-bromophenyl)-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N)C(Br)=C1 MDTQBRNXXDCMMY-UHFFFAOYSA-N 0.000 description 1
- DWYGLBNWNHFLDF-UHFFFAOYSA-N 6-(4-azidophenyl)-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N=[N+]=[N-])C=C1 DWYGLBNWNHFLDF-UHFFFAOYSA-N 0.000 description 1
- KBFPPHFYFSTKAT-UHFFFAOYSA-N 6-(4-hydroxyphenyl)-5-methyl-4,5-dihydro-2H-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(O)C=C1 KBFPPHFYFSTKAT-UHFFFAOYSA-N 0.000 description 1
- SJVUASGDOHAEMC-UHFFFAOYSA-N 6-[4-(3,5-dimethylpyrazol-1-yl)phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N2C(=CC(C)=N2)C)C=C1 SJVUASGDOHAEMC-UHFFFAOYSA-N 0.000 description 1
- VIRYLTVMSLYRRK-UHFFFAOYSA-N 6-[4-(3-aminopropylamino)phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(NCCCN)C=C1 VIRYLTVMSLYRRK-UHFFFAOYSA-N 0.000 description 1
- JUAXDUYHUWZEGX-UHFFFAOYSA-N 6-[4-[2-(2-methoxyethoxy)ethylamino]phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound C1=CC(NCCOCCOC)=CC=C1C1=NNC(=O)NC1C JUAXDUYHUWZEGX-UHFFFAOYSA-N 0.000 description 1
- FUWBVVDXIPJXKN-UHFFFAOYSA-N 6-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one;hydrochloride Chemical compound Cl.C1=CC(OCC(O)CNC(C)C)=CC=C1C1=NNC(=O)NC1C FUWBVVDXIPJXKN-UHFFFAOYSA-N 0.000 description 1
- SCAWKRQDJWLYLL-UHFFFAOYSA-N 6-[4-[bis(prop-2-ynyl)amino]phenyl]-5-methyl-4,5-dihydro-2h-1,2,4-triazin-3-one Chemical compound CC1NC(=O)NN=C1C1=CC=C(N(CC#C)CC#C)C=C1 SCAWKRQDJWLYLL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 102100026735 Coagulation factor VIII Human genes 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- PLUBXMRUUVWRLT-UHFFFAOYSA-N Ethyl methanesulfonate Chemical compound CCOS(C)(=O)=O PLUBXMRUUVWRLT-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical class OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- OSTDLYFRFHNWAF-UHFFFAOYSA-N N-[4-[N-(carbamothioylamino)-C-(N-hydroxy-C-methylcarbonimidoyl)carbonimidoyl]phenyl]-N-methylacetamide Chemical compound CC(=O)N(C)C1=CC=C(C(=NNC(N)=S)C(C)=NO)C=C1 OSTDLYFRFHNWAF-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-LZFNBGRKSA-N Potassium-45 Chemical compound [45K] ZLMJMSJWJFRBEC-LZFNBGRKSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- FJXZTWUAQWJCNQ-UHFFFAOYSA-N [2-[2-bromo-4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)anilino]-2-oxoethyl] acetate Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)COC(C)=O)C(Br)=C1 FJXZTWUAQWJCNQ-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 125000005910 alkyl carbonate group Chemical group 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 229940127217 antithrombotic drug Drugs 0.000 description 1
- 150000001484 arginines Chemical class 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 150000001510 aspartic acids Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229910052796 boron Inorganic materials 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
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 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
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000002592 cumenyl group Chemical group C1(=C(C=CC=C1)*)C(C)C 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- STRNXFOUBFLVIN-UHFFFAOYSA-N diethyl but-2-ynedioate Chemical compound CCOC(=O)C#CC(=O)OCC STRNXFOUBFLVIN-UHFFFAOYSA-N 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- KNZJJVNZJYYRFZ-UHFFFAOYSA-N ethyl 2-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)anilino]acetate Chemical compound C1=CC(NCC(=O)OCC)=CC=C1C1=NNC(=O)NC1C KNZJJVNZJYYRFZ-UHFFFAOYSA-N 0.000 description 1
