IL32309A - 4,6-dihydro-8-phenylpyrazolo(4,3-e)-(1,4)diazepin-5(1h)-one derivatives - Google Patents
4,6-dihydro-8-phenylpyrazolo(4,3-e)-(1,4)diazepin-5(1h)-one derivativesInfo
- Publication number
- IL32309A IL32309A IL32309A IL3230969A IL32309A IL 32309 A IL32309 A IL 32309A IL 32309 A IL32309 A IL 32309A IL 3230969 A IL3230969 A IL 3230969A IL 32309 A IL32309 A IL 32309A
- Authority
- IL
- Israel
- Prior art keywords
- ethyl
- methyl
- mixture
- amino
- benzoyl
- Prior art date
Links
- JHFFAFPOVIWASH-UHFFFAOYSA-N 8-phenyl-4,6-dihydro-1H-pyrazolo[4,3-e][1,4]diazepin-5-one Chemical class C1(=CC=CC=C1)C=1C2=C(NC(CN1)=O)C=NN2 JHFFAFPOVIWASH-UHFFFAOYSA-N 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- AXXNMFMZZSYXSN-UHFFFAOYSA-N 2h-pyrazolo[4,3-c]diazepin-3-one Chemical class C1=CC=NN=C2C(=O)NN=C21 AXXNMFMZZSYXSN-UHFFFAOYSA-N 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 74
- 239000000203 mixture Substances 0.000 description 74
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 48
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
- 150000001875 compounds Chemical class 0.000 description 36
- 238000000034 method Methods 0.000 description 31
- 238000002425 crystallisation Methods 0.000 description 30
- 230000008025 crystallization Effects 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- -1 heterocyclic nitrogen compounds Chemical class 0.000 description 28
- 239000007787 solid Substances 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 16
- 239000002585 base Substances 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000003208 petroleum Substances 0.000 description 14
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 238000007363 ring formation reaction Methods 0.000 description 9
- 239000012258 stirred mixture Substances 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 7
- 239000007868 Raney catalyst Substances 0.000 description 7
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical group [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 7
- 229910000564 Raney nickel Inorganic materials 0.000 description 7
- 239000003610 charcoal Substances 0.000 description 7
- 239000012458 free base Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical group [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 6
- MRLCGPCAHHAAFI-UHFFFAOYSA-N 1,2-dihydrodiazepin-5-one Chemical class O=C1C=CNNC=C1 MRLCGPCAHHAAFI-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- 239000006185 dispersion Substances 0.000 description 6
- 125000004494 ethyl ester group Chemical group 0.000 description 6
- 238000005984 hydrogenation reaction Methods 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 230000000049 anti-anxiety effect Effects 0.000 description 5
- 239000002249 anxiolytic agent Substances 0.000 description 5
- 235000013336 milk Nutrition 0.000 description 5
- 239000008267 milk Substances 0.000 description 5
- 210000004080 milk Anatomy 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 229910017604 nitric acid Inorganic materials 0.000 description 5
- 150000003217 pyrazoles Chemical class 0.000 description 5
- 208000019901 Anxiety disease Diseases 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 206010010904 Convulsion Diseases 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 4
