ES2479440T3 - Derivados de piridazina sustituidos que tienen actividad antagonista de histamina H3 - Google Patents
Derivados de piridazina sustituidos que tienen actividad antagonista de histamina H3 Download PDFInfo
- Publication number
- ES2479440T3 ES2479440T3 ES09706750.8T ES09706750T ES2479440T3 ES 2479440 T3 ES2479440 T3 ES 2479440T3 ES 09706750 T ES09706750 T ES 09706750T ES 2479440 T3 ES2479440 T3 ES 2479440T3
- Authority
- ES
- Spain
- Prior art keywords
- phenyl
- nmr
- propoxy
- alkyl
- pyridazine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 230000000694 effects Effects 0.000 title description 3
- 239000003395 histamine H3 receptor antagonist Substances 0.000 title 1
- 150000004892 pyridazines Chemical class 0.000 title 1
- -1 -OH Chemical group 0.000 abstract description 12
- 150000001875 compounds Chemical class 0.000 abstract description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 11
- 125000006546 (C4-C10) cycloalkyl group Chemical group 0.000 abstract 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 abstract 4
- 125000003118 aryl group Chemical group 0.000 abstract 4
- 229910052736 halogen Inorganic materials 0.000 abstract 4
- 150000002367 halogens Chemical class 0.000 abstract 4
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 abstract 3
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 abstract 2
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 abstract 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 33
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- 230000014759 maintenance of location Effects 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- XNQIOISZPFVUFG-RXMQYKEDSA-N (R)-alpha-methylhistamine Chemical compound C[C@@H](N)CC1=CN=CN1 XNQIOISZPFVUFG-RXMQYKEDSA-N 0.000 description 3
- MNZUASQQMDHYCQ-HXUWFJFHSA-N 3-benzylsulfanyl-6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(SCC=3C=CC=CC=3)=CC=2)C=C1 MNZUASQQMDHYCQ-HXUWFJFHSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- AWWYLUCTZLYBTG-QGZVFWFLSA-N 3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6-thiophen-2-ylpyridazine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(=CC=2)C=2SC=CC=2)C=C1 AWWYLUCTZLYBTG-QGZVFWFLSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 206010062519 Poor quality sleep Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000001371 alpha-amino acids Chemical class 0.000 description 2
- 235000008206 alpha-amino acids Nutrition 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- LJKASJQJHADFNZ-MRXNPFEDSA-N 1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-4-methylsulfanyl-6,7-dihydro-5h-cyclopenta[d]pyridazine Chemical compound C1=2CCCC=2C(SC)=NN=C1C(C=C1)=CC=C1OCCCN1CCC[C@H]1C LJKASJQJHADFNZ-MRXNPFEDSA-N 0.000 description 1
- IRCSUSACGMABQS-GOSISDBHSA-N 1-[6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-yl]piperidin-4-ol Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(=CC=2)N2CCC(O)CC2)C=C1 IRCSUSACGMABQS-GOSISDBHSA-N 0.000 description 1
- ANPINRFBSAUQDU-LJQANCHMSA-N 3-(1-benzofuran-2-yl)-6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(=CC=2)C=2OC3=CC=CC=C3C=2)C=C1 ANPINRFBSAUQDU-LJQANCHMSA-N 0.000 description 1
- DLBQMYQJBCWNHW-LJQANCHMSA-N 3-[(4-fluorophenyl)methoxy]-6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(OCC=3C=CC(F)=CC=3)=CC=2)C=C1 DLBQMYQJBCWNHW-LJQANCHMSA-N 0.000 description 1
