NO861266L - Analogifremgangsmaate for fremstilling av terapeutisk aktive pyridazinon-derivater. - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive pyridazinon-derivater.Info
- Publication number
- NO861266L NO861266L NO861266A NO861266A NO861266L NO 861266 L NO861266 L NO 861266L NO 861266 A NO861266 A NO 861266A NO 861266 A NO861266 A NO 861266A NO 861266 L NO861266 L NO 861266L
- Authority
- NO
- Norway
- Prior art keywords
- group
- atom
- methyl
- dihydro
- general formula
- Prior art date
Links
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims description 8
- 238000000034 method Methods 0.000 title claims description 6
- 230000001225 therapeutic effect Effects 0.000 title 1
- -1 sulphinyl Chemical group 0.000 claims abstract description 125
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 31
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 30
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 22
- 239000002253 acid Substances 0.000 claims abstract description 20
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
- 239000001301 oxygen Substances 0.000 claims abstract description 20
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 18
- 125000005843 halogen group Chemical group 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
- 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000005277 alkyl imino group Chemical group 0.000 claims abstract description 4
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 44
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 125000004434 sulfur atom Chemical group 0.000 claims description 11
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 9
- 238000005984 hydrogenation reaction Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 235000005985 organic acids Nutrition 0.000 claims description 5
- 230000010933 acylation Effects 0.000 claims description 4
- 238000005917 acylation reaction Methods 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 238000005695 dehalogenation reaction Methods 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 230000000269 nucleophilic effect Effects 0.000 claims description 3
- RZFBQWBFPTUWJO-UHFFFAOYSA-N 4-methyl-3-(2-piperazin-1-yl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(O2)N3CCNCC3)C2=C1 RZFBQWBFPTUWJO-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 150000003217 pyrazoles Chemical class 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- JUTQWCNIWCTVPD-UHFFFAOYSA-N 3-(2-imidazol-1-yl-1,3-benzoxazol-5-yl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(OC(=N2)N3C=NC=C3)C2=C1 JUTQWCNIWCTVPD-UHFFFAOYSA-N 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 150000003222 pyridines Chemical class 0.000 claims 1
- 150000001721 carbon Chemical group 0.000 abstract description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 8
- 239000001257 hydrogen Substances 0.000 abstract description 8
- 125000003884 phenylalkyl group Chemical group 0.000 abstract description 6
- 125000001425 triazolyl group Chemical group 0.000 abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 abstract 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 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 16
- 229960000583 acetic acid Drugs 0.000 description 16
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000012362 glacial acetic acid Substances 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 229920000137 polyphosphoric acid Polymers 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- XHFMZTGMZOPLPG-UHFFFAOYSA-N 3-(2-methylsulfanyl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound C1=C2OC(SC)=NC2=CC=C1C1=NNC(=O)CC1 XHFMZTGMZOPLPG-UHFFFAOYSA-N 0.000 description 9
- ORSUMIZRRGPJBR-UHFFFAOYSA-N 4,5-dihydro-1h-pyridazin-6-one Chemical compound O=C1CCC=NN1 ORSUMIZRRGPJBR-UHFFFAOYSA-N 0.000 description 9
- WEJXNMVJEXBSQF-UHFFFAOYSA-N 4-methyl-3-(2-methylsulfanyl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound C1=C2OC(SC)=NC2=CC=C1C1=NNC(=O)CC1C WEJXNMVJEXBSQF-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