- SOGYPDKWYFXYEG-UHFFFAOYSA-N 1,2-dihydro-1,4-diazepin-5-one Chemical compound O=C1C=CNCC=N1 SOGYPDKWYFXYEG-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- AGGNMPUDFUROJT-UHFFFAOYSA-N 4-methyl-5-nitro-1h-pyrazole Chemical compound CC=1C=NNC=1[N+]([O-])=O AGGNMPUDFUROJT-UHFFFAOYSA-N 0.000 description 3
- WCQYJWRMYFJLRQ-UHFFFAOYSA-N 5-ethyl-1h-pyrazole-3-carboxylic acid Chemical compound CCC1=CC(C(O)=O)=NN1 WCQYJWRMYFJLRQ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 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 3
- CJUMAFVKTCBCJK-UHFFFAOYSA-N N-benzyloxycarbonylglycine Chemical compound OC(=O)CNC(=O)OCC1=CC=CC=C1 CJUMAFVKTCBCJK-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 230000001773 anti-convulsant effect Effects 0.000 description 3
- 239000001961 anticonvulsive agent Substances 0.000 description 3
- 229960003965 antiepileptics Drugs 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229960004782 chlordiazepoxide Drugs 0.000 description 3
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
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- 229960001701 chloroform Drugs 0.000 description 3
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- 230000036461 convulsion Effects 0.000 description 3
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 3
- 229960003529 diazepam Drugs 0.000 description 3
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000012022 methylating agents Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- BGMBZPHJJAODDY-UHFFFAOYSA-N (4-amino-2-ethyl-5-methylpyrazol-3-yl)-(2-chlorophenyl)methanone Chemical compound NC=1C(=NN(C1C(C1=C(C=CC=C1)Cl)=O)CC)C BGMBZPHJJAODDY-UHFFFAOYSA-N 0.000 description 2
- PSORHPLJTHUYOZ-UHFFFAOYSA-N (4-amino-2-ethyl-5-methylpyrazol-3-yl)-phenylmethanone Chemical compound NC=1C(=NN(C1C(C1=CC=CC=C1)=O)CC)C PSORHPLJTHUYOZ-UHFFFAOYSA-N 0.000 description 2
- KOLDCZINANEOLL-UHFFFAOYSA-N (5-methyl-4-nitro-2-propan-2-ylpyrazol-3-yl)-phenylmethanone Chemical compound C(C1=CC=CC=C1)(=O)C1=C(C(=NN1C(C)C)C)[N+](=O)[O-] KOLDCZINANEOLL-UHFFFAOYSA-N 0.000 description 2
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- KAQJPDKZJDBXIV-UHFFFAOYSA-N 3-ethyl-1-methyl-4-nitropyrazole Chemical compound CCc1nn(C)cc1[N+]([O-])=O KAQJPDKZJDBXIV-UHFFFAOYSA-N 0.000 description 2
- 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 2
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- OJGMBLNIHDZDGS-UHFFFAOYSA-N N-Ethylaniline Chemical compound CCNC1=CC=CC=C1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 description 2
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940113088 dimethylacetamide Drugs 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002831 pharmacologic agent Substances 0.000 description 2
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 150000003511 tertiary amides Chemical class 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-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
- 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
- MSLWSFIYYHAOFB-UHFFFAOYSA-N (2-ethyl-5-methyl-4-nitropyrazol-3-yl)-phenylmethanone Chemical compound C(C1=CC=CC=C1)(=O)C1=C(C(=NN1CC)C)[N+](=O)[O-] MSLWSFIYYHAOFB-UHFFFAOYSA-N 0.000 description 1
- UKIDBMXOOMHYQV-UHFFFAOYSA-N (3-nitro-1h-pyrazol-5-yl)-phenylmethanone Chemical compound N1N=C([N+](=O)[O-])C=C1C(=O)C1=CC=CC=C1 UKIDBMXOOMHYQV-UHFFFAOYSA-N 0.000 description 1
- ODKAVYCKWJQMPG-UHFFFAOYSA-N (4-amino-5-ethyl-2-methylpyrazol-3-yl)-phenylmethanone Chemical compound NC=1C(=NN(C1C(C1=CC=CC=C1)=O)C)CC ODKAVYCKWJQMPG-UHFFFAOYSA-N 0.000 description 1