- XARCMYZPBBBSAG-HXUWFJFHSA-N 3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6-phenylmethoxypyridazine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(OCC=3C=CC=CC=3)=CC=2)C=C1 XARCMYZPBBBSAG-HXUWFJFHSA-N 0.000 description 1
- VSFQQSITUVDHTA-LJQANCHMSA-N 3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6-phenylpyridazine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(=CC=2)C=2C=CC=CC=2)C=C1 VSFQQSITUVDHTA-LJQANCHMSA-N 0.000 description 1
- ZWPRLLAZIQZNAG-QGZVFWFLSA-N 3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6-propan-2-yloxypyridazine Chemical compound N1=NC(OC(C)C)=CC=C1C(C=C1)=CC=C1OCCCN1[C@H](C)CCC1 ZWPRLLAZIQZNAG-QGZVFWFLSA-N 0.000 description 1
- VLPKPZKIZYOELA-GOSISDBHSA-N 3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6-pyrrolidin-1-ylpyridazine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(=CC=2)N2CCCC2)C=C1 VLPKPZKIZYOELA-GOSISDBHSA-N 0.000 description 1
- USECFGWRJBOAEK-UHFFFAOYSA-N 3-benzylsulfanyl-6-[4-(3-piperidin-1-ylpropoxy)phenyl]pyridazine Chemical compound C1CCCCN1CCCOC(C=C1)=CC=C1C(N=N1)=CC=C1SCC1=CC=CC=C1 USECFGWRJBOAEK-UHFFFAOYSA-N 0.000 description 1
- POGQXQOEERNJFB-UHFFFAOYSA-N 3-benzylsulfinyl-6-[4-(3-piperidin-1-ylpropoxy)phenyl]pyridazine Chemical compound C=1C=C(C=2C=CC(OCCCN3CCCCC3)=CC=2)N=NC=1S(=O)CC1=CC=CC=C1 POGQXQOEERNJFB-UHFFFAOYSA-N 0.000 description 1
- VEUONXQPMCACHO-DXHYANOHSA-N 3-benzylsulfinyl-6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(=CC=2)S(=O)CC=2C=CC=CC=2)C=C1 VEUONXQPMCACHO-DXHYANOHSA-N 0.000 description 1
- AJNZISMWSGKOCY-UHFFFAOYSA-N 3-benzylsulfonyl-6-[4-(3-piperidin-1-ylpropoxy)phenyl]pyridazine Chemical compound C=1C=C(C=2C=CC(OCCCN3CCCCC3)=CC=2)N=NC=1S(=O)(=O)CC1=CC=CC=C1 AJNZISMWSGKOCY-UHFFFAOYSA-N 0.000 description 1
- MCIKUTXFDWKRDG-HXUWFJFHSA-N 3-benzylsulfonyl-6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(=CC=2)S(=O)(=O)CC=2C=CC=CC=2)C=C1 MCIKUTXFDWKRDG-HXUWFJFHSA-N 0.000 description 1
- BFOKNONCWSKSNR-UHFFFAOYSA-N 3-chloro-6-[2-methyl-4-(3-piperidin-1-ylpropoxy)phenyl]pyridazine Chemical compound C=1C=C(C=2N=NC(Cl)=CC=2)C(C)=CC=1OCCCN1CCCCC1 BFOKNONCWSKSNR-UHFFFAOYSA-N 0.000 description 1
- VNNBSXMZBLFYON-UHFFFAOYSA-N 3-chloro-6-[3-methoxy-4-(3-piperidin-1-ylpropoxy)phenyl]pyridazine Chemical compound COC1=CC(C=2N=NC(Cl)=CC=2)=CC=C1OCCCN1CCCCC1 VNNBSXMZBLFYON-UHFFFAOYSA-N 0.000 description 1
- HXSABWRMROMERN-UHFFFAOYSA-N 3-chloro-6-[4-(3-piperidin-1-ylpropoxy)phenyl]pyridazine Chemical compound N1=NC(Cl)=CC=C1C(C=C1)=CC=C1OCCCN1CCCCC1 HXSABWRMROMERN-UHFFFAOYSA-N 0.000 description 1
- VXSLUXQRULNTNE-LSDHHAIUSA-N 3-chloro-6-[4-[(2s)-2-methyl-3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazine Chemical compound C([C@@H](C)CN1[C@@H](CCC1)C)OC(C=C1)=CC=C1C1=CC=C(Cl)N=N1 VXSLUXQRULNTNE-LSDHHAIUSA-N 0.000 description 1
- GTQROZRIYRHZHV-UHFFFAOYSA-N 3-methylsulfanyl-6-[4-(3-piperidin-1-ylpropoxy)phenyl]pyridazine Chemical compound N1=NC(SC)=CC=C1C(C=C1)=CC=C1OCCCN1CCCCC1 GTQROZRIYRHZHV-UHFFFAOYSA-N 0.000 description 1
- BLHPCLKYVQFWPU-UHFFFAOYSA-N 3-phenoxy-6-[4-(3-piperidin-1-ylpropoxy)phenyl]pyridazine Chemical compound C1CCCCN1CCCOC(C=C1)=CC=C1C(N=N1)=CC=C1OC1=CC=CC=C1 BLHPCLKYVQFWPU-UHFFFAOYSA-N 0.000 description 1
- IVDIJSIYQKBWDS-UHFFFAOYSA-N 3-phenylmethoxy-6-[4-(3-piperidin-1-ylpropoxy)phenyl]pyridazine Chemical compound C1CCCCN1CCCOC(C=C1)=CC=C1C(N=N1)=CC=C1OCC1=CC=CC=C1 IVDIJSIYQKBWDS-UHFFFAOYSA-N 0.000 description 1
