HRP930210A2 - Heterobicyclic compounds and pharmaceutical preparations containing them - Google Patents
Heterobicyclic compounds and pharmaceutical preparations containing them Download PDFInfo
- Publication number
- HRP930210A2 HRP930210A2 HR930210A HRP930210A HRP930210A2 HR P930210 A2 HRP930210 A2 HR P930210A2 HR 930210 A HR930210 A HR 930210A HR P930210 A HRP930210 A HR P930210A HR P930210 A2 HRP930210 A2 HR P930210A2
- Authority
- HR
- Croatia
- Prior art keywords
- benzopyran
- oxo
- phenyl
- methyl
- piperazinyl
- Prior art date
Links
- 125000002618 bicyclic heterocycle group Chemical group 0.000 title claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 391
- -1 hydroxylmethylene group Chemical group 0.000 claims description 82
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 15
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 239000000651 prodrug Substances 0.000 claims description 9
- 229940002612 prodrug Drugs 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 150000001204 N-oxides Chemical class 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000004442 acylamino group Chemical group 0.000 claims description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 3
- JUXHWXSCFVJNBO-UHFFFAOYSA-N 3-methyl-4-oxo-n-[3-[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]propyl]-2-phenylchromene-8-carboxamide Chemical compound O1C2=C(C(=O)NCCCN3CCC(CC3)N3C(NC4=CC=CC=C43)=O)C=CC=C2C(=O)C(C)=C1C1=CC=CC=C1 JUXHWXSCFVJNBO-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 125000005277 alkyl imino group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 2
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- AIHBTWJKGJLMQK-UHFFFAOYSA-N 1-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-3-(3-methyl-4-oxo-2-phenylchromen-8-yl)urea Chemical compound COC1=CC=CC=C1N1CCN(CCNC(=O)NC=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=CC=2)CC1 AIHBTWJKGJLMQK-UHFFFAOYSA-N 0.000 claims 1
- YGDSUOONUHSVLM-UHFFFAOYSA-N 3-(4-phenylpiperazin-1-yl)propyl 3-methyl-4-oxo-2-phenylchromene-8-carboxylate Chemical compound C1=CC=C2C(=O)C(C)=C(C=3C=CC=CC=3)OC2=C1C(=O)OCCCN(CC1)CCN1C1=CC=CC=C1 YGDSUOONUHSVLM-UHFFFAOYSA-N 0.000 claims 1
- ONWDJAVBRVVPJB-UHFFFAOYSA-N 3-[4-(2-chlorophenyl)piperazin-1-yl]propyl 3-methyl-4-oxo-2-phenylchromene-8-carboxylate Chemical compound C1=CC=C2C(=O)C(C)=C(C=3C=CC=CC=3)OC2=C1C(=O)OCCCN(CC1)CCN1C1=CC=CC=C1Cl ONWDJAVBRVVPJB-UHFFFAOYSA-N 0.000 claims 1
- PLUMFQNYUVGHER-UHFFFAOYSA-N 3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl 3-methyl-4-oxo-2-phenylchromene-8-carboxylate Chemical compound COC1=CC=CC=C1N1CCN(CCCOC(=O)C=2C3=C(C(C(C)=C(C=4C=CC=CC=4)O3)=O)C=CC=2)CC1 PLUMFQNYUVGHER-UHFFFAOYSA-N 0.000 claims 1
- SYEJJGSUNDDJNN-UHFFFAOYSA-N 6-amino-n-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCCNC(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=C(N)C=2)CC1 SYEJJGSUNDDJNN-UHFFFAOYSA-N 0.000 claims 1
- FZCYCHSLXKNZEO-UHFFFAOYSA-N 7-methoxy-n-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCCNC(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=CC=2OC)CC1 FZCYCHSLXKNZEO-UHFFFAOYSA-N 0.000 claims 1
- CVIYJJLZWPEVRU-UHFFFAOYSA-N 8-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propanoyl]-3-methyl-2-phenylchromen-4-one Chemical compound COC1=CC=CC=C1N1CCN(CCC(=O)C=2C3=C(C(C(C)=C(C=4C=CC=CC=4)O3)=O)C=CC=2)CC1 CVIYJJLZWPEVRU-UHFFFAOYSA-N 0.000 claims 1
- LNGUSSHELAJOGC-UHFFFAOYSA-N 8-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butanoyl]-3-methyl-2-phenylchromen-4-one Chemical compound COC1=CC=CC=C1N1CCN(CCCC(=O)C=2C3=C(C(C(C)=C(C=4C=CC=CC=4)O3)=O)C=CC=2)CC1 LNGUSSHELAJOGC-UHFFFAOYSA-N 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- 125000003435 aroyl group Chemical group 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- FWSZQMLRAZLIOL-UHFFFAOYSA-N n-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCNC(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=CC=2)CC1 FWSZQMLRAZLIOL-UHFFFAOYSA-N 0.000 claims 1