- VRZVPALEJCLXPR-UHFFFAOYSA-N ethyl 4-methylbenzenesulfonate Chemical compound CCOS(=O)(=O)C1=CC=C(C)C=C1 VRZVPALEJCLXPR-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- HFBPPUZNEZGMRI-UHFFFAOYSA-N n-[4-(2-hydroxyiminopropanoyl)phenyl]-n-methylacetamide Chemical compound CC(=O)N(C)C1=CC=C(C(=O)C(C)=NO)C=C1 HFBPPUZNEZGMRI-UHFFFAOYSA-N 0.000 description 1
- FFFXZQGFKFDRLU-UHFFFAOYSA-N n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]-2-morpholin-4-ylacetamide Chemical compound CC1NC(=O)NN=C1C(C=C1)=CC=C1NC(=O)CN1CCOCC1 FFFXZQGFKFDRLU-UHFFFAOYSA-N 0.000 description 1
- ISOAQILKDHYKEO-UHFFFAOYSA-N n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]-2-oxopropanamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)C(C)=O)C=C1 ISOAQILKDHYKEO-UHFFFAOYSA-N 0.000 description 1
- ZYBZOSLBARDLFS-UHFFFAOYSA-N n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]-3-morpholin-4-ylpropanamide Chemical compound CC1NC(=O)NN=C1C(C=C1)=CC=C1NC(=O)CCN1CCOCC1 ZYBZOSLBARDLFS-UHFFFAOYSA-N 0.000 description 1
- KATQISVHWJIMEL-UHFFFAOYSA-N n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]-3-oxobutanamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)CC(C)=O)C=C1 KATQISVHWJIMEL-UHFFFAOYSA-N 0.000 description 1
- WTQASZCLLKBGKN-UHFFFAOYSA-N n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]acetamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(C)=O)C=C1 WTQASZCLLKBGKN-UHFFFAOYSA-N 0.000 description 1
- DLIUORYJTYOLHP-UHFFFAOYSA-N n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]prop-2-enamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)C=C)C=C1 DLIUORYJTYOLHP-UHFFFAOYSA-N 0.000 description 1
- CMKHKZQYFIPGGH-UHFFFAOYSA-N n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]prop-2-ynamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(NC(=O)C#C)C=C1 CMKHKZQYFIPGGH-UHFFFAOYSA-N 0.000 description 1
- XIDNHZMOZXQNSP-UHFFFAOYSA-N n-methyl-n-[4-(5-methyl-3-methylsulfanyl-1,2,4-triazin-6-yl)phenyl]acetamide Chemical compound CC1=NC(SC)=NN=C1C1=CC=C(N(C)C(C)=O)C=C1 XIDNHZMOZXQNSP-UHFFFAOYSA-N 0.000 description 1
- QEEOQDLFNOFPPY-UHFFFAOYSA-N n-methyl-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]-3-phenylprop-2-enamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(N(C)C(=O)C=CC=2C=CC=CC=2)C=C1 QEEOQDLFNOFPPY-UHFFFAOYSA-N 0.000 description 1
- QFMJIACQVKAUMN-UHFFFAOYSA-N n-methyl-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]acetamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(N(C)C(C)=O)C=C1 QFMJIACQVKAUMN-UHFFFAOYSA-N 0.000 description 1
- KICDPNUZNFIOJI-UHFFFAOYSA-N n-methyl-n-[4-(5-methyl-3-oxo-4,5-dihydro-2h-1,2,4-triazin-6-yl)phenyl]benzamide Chemical compound CC1NC(=O)NN=C1C1=CC=C(N(C)C(=O)C=2C=CC=CC=2)C=C1 KICDPNUZNFIOJI-UHFFFAOYSA-N 0.000 description 1
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- FHSWXOCOMAVQKE-UHFFFAOYSA-N phenylazanium;acetate Chemical compound CC([O-])=O.[NH3+]C1=CC=CC=C1 FHSWXOCOMAVQKE-UHFFFAOYSA-N 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
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 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
- 238000000926 separation method Methods 0.000 description 1
- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 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
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D403/10—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 carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—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
- C07D405/12—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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB838310435A GB8310435D0 (en) | 1983-04-18 | 1983-04-18 | Triazine derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
NO841439L true NO841439L (no) | 1984-10-19 |
Family
ID=10541255