- 238000001819 mass spectrum Methods 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- UHYVTWWKARNAPE-UHFFFAOYSA-N 4-methyl-3-(2-methylsulfanyl-1,3-benzoxazol-5-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound C=1C=C2OC(SC)=NC2=CC=1C1=NNC(=O)CC1C UHYVTWWKARNAPE-UHFFFAOYSA-N 0.000 description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229940093915 gynecological organic acid Drugs 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 230000002785 anti-thrombosis Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- DCDYNCXCJUOYCO-UHFFFAOYSA-N methyl 4-(2-chloro-3H-benzimidazol-5-yl)-3-methyl-4-oxobutanoate Chemical compound COC(CC(C(=O)C1=CC2=C(N=C(N2)Cl)C=C1)C)=O DCDYNCXCJUOYCO-UHFFFAOYSA-N 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 description 2
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 description 2
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 2
- OQFWEYYPGHWIHY-UHFFFAOYSA-N 3-(2-methylsulfanyl-1,3-benzoxazol-5-yl)-4-propyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CCCC1CC(=O)NN=C1C1=CC=C(OC(SC)=N2)C2=C1 OQFWEYYPGHWIHY-UHFFFAOYSA-N 0.000 description 2
- JKRCTHRZIZKECH-UHFFFAOYSA-N 3-(4-amino-3-hydroxyphenyl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N)C(O)=C1 JKRCTHRZIZKECH-UHFFFAOYSA-N 0.000 description 2
- KOYZLXFXQWUVFN-UHFFFAOYSA-N 3-[2-(2,6-dichloropyridin-4-yl)-3h-benzimidazol-5-yl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound ClC1=NC(Cl)=CC(C=2NC3=CC(=CC=C3N=2)C=2CCC(=O)NN=2)=C1 KOYZLXFXQWUVFN-UHFFFAOYSA-N 0.000 description 2
- KMQLIDDEQAJAGJ-UHFFFAOYSA-N 4-oxo-4-phenylbutyric acid Chemical class OC(=O)CCC(=O)C1=CC=CC=C1 KMQLIDDEQAJAGJ-UHFFFAOYSA-N 0.000 description 2
- SNOPELNBTQTPEU-UHFFFAOYSA-N 6-acetamido-N-[2-hydroxy-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]pyridine-3-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C=1C=CC(=NC=1)NC(=O)C SNOPELNBTQTPEU-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000003177 cardiotonic effect Effects 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- LNOQURRKNJKKBU-UHFFFAOYSA-N ethyl piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCNCC1 LNOQURRKNJKKBU-UHFFFAOYSA-N 0.000 description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 230000009090 positive inotropic effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-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
- 230000007306 turnover Effects 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- OHAHTBJTWFHKLW-UHFFFAOYSA-N 1-acetyl-N-[2-hydroxy-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]piperidine-4-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C1CCN(CC1)C(C)=O OHAHTBJTWFHKLW-UHFFFAOYSA-N 0.000 description 1
- ZVPDNRVYHLRXLX-UHFFFAOYSA-N 1-ter-butyl-3-p-tolyl-1h-pyrazolo[3,4-d]pyrimidin-4-ylamine Chemical compound C1=CC(C)=CC=C1C1=NN(C(C)(C)C)C2=NC=NC(N)=C12 ZVPDNRVYHLRXLX-UHFFFAOYSA-N 0.000 description 1
- JNLBRMDGJDSLLQ-UHFFFAOYSA-N 1h-pyridazin-6-one;hydrochloride Chemical compound Cl.O=C1C=CC=NN1 JNLBRMDGJDSLLQ-UHFFFAOYSA-N 0.000 description 1
- FBAOVPVVMDOHPK-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfinyl)-1h-imidazole Chemical compound N=1C=CNC=1S(=O)C1=NC=CN1 FBAOVPVVMDOHPK-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- IHCCLXNEEPMSIO-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 IHCCLXNEEPMSIO-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- FLFWJIBUZQARMD-UHFFFAOYSA-N 2-mercapto-1,3-benzoxazole Chemical compound C1=CC=C2OC(S)=NC2=C1 FLFWJIBUZQARMD-UHFFFAOYSA-N 0.000 description 1
- RPSKGTHUYYLURN-UHFFFAOYSA-N 3-(2-chloro-3h-benzimidazol-5-yl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(Cl)N2)C2=C1 RPSKGTHUYYLURN-UHFFFAOYSA-N 0.000 description 1
- JVDKSRXXEBKANQ-UHFFFAOYSA-N 3-(2-imidazol-1-yl-3h-benzimidazol-5-yl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(N2)N3C=NC=C3)C2=C1 JVDKSRXXEBKANQ-UHFFFAOYSA-N 0.000 description 1
- VCTMAOPXSADEHZ-UHFFFAOYSA-N 3-(2-methylsulfanyl-1,3-benzoxazol-5-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound C=1C=C2OC(SC)=NC2=CC=1C1=NNC(=O)CC1 VCTMAOPXSADEHZ-UHFFFAOYSA-N 0.000 description 1