- BUOVEJIAFCFZBX-UHFFFAOYSA-N (4-amino-5-methyl-2-propan-2-ylpyrazol-3-yl)-phenylmethanone Chemical compound NC=1C(=NN(C1C(C1=CC=CC=C1)=O)C(C)C)C BUOVEJIAFCFZBX-UHFFFAOYSA-N 0.000 description 1
- AWNKHZKMHHTOQV-UHFFFAOYSA-N (5-ethyl-2-methyl-4-nitropyrazol-3-yl)-phenylmethanone Chemical compound C(C1=CC=CC=C1)(=O)C1=C(C(=NN1C)CC)[N+](=O)[O-] AWNKHZKMHHTOQV-UHFFFAOYSA-N 0.000 description 1
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- QBELEDRHMPMKHP-UHFFFAOYSA-N 1-bromo-2-chlorobenzene Chemical compound ClC1=CC=CC=C1Br QBELEDRHMPMKHP-UHFFFAOYSA-N 0.000 description 1
- TYUHNNYPMAKLIQ-UHFFFAOYSA-N 1-ethyl-3-methyl-4-nitropyrazole Chemical compound CCN1C=C([N+]([O-])=O)C(C)=N1 TYUHNNYPMAKLIQ-UHFFFAOYSA-N 0.000 description 1
- JMCHQKIBVJRNIP-UHFFFAOYSA-N 1-ethyl-3-methylpyrazole-4-carbonitrile Chemical compound CCN1C=C(C#N)C(C)=N1 JMCHQKIBVJRNIP-UHFFFAOYSA-N 0.000 description 1
- ZROILLPDIUNLSE-UHFFFAOYSA-N 1-phenyl-1h-pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1C1=CC=CC=C1 ZROILLPDIUNLSE-UHFFFAOYSA-N 0.000 description 1
- MCTUAJONAXPWLC-UHFFFAOYSA-N 2,5-dimethyl-4-nitropyrazole-3-carboxylic acid Chemical compound CC1=NN(C)C(C(O)=O)=C1[N+]([O-])=O MCTUAJONAXPWLC-UHFFFAOYSA-N 0.000 description 1
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 1
- SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
- TVVKTQYJFGLHCA-UHFFFAOYSA-N 3-ethyl-1-methyl-8-phenyl-4,6-dihydropyrazolo[4,3-e][1,4]diazepin-5-one Chemical compound C(C)C1=NN(C2=C1NC(CN=C2C1=CC=CC=C1)=O)C TVVKTQYJFGLHCA-UHFFFAOYSA-N 0.000 description 1
- OZHZGLSRKJEDMM-UHFFFAOYSA-N 4-amino-2-ethyl-5-methylpyrazole-3-carbonitrile Chemical compound CCN1N=C(C)C(N)=C1C#N OZHZGLSRKJEDMM-UHFFFAOYSA-N 0.000 description 1
- KKKAWBDMVLFWNC-UHFFFAOYSA-N 4-amino-2-ethyl-5-methylpyrazole-3-carboxylic acid Chemical compound CCN1N=C(C)C(N)=C1C(O)=O KKKAWBDMVLFWNC-UHFFFAOYSA-N 0.000 description 1
- XORHNJQEWQGXCN-UHFFFAOYSA-N 4-nitro-1h-pyrazole Chemical compound [O-][N+](=O)C=1C=NNC=1 XORHNJQEWQGXCN-UHFFFAOYSA-N 0.000 description 1
- RZBGKBIWPRUUTO-UHFFFAOYSA-N 4-nitro-1h-pyrazole-5-carbonyl chloride Chemical compound [O-][N+](=O)C1=CNN=C1C(Cl)=O RZBGKBIWPRUUTO-UHFFFAOYSA-N 0.000 description 1
- VUWDXGXIWAZCJG-UHFFFAOYSA-N 5-(benzenecarboximidoyl)-1-ethyl-3-methylpyrazol-4-amine Chemical compound NC=1C(=NN(C1C(C1=CC=CC=C1)=N)CC)C VUWDXGXIWAZCJG-UHFFFAOYSA-N 0.000 description 1
- KDHBZATWTZDSDR-UHFFFAOYSA-N 5-(benzenecarboximidoyl)-1H-pyrazol-4-amine Chemical compound NC=1C=NNC=1C(C1=CC=CC=C1)=N KDHBZATWTZDSDR-UHFFFAOYSA-N 0.000 description 1
- AYPCLZDGADHRDL-UHFFFAOYSA-N 5-ethyl-2-methylpyrazole-3-carboxylic acid Chemical compound CCC=1C=C(C(O)=O)N(C)N=1 AYPCLZDGADHRDL-UHFFFAOYSA-N 0.000 description 1
- HQLZTRVXUUAPGX-UHFFFAOYSA-N 5-ethyl-2-methylpyrazole-3-carboxylic acid hydrate Chemical compound O.C(C)C1=NN(C(=C1)C(=O)O)C HQLZTRVXUUAPGX-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
- 241000220479 Acacia Species 0.000 description 1
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- CKLQSGKTUUUBRL-UHFFFAOYSA-N C(C1=CC=CC=C1)(=O)C1=C(C(=NN1CC)C)NC(CN=[N+]=[N-])=O Chemical compound C(C1=CC=CC=C1)(=O)C1=C(C(=NN1CC)C)NC(CN=[N+]=[N-])=O CKLQSGKTUUUBRL-UHFFFAOYSA-N 0.000 description 1
