BG63916B1 - Имидазолови производни с афинитет към активносттана алфа 2 рецептори - Google Patents
Имидазолови производни с афинитет към активносттана алфа 2 рецептори Download PDFInfo
- Publication number
- BG63916B1 BG63916B1 BG102324A BG10232498A BG63916B1 BG 63916 B1 BG63916 B1 BG 63916B1 BG 102324 A BG102324 A BG 102324A BG 10232498 A BG10232498 A BG 10232498A BG 63916 B1 BG63916 B1 BG 63916B1
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- BG
- Bulgaria
- Prior art keywords
- hydrogen
- alkyl
- nmr
- compound
- hydroxy
- Prior art date
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- 150000002460 imidazoles Chemical class 0.000 title claims abstract description 9
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 65
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 62
- 239000001257 hydrogen Substances 0.000 claims abstract description 61
- 239000000203 mixture Substances 0.000 claims abstract description 57
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 39
- -1 C3-C7 glicoalkyl Chemical group 0.000 claims abstract description 30
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 18
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 15
- 208000002193 Pain Diseases 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 9
- 230000036506 anxiety Effects 0.000 claims abstract description 9
- 150000002148 esters Chemical class 0.000 claims abstract description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 7
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims abstract description 6
- 206010012735 Diarrhoea Diseases 0.000 claims abstract description 6
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 6
- 206010020772 Hypertension Diseases 0.000 claims abstract description 6
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 6
- 208000028867 ischemia Diseases 0.000 claims abstract description 6
- 206010027599 migraine Diseases 0.000 claims abstract description 6
- 230000000926 neurological effect Effects 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 6
- 208000000094 Chronic Pain Diseases 0.000 claims abstract description 5
- 208000005298 acute pain Diseases 0.000 claims abstract description 5
- 125000003277 amino group Chemical group 0.000 claims abstract description 5
- 230000001684 chronic effect Effects 0.000 claims abstract description 5
- 208000020016 psychiatric disease Diseases 0.000 claims abstract description 5
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 4
- 150000003573 thiols Chemical class 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 150000001721 carbon Chemical group 0.000 claims abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000000556 agonist Substances 0.000 claims description 5
- 208000010877 cognitive disease Diseases 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 206010002091 Anaesthesia Diseases 0.000 claims description 3
- 230000037005 anaesthesia Effects 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 206010052804 Drug tolerance Diseases 0.000 claims 2
- 230000026781 habituation Effects 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 201000009240 nasopharyngitis Diseases 0.000 claims 2
- 208000023178 Musculoskeletal disease Diseases 0.000 claims 1
- 208000012902 Nervous system disease Diseases 0.000 claims 1
- 208000025966 Neurological disease Diseases 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 8
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