- XOJQFYDKGRNAGE-UHFFFAOYSA-N 3-(2-piperazin-1-yl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound N1C(=O)CCC(C=2C=C3OC(=NC3=CC=2)N2CCNCC2)=N1 XOJQFYDKGRNAGE-UHFFFAOYSA-N 0.000 description 1
- JJDHQIXXASOFEU-UHFFFAOYSA-N 3-(2-pyridin-2-yl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound N1C(=O)CCC(C=2C=C3OC(=NC3=CC=2)C=2N=CC=CC=2)=N1 JJDHQIXXASOFEU-UHFFFAOYSA-N 0.000 description 1
- NUENUAKRFGZENA-UHFFFAOYSA-N 3-(2-pyrrolidin-1-yl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound N1C(=O)CCC(C=2C=C3OC(=NC3=CC=2)N2CCCC2)=N1 NUENUAKRFGZENA-UHFFFAOYSA-N 0.000 description 1
- BXGRTKMGXMFZDD-UHFFFAOYSA-N 3-(2-thiophen-3-yl-1,3-benzoxazol-5-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound N1C(=O)CCC(C=2C=C3N=C(OC3=CC=2)C2=CSC=C2)=N1 BXGRTKMGXMFZDD-UHFFFAOYSA-N 0.000 description 1
- VJRBSHZAWWZIKM-UHFFFAOYSA-N 3-(2-thiophen-3-yl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound N1C(=O)CCC(C=2C=C3OC(=NC3=CC=2)C2=CSC=C2)=N1 VJRBSHZAWWZIKM-UHFFFAOYSA-N 0.000 description 1
- DPWPMUSGLLXNQL-UHFFFAOYSA-N 3-[2-(2,6-dichloropyridin-3-yl)-1,3-benzoxazol-6-yl]-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(O2)C=3C(=NC(Cl)=CC=3)Cl)C2=C1 DPWPMUSGLLXNQL-UHFFFAOYSA-N 0.000 description 1
- CMQGUDFDPOBKGI-UHFFFAOYSA-N 3-[2-(2-methylimidazol-1-yl)-1,3-benzoxazol-5-yl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1=NC=CN1C1=NC2=CC(C=3CCC(=O)NN=3)=CC=C2O1 CMQGUDFDPOBKGI-UHFFFAOYSA-N 0.000 description 1
- ONQJAHPGSXJCAC-UHFFFAOYSA-N 3-[2-(4-methylpiperazin-1-yl)-1,3-benzoxazol-6-yl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound C1CN(C)CCN1C1=NC2=CC=C(C=3CCC(=O)NN=3)C=C2O1 ONQJAHPGSXJCAC-UHFFFAOYSA-N 0.000 description 1
- ZAUCTQWJCVGYJO-UHFFFAOYSA-N 3-[2-(6-aminopyridin-3-yl)-1,3-benzoxazol-6-yl]-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(O2)C=3C=NC(N)=CC=3)C2=C1 ZAUCTQWJCVGYJO-UHFFFAOYSA-N 0.000 description 1
- GMUOHBUWIXJMLD-UHFFFAOYSA-N 3-[2-(azepan-1-yl)-3h-benzimidazol-5-yl]-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(N2)N3CCCCCC3)C2=C1 GMUOHBUWIXJMLD-UHFFFAOYSA-N 0.000 description 1
- KXAXSCKODDCDEI-UHFFFAOYSA-N 3-[2-(furan-2-yl)-1,3-benzoxazol-6-yl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound N1C(=O)CCC(C=2C=C3OC(=NC3=CC=2)C=2OC=CC=2)=N1 KXAXSCKODDCDEI-UHFFFAOYSA-N 0.000 description 1
- ONMHFWXBCYQUHR-UHFFFAOYSA-N 3-[2-(furan-2-yl)-1,3-benzoxazol-6-yl]-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(O2)C=3OC=CC=3)C2=C1 ONMHFWXBCYQUHR-UHFFFAOYSA-N 0.000 description 1
- CFSCXFNBEXFTJO-UHFFFAOYSA-N 3-[2-(furan-2-yl)-3h-benzimidazol-5-yl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound N1C(=O)CCC(C=2C=C3NC(=NC3=CC=2)C=2OC=CC=2)=N1 CFSCXFNBEXFTJO-UHFFFAOYSA-N 0.000 description 1
- SKAGJVNSBFSHCW-UHFFFAOYSA-N 3-[2-(furan-2-yl)-3h-benzimidazol-5-yl]-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(N2)C=3OC=CC=3)C2=C1 SKAGJVNSBFSHCW-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
- LKWIQGZYCAYEGW-UHFFFAOYSA-N 3-methyl-4-oxo-4-(2-sulfo-3H-benzimidazol-5-yl)butanoic acid Chemical compound S(=O)(=O)(O)C=1NC2=C(N=1)C=CC(=C2)C(C(CC(=O)O)C)=O LKWIQGZYCAYEGW-UHFFFAOYSA-N 0.000 description 1
- PEYREFTTXSMFJA-UHFFFAOYSA-N 4-methyl-3-(2-pyrazin-2-yl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(O2)C=3N=CC=NC=3)C2=C1 PEYREFTTXSMFJA-UHFFFAOYSA-N 0.000 description 1
- WBLUKZKWOCUDNJ-UHFFFAOYSA-N 4-methyl-3-(2-pyridin-2-yl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(O2)C=3N=CC=CC=3)C2=C1 WBLUKZKWOCUDNJ-UHFFFAOYSA-N 0.000 description 1
- HZPCPJCKBVVBPN-UHFFFAOYSA-N 4-methyl-3-(2-pyridin-3-yl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(O2)C=3C=NC=CC=3)C2=C1 HZPCPJCKBVVBPN-UHFFFAOYSA-N 0.000 description 1
- KZRDJRHPXSWGPR-UHFFFAOYSA-N 4-methyl-3-(2-pyridin-4-yl-1,3-benzoxazol-5-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(OC(=N2)C=3C=CN=CC=3)C2=C1 KZRDJRHPXSWGPR-UHFFFAOYSA-N 0.000 description 1
- GVFKMZWXGLRDSL-UHFFFAOYSA-N 4-methyl-3-(2-pyridin-4-yl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(O2)C=3C=CN=CC=3)C2=C1 GVFKMZWXGLRDSL-UHFFFAOYSA-N 0.000 description 1