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- JGFBKJBAYISHAG-UHFFFAOYSA-N Ethyl 2,4-dioxohexanoate Chemical compound CCOC(=O)C(=O)CC(=O)CC JGFBKJBAYISHAG-UHFFFAOYSA-N 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- IFTXZSNYKMAKIT-UHFFFAOYSA-N N-(5-benzoyl-1-ethyl-3-methylpyrazol-4-yl)-2-bromoacetamide hydrobromide Chemical compound Br.C(C1=CC=CC=C1)(=O)C1=C(C(=NN1CC)C)NC(CBr)=O IFTXZSNYKMAKIT-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- SXAMKAPQIYCSKG-UHFFFAOYSA-N [2-ethyl-5-methyl-4-(methylamino)pyrazol-3-yl]-phenylmethanone Chemical compound C(C1=CC=CC=C1)(=O)C1=C(C(=NN1CC)C)NC SXAMKAPQIYCSKG-UHFFFAOYSA-N 0.000 description 1
- BQRIIWKHNJGQFH-UHFFFAOYSA-M [Br-].[Mg+]C1=CC=CC=C1Cl Chemical compound [Br-].[Mg+]C1=CC=CC=C1Cl BQRIIWKHNJGQFH-UHFFFAOYSA-M 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 230000002082 anti-convulsion Effects 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- KPSSOPDYGVGZNS-UHFFFAOYSA-N benzyl N-[2-[(5-benzoyl-1-ethyl-3-methylpyrazol-4-yl)amino]-2-oxoethyl]carbamate Chemical compound C(C1=CC=CC=C1)(=O)C1=C(C(=NN1CC)C)NC(CNC(=O)OCC1=CC=CC=C1)=O KPSSOPDYGVGZNS-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 230000002566 clonic effect Effects 0.000 description 1
- 235000020186 condensed milk Nutrition 0.000 description 1
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- UYMQWGLCXYHTES-UHFFFAOYSA-N phenyl(1h-pyrazol-5-yl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=NN1 UYMQWGLCXYHTES-UHFFFAOYSA-N 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- HKYHBMLIEAMWRO-UHFFFAOYSA-N sy002454 Chemical compound OC(=O)C1=CC([N+]([O-])=O)=NN1 HKYHBMLIEAMWRO-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- DWCSXQCXXITVKE-UHFFFAOYSA-N triethyloxidanium Chemical compound CC[O+](CC)CC DWCSXQCXXITVKE-UHFFFAOYSA-N 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
Classifications
-
- 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
- C07D231/14—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 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
- C07D231/38—Nitrogen atoms
-
- 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
- C07D231/14—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 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
- 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
- C07D231/14—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 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
- C07D231/16—Halogen atoms or nitro radicals
-
- 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
- C07D231/14—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 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
- C07D231/38—Nitrogen atoms
- C07D231/40—Acylated on said nitrogen atom
-
- 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
- C07D231/14—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 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
- C07D231/38—Nitrogen atoms
- C07D231/42—Benzene-sulfonamido pyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73324368A | 1968-05-31 | 1968-05-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL32309A0 IL32309A0 (en) | 1969-07-30 |
| IL32309A true IL32309A (en) | 1972-10-29 |
Family
ID=24946811
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL32309A IL32309A (en) | 1968-05-31 | 1969-05-29 | 4,6-dihydro-8-phenylpyrazolo(4,3-e)-(1,4)diazepin-5(1h)-one derivatives |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US3557095A (de) |
| JP (3) | JPS4843517B1 (de) |
| AT (3) | AT289818B (de) |
| BE (1) | BE733803A (de) |
| BR (1) | BR6909343D0 (de) |