- KDLDDFQFOSUQGH-UHFFFAOYSA-N n-[3-[2-(2-methoxyphenoxy)ethylamino]propyl]-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound COC1=CC=CC=C1OCCNCCCNC(=O)C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O KDLDDFQFOSUQGH-UHFFFAOYSA-N 0.000 claims 1
- BZJYCSXPKYJDOC-UHFFFAOYSA-N n-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]-3,6-dimethyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCCNC(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=C(C)C=2)CC1 BZJYCSXPKYJDOC-UHFFFAOYSA-N 0.000 claims 1
- OUTKNWJZTFUTJQ-UHFFFAOYSA-N n-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]-3-methyl-6-nitro-4-oxo-2-phenylchromene-8-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCCNC(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=C(C=2)[N+]([O-])=O)CC1 OUTKNWJZTFUTJQ-UHFFFAOYSA-N 0.000 claims 1
- WYUJYNXKIBXCJO-UHFFFAOYSA-N n-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-3-methyl-4-oxo-2-phenylchromene-8-sulfonamide Chemical compound COC1=CC=CC=C1N1CCN(CCCCNS(=O)(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=CC=2)CC1 WYUJYNXKIBXCJO-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 432
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 292
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 284
- 239000000543 intermediate Substances 0.000 description 273
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 260
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 234
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 186
- 239000000243 solution Substances 0.000 description 186
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 176
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 171
- 239000000203 mixture Substances 0.000 description 170
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 165
- 239000002904 solvent Substances 0.000 description 138
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 129
- 238000006243 chemical reaction Methods 0.000 description 117
- 238000000034 method Methods 0.000 description 108
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 107
- 235000019439 ethyl acetate Nutrition 0.000 description 95
- 229940093499 ethyl acetate Drugs 0.000 description 94
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 87
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 85
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 82
- 239000011541 reaction mixture Substances 0.000 description 79
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 75
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 73
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 72
- 238000010992 reflux Methods 0.000 description 71
- 238000004587 chromatography analysis Methods 0.000 description 64
- 239000000047 product Substances 0.000 description 64
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 60
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 60
- 238000003756 stirring Methods 0.000 description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 53
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- 239000002585 base Substances 0.000 description 49
- 239000000741 silica gel Substances 0.000 description 46
- 229910002027 silica gel Inorganic materials 0.000 description 46
- 238000002425 crystallisation Methods 0.000 description 41
- 230000008025 crystallization Effects 0.000 description 41
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 38
- 238000001816 cooling Methods 0.000 description 38
- 229910000027 potassium carbonate Inorganic materials 0.000 description 37
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 36
- 238000000967 suction filtration Methods 0.000 description 35
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 34
- 238000001704 evaporation Methods 0.000 description 33
- 239000012044 organic layer Substances 0.000 description 33
- 239000003208 petroleum Substances 0.000 description 33
- 238000000746 purification Methods 0.000 description 33
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- 229960000583 acetic acid Drugs 0.000 description 31
- 230000008020 evaporation Effects 0.000 description 31
- 239000000155 melt Substances 0.000 description 31