- GWVGQEHDTMTWGA-UHFFFAOYSA-N 4-methyl-3-(2-pyrimidin-5-yl-1,3-benzoxazol-6-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(O2)C=3C=NC=NC=3)C2=C1 GWVGQEHDTMTWGA-UHFFFAOYSA-N 0.000 description 1
- FNVMCSUDRWDONS-UHFFFAOYSA-N 4-methyl-3-(2-pyrrolidin-1-yl-3h-benzimidazol-5-yl)-1h-pyridazin-6-one Chemical compound CC1=CC(=O)NN=C1C1=CC=C(N=C(N2)N3CCCC3)C2=C1 FNVMCSUDRWDONS-UHFFFAOYSA-N 0.000 description 1
- RMLXSVHNVQIFTQ-UHFFFAOYSA-N 4-methyl-3-(2-pyrrolidin-1-yl-3h-benzimidazol-5-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(N2)N3CCCC3)C2=C1 RMLXSVHNVQIFTQ-UHFFFAOYSA-N 0.000 description 1
- OCDVTFLVYWNCJA-UHFFFAOYSA-N 4-methyl-3-(2-thiophen-2-yl-1,3-benzothiazol-5-yl)-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(SC(=N2)C=3SC=CC=3)C2=C1 OCDVTFLVYWNCJA-UHFFFAOYSA-N 0.000 description 1
- JHSPFPIXWVTTAA-UHFFFAOYSA-N 4-methyl-3-[2-(3-methylpyrazol-1-yl)-3h-benzimidazol-5-yl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(N2)N3N=C(C)C=C3)C2=C1 JHSPFPIXWVTTAA-UHFFFAOYSA-N 0.000 description 1
- CZPRHQWMFUDXEY-UHFFFAOYSA-N 4-methyl-3-[2-(4-methyl-1,3-oxazol-5-yl)-1,3-benzoxazol-6-yl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(O2)C3=C(N=CO3)C)C2=C1 CZPRHQWMFUDXEY-UHFFFAOYSA-N 0.000 description 1
- HHRXOEBTNKDAJV-UHFFFAOYSA-N 4-methyl-3-[2-(4-methylpiperazin-1-yl)-1,3-benzoxazol-5-yl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(OC(=N2)N3CCN(C)CC3)C2=C1 HHRXOEBTNKDAJV-UHFFFAOYSA-N 0.000 description 1
- ASELOHXKWDJOFE-UHFFFAOYSA-N 4-methyl-3-[2-(4-methylpiperazin-1-yl)-3h-benzimidazol-5-yl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(N=C(N2)N3CCN(C)CC3)C2=C1 ASELOHXKWDJOFE-UHFFFAOYSA-N 0.000 description 1
- WERIVQKXUMHWLX-UHFFFAOYSA-N 4-methyl-3-[2-(4-methylpyrazol-1-yl)-1,3-benzoxazol-5-yl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(OC(=N2)N3N=CC(C)=C3)C2=C1 WERIVQKXUMHWLX-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
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- XKVUYEYANWFIJX-UHFFFAOYSA-N 5-methyl-1h-pyrazole Chemical compound CC1=CC=NN1 XKVUYEYANWFIJX-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OEKHBIBEGBUWID-UHFFFAOYSA-N COC(CC(C(=O)C1=CC2=C(N=C(N2)N2N=CC(=C2O)C)C=C1)C)=O Chemical compound COC(CC(C(=O)C1=CC2=C(N=C(N2)N2N=CC(=C2O)C)C=C1)C)=O OEKHBIBEGBUWID-UHFFFAOYSA-N 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 206010014513 Embolism arterial Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AZBSXPVSRIJUAG-UHFFFAOYSA-N N-[2-amino-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]-2,6-dichloropyridine-4-carboxamide Chemical compound NC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C1=CC(=NC(=C1)Cl)Cl AZBSXPVSRIJUAG-UHFFFAOYSA-N 0.000 description 1
- HUQLCJRAARLBLT-UHFFFAOYSA-N N-[2-amino-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]furan-2-carboxamide Chemical compound NC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C=1OC=CC=1 HUQLCJRAARLBLT-UHFFFAOYSA-N 0.000 description 1
- GWRHLGBUTURIHL-UHFFFAOYSA-N N-[2-amino-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]pyrazine-2-carboxamide Chemical compound N1=C(C=NC=C1)C(=O)NC1=C(C=C(C=C1)C=1C(CC(NN=1)=O)C)N GWRHLGBUTURIHL-UHFFFAOYSA-N 0.000 description 1
- OBHWFNMQHMHOEV-UHFFFAOYSA-N N-[2-amino-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]thiophene-3-carboxamide Chemical compound NC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C1=CSC=C1 OBHWFNMQHMHOEV-UHFFFAOYSA-N 0.000 description 1
- NZWYKFZLFOKQBZ-UHFFFAOYSA-N N-[2-amino-4-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]furan-2-carboxamide Chemical compound NC1=C(C=CC(=C1)C=1CCC(NN=1)=O)NC(=O)C=1OC=CC=1 NZWYKFZLFOKQBZ-UHFFFAOYSA-N 0.000 description 1
- NYRIQGBYQKHBKA-UHFFFAOYSA-N N-[2-amino-4-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]thiophene-3-carboxamide Chemical compound NC1=C(C=CC(=C1)C=1CCC(NN=1)=O)NC(=O)C1=CSC=C1 NYRIQGBYQKHBKA-UHFFFAOYSA-N 0.000 description 1
- CJKWEMVDCNWJJI-UHFFFAOYSA-N N-[2-hydroxy-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]-4-methyl-1,3-oxazole-5-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C1=C(N=CO1)C CJKWEMVDCNWJJI-UHFFFAOYSA-N 0.000 description 1