| CH (2) | CH505124A (de) |
| DE (1) | DE1927429C3 (de) |
| DK (1) | DK128540B (de) |
| ES (1) | ES367846A1 (de) |
| FR (1) | FR2009732A1 (de) |
| GB (1) | GB1206088A (de) |
| IE (1) | IE33126B1 (de) |
| IL (1) | IL32309A (de) |
| NL (1) | NL143571B (de) |
| SE (1) | SE347265B (de) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1908068C2 (de) * | 1969-02-18 | 1983-12-29 | Hans-Ulrich 5408 Nassau Sohr | Reißverschluß |
| AT326067B (de) * | 1971-06-17 | 1975-11-25 | Yoshida Kogyo Kk | Reissverschluss |
| BE794993A (fr) * | 1972-02-07 | 1973-05-29 | Yoshida Kogyo Kk | Structure a curseur dissimulee |
| JPS50157810U (de) * | 1974-06-17 | 1975-12-27 | ||
| DE19701277A1 (de) * | 1997-01-16 | 1998-07-23 | Bayer Ag | Verfahren zur Herstellung von 1-Alkyl-pyrazol-5-carbonsäureestern |
| DE19829616A1 (de) | 1998-07-02 | 2000-01-05 | Bayer Ag | Verfahren zur Herstellung von 1-Alkyl-pyrazol-5-carbonsäureestern |
| DE19837067A1 (de) | 1998-08-17 | 2000-02-24 | Bayer Ag | Verfahren zur Herstellung von 1-Alkyl-pyrazol-5-carbonsäureestern |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3314941A (en) * | 1964-06-23 | 1967-04-18 | American Cyanamid Co | Novel substituted pyridodiazepins |
-
1968
- 1968-05-31 US US733243A patent/US3557095A/en not_active Expired - Lifetime
-
1969
- 1969-05-29 AT AT525070A patent/AT289818B/de not_active IP Right Cessation
- 1969-05-29 DK DK291969AA patent/DK128540B/da unknown
- 1969-05-29 DE DE1927429A patent/DE1927429C3/de not_active Expired
- 1969-05-29 ES ES367846A patent/ES367846A1/es not_active Expired
- 1969-05-29 CH CH115271D patent/CH505124A/fr not_active IP Right Cessation
- 1969-05-29 BE BE733803D patent/BE733803A/xx unknown
- 1969-05-29 FR FR6917537A patent/FR2009732A1/fr not_active Withdrawn
- 1969-05-29 BR BR209343/69A patent/BR6909343D0/pt unknown
- 1969-05-29 SE SE07555/69A patent/SE347265B/xx unknown
- 1969-05-29 GB GB27232/69A patent/GB1206088A/en not_active Expired
- 1969-05-29 IE IE733/69A patent/IE33126B1/xx unknown
- 1969-05-29 CH CH814969A patent/CH505123A/fr not_active IP Right Cessation
- 1969-05-29 AT AT525170A patent/AT293401B/de not_active IP Right Cessation
- 1969-05-29 NL NL696908208A patent/NL143571B/xx unknown
- 1969-05-29 IL IL32309A patent/IL32309A/en unknown
- 1969-05-29 AT AT509069A patent/AT289124B/de not_active IP Right Cessation
-
1971
- 1971-07-02 JP JP46048142A patent/JPS4843517B1/ja active Pending
- 1971-07-02 JP JP46048143A patent/JPS4839956B1/ja active Pending
- 1971-07-02 JP JP46048141A patent/JPS4843516B1/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| BR6909343D0 (pt) | 1973-03-13 |
| ES367846A1 (es) | 1971-04-16 |
| DK128540B (da) | 1974-05-20 |
| DE1927429B2 (de) | 1977-08-18 |
| DE1927429A1 (de) | 1969-12-04 |
| IL32309A0 (en) | 1969-07-30 |
| GB1206088A (en) | 1970-09-23 |
| AT289818B (de) | 1971-05-10 |
| JPS4843516B1 (de) | 1973-12-19 |
| CH505123A (fr) | 1971-03-31 |
| FR2009732A1 (de) | 1970-02-06 |
| DE1927429C3 (de) | 1978-04-06 |
| AT289124B (de) | 1971-04-13 |
| JPS4843517B1 (de) | 1973-12-19 |
| CH505124A (fr) | 1971-03-31 |
| IE33126B1 (en) | 1974-03-20 |
| BE733803A (de) | 1969-11-03 |
| NL143571B (nl) | 1974-10-15 |
| SE347265B (de) | 1972-07-31 |
| IE33126L (en) | 1969-11-30 |
| AT293401B (de) | 1971-10-11 |
| JPS4839956B1 (de) | 1973-11-28 |
| NL6908208A (de) | 1969-12-02 |
| US3557095A (en) | 1971-01-19 |
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