- 125000004414 alkyl thio group Chemical group 0.000 abstract 1
- 150000001356 alkyl thiols Chemical class 0.000 abstract 1
- 230000003930 cognitive ability Effects 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 238000009472 formulation Methods 0.000 abstract 1
- 208000011117 substance-related disease Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
- 238000005481 NMR spectroscopy Methods 0.000 description 93
- 150000003840 hydrochlorides Chemical class 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000000047 product Substances 0.000 description 31
- 238000000034 method Methods 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
- 229910052938 sodium sulfate Inorganic materials 0.000 description 21
- 235000011152 sodium sulphate Nutrition 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 19
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 14
- 238000003756 stirring Methods 0.000 description 13
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 12
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000908 ammonium hydroxide Substances 0.000 description 12
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 12
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical group C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 6
- 150000002576 ketones Chemical class 0.000 description 6
- 229940098779 methanesulfonic acid Drugs 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- QONDAZCJAPQGRX-UHFFFAOYSA-N 3-benzylimidazole-4-carbaldehyde Chemical compound O=CC1=CN=CN1CC1=CC=CC=C1 QONDAZCJAPQGRX-UHFFFAOYSA-N 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- XEXPATNGWGSUHA-UHFFFAOYSA-N 6-(hydroxymethyl)-3-(1h-imidazol-5-ylmethyl)-2,3-dihydro-1h-inden-5-ol Chemical compound C1=2C=C(O)C(CO)=CC=2CCC1CC1=CNC=N1 XEXPATNGWGSUHA-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- BLQNOZHGIDFFAS-UHFFFAOYSA-N 1-(3-benzylimidazol-4-yl)ethanone Chemical compound CC(=O)C1=CN=CN1CC1=CC=CC=C1 BLQNOZHGIDFFAS-UHFFFAOYSA-N 0.000 description 3
- ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical compound O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 3
- NOEANSSBIYXYCA-UHFFFAOYSA-N 3-(1h-imidazol-5-yl)-5-methoxy-6,7-dimethyl-2,3-dihydro-1h-inden-1-ol Chemical compound C1C(O)C=2C(C)=C(C)C(OC)=CC=2C1C1=CNC=N1 NOEANSSBIYXYCA-UHFFFAOYSA-N 0.000 description 3
- ABBXOJTZYKLTBP-UHFFFAOYSA-N 5-(2,3-dihydro-1h-inden-1-yl)-1h-imidazole Chemical compound C1CC2=CC=CC=C2C1C1=CNC=N1 ABBXOJTZYKLTBP-UHFFFAOYSA-N 0.000 description 3
- HEDLYDWGJOTEQS-UHFFFAOYSA-N 5-(5-chloro-1,2,3,4-tetrahydronaphthalen-1-yl)-1h-imidazole Chemical compound C1CCC=2C(Cl)=CC=CC=2C1C1=CNC=N1 HEDLYDWGJOTEQS-UHFFFAOYSA-N 0.000 description 3
- DCPDKKDLGGMCDM-UHFFFAOYSA-N 5-[(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl]-1h-imidazole Chemical compound C1CCC2=CC(OC)=CC=C2C1CC1=CNC=N1 DCPDKKDLGGMCDM-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 206010012335 Dependence Diseases 0.000 description 3
- 238000003747 Grignard reaction Methods 0.000 description 3
- 239000007818 Grignard reagent Substances 0.000 description 3
- 230000008484 agonism Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000001423 neocortical effect Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- DKMJTMGANVYTDU-UHFFFAOYSA-N 3-(1h-imidazol-5-yl)-5-(2-methylpropyl)-2,3-dihydro-1h-inden-1-ol Chemical compound C12=CC(CC(C)C)=CC=C2C(O)CC1C1=CNC=N1 DKMJTMGANVYTDU-UHFFFAOYSA-N 0.000 description 2