- ADRYHRMBTICFMB-GOSISDBHSA-N 4-[6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-yl]morpholine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(=CC=2)N2CCOCC2)C=C1 ADRYHRMBTICFMB-GOSISDBHSA-N 0.000 description 1
- AWTAJTYCGQYBHX-OAQYLSRUSA-N 4-benzylsulfanyl-1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6,7-dihydro-5h-cyclopenta[d]pyridazine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C=3CCCC=3C(SCC=3C=CC=CC=3)=NN=2)C=C1 AWTAJTYCGQYBHX-OAQYLSRUSA-N 0.000 description 1
- QWRAVYBIWLFPQN-UHFFFAOYSA-N 4-chloro-1-[4-(3-piperidin-1-ylpropoxy)phenyl]-6,7-dihydro-5h-cyclopenta[d]pyridazine Chemical compound C1=2CCCC=2C(Cl)=NN=C1C(C=C1)=CC=C1OCCCN1CCCCC1 QWRAVYBIWLFPQN-UHFFFAOYSA-N 0.000 description 1
- IBOGRSGEINDRLY-MRXNPFEDSA-N 4-methoxy-1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6,7-dihydro-5h-cyclopenta[d]pyridazine Chemical compound C1=2CCCC=2C(OC)=NN=C1C(C=C1)=CC=C1OCCCN1CCC[C@H]1C IBOGRSGEINDRLY-MRXNPFEDSA-N 0.000 description 1
- GAPZGVQUOCWPPW-UHFFFAOYSA-N 5-(6-chloropyridazin-3-yl)-2-(3-piperidin-1-ylpropoxy)benzonitrile Chemical compound N1=NC(Cl)=CC=C1C(C=C1C#N)=CC=C1OCCCN1CCCCC1 GAPZGVQUOCWPPW-UHFFFAOYSA-N 0.000 description 1
- DKXPWQDBPJOGQW-CQSZACIVSA-N 5-(6-chloropyridazin-3-yl)-2-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]benzonitrile Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(Cl)=CC=2)C=C1C#N DKXPWQDBPJOGQW-CQSZACIVSA-N 0.000 description 1
- TYLXTAQPFOKERE-CQSZACIVSA-N 6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-amine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(N)=CC=2)C=C1 TYLXTAQPFOKERE-CQSZACIVSA-N 0.000 description 1
- 240000002989 Euphorbia neriifolia Species 0.000 description 1
- 102000004384 Histamine H3 receptors Human genes 0.000 description 1
- 108090000981 Histamine H3 receptors Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- QKDDJDBFONZGBW-UHFFFAOYSA-N N-Cyclohexy-4-(imidazol-4-yl)-1-piperidinecarbothioamide Chemical compound C1CC(C=2NC=NC=2)CCN1C(=S)NC1CCCCC1 QKDDJDBFONZGBW-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000003453 histamine agonist Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- OXXNYHZDPHROBF-HXUWFJFHSA-N n-benzyl-6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-amine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2N=NC(NCC=3C=CC=CC=3)=CC=2)C=C1 OXXNYHZDPHROBF-HXUWFJFHSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002245 particle Substances 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
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 238000007832 transition metal-catalyzed coupling reaction Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000002618 waking effect Effects 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
- C07D237/12—Halogen atoms or nitro radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
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- 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
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- 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
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US6290808P | 2008-01-30 | 2008-01-30 | |
| US62908P | 2008-01-30 | ||
| PCT/US2009/032187 WO2009097306A1 (en) | 2008-01-30 | 2009-01-28 | Substituted pyridazine derivatives which have histamine h3 antagonist activity |
Publications (1)
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| ES2479440T3 true ES2479440T3 (es) | 2014-07-24 |
