SK280786B6 - Deriváty pyridazinónu, spôsob ich prípravy, bronch - Google Patents
Deriváty pyridazinónu, spôsob ich prípravy, bronch Download PDFInfo
- Publication number
- SK280786B6 SK280786B6 SK1624-95A SK162495A SK280786B6 SK 280786 B6 SK280786 B6 SK 280786B6 SK 162495 A SK162495 A SK 162495A SK 280786 B6 SK280786 B6 SK 280786B6
- Authority
- SK
- Slovakia
- Prior art keywords
- ome
- alkyl
- group
- hydrogen
- optionally substituted
- Prior art date
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- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims description 29
- 238000000034 method Methods 0.000 claims abstract description 52
- -1 4-substituted piperazine ring Chemical group 0.000 claims abstract description 38
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
- 230000008569 process Effects 0.000 claims abstract description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 18
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 15
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims abstract description 7
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract 3
- 239000000460 chlorine Substances 0.000 claims description 426
- 150000001875 compounds Chemical class 0.000 claims description 118
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- 229910052739 hydrogen Inorganic materials 0.000 claims description 50
- 239000001257 hydrogen Substances 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 150000002431 hydrogen Chemical class 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 9
- 150000001721 carbon Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 229910052794 bromium Chemical group 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229940124630 bronchodilator Drugs 0.000 claims description 7
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 230000003266 anti-allergic effect Effects 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 abstract description 12
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 125000003277 amino group Chemical group 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 541
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 109
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 109
- 239000000203 mixture Substances 0.000 description 64
- 239000002904 solvent Substances 0.000 description 61
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 60
- 238000006243 chemical reaction Methods 0.000 description 57
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 56
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 36
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- 230000002829 reductive effect Effects 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
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- 239000012074 organic phase Substances 0.000 description 21
- 238000012360 testing method Methods 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- 239000011780 sodium chloride Substances 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 239000013078 crystal Substances 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- 238000003756 stirring Methods 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
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- 150000003939 benzylamines Chemical class 0.000 description 13
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
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- 235000011181 potassium carbonates Nutrition 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 235000011121 sodium hydroxide Nutrition 0.000 description 9
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000009833 condensation Methods 0.000 description 7
- 230000005494 condensation Effects 0.000 description 7
- 229910052987 metal hydride Inorganic materials 0.000 description 7
- 150000004681 metal hydrides Chemical class 0.000 description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
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- 206010006482 Bronchospasm Diseases 0.000 description 6
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 230000007885 bronchoconstriction Effects 0.000 description 6
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- 150000007529 inorganic bases Chemical class 0.000 description 6
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 6
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- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
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- RAOUIPCRBFXZGY-UHFFFAOYSA-N 4,5-dichloro-3-ethoxy-1h-pyridazin-6-one Chemical compound CCOC1=NNC(=O)C(Cl)=C1Cl RAOUIPCRBFXZGY-UHFFFAOYSA-N 0.000 description 4