- 238000002844 melting Methods 0.000 description 31
- 230000008018 melting Effects 0.000 description 31
- VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 description 30
- 235000011181 potassium carbonates Nutrition 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 26
- 239000003586 protic polar solvent Substances 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
- 239000002244 precipitate Substances 0.000 description 24
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 23
- 238000001914 filtration Methods 0.000 description 23
- 239000012074 organic phase Substances 0.000 description 23
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 21
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 21
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 20
- 239000007864 aqueous solution Substances 0.000 description 20
- 239000000284 extract Substances 0.000 description 20
- 238000010438 heat treatment Methods 0.000 description 20
- 239000012279 sodium borohydride Substances 0.000 description 20
- 229910000033 sodium borohydride Inorganic materials 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- 239000007858 starting material Substances 0.000 description 20
- 239000003054 catalyst Substances 0.000 description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- 239000002798 polar solvent Substances 0.000 description 19
- 230000008569 process Effects 0.000 description 19
- 239000011780 sodium chloride Substances 0.000 description 19
- 239000012043 crude product Substances 0.000 description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 18
- 239000000377 silicon dioxide Substances 0.000 description 18
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- 239000000010 aprotic solvent Substances 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 15
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- 238000009835 boiling Methods 0.000 description 15
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
- NBOMNTLFRHMDEZ-UHFFFAOYSA-N thiosalicylic acid Chemical class OC(=O)C1=CC=CC=C1S NBOMNTLFRHMDEZ-UHFFFAOYSA-N 0.000 description 15
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical group C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 14
- 125000003118 aryl group Chemical group 0.000 description 14
- 238000002156 mixing Methods 0.000 description 14
- 239000003513 alkali Substances 0.000 description 13
- 238000010828 elution Methods 0.000 description 13
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 12
- 239000005457 ice water Substances 0.000 description 12
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- 239000002841 Lewis acid Substances 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- 235000019256 formaldehyde Nutrition 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 238000007363 ring formation reaction Methods 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 150000007517 lewis acids Chemical class 0.000 description 9
- 229920000137 polyphosphoric acid Polymers 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 8
- GPFVBEXADULZAD-UHFFFAOYSA-N 3-methyl-4-oxo-2-phenylchromene-8-carbonyl chloride Chemical compound O1C2=C(C(Cl)=O)C=CC=C2C(=O)C(C)=C1C1=CC=CC=C1 GPFVBEXADULZAD-UHFFFAOYSA-N 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
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- USSBDBZGEDUBHE-UHFFFAOYSA-L magnesium;2-oxidooxycarbonylbenzoate Chemical compound [Mg+2].[O-]OC(=O)C1=CC=CC=C1C([O-])=O USSBDBZGEDUBHE-UHFFFAOYSA-L 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- LHRAZWLERDCLKI-UHFFFAOYSA-N methanesulfonic acid;3-methyl-4-oxo-2-phenyl-n-[3-(4-phenylpiperidin-1-yl)propyl]chromene-8-carboxamide Chemical compound CS(O)(=O)=O.C1=CC=C2C(=O)C(C)=C(C=3C=CC=CC=3)OC2=C1C(=O)NCCCN(CC1)CCC1C1=CC=CC=C1 LHRAZWLERDCLKI-UHFFFAOYSA-N 0.000 description 1
- GGCXSNDVGMLWCR-UHFFFAOYSA-N methanesulfonic acid;3-methyl-4-oxo-2-phenyl-n-[3-(4-pyrimidin-2-ylpiperazin-1-yl)propyl]chromene-8-carboxamide Chemical compound CS(O)(=O)=O.C1=CC=C2C(=O)C(C)=C(C=3C=CC=CC=3)OC2=C1C(=O)NCCCN(CC1)CCN1C1=NC=CC=N1 GGCXSNDVGMLWCR-UHFFFAOYSA-N 0.000 description 1