- HMBWEFQRLYYKGK-UHFFFAOYSA-N 3-(1h-imidazol-5-yl)-5-methoxy-6,7-dimethyl-2,3-dihydroinden-1-one Chemical compound C1C(=O)C=2C(C)=C(C)C(OC)=CC=2C1C1=CNC=N1 HMBWEFQRLYYKGK-UHFFFAOYSA-N 0.000 description 2
- JJKKPNBICLHKCB-UHFFFAOYSA-N 3-(1h-imidazol-5-ylmethyl)-6-methoxy-2,3-dihydro-1h-indene-5-carbaldehyde Chemical compound C1=2C=C(C=O)C(OC)=CC=2CCC1CC1=CNC=N1 JJKKPNBICLHKCB-UHFFFAOYSA-N 0.000 description 2
- DPGCTXQRUWDQNA-UHFFFAOYSA-N 3-[1-(1h-imidazol-5-yl)propyl]-2,3-dihydro-1h-inden-5-ol Chemical compound C1CC2=CC=C(O)C=C2C1C(CC)C1=CNC=N1 DPGCTXQRUWDQNA-UHFFFAOYSA-N 0.000 description 2
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 description 2
- SYMYTXFERCKGJI-UHFFFAOYSA-N 4-(2-chlorophenyl)-1-(1h-imidazol-5-yl)butan-1-ol Chemical compound C=1NC=NC=1C(O)CCCC1=CC=CC=C1Cl SYMYTXFERCKGJI-UHFFFAOYSA-N 0.000 description 2
- DLNQRCUXHQSALB-UHFFFAOYSA-N 5-(3h-inden-1-yl)-1h-imidazole Chemical compound C12=CC=CC=C2CC=C1C1=CNC=N1 DLNQRCUXHQSALB-UHFFFAOYSA-N 0.000 description 2
- XXQLSAWUSXSJTK-UHFFFAOYSA-N 5-(4-methyl-2,3-dihydro-1h-inden-1-yl)-1h-imidazole Chemical compound C1CC=2C(C)=CC=CC=2C1C1=CNC=N1 XXQLSAWUSXSJTK-UHFFFAOYSA-N 0.000 description 2
- NJZVTLVQUICYRE-UHFFFAOYSA-N 5-(6-methoxy-4,5-dimethyl-2,3-dihydro-1h-inden-1-yl)-1h-imidazole Chemical compound C1CC=2C(C)=C(C)C(OC)=CC=2C1C1=CNC=N1 NJZVTLVQUICYRE-UHFFFAOYSA-N 0.000 description 2
- PLIPPAVFBJYEPZ-UHFFFAOYSA-N 5-(6-tert-butyl-2,3-dihydro-1h-inden-1-yl)-1h-imidazole Chemical compound C12=CC(C(C)(C)C)=CC=C2CCC1C1=CNC=N1 PLIPPAVFBJYEPZ-UHFFFAOYSA-N 0.000 description 2
- WOVCHPLIEOXTHP-UHFFFAOYSA-N 5-[(5-methoxy-2,3-dihydro-1h-inden-1-yl)methyl]-1h-imidazole Chemical compound C1CC2=CC(OC)=CC=C2C1CC1=CNC=N1 WOVCHPLIEOXTHP-UHFFFAOYSA-N 0.000 description 2
- GDCKWMLPTVCZGU-UHFFFAOYSA-N 5-[(6-methoxy-2,3-dihydro-1h-inden-1-yl)methyl]-1h-imidazole Chemical compound C12=CC(OC)=CC=C2CCC1CC1=CNC=N1 GDCKWMLPTVCZGU-UHFFFAOYSA-N 0.000 description 2
- FUSLZONREWHZRR-UHFFFAOYSA-N 5-[1-(6-methoxy-2,3-dihydro-1h-inden-1-yl)propyl]-1h-imidazole Chemical compound C1CC2=CC=C(OC)C=C2C1C(CC)C1=CNC=N1 FUSLZONREWHZRR-UHFFFAOYSA-N 0.000 description 2
- JFFOKYWPLPKADR-UHFFFAOYSA-N 6-hydroxy-3-(1h-imidazol-5-ylmethyl)-2,3-dihydro-1h-indene-5-carbaldehyde Chemical compound C1=2C=C(C=O)C(O)=CC=2CCC1CC1=CNC=N1 JFFOKYWPLPKADR-UHFFFAOYSA-N 0.000 description 2
- 108060003345 Adrenergic Receptor Proteins 0.000 description 2
- 102000017910 Adrenergic receptor Human genes 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000028698 Cognitive impairment Diseases 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 229910052719 titanium Inorganic materials 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- 238000011925 1,2-addition Methods 0.000 description 1
- IZPWMMFRJUNNEJ-UHFFFAOYSA-N 1-(1h-imidazol-5-yl)-2,3-dihydro-1h-inden-5-ol Chemical compound C1CC2=CC(O)=CC=C2C1C1=CNC=N1 IZPWMMFRJUNNEJ-UHFFFAOYSA-N 0.000 description 1
- ODKWDDGJPRXIBL-UHFFFAOYSA-N 1-(1h-imidazol-5-ylmethyl)-2,3-dihydro-1h-inden-4-ol Chemical compound C1CC=2C(O)=CC=CC=2C1CC1=CNC=N1 ODKWDDGJPRXIBL-UHFFFAOYSA-N 0.000 description 1
- QZYSKQGSSWHXRM-UHFFFAOYSA-N 1-(1h-imidazol-5-ylmethyl)-2,3-dihydro-1h-indene-5,6-diol Chemical compound C1=2C=C(O)C(O)=CC=2CCC1CC1=CNC=N1 QZYSKQGSSWHXRM-UHFFFAOYSA-N 0.000 description 1
- CKAGIFUDMZHJPB-UHFFFAOYSA-N 1-(1h-imidazol-5-ylmethyl)-3,3-dimethyl-1,2-dihydroindene-5,6-diol Chemical compound C12=CC(O)=C(O)C=C2C(C)(C)CC1CC1=CNC=N1 CKAGIFUDMZHJPB-UHFFFAOYSA-N 0.000 description 1