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- NXSOFSOGWSOKAQ-UHFFFAOYSA-N benzyl n-[(3-hydroxy-4-methoxyphenyl)methyl]carbamate Chemical compound C1=C(O)C(OC)=CC=C1CNC(=O)OCC1=CC=CC=C1 NXSOFSOGWSOKAQ-UHFFFAOYSA-N 0.000 description 4
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- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
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- 238000004821 distillation Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
- FLIBKIRHXYPCJV-UHFFFAOYSA-N ethanol;propan-2-yl tetradecanoate Chemical compound CCO.CCCCCCCCCCCCCC(=O)OC(C)C FLIBKIRHXYPCJV-UHFFFAOYSA-N 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- PZBIQTNHDYNFHM-UHFFFAOYSA-N ethyl 4-[(4-methoxyphenyl)methyl-phenylmethoxycarbonylamino]oxybutanoate Chemical compound C=1C=CC=CC=1COC(=O)N(OCCCC(=O)OCC)CC1=CC=C(OC)C=C1 PZBIQTNHDYNFHM-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
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- 125000000524 functional group Chemical group 0.000 description 1
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- 229930195712 glutamate Natural products 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
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- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
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- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
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- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
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- 230000009401 metastasis Effects 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- LVCDXCQFSONNDO-UHFFFAOYSA-N n-benzylhydroxylamine Chemical class ONCC1=CC=CC=C1 LVCDXCQFSONNDO-UHFFFAOYSA-N 0.000 description 1
- UCUAOJGWURYBCX-UHFFFAOYSA-N n-ethoxy-1-(4-methoxyphenyl)methanamine Chemical compound CCONCC1=CC=C(OC)C=C1 UCUAOJGWURYBCX-UHFFFAOYSA-N 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
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- 230000000414 obstructive effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000056 polyoxyethylene ether Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000004526 pyridazin-2-yl group Chemical group N1N(C=CC=C1)* 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229940082004 sodium laurate Drugs 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-N sorbic acid group Chemical class C(\C=C\C=C\C)(=O)O WSWCOQWTEOXDQX-MQQKCMAXSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- UBSGDLHYSHCAIE-UHFFFAOYSA-N tert-butyl n-[4-(piperazin-1-ylmethyl)phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1CN1CCNCC1 UBSGDLHYSHCAIE-UHFFFAOYSA-N 0.000 description 1
- RVHALLWEGWTPNM-UHFFFAOYSA-N tert-butyl n-[4-[[1-[2-[2-methoxy-5-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]phenoxy]acetyl]piperazin-2-yl]methyl]phenyl]carbamate Chemical compound COC1=CC=C(CNC(=O)OC(C)(C)C)C=C1OCC(=O)N1C(CC=2C=CC(NC(=O)OC(C)(C)C)=CC=2)CNCC1 RVHALLWEGWTPNM-UHFFFAOYSA-N 0.000 description 1
- OIPRKFMGICRHSC-UHFFFAOYSA-N tert-butyl n-[[3-[2-(4-benzylpiperidin-1-yl)-2-oxoethoxy]-4-methoxyphenyl]methyl]carbamate Chemical compound COC1=CC=C(CNC(=O)OC(C)(C)C)C=C1OCC(=O)N1CCC(CC=2C=CC=CC=2)CC1 OIPRKFMGICRHSC-UHFFFAOYSA-N 0.000 description 1
- NESFGDHBQDLVCB-UHFFFAOYSA-N tert-butyl n-[[4-methoxy-3-[2-oxo-2-[4-(quinolin-2-ylmethyl)piperazin-1-yl]ethoxy]phenyl]methyl]carbamate Chemical compound COC1=CC=C(CNC(=O)OC(C)(C)C)C=C1OCC(=O)N1CCN(CC=2N=C3C=CC=CC3=CC=2)CC1 NESFGDHBQDLVCB-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/22—Nitrogen and oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/20—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15919493 | 1993-06-29 | ||
| JP11272194 | 1994-05-26 | ||
| PCT/JP1994/001015 WO1995001343A1 (en) | 1993-06-29 | 1994-06-24 | Pyridazinone derivatives with pharmaceutical activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK162495A3 SK162495A3 (en) | 1996-11-06 |
| SK280786B6 true SK280786B6 (sk) | 2000-07-11 |
Family
ID=26451823
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1624-95A SK280786B6 (sk) | 1993-06-29 | 1994-06-24 | Deriváty pyridazinónu, spôsob ich prípravy, bronch |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US5728702A (cs) |
| EP (1) | EP0706517B1 (cs) |
| KR (1) | KR100255416B1 (cs) |
| CN (1) | CN1044906C (cs) |
| AT (1) | ATE172454T1 (cs) |
| AU (1) | AU676341B2 (cs) |
| CA (1) | CA2166326C (cs) |
| CZ (1) | CZ289231B6 (cs) |
| DE (1) | DE69414112T2 (cs) |
| DK (1) | DK0706517T3 (cs) |
| ES (1) | ES2124413T3 (cs) |
| FI (1) | FI113963B (cs) |
| HU (1) | HU221009B1 (cs) |
| IL (1) | IL110040A (cs) |