- MJVCLNSBBDXFMT-UHFFFAOYSA-N methanesulfonic acid;8-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butanoyl]-3-methyl-2-phenylchromen-4-one Chemical compound CS(O)(=O)=O.COC1=CC=CC=C1N1CCN(CCCC(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=CC=2)CC1 MJVCLNSBBDXFMT-UHFFFAOYSA-N 0.000 description 1
- NZBUQWLFUNKDGI-UHFFFAOYSA-N methanesulfonic acid;n-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]-4-oxo-3-phenylchromene-8-carboxamide Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.COC1=CC=CC=C1N1CCN(CCCNC(=O)C=2C3=C(C(C(C=4C=CC=CC=4)=CO3)=O)C=CC=2)CC1 NZBUQWLFUNKDGI-UHFFFAOYSA-N 0.000 description 1
- BDPIZWCNTCVHAJ-UHFFFAOYSA-N methyl 2-(4-methylbenzoyl)oxy-3-propanoylbenzoate Chemical compound CCC(=O)C1=CC=CC(C(=O)OC)=C1OC(=O)C1=CC=C(C)C=C1 BDPIZWCNTCVHAJ-UHFFFAOYSA-N 0.000 description 1
- UFGVWANOISVHGQ-UHFFFAOYSA-N methyl 2-hydroxy-3-propanoylbenzoate Chemical compound CCC(=O)C1=CC=CC(C(=O)OC)=C1O UFGVWANOISVHGQ-UHFFFAOYSA-N 0.000 description 1
- ZTIFDLYMYBXRLT-UHFFFAOYSA-N methyl 3-methyl-2-(4-methylphenyl)-4-oxochromene-8-carboxylate Chemical compound COC(=O)C1=CC=CC(C(C=2C)=O)=C1OC=2C1=CC=C(C)C=C1 ZTIFDLYMYBXRLT-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 125000006362 methylene amino carbonyl group Chemical group [H]N(C([*:2])=O)C([H])([H])[*:1] 0.000 description 1
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical compound C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- QAXZWHGWYSJAEI-UHFFFAOYSA-N n,n-dimethylformamide;ethanol Chemical compound CCO.CN(C)C=O QAXZWHGWYSJAEI-UHFFFAOYSA-N 0.000 description 1
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 1
- JHEGXAJWTZBWPX-UHFFFAOYSA-N n-(2-chloroethyl)-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound O1C2=C(C(=O)NCCCl)C=CC=C2C(=O)C(C)=C1C1=CC=CC=C1 JHEGXAJWTZBWPX-UHFFFAOYSA-N 0.000 description 1
- WMEXLJWQUOXKOU-UHFFFAOYSA-N n-(2-chloroethyl)-n,3-dimethyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound ClCCN(C)C(=O)C1=CC=CC(C(C=2C)=O)=C1OC=2C1=CC=CC=C1 WMEXLJWQUOXKOU-UHFFFAOYSA-N 0.000 description 1
- PMIXTRZLOQRROF-UHFFFAOYSA-N n-(2-hydroxyethyl)-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound O1C2=C(C(=O)NCCO)C=CC=C2C(=O)C(C)=C1C1=CC=CC=C1 PMIXTRZLOQRROF-UHFFFAOYSA-N 0.000 description 1
- MHDWZQKAZVCWOS-UHFFFAOYSA-N n-(2-hydroxyethyl)-3-methyl-4-oxo-2-phenylchromene-8-sulfonamide Chemical compound O1C2=C(S(=O)(=O)NCCO)C=CC=C2C(=O)C(C)=C1C1=CC=CC=C1 MHDWZQKAZVCWOS-UHFFFAOYSA-N 0.000 description 1
- MOOFRIDRSWHYST-UHFFFAOYSA-N n-(3-chloropropyl)-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound O1C2=C(C(=O)NCCCCl)C=CC=C2C(=O)C(C)=C1C1=CC=CC=C1 MOOFRIDRSWHYST-UHFFFAOYSA-N 0.000 description 1
- FYMVNVJQSHEMLP-UHFFFAOYSA-N n-(3-hydroxypropyl)-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound O1C2=C(C(=O)NCCCO)C=CC=C2C(=O)C(C)=C1C1=CC=CC=C1 FYMVNVJQSHEMLP-UHFFFAOYSA-N 0.000 description 1
- QHADQZZLTAUQAF-UHFFFAOYSA-N n-[(3-methyl-4-oxo-2-phenylchromen-8-yl)methyl]ethenesulfonamide Chemical compound O1C2=C(CNS(=O)(=O)C=C)C=CC=C2C(=O)C(C)=C1C1=CC=CC=C1 QHADQZZLTAUQAF-UHFFFAOYSA-N 0.000 description 1
- PKFBZNMIBOQUNY-UHFFFAOYSA-N n-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-3-methyl-4-oxo-2-phenylchromene-8-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=CC=C1N1CCN(CCNC(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=CC=2)CC1 PKFBZNMIBOQUNY-UHFFFAOYSA-N 0.000 description 1
- DDFYCVRUAGUKHQ-UHFFFAOYSA-N n-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-3-methyl-4-oxo-2-phenylchromene-8-sulfonamide;hydrochloride Chemical compound Cl.COC1=CC=CC=C1N1CCN(CCNS(=O)(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=CC=2)CC1 DDFYCVRUAGUKHQ-UHFFFAOYSA-N 0.000 description 1
- GCYKLJGANUUQML-UHFFFAOYSA-N n-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-n,3-dimethyl-4-oxo-2-phenylchromene-8-sulfonamide;hydrochloride Chemical compound Cl.COC1=CC=CC=C1N1CCN(CCN(C)S(=O)(=O)C=2C3=C(C(C(C)=C(C=4C=CC=CC=4)O3)=O)C=CC=2)CC1 GCYKLJGANUUQML-UHFFFAOYSA-N 0.000 description 1