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| ES09706750.8T Active ES2479440T3 (es) | 2008-01-30 | 2009-01-28 | Derivados de piridazina sustituidos que tienen actividad antagonista de histamina H3 |
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| JP5335675B2 (ja) * | 2006-07-25 | 2013-11-06 | セファロン、インク. | ピリジジノン誘導体 |
| WO2009097306A1 (en) | 2008-01-30 | 2009-08-06 | Cephalon, Inc. | Substituted pyridazine derivatives which have histamine h3 antagonist activity |
| EP2328586A2 (en) * | 2008-05-20 | 2011-06-08 | Cephalon, Inc. | Substituted pyridazinone derivatives as histamine-3 (h3) receptor ligands |
| WO2013151982A1 (en) | 2012-04-03 | 2013-10-10 | Arena Pharmaceuticals, Inc. | Methods and compounds useful in treating pruritus, and methods for identifying such compounds |
| TWI568942B (zh) * | 2013-09-26 | 2017-02-01 | 崔文德 | 球座標轉向平行機構 |
| CN109111400B (zh) * | 2017-06-23 | 2020-10-16 | 杭州百诚医药科技股份有限公司 | 苯基喹啉酮类和黄酮类衍生物的制备和应用 |
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| US3239523A (en) * | 1965-05-06 | 1966-03-08 | Harman S Lowrie | 3-(4-dialkylaminoalkoxyphenyl) cinnolines |
| US5241062A (en) | 1993-01-19 | 1993-08-31 | Sun Company, Inc. (R&M) | Synthetic route to meso-tetra hydrocarbyl or substituted hydrocarbyl porphyrins and derivatives |
| MXPA06011167A (es) * | 2004-04-01 | 2007-01-25 | Eli Lilli And Company | Agentes del receptor h3 de histamina, preparacion y usos terapeuticos. |
| EP1717235A3 (en) * | 2005-04-29 | 2007-02-28 | Bioprojet | Phenoxypropylpiperidines and -pyrrolidines and their use as histamine H3-receptor ligands |
| BRPI0613564A2 (pt) * | 2005-07-04 | 2011-01-18 | Novo Nordisk As | compostos, seus usos na preparação de composições farmacêuticas e composições farmacêuticas compreendendo os mesmos |
| JP5335675B2 (ja) | 2006-07-25 | 2013-11-06 | セファロン、インク. | ピリジジノン誘導体 |
| AU2008248168B2 (en) * | 2007-05-03 | 2013-03-21 | Cephalon, Inc. | Processes for preparing (R)-2-methylpyrrolidine and (S)-2-methylpyrrolidine and tartrate salts thereof |
| WO2009097306A1 (en) | 2008-01-30 | 2009-08-06 | Cephalon, Inc. | Substituted pyridazine derivatives which have histamine h3 antagonist activity |
| ES2390004T3 (es) | 2008-01-30 | 2012-11-05 | Cephalon, Inc. | Derivados sustituidos de piperidina espirocíclica como ligandos del receptor de la histamina 3(H3) |
| JP5524082B2 (ja) | 2008-01-30 | 2014-06-18 | セファロン、インク. | ヒスタミン−3(h3)受容体リガンドとしての置換スピロ環状ピペリジン誘導体 |
| AU2009237650B2 (en) * | 2008-04-17 | 2012-05-31 | Proximagen Limited | Indoles as modulators of nicoticic acetylcholine receptor subtype alpha-7 |
| EP2328586A2 (en) | 2008-05-20 | 2011-06-08 | Cephalon, Inc. | Substituted pyridazinone derivatives as histamine-3 (h3) receptor ligands |
| WO2011002984A1 (en) | 2009-07-02 | 2011-01-06 | Cephalon, Inc. | Substituted phenoxypropylcycloamine derivatives as histamine-3 (h3) receptor ligands |
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| US8076331B2 (en) | 2011-12-13 |
| EP2252593B1 (en) | 2014-04-23 |
| US20100311752A1 (en) | 2010-12-09 |
| JP2011510991A (ja) | 2011-04-07 |
| JP5539230B2 (ja) | 2014-07-02 |
| US20120004231A1 (en) | 2012-01-05 |
| EP2752406A1 (en) | 2014-07-09 |
| HRP20140568T1 (hr) | 2014-10-24 |
| CA2712885A1 (en) | 2009-08-06 |
| HK1149554A1 (en) | 2011-10-07 |
| MX2010008384A (es) | 2010-11-30 |
| US8912183B2 (en) | 2014-12-16 |
| WO2009097306A1 (en) | 2009-08-06 |
| EP2252593A1 (en) | 2010-11-24 |
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