- KSSGGKQKCUUEOD-UHFFFAOYSA-N N-[2-hydroxy-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]furan-2-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C=1OC=CC=1 KSSGGKQKCUUEOD-UHFFFAOYSA-N 0.000 description 1
- IQAIWBGBKVEWPO-UHFFFAOYSA-N N-[2-hydroxy-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]pyrazine-2-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C1=NC=CN=C1 IQAIWBGBKVEWPO-UHFFFAOYSA-N 0.000 description 1
- JVMSQUQENCNDEM-UHFFFAOYSA-N N-[2-hydroxy-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]pyridine-2-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C1=NC=CC=C1 JVMSQUQENCNDEM-UHFFFAOYSA-N 0.000 description 1
- OUQOYVDLSWNEMA-UHFFFAOYSA-N N-[2-hydroxy-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]pyridine-3-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C=1C=NC=CC=1 OUQOYVDLSWNEMA-UHFFFAOYSA-N 0.000 description 1
- HQPUHVNGUVWJJO-UHFFFAOYSA-N N-[2-hydroxy-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]pyridine-4-carboxamide Chemical class OC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C1=CC=NC=C1 HQPUHVNGUVWJJO-UHFFFAOYSA-N 0.000 description 1
- JOLUKSVKRMVLLV-UHFFFAOYSA-N N-[2-hydroxy-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]pyrimidine-5-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C=1C=NC=NC=1 JOLUKSVKRMVLLV-UHFFFAOYSA-N 0.000 description 1
- FQLDFMGHVKENGO-UHFFFAOYSA-N N-[2-hydroxy-4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]thiophene-3-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1C(CC(NN=1)=O)C)NC(=O)C1=CSC=C1 FQLDFMGHVKENGO-UHFFFAOYSA-N 0.000 description 1
- BMVLWTAGVVTZKE-UHFFFAOYSA-N N-[2-hydroxy-4-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]furan-2-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1CCC(NN=1)=O)NC(=O)C=1OC=CC=1 BMVLWTAGVVTZKE-UHFFFAOYSA-N 0.000 description 1
- ZAPYWRIFQWPWQF-UHFFFAOYSA-N N-[2-hydroxy-4-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]pyridine-2-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1CCC(NN=1)=O)NC(=O)C1=NC=CC=C1 ZAPYWRIFQWPWQF-UHFFFAOYSA-N 0.000 description 1
- ZWZVPULDRGFDOM-UHFFFAOYSA-N N-[2-hydroxy-4-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]thiophene-3-carboxamide Chemical compound OC1=C(C=CC(=C1)C=1CCC(NN=1)=O)NC(=O)C1=CSC=C1 ZWZVPULDRGFDOM-UHFFFAOYSA-N 0.000 description 1
- LFSBFUVEHHUAPY-UHFFFAOYSA-N N-[2-hydroxy-5-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]furan-2-carboxamide Chemical compound OC1=C(C=C(C=C1)C=1C(CC(NN=1)=O)C)NC(=O)C=1OC=CC=1 LFSBFUVEHHUAPY-UHFFFAOYSA-N 0.000 description 1
- ZVSVTTNZOOPVPW-UHFFFAOYSA-N N-[2-hydroxy-5-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]pyridine-4-carboxamide Chemical compound OC1=C(C=C(C=C1)C=1C(CC(NN=1)=O)C)NC(=O)C1=CC=NC=C1 ZVSVTTNZOOPVPW-UHFFFAOYSA-N 0.000 description 1
- SCOHTHRDKMBROT-UHFFFAOYSA-N N-[2-hydroxy-5-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]thiophene-2-carboxamide Chemical compound OC1=C(C=C(C=C1)C=1C(CC(NN=1)=O)C)NC(=O)C=1SC=CC=1 SCOHTHRDKMBROT-UHFFFAOYSA-N 0.000 description 1
- SJMYSBVNSBHXFS-UHFFFAOYSA-N N-[2-hydroxy-5-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]thiophene-3-carboxamide Chemical compound OC1=C(C=C(C=C1)C=1C(CC(NN=1)=O)C)NC(=O)C1=CSC=C1 SJMYSBVNSBHXFS-UHFFFAOYSA-N 0.000 description 1
- IPLUQJBWDMVRDP-UHFFFAOYSA-N N-[2-hydroxy-5-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]-4-methyl-1,3-oxazole-5-carboxamide Chemical compound OC1=C(C=C(C=C1)C=1CCC(NN=1)=O)NC(=O)C1=C(N=CO1)C IPLUQJBWDMVRDP-UHFFFAOYSA-N 0.000 description 1
- WRZHOLIHIDGVLV-UHFFFAOYSA-N N-[2-hydroxy-5-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenyl]thiophene-3-carboxamide Chemical compound OC1=C(C=C(C=C1)C=1CCC(NN=1)=O)NC(=O)C1=CSC=C1 WRZHOLIHIDGVLV-UHFFFAOYSA-N 0.000 description 1
- WKFBHMWVFITLKI-UHFFFAOYSA-N N-[2-hydroxy-5-(6-oxo-4-propyl-4,5-dihydro-1H-pyridazin-3-yl)phenyl]pyridine-4-carboxamide Chemical compound OC1=C(C=C(C=C1)C=1C(CC(NN=1)=O)CCC)NC(=O)C1=CC=NC=C1 WKFBHMWVFITLKI-UHFFFAOYSA-N 0.000 description 1