- XWPVUNQTLDQLFZ-UHFFFAOYSA-N n-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-n-[(3-methyl-4-oxo-2-phenylchromen-8-yl)methyl]acetamide;hydrochloride Chemical compound Cl.COC1=CC=CC=C1N1CCN(CCN(CC=2C3=C(C(C(C)=C(C=4C=CC=CC=4)O3)=O)C=CC=2)C(C)=O)CC1 XWPVUNQTLDQLFZ-UHFFFAOYSA-N 0.000 description 1
- VPBUPEOPJDZGJV-UHFFFAOYSA-N n-[3-(4,4-diphenylpiperidin-1-yl)propyl]-3-methyl-4-oxo-2-phenylchromene-8-carboxamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=CC=C2C(=O)C(C)=C(C=3C=CC=CC=3)OC2=C1C(=O)NCCCN(CC1)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 VPBUPEOPJDZGJV-UHFFFAOYSA-N 0.000 description 1
- TUHFDUIDLOQBTN-UHFFFAOYSA-N n-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]-3-methyl-4-oxo-2-phenylchromene-8-carboxamide;dihydrochloride Chemical compound Cl.Cl.COC1=CC=CC=C1N1CCN(CCCNC(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=CC=2)CC1 TUHFDUIDLOQBTN-UHFFFAOYSA-N 0.000 description 1
- PRBDIUDXSSGNFR-UHFFFAOYSA-N n-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]-n-(3-methyl-4-oxo-2-phenylchromen-8-yl)acetamide;hydrate;hydrochloride Chemical compound O.Cl.COC1=CC=CC=C1N1CCN(CCCN(C(C)=O)C=2C3=C(C(C(C)=C(C=4C=CC=CC=4)O3)=O)C=CC=2)CC1 PRBDIUDXSSGNFR-UHFFFAOYSA-N 0.000 description 1
- IQTMRJWHZXBCTB-UHFFFAOYSA-N n-[3-[4-(4-fluorobenzoyl)piperidin-1-yl]propyl]-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound C1=CC=C2C(=O)C(C)=C(C=3C=CC=CC=3)OC2=C1C(=O)NCCCN(CC1)CCC1C(=O)C1=CC=C(F)C=C1 IQTMRJWHZXBCTB-UHFFFAOYSA-N 0.000 description 1
- QZFOKLPWYHXGFN-UHFFFAOYSA-N n-acetyl-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound CC(=O)NC(=O)C1=CC=CC(C(C=2C)=O)=C1OC=2C1=CC=CC=C1 QZFOKLPWYHXGFN-UHFFFAOYSA-N 0.000 description 1
- LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- NLXXVSKHVGDQAT-UHFFFAOYSA-N o-(oxan-2-yl)hydroxylamine Chemical compound NOC1CCCCO1 NLXXVSKHVGDQAT-UHFFFAOYSA-N 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- MMKQSIQNDMIVIN-UHFFFAOYSA-N oxido-(oxido(dioxo)chromio)oxy-dioxochromium;tetrabutylazanium Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC MMKQSIQNDMIVIN-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl chloride Substances ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 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
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 1
- FJWLWIRHZOHPIY-UHFFFAOYSA-N potassium;hydroiodide Chemical compound [K].I FJWLWIRHZOHPIY-UHFFFAOYSA-N 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical group C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- 230000002295 serotoninergic effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- KIEOKOFEPABQKJ-UHFFFAOYSA-N sodium dichromate Chemical compound [Na+].[Na+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KIEOKOFEPABQKJ-UHFFFAOYSA-N 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- VLLATRQRPYHZLR-UHFFFAOYSA-M sodium;3-methyl-4-oxo-2-phenylchromene-8-carboxylate Chemical compound [Na+].O1C2=C(C([O-])=O)C=CC=C2C(=O)C(C)=C1C1=CC=CC=C1 VLLATRQRPYHZLR-UHFFFAOYSA-M 0.000 description 1
- GNCGTEQGBYYYBX-UHFFFAOYSA-M sodium;4-methylbenzoate Chemical compound [Na+].CC1=CC=C(C([O-])=O)C=C1 GNCGTEQGBYYYBX-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 229950003559 terflavoxate Drugs 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- WQMRAWFGWVTLHX-UHFFFAOYSA-N thiophen-2-yl carbonochloridate Chemical compound ClC(=O)OC1=CC=CS1 WQMRAWFGWVTLHX-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- WORJEOGGNQDSOE-ASTXPPQBSA-N trichloro(deuterio)methane;trideuterio(deuteriooxy)methane Chemical compound [2H]C(Cl)(Cl)Cl.[2H]OC([2H])([2H])[2H] WORJEOGGNQDSOE-ASTXPPQBSA-N 0.000 description 1
- HFFLGKNGCAIQMO-UHFFFAOYSA-N trichloroacetaldehyde Chemical compound ClC(Cl)(Cl)C=O HFFLGKNGCAIQMO-UHFFFAOYSA-N 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- ZBZJXHCVGLJWFG-UHFFFAOYSA-N trichloromethyl(.) Chemical compound Cl[C](Cl)Cl ZBZJXHCVGLJWFG-UHFFFAOYSA-N 0.000 description 1