| NO (1) | NO306675B1 (cs) |
| NZ (1) | NZ267510A (cs) |
| RO (1) | RO114791B1 (cs) |
| RU (1) | RU2138486C1 (cs) |
| SK (1) | SK280786B6 (cs) |
| TW (1) | TW408114B (cs) |
| UA (1) | UA34481C2 (cs) |
| WO (1) | WO1995001343A1 (cs) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2147841T3 (es) * | 1994-01-25 | 2000-10-01 | Nissan Chemical Ind Ltd | Derivados de piridazinona. |
| DE4430755A1 (de) * | 1994-08-30 | 1996-03-07 | Boehringer Mannheim Gmbh | Neue Phosphanoxide, Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel |
| DE19533975A1 (de) * | 1995-09-14 | 1997-03-20 | Merck Patent Gmbh | Arylalkyl-diazinone |
| US6207665B1 (en) | 1997-06-12 | 2001-03-27 | Schering Aktiengesellschaft | Piperazine derivatives and their use as anti-inflammatory agents |
| WO1999050248A1 (en) * | 1998-03-31 | 1999-10-07 | Nissan Chemical Industries, Ltd. | Pyridazinone hydrochloride compound and method for producing the same |
| KR100717557B1 (ko) * | 1999-11-11 | 2007-05-15 | 닛산 가가쿠 고교 가부시키 가이샤 | 벤질아민 화합물의 제조 방법 |
| SE9904377D0 (sv) * | 1999-12-01 | 1999-12-01 | Astra Pharma Prod | Pharmaceutical combinations |
| RU2179848C1 (ru) * | 2001-03-30 | 2002-02-27 | Государственное учреждение Тверская государственная медицинская академия | Применение антидепрессанта амитриптилина у больных раком легкого |
| AP2004003008A0 (en) | 2001-10-22 | 2004-06-30 | Pfizer Prod Inc | Piperazine derivatives with CCR1 receptor antagonist activity |
| RU2220738C1 (ru) * | 2002-08-30 | 2004-01-10 | Гапонюк Петр Яковлевич | Средство для лечения ринита |
| US20060080140A1 (en) * | 2004-02-09 | 2006-04-13 | Epic Systems Corporation | System and method for providing a clinical summary of patient information in various health care settings |
| WO2010099388A1 (en) * | 2009-02-27 | 2010-09-02 | Indigo Pharmaceuticals | Combinational use of a pde3 inhibitor and other agents |
| CN116768868B (zh) * | 2023-08-15 | 2023-12-08 | 云南省药物研究所 | 一种哒嗪酮硫代衍生物及其制备方法和应用 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1265798A (en) * | 1984-12-10 | 1990-02-13 | Motoo Mutsukado | 3(2h)pyridazinone, process for its preparation and anti-allergic agent containing it |
| JPH0641454B2 (ja) * | 1985-02-27 | 1994-06-01 | 日産化学工業株式会社 | ピリダジノン誘導体 |
| US4892947A (en) * | 1985-04-27 | 1990-01-09 | Nissan Chemical Industries Ltd. | 3(2H)Pyridazinone, process for its preparation and anti-allergic agent containing it |
| US4978665A (en) * | 1987-01-20 | 1990-12-18 | Nissan Chemical Industries Ltd. | 3(2H)pyridazinone, and antagonistic agent against SRS-A containing it |
| JPH02256668A (ja) * | 1988-12-20 | 1990-10-17 | Nissan Chem Ind Ltd | ピリダジノン誘導体 |
| DE69132329T2 (de) * | 1990-04-25 | 2000-11-30 | Nissan Chemical Industries, Ltd. | Pyridazinonderivat |
| ES2147841T3 (es) * | 1994-01-25 | 2000-10-01 | Nissan Chemical Ind Ltd | Derivados de piridazinona. |
-
1994
- 1994-06-17 IL IL11004094A patent/IL110040A/xx not_active IP Right Cessation
- 1994-06-24 EP EP94918564A patent/EP0706517B1/en not_active Expired - Lifetime
- 1994-06-24 CZ CZ19953299A patent/CZ289231B6/cs not_active IP Right Cessation
- 1994-06-24 UA UA95125405A patent/UA34481C2/uk unknown
- 1994-06-24 AU AU69833/94A patent/AU676341B2/en not_active Ceased
- 1994-06-24 KR KR1019950705969A patent/KR100255416B1/ko not_active Expired - Fee Related
- 1994-06-24 RO RO95-02293A patent/RO114791B1/ro unknown
- 1994-06-24 ES ES94918564T patent/ES2124413T3/es not_active Expired - Lifetime
- 1994-06-24 AT AT94918564T patent/ATE172454T1/de not_active IP Right Cessation
- 1994-06-24 CA CA002166326A patent/CA2166326C/en not_active Expired - Fee Related
- 1994-06-24 DE DE69414112T patent/DE69414112T2/de not_active Expired - Fee Related
- 1994-06-24 US US08/564,277 patent/US5728702A/en not_active Expired - Lifetime
- 1994-06-24 RU RU96101173A patent/RU2138486C1/ru not_active IP Right Cessation
- 1994-06-24 CN CN94192618A patent/CN1044906C/zh not_active Expired - Fee Related
- 1994-06-24 NZ NZ267510A patent/NZ267510A/en not_active IP Right Cessation
- 1994-06-24 DK DK94918564T patent/DK0706517T3/da active
- 1994-06-24 WO PCT/JP1994/001015 patent/WO1995001343A1/en active IP Right Grant
- 1994-06-24 SK SK1624-95A patent/SK280786B6/sk unknown
- 1994-06-24 HU HU9503807A patent/HU221009B1/hu not_active IP Right Cessation
- 1994-06-25 TW TW083105779A patent/TW408114B/zh not_active IP Right Cessation
-
1995
- 1995-12-28 NO NO955328A patent/NO306675B1/no unknown
- 1995-12-28 FI FI956300A patent/FI113963B/fi not_active IP Right Cessation
-
1997
- 1997-12-08 US US08/986,420 patent/US5929074A/en not_active Expired - Fee Related
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