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO841439A NO841439L (no) | 1983-04-18 | 1984-04-11 | Fremgangsmaate for fremstilling av terapeutisk aktive triazin-derivater |
Country Status (13)
Country | Link |
---|---|
US (1) | US4616015A (el) |
EP (1) | EP0122627A3 (el) |
JP (1) | JPS601171A (el) |
KR (1) | KR840008340A (el) |
AU (1) | AU2701484A (el) |
DK (1) | DK195384A (el) |
ES (2) | ES531792A0 (el) |
FI (1) | FI841475A (el) |
GB (1) | GB8310435D0 (el) |
GR (1) | GR81781B (el) |
HU (1) | HUT34172A (el) |
NO (1) | NO841439L (el) |
ZA (1) | ZA842695B (el) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS59196874A (ja) * | 1983-04-22 | 1984-11-08 | Fujisawa Pharmaceut Co Ltd | トリアジン誘導体 |
US4898862A (en) * | 1986-03-20 | 1990-02-06 | Sankyo Company Limited | 1,2,4-triazinone derivatives, their preparation and use |
US4970210A (en) * | 1987-07-17 | 1990-11-13 | Abbott Laboratories | Triazinone lipoxygenase compounds |
GB8903130D0 (en) * | 1989-02-11 | 1989-03-30 | Orion Yhtymae Oy | Substituted pyridazinones |
DE4239540A1 (de) * | 1992-11-25 | 1994-05-26 | Asta Medica Ag | Neue heterocyclische Verbindungen mit antiasthmatischer/antiallergischer, entzündungshemmender, positiv inotroper und blutdrucksenkender Wirkung |
DE19540361A1 (de) * | 1995-10-30 | 1997-05-07 | Basf Ag | Phenylessigsäurederivate, Verfahren und Zwischenprodukte zu ihrer Herstellung und ihre Verwendung zur Bekämpfung von Schadpilzen und tierischen Schädlingen |
DE19929781A1 (de) * | 1999-06-29 | 2001-01-04 | Bayer Ag | N-[4-(6-Oxotetrahydrotriazinyl)phenyl]amide und ihre Verwendung |
US6867299B2 (en) * | 2000-02-24 | 2005-03-15 | Hoffmann-La Roche Inc. | Oxamide IMPDH inhibitors |
EP3661917B1 (en) | 2017-08-04 | 2022-05-11 | Bayer Aktiengesellschaft | 6-((3-trifluoromethyl)phenyl)-4,5-dihydropyridazin-3(2h)-one derivatives as pde3a and pde3b inhibitors for treating cancer |
JOP20200024A1 (ar) | 2017-08-04 | 2020-02-02 | Bayer Ag | مركبات ثنائي هيدروكساديازينون |
EP3917915A1 (en) | 2019-02-01 | 2021-12-08 | Bayer Aktiengesellschaft | 1,2,4-triazin-3(2h)-one compounds for the treatment of hyperproliferative diseases |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3172252D1 (en) * | 1980-11-14 | 1985-10-17 | Ici Plc | Heterocyclic compounds |
HU190412B (en) * | 1981-09-17 | 1986-09-29 | Warner-Lambert Co,Us | Process for producing substituted 4,5-dihiydro-6-bracket-substituted-bracket closed-phenyl-3-bracket-2h-bracket closed-pyridazinones and 6-bracket-substituted-bracket closed-phenyl-3-bracket-2h-bracket closed-pyridazinones |
US4639451A (en) * | 1981-10-20 | 1987-01-27 | Mitsui Toatsu Kagaku-Kabushiki Kaisha | Pyridazinone derivatives |
US4495185A (en) * | 1981-11-12 | 1985-01-22 | Imperial Chemical Industries, Plc | 1,2,4-Triazin-3(2H) ones |
ZA827641B (en) * | 1981-11-12 | 1983-09-28 | Ici Plc | Thiadiazine, oxadiazine and triazine derivatives which possess cardiotonic and/or antihypertensive activity |
US4581356A (en) * | 1983-03-22 | 1986-04-08 | Fujisawa Pharmaceutical Co., Ltd. | Triazine derivatives, and pharmaceutical compositions comprising the same |
-
1983
- 1983-04-18 GB GB838310435A patent/GB8310435D0/en active Pending
-
1984
- 1984-04-10 US US06/598,685 patent/US4616015A/en not_active Expired - Fee Related
- 1984-04-11 NO NO841439A patent/NO841439L/no unknown
- 1984-04-11 ZA ZA842695A patent/ZA842695B/xx unknown
- 1984-04-12 GR GR74404A patent/GR81781B/el unknown
- 1984-04-13 FI FI841475A patent/FI841475A/fi not_active Application Discontinuation
- 1984-04-14 EP EP84104241A patent/EP0122627A3/en not_active Withdrawn
- 1984-04-16 DK DK195384A patent/DK195384A/da not_active Application Discontinuation