- DCFKHNIGBAHNSS-UHFFFAOYSA-N triethylsilyl chloride Natural products CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- SCHZCUMIENIQMY-UHFFFAOYSA-N tris(trimethylsilyl)silicon Chemical compound C[Si](C)(C)[Si]([Si](C)(C)C)[Si](C)(C)C SCHZCUMIENIQMY-UHFFFAOYSA-N 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229910001845 yogo sapphire Inorganic materials 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/80—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/32—2,3-Dihydro derivatives, e.g. flavanones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D407/02—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 two hetero rings
- C07D407/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI920408A IT1254469B (it) | 1992-02-25 | 1992-02-25 | Derivati benzopiranici e benzotiopiranici |
US07/888,775 US5403842A (en) | 1992-02-25 | 1992-05-26 | Benzopyran and benzothiopyran derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP930210A2 true HRP930210A2 (en) | 1995-06-30 |
Family
ID=26330842
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR930210A HRP930210A2 (en) | 1992-02-25 | 1993-02-22 | Heterobicyclic compounds and pharmaceutical preparations containing them |
Country Status (25)
Country | Link |
---|---|
EP (1) | EP0558245A1 (fi) |
JP (1) | JPH069606A (fi) |
AU (2) | AU3629693A (fi) |
BG (1) | BG61946B1 (fi) |
CA (1) | CA2090156A1 (fi) |
CZ (1) | CZ205994A3 (fi) |
DZ (1) | DZ1666A1 (fi) |
EE (1) | EE03177B1 (fi) |
EG (1) | EG20333A (fi) |
FI (1) | FI943876A0 (fi) |
HR (1) | HRP930210A2 (fi) |
HU (1) | HUT72448A (fi) |
IL (1) | IL104824A (fi) |
LT (1) | LT3038B (fi) |
LV (1) | LV10099B (fi) |
MX (1) | MX9300977A (fi) |
NO (1) | NO943140L (fi) |
NZ (1) | NZ245995A (fi) |
PL (1) | PL175556B1 (fi) |
SG (1) | SG65570A1 (fi) |
SI (1) | SI9300094A (fi) |
SK (1) | SK280143B6 (fi) |
TW (1) | TW382628B (fi) |
WO (1) | WO1993017007A1 (fi) |
ZA (1) | ZA931278B (fi) |
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MX9300312A (es) * | 1992-01-23 | 1993-07-31 | Pfizer | Antagonistas benzopiranicos y relacionado de ltb. |
FR2689127B1 (fr) * | 1992-03-31 | 1994-05-06 | Adir Cie | Nouvelles 3', 5' -ditertbutyl-4'-hydroxy flavones, leur procede de preparation et les compositions pharmaceutiques les renfermant. |
IT1266582B1 (it) * | 1993-07-30 | 1997-01-09 | Recordati Chem Pharm | Derivati (di)azacicloesanici e diazacicloeptanici |
GB9317071D0 (en) * | 1993-08-17 | 1993-09-29 | Univ Strathclyde | Flavonoids |
JP3426242B2 (ja) * | 1994-01-14 | 2003-07-14 | 株式会社アズウェル | ジアザシクロアルカンアルキルスルホンアミド誘導体 |
FR2717175B1 (fr) * | 1994-03-11 | 1996-06-14 | Adir | Nouveaux composés alkylaminoindanes, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent. |
IL112764A0 (en) * | 1994-03-18 | 1995-05-26 | Ferrer Int | New chromene derivatives |
ES2101620B1 (es) * | 1994-03-18 | 1998-04-01 | Ferrer Int | Nuevo compuesto derivado del cromeno. |
PT753511E (pt) * | 1994-03-30 | 2001-11-30 | Zeria Pharm Co Ltd | Derivados de acido 4-indol-1-butirico, sua preparacao e utilizacao como inibidores dos receptores alfa-1-adrenergicos e das 5-alfa-redutases da testosterona |
US5503843A (en) * | 1994-04-22 | 1996-04-02 | Flora Inc. | Transdermal delivery of alpha adrenoceptor blocking agents |
DE4425146A1 (de) * | 1994-07-15 | 1996-01-18 | Basf Ag | Verwendung heterocyclischer Verbindungen |
GB9417135D0 (en) * | 1994-08-23 | 1994-10-12 | Medinnova S F | Method |
CA2188924C (en) * | 1995-02-28 | 2008-04-08 | Hirokazu Annoura | Arylpiperidine and arylpiperazine derivatives and drugs containing the same |
GB9507288D0 (en) * | 1995-04-07 | 1995-05-31 | Sod Conseils Rech Applic | Phenoxyethylamine derivatives with high affinity for 5-HT1A receptors |
US5859014A (en) * | 1995-06-09 | 1999-01-12 | Syntex (U.S.A.) Inc. | Pyrimidinedione, pyrimidinetrione, triazinedione and tetrahydroquinazolinedione derivatives as α1 -adrenergic receptor antagonists |
ATE201016T1 (de) * | 1995-06-09 | 2001-05-15 | Hoffmann La Roche | Pyrimidindion-, pyrimidintrion-, triazindion- derivate als alpha-1-adrenergische rezeptorantagonisten |