- AKMIGKNTCCSJNQ-UHFFFAOYSA-N 1-(3-bromopropyl)-2-chlorobenzene Chemical compound ClC1=CC=CC=C1CCCBr AKMIGKNTCCSJNQ-UHFFFAOYSA-N 0.000 description 1
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- HRLIOXLXPOHXTA-NSHDSACASA-N dexmedetomidine Chemical compound C1([C@@H](C)C=2C(=C(C)C=CC=2)C)=CN=C[N]1 HRLIOXLXPOHXTA-NSHDSACASA-N 0.000 description 1
- 229960004253 dexmedetomidine Drugs 0.000 description 1
- VPNGEIHDPSLNMU-MERQFXBCSA-N dexmedetomidine hydrochloride Chemical compound Cl.C1([C@@H](C)C=2C(=C(C)C=CC=2)C)=CNC=N1 VPNGEIHDPSLNMU-MERQFXBCSA-N 0.000 description 1
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- MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 description 1
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- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 108090000623 proteins and genes Proteins 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Physical Education & Sports Medicine (AREA)
- Communicable Diseases (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Oncology (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Anesthesiology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Resins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9520150.5A GB9520150D0 (en) | 1995-10-03 | 1995-10-03 | New imidazole derivatives |
| PCT/FI1996/000518 WO1997012874A1 (en) | 1995-10-03 | 1996-10-02 | Imidazole derivatives having affinity for alpha2 receptors activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BG102324A BG102324A (en) | 1999-01-29 |
| BG63916B1 true BG63916B1 (bg) | 2003-06-30 |
Family
ID=10781676
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG102324A BG63916B1 (bg) | 1995-10-03 | 1998-03-12 | Имидазолови производни с афинитет към активносттана алфа 2 рецептори |
Country Status (29)
| Country | Link |
|---|---|
| US (2) | US6313311B1 (cs) |
| EP (1) | EP0888309B1 (cs) |
| JP (1) | JP4129891B2 (cs) |
| KR (1) | KR19990064013A (cs) |
| CN (1) | CN1068592C (cs) |
| AT (1) | ATE234819T1 (cs) |
| AU (1) | AU708002B2 (cs) |
| BG (1) | BG63916B1 (cs) |
| CA (1) | CA2231535C (cs) |
| CZ (1) | CZ291576B6 (cs) |
| DE (1) | DE69626862T2 (cs) |
| DK (1) | DK0888309T3 (cs) |
| EE (1) | EE04436B1 (cs) |
| ES (1) | ES2195013T3 (cs) |
| GB (1) | GB9520150D0 (cs) |
| HU (1) | HU224197B1 (cs) |
| IL (1) | IL123721A (cs) |
| LT (1) | LT4460B (cs) |
| LV (1) | LV12108B (cs) |
| NO (1) | NO311024B1 (cs) |
| NZ (1) | NZ319169A (cs) |
| PL (1) | PL189110B1 (cs) |
| PT (1) | PT888309E (cs) |
| RO (1) | RO120409B1 (cs) |
| RU (1) | RU2188194C2 (cs) |
| SI (1) | SI9620111B (cs) |
| SK (1) | SK283542B6 (cs) |
| UA (1) | UA49847C2 (cs) |
| WO (1) | WO1997012874A1 (cs) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA981080B (en) | 1997-02-11 | 1998-08-12 | Warner Lambert Co | Bicyclic inhibitors of protein farnesyl transferase |
| DE69823868T2 (de) * | 1997-12-04 | 2005-04-21 | Allergan Inc | Substituierte imidazole derivate mit agonistischähnlicher wirkung auf die alpha 2b oder 2b/2c adrenergischen rezeptoren |
| US6329369B1 (en) | 1997-12-04 | 2001-12-11 | Allergan Sales, Inc. | Methods of treating pain and other conditions |
| US6841684B2 (en) * | 1997-12-04 | 2005-01-11 | Allergan, Inc. | Imidiazoles having reduced side effects |
| AU2002254265B2 (en) * | 1997-12-04 | 2008-05-15 | Allergan, Inc. | Imidiazole derivatives and their use as agonists selective at alpha 2B or 2B/2C adrenergic receptors |