- 1984-04-17 HU HU841486A patent/HUT34172A/hu unknown
- 1984-04-17 KR KR1019840002015A patent/KR840008340A/ko not_active Application Discontinuation
- 1984-04-17 AU AU27014/84A patent/AU2701484A/en not_active Abandoned
- 1984-04-18 JP JP59078063A patent/JPS601171A/ja active Pending
- 1984-04-18 ES ES531792A patent/ES531792A0/es active Granted
-
1985
- 1985-02-14 ES ES540415A patent/ES8607953A1/es not_active Expired
Also Published As
Publication number | Publication date |
---|---|
GB8310435D0 (en) | 1983-05-25 |
ZA842695B (en) | 1984-11-28 |
HUT34172A (en) | 1985-02-28 |
ES8602705A1 (es) | 1985-12-01 |
KR840008340A (ko) | 1984-12-14 |
JPS601171A (ja) | 1985-01-07 |
US4616015A (en) | 1986-10-07 |
EP0122627A3 (en) | 1987-06-03 |
ES8607953A1 (es) | 1986-06-01 |
FI841475A0 (fi) | 1984-04-13 |
FI841475A (fi) | 1984-10-19 |
ES531792A0 (es) | 1985-12-01 |
AU2701484A (en) | 1985-01-03 |
DK195384A (da) | 1984-10-19 |
ES540415A0 (es) | 1986-06-01 |
EP0122627A2 (en) | 1984-10-24 |
DK195384D0 (da) | 1984-04-16 |
GR81781B (el) | 1984-12-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP3356345B1 (en) | Heteroaryl derivatives as sepiapterin reductase inhibitors | |
US5932576A (en) | 3(5)-heteroaryl substituted pyrazoles as p38 kinase inhibitors | |
Chavez et al. | Synthesis of the bi‐heterocyclic parent ring system 1, 2, 4‐triazolo [4, 3‐b][1, 2, 4, 5] tetrazine and some 3, 6‐disubstituted derivatives | |
EP2922846B1 (en) | Amide-substituted heterocyclic compounds useful as modulators of il-12, il-23 and/or ifn-alpha | |
ES2293064T3 (es) | 6-alcoxi-pirido-pirimidinas como inhibidores de la p-38 map quinasa. | |
AU744016C (en) | Pyrazolo-pyridine derivatives as ligands for gaba receptors | |
CZ376799A3 (cs) | Pyrazolopyrimidinony, které inhibují typ 5 cyklické guanosin 3',5'-monofosfatfosfodiesterasy (cGMP /DE5) pro léčení sexuální dysfunkce | |
EP0502314A1 (de) | Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung | |
AU2011366498A1 (en) | Derivatives of N- [(1H-pyrazol-1-yl) aryl] - 1H - indole or 1H - indazole - 3 - carboxamide, their preparation and their use as P2Y12 antagonists | |
DE69008906T2 (de) | Antiallergische Mittel auf der Basis von Diazepin. | |
EP2225227A2 (de) | Verbindungen | |
PT97776A (pt) | Processo para a preparacao de derivados de azol e de composicoes farmaceuticas que os contem | |
WO2011114148A1 (en) | 4h- [1, 2, 4] triazolo [5, 1 -b] pyrimidin-7 -one derivatives as ccr2b receptor antagonists | |
NO841439L (no) | Fremgangsmaate for fremstilling av terapeutisk aktive triazin-derivater | |
WO2014195400A1 (en) | Kinase inhibitors | |
EA027752B1 (ru) | Терапевтически активные производные пиразолопиримидина | |
WO2017082759A1 (ru) | {3-[(7н-пирролo[2,3-d]пиримидин-4-ил)-азолил]азетидин-3-ил}-ацетонитрилы в качестве ингибиторов янус киназ | |
PT89468A (pt) | Processo para a preparacao de 6-fenil{di-hidro-3(2h)-piridazinonas substituidas e de composicoes farmaceuticas que as contem | |
US4581356A (en) | Triazine derivatives, and pharmaceutical compositions comprising the same | |
EP0077983A1 (en) | Triazine derivatives, processes for preparation thereof and pharmaceutical compositions comprising the same | |
DD248362A5 (de) | Verfahren zur herstellung neuer pyridazinone | |
Kobe et al. | The synthesis and chemical reactions of certain pyrazolo [1, 5‐a]‐1, 3, 5‐triazines | |
EP0656002A1 (en) | 3-oxo-pyrido(1,2-a -)benzimidazole-4-carboxyl and 4-oxo-azepino(1,2-a -)benzimidazole-5-carboxyl derivatives useful in treating central nervous system disorders | |
EP3080098A1 (en) | Inhibitors of bruton's tyrosine kinase | |
WO2008059238A1 (en) | Benzenesulfonamide compounds as edg-1 antagonists useful in the treatment of cancer |