JPH0967367A (ja) * | 1995-06-23 | 1997-03-11 | Suntory Ltd | チオピラン誘導体 |
WO1997014419A1 (en) * | 1995-10-20 | 1997-04-24 | Flora Inc. | Transdermal delivery of alpha adrenoceptor blocking agents |
US5990114A (en) * | 1996-02-28 | 1999-11-23 | Recordati, S.A., Chemical And Pharmaceutical Company | Use of 5-HT1A receptor antagonists for the treatment of urinary incontinence |
IT1282705B1 (it) * | 1996-02-28 | 1998-03-31 | Recordati Chem Pharm | Uso di antagonisti del recettore serotoninergico 5-ht|a per il trattamento dell'incontinenza urinaria |
AU2030197A (en) * | 1996-03-08 | 1997-09-22 | Synthelabo | 2-aminoethyl-benzofuran derivatives, preparation thereof and therapeutical use thereof |
FR2745815B1 (fr) * | 1996-03-08 | 1998-06-26 | Synthelabo | Derives de benzofurane, leur preparations et compositions pharmaceutiques les comprenant |
EP0929537A1 (en) * | 1996-08-22 | 1999-07-21 | Hoechst Marion Roussel, Inc. | Troponyl piperazines as selective dopamine d4 receptor ligands |
AU2002300904B2 (en) * | 1997-05-12 | 2004-12-23 | Ortho-Mcneil Pharmaceutical, Inc. | Arylsubstituted piperazines useful in the treatment of benign prostatic hyperplasia |
EA001904B1 (ru) | 1997-05-12 | 2001-10-22 | ОРТО МакНЕЙЛ ФАРМАСЬЮТИКАЛ, ИНК. | Арилзамещенные пиперазины для лечения доброкачественной гиперплазии простаты |
DE69818079T2 (de) | 1997-06-04 | 2004-06-03 | Azwell Inc. | Verfahren zur herstellung von piperazinsulfonamid-derivaten und ihren salzen |
AU8130298A (en) * | 1997-07-15 | 1999-02-10 | Sankyo Company Limited | Piperazine derivatives |
IT1313581B1 (it) * | 1999-07-30 | 2002-09-09 | Recordati Chem Pharm | Derivati tienopirancarbossamidici. |
US6387909B1 (en) | 1999-07-30 | 2002-05-14 | Recordati S.A. Chemical And Pharmaceutical Company | Thienopyranecarboxamide derivatives |
US6306861B1 (en) | 1999-07-30 | 2001-10-23 | Recordati S.A. Chemical And Pharmaceutical Company | Thienopyrancecarboxamide derivatives |
DE19941657A1 (de) * | 1999-09-01 | 2001-03-08 | Schwabe Willmar Gmbh & Co | Zimtsäurenitrile, Verfahren zu ihrer Herstellung und Verwendung |
US6403594B1 (en) | 1999-10-18 | 2002-06-11 | Recordati, S.A. Chemical And Pharmaceutical Company | Benzopyran derivatives |
IT1314192B1 (it) * | 1999-10-18 | 2002-12-06 | Recordati Chem Pharm | Derivati benzopiranici |
JP2002113006A (ja) | 2000-10-10 | 2002-04-16 | Toshiba Medical System Co Ltd | 診断機器設定方法および診断装置 |
CN1150176C (zh) * | 2002-05-22 | 2004-05-19 | 上海医药工业研究院 | 芳烷酮哌嗪衍生物及其应用 |
JP2006511500A (ja) * | 2002-10-30 | 2006-04-06 | メルク エンド カムパニー インコーポレーテッド | γ−アミノアミド系のケモカイン受容体活性調節剤 |
AU2005275181A1 (en) | 2004-07-14 | 2006-02-23 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US7772271B2 (en) | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US7645881B2 (en) | 2004-07-22 | 2010-01-12 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
CA2597616A1 (en) | 2005-02-17 | 2006-08-24 | Wyeth | Cycloalkylfused indole, benzothiophene, benzofuran and indene derivatives |
CA2738809C (en) * | 2008-09-29 | 2015-11-24 | Sirtris Pharmaceuticals, Inc. | Quinazolinone, quinolone and related analogs as sirtuin modulators |
CZ304045B6 (cs) | 2012-04-10 | 2013-09-04 | Univerzita Palackého | Pouzití komplexu medi obsahujících 2-fenyl-3-hydroxychinolin-4(1H)-on a deriváty 1,10-fenanthrolinu pro prípravu léciv pro lécbu nádorových onemocnení |
JP2019508400A (ja) | 2016-02-09 | 2019-03-28 | ファーマケア,インク. | キノリノンリシルオキシダーゼ様2阻害剤とその使用 |
WO2020095912A1 (ja) * | 2018-11-06 | 2020-05-14 | 第一三共株式会社 | ベンズイミダゾール誘導体 |
EP4058425A4 (en) | 2019-11-11 | 2023-11-22 | Southwest Research Institute | RECRYSTALLIZED HI-6 DIMETHYL SULFATE |
AR120680A1 (es) | 2019-12-06 | 2022-03-09 | Vertex Pharma | Tetrahidrofuranos sustituidos como moduladores de canales de sodio |
AR126073A1 (es) | 2021-06-04 | 2023-09-06 | Vertex Pharma | N-(hidroxialquil(hetero)aril)tetrahidrofuran carboxamidas como moduladores de canales de sodio |
EP4426434A1 (en) | 2021-11-02 | 2024-09-11 | Flare Therapeutics, Inc. | Pparg inverse agonists and uses thereof |
CN115160279B (zh) * | 2022-07-27 | 2023-11-24 | 中国药科大学 | 苯并吡喃酮类化合物、药物组合物和应用 |