- MGWAESXBWUTMGZ-UHFFFAOYSA-N N-[5-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)-2-sulfanylphenyl]thiophene-2-carboxamide Chemical compound SC1=C(C=C(C=C1)C=1C(CC(NN=1)=O)C)NC(=O)C=1SC=CC=1 MGWAESXBWUTMGZ-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 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
- 229910000831 Steel Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 230000000274 adsorptive effect Effects 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 210000005242 cardiac chamber Anatomy 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- RIKMMFOAQPJVMX-UHFFFAOYSA-N fomepizole Chemical compound CC=1C=NNC=1 RIKMMFOAQPJVMX-UHFFFAOYSA-N 0.000 description 1
- 229960004285 fomepizole Drugs 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 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
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- XVOXPOMAKXCLMP-UHFFFAOYSA-N methyl 3-methyl-4-[2-(4-methylpiperazin-1-yl)-3H-benzimidazol-5-yl]-4-oxobutanoate Chemical compound COC(CC(C(=O)C1=CC2=C(N=C(N2)N2CCN(CC2)C)C=C1)C)=O XVOXPOMAKXCLMP-UHFFFAOYSA-N 0.000 description 1
- KEOLRVNSYZCDNM-UHFFFAOYSA-N methyl 3-methyl-4-oxo-4-(2-oxobenzimidazol-5-yl)butanoate Chemical compound COC(CC(C(=O)C1=CC=2C(=NC(N=2)=O)C=C1)C)=O KEOLRVNSYZCDNM-UHFFFAOYSA-N 0.000 description 1
- NZJLLALIZZEGGL-UHFFFAOYSA-N methyl 3-methyl-4-oxo-4-(2-pyrazol-1-yl-3H-benzimidazol-5-yl)butanoate Chemical compound COC(CC(C(=O)C1=CC2=C(N=C(N2)N2N=CC=C2)C=C1)C)=O NZJLLALIZZEGGL-UHFFFAOYSA-N 0.000 description 1
- VVKGYSXTHOUSLW-UHFFFAOYSA-N methyl 3-methyl-4-oxo-4-(2-pyrrolidin-1-yl-3H-benzimidazol-5-yl)butanoate Chemical compound COC(CC(C(=O)C1=CC2=C(N=C(N2)N2CCCC2)C=C1)C)=O VVKGYSXTHOUSLW-UHFFFAOYSA-N 0.000 description 1
- GZWMWVCKGYXHAZ-UHFFFAOYSA-N methyl 3-methyl-4-oxo-4-[2-(1H-pyrrol-2-yl)-3H-benzimidazol-5-yl]butanoate Chemical compound N1C(=CC=C1)C=1NC2=C(N=1)C=CC(=C2)C(C(CC(=O)OC)C)=O GZWMWVCKGYXHAZ-UHFFFAOYSA-N 0.000 description 1
- IPHXWCLWSJPOGN-UHFFFAOYSA-N methyl 4-(2-imidazol-1-yl-3H-benzimidazol-5-yl)-3-methyl-4-oxobutanoate Chemical compound COC(CC(C(=O)C1=CC2=C(N=C(N2)N2C=NC=C2)C=C1)C)=O IPHXWCLWSJPOGN-UHFFFAOYSA-N 0.000 description 1
- FUOKKYNLHAWDOY-UHFFFAOYSA-N methyl 4-[2-(4-acetylpiperazin-1-yl)-3H-benzimidazol-5-yl]-3-methyl-4-oxobutanoate Chemical compound COC(CC(C(=O)C1=CC2=C(N=C(N2)N2CCN(CC2)C(C)=O)C=C1)C)=O FUOKKYNLHAWDOY-UHFFFAOYSA-N 0.000 description 1
- OXIYNWVEQRMACG-UHFFFAOYSA-N methyl 4-[2-(azepan-1-yl)-3H-benzimidazol-5-yl]-3-methyl-4-oxobutanoate Chemical compound N1(CCCCCC1)C=1NC2=C(N=1)C=CC(=C2)C(C(CC(=O)OC)C)=O OXIYNWVEQRMACG-UHFFFAOYSA-N 0.000 description 1
- JPCYSYNQDLWWHK-UHFFFAOYSA-N n-[5-[5-(4-methyl-6-oxo-4,5-dihydro-1h-pyridazin-3-yl)-1,3-benzoxazol-2-yl]pyridin-2-yl]acetamide Chemical compound CC1CC(=O)NN=C1C1=CC=C(OC(=N2)C=3C=NC(NC(C)=O)=CC=3)C2=C1 JPCYSYNQDLWWHK-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000002071 phenylalkoxy group Chemical group 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000005245 sintering Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000008096 xylene Substances 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
- C07D231/12—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
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
-
- 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
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (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)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853511110 DE3511110A1 (de) | 1985-03-27 | 1985-03-27 | Neue pyridazinone, ihre herstellung und diese verbindungen enthaltende arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO861266L true NO861266L (no) | 1986-09-29 |
Family
ID=6266489
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO861266A NO861266L (no) | 1985-03-27 | 1986-03-26 | Analogifremgangsmaate for fremstilling av terapeutisk aktive pyridazinon-derivater. |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP0196005B1 (xx) |
| JP (1) | JPS61227582A (xx) |
| KR (1) | KR860007253A (xx) |
| AT (1) | ATE48841T1 (xx) |
| AU (1) | AU5530386A (xx) |