| WO2000018400A1 (en) | 1998-09-28 | 2000-04-06 | Orion Corporation | Use of 3-(1h-imidazol-4-ylmethyl)-indan-5-ol in the manufacture of a medicament for intraspinal, intrathecal or epidural administration |
| TWI283669B (en) * | 1999-06-10 | 2007-07-11 | Allergan Inc | Compounds and method of treatment having agonist-like activity selective at alpha 2B or 2B/2C adrenergic receptors |
| EP1196168A2 (en) * | 1999-06-25 | 2002-04-17 | Orion Corporation | Method of admistering an imidazole derivative to obtain analgesia |
| NZ518447A (en) | 1999-10-29 | 2004-10-29 | Orion Corp | Treatment or prevention of hypotension and shock |
| US6388090B2 (en) | 2000-01-14 | 2002-05-14 | Orion Corporation | Imidazole derivatives |
| FI20000073A0 (fi) * | 2000-01-14 | 2000-01-14 | Orion Yhtymae Oy | Uusia imidatsolijohdannaisia |
| CA2408290A1 (en) | 2000-05-08 | 2001-11-15 | Orion Corporation | New polycyclic indanylimidazoles with alpha2 adrenergic activity |
| TW200930291A (en) * | 2002-04-29 | 2009-07-16 | Bayer Cropscience Ag | Pesticidal heterocycles |
| FR2839719B1 (fr) * | 2002-05-16 | 2004-08-06 | Pf Medicament | Nouveaux composes imidazoliques, leur procede de preparation et leur utilisation a titre de medicaments |
| FI20022159A0 (fi) | 2002-12-05 | 2002-12-05 | Orion Corp | Uusia farmaseuttisia yhdisteitä |
| FI116292B (fi) * | 2003-01-08 | 2005-10-31 | Juvantia Pharma Ltd Oy | Menetelmä substituoitujen imidatsolijohdannaisten valmistamiseksi ja menetelmässä käytettäviä välituotteita |
| DE102004035322A1 (de) * | 2004-07-21 | 2006-02-16 | Universität des Saarlandes | Selektive Hemmstoffe humaner Corticoidsynthasen |
| ATE517883T1 (de) | 2005-08-25 | 2011-08-15 | Schering Corp | Imidazolderivate als funktionelle selektive agonisten des alpha2c-adrenorezeptors |
| KR20080037070A (ko) | 2005-08-25 | 2008-04-29 | 쉐링 코포레이션 | 알파２ｃ 아드레날린성 수용체 효능제 |
| US7700592B2 (en) | 2005-08-25 | 2010-04-20 | Schering Corporation | α2C adrenoreceptor agonists |
| KR20080090545A (ko) * | 2006-01-27 | 2008-10-08 | 에프. 호프만-라 로슈 아게 | Ｃｎｓ 장애 치료용 2-이미다졸의 용도 |
| MX2009003801A (es) | 2006-10-19 | 2009-04-22 | Hoffmann La Roche | Aminometil-4-imidazoles. |
| WO2008052907A1 (en) | 2006-11-02 | 2008-05-08 | F. Hoffmann-La Roche Ag | Substituted 2-imidazoles as modulators of the trace amine associated receptors |
| AU2007321376A1 (en) * | 2006-11-16 | 2008-05-22 | F. Hoffmann-La Roche Ag | Substituted 4-imidazoles |
| MX2009005920A (es) | 2006-12-13 | 2009-06-16 | Hoffmann La Roche | Nuevos 2-imidazoles como ligandos para receptores asociados con trazas de amina. |
| US20080146523A1 (en) | 2006-12-18 | 2008-06-19 | Guido Galley | Imidazole derivatives |
| ES2510546T3 (es) | 2007-02-02 | 2014-10-21 | F. Hoffmann-La Roche Ag | Nuevas 2-aminooxazolinas como ligandos TAAR1 para trastornos del SNC |
| WO2008100456A2 (en) | 2007-02-13 | 2008-08-21 | Schering Corporation | Functionally selective alpha2c adrenoreceptor agonists |
| ATE530547T1 (de) | 2007-02-13 | 2011-11-15 | Schering Corp | Derivate und analoge von chroman als funktionell selektive alpha2c-adrenorezeptor-agonisten |
| CA2678072A1 (en) | 2007-02-13 | 2008-08-21 | Schering Corporation | Functionally selective alpha2c adrenoreceptor agonists |
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| US3636002A (en) * | 1969-12-15 | 1972-01-18 | Janssen Pharmaceutica Nv | 1-(2-halobenzyloxy-1-indanyl)-imidazoles |
| ES523609A0 (es) * | 1982-07-05 | 1985-03-01 | Erba Farmitalia | Procedimiento para preparar derivados n-imidazolilicos de compuestos biciclicos. |