Family Cites Families (9)
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US2921070A (en) * | 1957-11-05 | 1960-01-12 | Recordati Lab Farmacologico S | Basic esters of 3-methylflavone-8-carboxylic acid |
GB1156973A (en) | 1965-07-06 | 1969-07-02 | Quinazoline Derivatives | |
DE2123923A1 (de) * | 1971-05-14 | 1972-11-23 | Boehringer Mannheim Gmbh, 6800 Mannheim | 4-eckige Klammer auf omega- (Flavon-7yl-oxy) -alkyl eckige Klammer zu -pigerazin-Derivate und Verfahren zu ihrer Herstellung |
NZ200981A (en) | 1981-07-17 | 1984-10-19 | Recordati Chem Pharm | 3-methylflavone-8-carboxylic acid derivatives and pharmaceutical compositions |
JPS60202872A (ja) * | 1984-03-27 | 1985-10-14 | Kaken Pharmaceut Co Ltd | ベンゾフラン誘導体、その製法およびそれを有効成分とする降圧剤 |
US4678787A (en) * | 1985-01-30 | 1987-07-07 | Warner-Lambert Company | 4H-1-benzopyran-4-ones and their sulfur containing analogs |
JPS63139180A (ja) * | 1986-12-02 | 1988-06-10 | Tanabe Seiyaku Co Ltd | カルボン酸誘導体 |
IL87451A0 (en) * | 1987-09-04 | 1989-01-31 | Tanabe Seiyaku Co | Benzofuran derivatives,their preparation and pharmaceutical compositions containing them |
US5278174A (en) * | 1990-06-04 | 1994-01-11 | Scios Nova, Inc. | Sigma binding site agents |
-
1993
- 1993-02-22 SG SG1996004802A patent/SG65570A1/en unknown
- 1993-02-22 EP EP93301264A patent/EP0558245A1/en not_active Withdrawn
- 1993-02-22 HR HR930210A patent/HRP930210A2/hr not_active Application Discontinuation
- 1993-02-23 CZ CZ942059A patent/CZ205994A3/cs unknown
- 1993-02-23 SK SK1007-94A patent/SK280143B6/sk unknown
- 1993-02-23 HU HU9402443A patent/HUT72448A/hu unknown
- 1993-02-23 AU AU36296/93A patent/AU3629693A/en not_active Abandoned
- 1993-02-23 IL IL10482493A patent/IL104824A/en not_active IP Right Cessation
- 1993-02-23 PL PL93304889A patent/PL175556B1/pl unknown
- 1993-02-23 MX MX9300977A patent/MX9300977A/es not_active IP Right Cessation
- 1993-02-23 WO PCT/EP1993/000420 patent/WO1993017007A1/en not_active Application Discontinuation
- 1993-02-23 CA CA002090156A patent/CA2090156A1/en not_active Abandoned
- 1993-02-24 ZA ZA931278A patent/ZA931278B/xx unknown
- 1993-02-24 DZ DZ930019A patent/DZ1666A1/fr active
- 1993-02-24 LV LVP-93-136A patent/LV10099B/en unknown
- 1993-02-24 AU AU33773/93A patent/AU660067B2/en not_active Ceased
- 1993-02-24 LT LTIP354A patent/LT3038B/lt not_active IP Right Cessation
- 1993-02-25 SI SI19939300094A patent/SI9300094A/sl unknown
- 1993-02-25 EG EG1193A patent/EG20333A/xx active
- 1993-02-25 NZ NZ245995A patent/NZ245995A/en unknown
- 1993-02-25 JP JP5036605A patent/JPH069606A/ja active Pending
- 1993-05-20 TW TW082103988A patent/TW382628B/zh active
-
1994
- 1994-08-19 BG BG98990A patent/BG61946B1/bg unknown
- 1994-08-23 FI FI943876A patent/FI943876A0/fi unknown
- 1994-08-25 NO NO943140A patent/NO943140L/no unknown
- 1994-11-10 EE EE9400374A patent/EE03177B1/xx unknown
Also Published As
Publication number | Publication date |
---|---|
LV10099A (lv) | 1994-05-10 |
AU3629693A (en) | 1993-09-13 |
PL175556B1 (pl) | 1999-01-29 |
NO943140D0 (no) | 1994-08-25 |
WO1993017007A1 (en) | 1993-09-02 |
HUT72448A (en) | 1996-04-29 |
AU660067B2 (en) | 1995-06-08 |
BG98990A (bg) | 1995-05-31 |
LV10099B (en) | 1995-02-20 |
BG61946B1 (bg) | 1998-10-30 |
CZ205994A3 (en) | 1995-02-15 |
IL104824A0 (en) | 1993-06-10 |
TW382628B (en) | 2000-02-21 |
NO943140L (no) | 1994-08-25 |
SI9300094A (en) | 1993-09-30 |
FI943876A (fi) | 1994-08-23 |
JPH069606A (ja) | 1994-01-18 |
LTIP354A (lt) | 1994-04-25 |
ZA931278B (en) | 1993-11-18 |
NZ245995A (en) | 1994-09-27 |
SK280143B6 (sk) | 1999-09-10 |
DZ1666A1 (fr) | 2002-02-17 |
EP0558245A1 (en) | 1993-09-01 |
IL104824A (en) | 1999-12-22 |
EG20333A (en) | 1998-10-31 |
SK100794A3 (en) | 1995-04-12 |
AU3377393A (en) | 1993-08-26 |
MX9300977A (es) | 1993-12-01 |
CA2090156A1 (en) | 1993-08-26 |
EE03177B1 (et) | 1999-04-15 |
FI943876A0 (fi) | 1994-08-23 |
HU9402443D0 (en) | 1994-10-28 |
SG65570A1 (en) | 1999-06-22 |
LT3038B (en) | 1994-09-25 |
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