| CA (1) | CA1257588A (xx) |
| DD (1) | DD248362A5 (xx) |
| DE (2) | DE3511110A1 (xx) |
| DK (1) | DK131886A (xx) |
| ES (4) | ES8705882A1 (xx) |
| FI (1) | FI861288A (xx) |
| GR (1) | GR860801B (xx) |
| HU (1) | HUT42085A (xx) |
| IL (1) | IL78251A0 (xx) |
| NO (1) | NO861266L (xx) |
| NZ (1) | NZ215616A (xx) |
| PT (1) | PT82272B (xx) |
| ZA (1) | ZA862248B (xx) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3505609A1 (de) * | 1985-02-19 | 1986-08-21 | Merck Patent Gmbh, 6100 Darmstadt | Benzimidazolyl-pyridazinone |
| US4725686A (en) * | 1985-11-22 | 1988-02-16 | William H. Rorer, Inc. | Benzodiazinone-pyridazinone and hydroxy-pyrazolyl compounds, cardiotonic compositions including the same, and their uses |
| DE3611343A1 (de) * | 1986-04-04 | 1987-10-08 | Boehringer Mannheim Gmbh | Heterocyclisch substituierte benzimidazole, verfahren zu ihrer herstellung, arzneimittel sowie zwischenprodukte |
| DE3734083A1 (de) * | 1987-10-08 | 1989-04-20 | Heumann Pharma Gmbh & Co | Benzimidazole, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3735207A1 (de) * | 1987-10-17 | 1989-04-27 | Basf Ag | Mittel auf der basis von phenylpyridazinon-derivaten zur wachstumsfoerderung und fettreduktion bei tieren |
| ES2080064T3 (es) * | 1988-07-11 | 1996-02-01 | Akzo Nobel Nv | Derivados de piridazinona. |
| FR2643903A1 (fr) * | 1989-03-03 | 1990-09-07 | Union Pharma Scient Appl | Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux |
| DE4237656A1 (de) * | 1992-06-13 | 1993-12-16 | Merck Patent Gmbh | Benzimidazolderivate |
| FR2806093B1 (fr) * | 2000-03-08 | 2002-05-03 | Inst Francais Du Petrole | Procede d'hydrogenation selective comprenant une separation partielle d'hydrogene par membrane en amont d'une colonne reactive |
| WO2007110364A1 (en) | 2006-03-28 | 2007-10-04 | High Point Pharmaceuticals, Llc | Benzothiazoles having histamine h3 receptor activity |
| US8772323B2 (en) | 2010-05-07 | 2014-07-08 | Boehringer Ingelheim International Gmbh | Benzoxazole- and tetrahydrobenzoxazole-substituted pyridazinones as GPR119 agonists |
| JP6240063B2 (ja) | 2011-04-28 | 2017-11-29 | ザ ブロード インスティテュート， インコーポレイテッド | ヒストンデアセチラーゼ阻害剤 |
| CA2880117C (en) | 2012-07-27 | 2021-04-06 | The Broad Institute, Inc. | Inhibitors of histone deacetylase |
| WO2014100438A1 (en) | 2012-12-20 | 2014-06-26 | The Broad Institute, Inc. | Cycloalkenyl hydroxamic acid derivatives and their use as histone deacetylase inhibitors |
| WO2018086703A1 (en) | 2016-11-11 | 2018-05-17 | Bayer Pharma Aktiengesellschaft | Dihydropyridazinones substituted with phenylureas |
| JP2021512103A (ja) | 2018-01-31 | 2021-05-13 | バイエル アクチェンゲゼルシャフトＢａｙｅｒ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｎａｍｐｔ阻害剤を含む抗体薬物複合体（ａｄｃｓ） |
| WO2021013693A1 (en) | 2019-07-23 | 2021-01-28 | Bayer Pharma Aktiengesellschaft | Antibody drug conjugates (adcs) with nampt inhibitors |
| WO2023003468A1 (en) | 2021-07-23 | 2023-01-26 | Rijksuniversiteit Groningen | Novel inhibitors of histone deacetylase (hdac), and methods, compositions and uses related thereto. |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES8101067A1 (es) * | 1978-08-25 | 1980-12-01 | Thomae Gmbh Dr K | Procedimiento para la preparacion de nuevos bencimidazoles sustituidos en posicion 5 o 6 con un anillo de piridazinona |
| DE3129447A1 (de) * | 1981-07-25 | 1983-02-10 | Dr. Karl Thomae Gmbh, 7950 Biberach | "neue benztriazole, ihre herstellung und ihre verwendung als arzneimittel" |
| DE3505609A1 (de) * | 1985-02-19 | 1986-08-21 | Merck Patent Gmbh, 6100 Darmstadt | Benzimidazolyl-pyridazinone |
-
1985
- 1985-03-27 DE DE19853511110 patent/DE3511110A1/de not_active Withdrawn
-
1986
- 1986-03-18 DE DE8686103687T patent/DE3667664D1/de not_active Expired - Fee Related
- 1986-03-18 EP EP86103687A patent/EP0196005B1/de not_active Expired
- 1986-03-18 AT AT86103687T patent/ATE48841T1/de not_active IP Right Cessation
- 1986-03-21 DK DK131886A patent/DK131886A/da not_active Application Discontinuation
- 1986-03-25 IL IL78251A patent/IL78251A0/xx unknown
- 1986-03-25 CA CA000505012A patent/CA1257588A/en not_active Expired