| US4634705A (en) * | 1984-06-06 | 1987-01-06 | Abbott Laboratories | Adrenergic amidines |
| US4659730A (en) * | 1984-06-18 | 1987-04-21 | Eli Lilly And Company | Aromatase inhibiting imidazole derivatives |
| GB2167408B (en) * | 1984-11-23 | 1988-05-25 | Farmos Oy | Substituted imidazole derivatives and their preparation and use |
| FI81092C (fi) * | 1986-05-15 | 1990-09-10 | Farmos Oy | Foerfarande foer framstaellning av terapeutiskt aktiva 4(5)-(2,3-dihydro-1h-inden-2-yl)-imidazolderivat. |
| US4878940A (en) * | 1987-04-02 | 1989-11-07 | Janssen Pharmaceutica N.V. | Herbicidal 1,5-substituted 1H-imidazoles |
| IL91542A0 (en) * | 1988-10-06 | 1990-04-29 | Erba Carlo Spa | N-imidazolyl-and n-imidazolyl-methyl derivatives of substituted bicyclic compounds,their preparation and pharmaceutical compositions containing them |
| GB2225782A (en) * | 1988-12-09 | 1990-06-13 | Farmos Group Limited | Imidazole derivatives useful for treatment of diabetes |
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| GB9425211D0 (en) * | 1994-12-14 | 1995-02-15 | Ucb Sa | Substituted 1H-imidazoles |
| US6388090B2 (en) * | 2000-01-14 | 2002-05-14 | Orion Corporation | Imidazole derivatives |
-
1995
- 1995-10-03 GB GBGB9520150.5A patent/GB9520150D0/en active Pending
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1996
- 1996-10-02 CZ CZ19981018A patent/CZ291576B6/cs not_active IP Right Cessation
- 1996-10-02 US US09/051,151 patent/US6313311B1/en not_active Expired - Lifetime
- 1996-10-02 DE DE69626862T patent/DE69626862T2/de not_active Expired - Lifetime
- 1996-10-02 JP JP51399497A patent/JP4129891B2/ja not_active Expired - Lifetime
- 1996-10-02 IL IL12372196A patent/IL123721A/en not_active IP Right Cessation
- 1996-10-02 RU RU98108027/04A patent/RU2188194C2/ru active
- 1996-10-02 NZ NZ319169A patent/NZ319169A/xx not_active IP Right Cessation
- 1996-10-02 EE EE9800101A patent/EE04436B1/xx unknown
- 1996-10-02 EP EP96932609A patent/EP0888309B1/en not_active Expired - Lifetime
- 1996-10-02 RO RO98-00825A patent/RO120409B1/ro unknown
- 1996-10-02 ES ES96932609T patent/ES2195013T3/es not_active Expired - Lifetime
- 1996-10-02 CN CN96197438A patent/CN1068592C/zh not_active Expired - Lifetime
- 1996-10-02 AU AU71327/96A patent/AU708002B2/en not_active Expired
- 1996-10-02 KR KR1019980702490A patent/KR19990064013A/ko not_active Ceased
- 1996-10-02 PT PT96932609T patent/PT888309E/pt unknown
- 1996-10-02 DK DK96932609T patent/DK0888309T3/da active
- 1996-10-02 PL PL96328167A patent/PL189110B1/pl unknown
- 1996-10-02 SI SI9620111A patent/SI9620111B/sl unknown
- 1996-10-02 SK SK439-98A patent/SK283542B6/sk not_active IP Right Cessation
- 1996-10-02 CA CA002231535A patent/CA2231535C/en not_active Expired - Lifetime
- 1996-10-02 AT AT96932609T patent/ATE234819T1/de active
- 1996-10-02 UA UA98031588A patent/UA49847C2/uk unknown
- 1996-10-02 WO PCT/FI1996/000518 patent/WO1997012874A1/en not_active Application Discontinuation
- 1996-10-02 HU HU9802927A patent/HU224197B1/hu active IP Right Grant
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1998
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- 1998-03-31 LV LVP-98-61A patent/LV12108B/en unknown
- 1998-04-02 NO NO19981496A patent/NO311024B1/no not_active IP Right Cessation
- 1998-04-22 LT LT98-057A patent/LT4460B/lt not_active IP Right Cessation
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