- 1986-03-25 DD DD86288285A patent/DD248362A5/de unknown
- 1986-03-26 FI FI861288A patent/FI861288A/fi not_active IP Right Cessation
- 1986-03-26 HU HU861275A patent/HUT42085A/hu unknown
- 1986-03-26 JP JP61068255A patent/JPS61227582A/ja active Pending
- 1986-03-26 AU AU55303/86A patent/AU5530386A/en not_active Abandoned
- 1986-03-26 ZA ZA862248A patent/ZA862248B/xx unknown
- 1986-03-26 PT PT82272A patent/PT82272B/pt unknown
- 1986-03-26 GR GR860801A patent/GR860801B/el unknown
- 1986-03-26 ES ES553463A patent/ES8705882A1/es not_active Expired
- 1986-03-26 KR KR1019860002262A patent/KR860007253A/ko not_active Application Discontinuation
- 1986-03-26 NO NO861266A patent/NO861266L/no unknown
- 1986-03-26 NZ NZ215616A patent/NZ215616A/en unknown
- 1986-11-21 ES ES557219A patent/ES8705884A1/es not_active Expired
- 1986-11-21 ES ES557218A patent/ES8705883A1/es not_active Expired
- 1986-11-21 ES ES557220A patent/ES8705885A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| EP0196005A1 (de) | 1986-10-01 |
| PT82272B (de) | 1988-01-06 |
| ATE48841T1 (de) | 1990-01-15 |
| ES8705883A1 (es) | 1987-05-16 |
| GR860801B (en) | 1986-07-21 |
| ZA862248B (en) | 1987-11-25 |
| CA1257588A (en) | 1989-07-18 |
| ES8705884A1 (es) | 1987-05-16 |
| ES557219A0 (es) | 1987-05-16 |
| ES557220A0 (es) | 1987-05-16 |
| DE3511110A1 (de) | 1986-10-02 |
| ES8705885A1 (es) | 1987-05-16 |
| JPS61227582A (ja) | 1986-10-09 |
| IL78251A0 (en) | 1986-07-31 |
| HUT42085A (en) | 1987-06-29 |
| EP0196005B1 (de) | 1989-12-20 |
| FI861288A (fi) | 1986-09-28 |
| DK131886A (da) | 1986-09-28 |
| FI861288A0 (fi) | 1986-03-26 |
| DK131886D0 (da) | 1986-03-21 |
| KR860007253A (ko) | 1986-10-10 |
| ES8705882A1 (es) | 1987-05-16 |
| DE3667664D1 (de) | 1990-01-25 |
| AU5530386A (en) | 1986-10-02 |
| PT82272A (de) | 1986-04-01 |
| ES557218A0 (es) | 1987-05-16 |
| NZ215616A (en) | 1990-01-29 |
| DD248362A5 (de) | 1987-08-05 |
| ES553463A0 (es) | 1987-05-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO861266L (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive pyridazinon-derivater. | |
| CA2241787C (en) | Substituted aza- and diazacycloheptane and cyclooctane compounds and their use | |
| JP5328816B2 (ja) | アミロイドβの調節薬 | |
| AU2004212421B2 (en) | Heteroaryl substituted pyrolls useful as inhibitors of protein kinases | |
| EP1730134A1 (en) | Pyridine inhibitors of erk2 and uses thereof | |
| MXPA06013954A (es) | Indazoles sustituidos, composiciones que contienen los mismos, preparacion y uso. | |
| TW200524907A (en) | Aryl-heteroaromatic products, compositions comprising them and use | |
| TW201043635A (en) | New compounds 745 | |
| WO1998002430A1 (en) | Pyridylpyrrole compounds useful as interleukin- and tnf antagonists | |
| AU2007304475A1 (en) | Substituted sulfonamide derivatives | |
| WO2006048248A2 (en) | Novel anthranilamide pyridinureas as vegf receptor kinase imhibitors | |
| JP4904267B2 (ja) | ドーパミンｄ３受容体の調節に応答する障害の治療に好適な４−ピペラジニル−ピリミジン化合物 | |
| SK121498A3 (en) | Quinoxalinediones, method and intermediates for their producing, use thereof and pharmaceutical compositions based thereupon | |
| MXPA06013815A (es) | Compuestos de piridin-2-ona y su uso como moduladores del receptor d3 de dopamina. | |
| NO874153L (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive imidazo-benzoksazinon-derivater. | |
| FI93956C (fi) | Menetelmä uusien piperatsinyylialkyyli-3(2H)-pyridatsinonien valmistamiseksi | |
| CA3175429A1 (en) | Gpr52 modulator compounds | |
| AU640302B2 (en) | Pyridine compounds | |
| KR101161070B1 (ko) | 5-ｈｔ7 수용체 길항제 | |
| IL118631A (en) | History of pyridazinone and processes for their preparation | |
| NO151620B (no) | Analogifremgangsmaate for fremstilling av terapeutisk virksomme, nye pyrrolyl-3-pyridazinaminer | |
| WO2000050417A1 (en) | Anti-cancer dihydroquinazoline derivatives | |
| US3183229A (en) | Hydrazones derived from 1-amino-4-diphenylalkylpiperazines and heterocyclic aldehydes and ketones | |
| KR20050092761A (ko) | 티에노피리다지논 및 그들의 자가면역 질환 조절 용도 | |
| WO2000078758A1 (fr) | Nouveaux derives d'imidazole |