HRP20000731A2 - Aryl fused azapolycyclic compounds - Google Patents
Aryl fused azapolycyclic compounds Download PDFInfo
- Publication number
- HRP20000731A2 HRP20000731A2 HR20000731A HRP20000731A HRP20000731A2 HR P20000731 A2 HRP20000731 A2 HR P20000731A2 HR 20000731 A HR20000731 A HR 20000731A HR P20000731 A HRP20000731 A HR P20000731A HR P20000731 A2 HRP20000731 A2 HR P20000731A2
- Authority
- HR
- Croatia
- Prior art keywords
- trideca
- triene
- aza
- tricyclo
- alkyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 291
- 125000003118 aryl group Chemical group 0.000 title claims description 19
- 238000000034 method Methods 0.000 claims description 108
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- 239000001257 hydrogen Substances 0.000 claims description 48
- -1 hydroxy, nitro, amino Chemical group 0.000 claims description 42
- 229920006395 saturated elastomer Polymers 0.000 claims description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 35
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 125000001153 fluoro group Chemical group F* 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 206010012335 Dependence Diseases 0.000 claims description 15
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 230000009529 traumatic brain injury Effects 0.000 claims description 14
- 208000018737 Parkinson disease Diseases 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 12
- 241000208125 Nicotiana Species 0.000 claims description 12
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 125000005605 benzo group Chemical group 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 208000002193 Pain Diseases 0.000 claims description 10
- 125000002619 bicyclic group Chemical group 0.000 claims description 10
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 10
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 9
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 208000010877 cognitive disease Diseases 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000002950 monocyclic group Chemical group 0.000 claims description 9
- 229960002715 nicotine Drugs 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 208000023105 Huntington disease Diseases 0.000 claims description 8
- 208000006011 Stroke Diseases 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 230000007000 age related cognitive decline Effects 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
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- 208000000323 Tourette Syndrome Diseases 0.000 claims description 5
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- 208000025865 Ulcer Diseases 0.000 claims description 5
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- 208000022531 anorexia Diseases 0.000 claims description 5
- 230000036506 anxiety Effects 0.000 claims description 5
- 206010003119 arrhythmia Diseases 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 229940125717 barbiturate Drugs 0.000 claims description 5
- 229940049706 benzodiazepine Drugs 0.000 claims description 5
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 229960003920 cocaine Drugs 0.000 claims description 5
- 206010061428 decreased appetite Diseases 0.000 claims description 5
- 206010013932 dyslexia Diseases 0.000 claims description 5
- 208000010118 dystonia Diseases 0.000 claims description 5
- 206010015037 epilepsy Diseases 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 210000004211 gastric acid Anatomy 0.000 claims description 5
- 231100000869 headache Toxicity 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000002346 iodo group Chemical group I* 0.000 claims description 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- 201000010901 lateral sclerosis Diseases 0.000 claims description 5
- 208000005264 motor neuron disease Diseases 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 229940005483 opioid analgesics Drugs 0.000 claims description 5
- 208000021090 palsy Diseases 0.000 claims description 5
- 208000019906 panic disease Diseases 0.000 claims description 5
- 208000028591 pheochromocytoma Diseases 0.000 claims description 5
- 230000000750 progressive effect Effects 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 5
- 208000019116 sleep disease Diseases 0.000 claims description 5
- 230000001148 spastic effect Effects 0.000 claims description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 235000019505 tobacco product Nutrition 0.000 claims description 5
- 231100000397 ulcer Toxicity 0.000 claims description 5
- 230000025033 vasoconstriction Effects 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 206010057852 Nicotine dependence Diseases 0.000 claims description 4
- 206010034759 Petit mal epilepsy Diseases 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 208000025569 Tobacco Use disease Diseases 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 201000003146 cystitis Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 3
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 3
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 208000020685 sleep-wake disease Diseases 0.000 claims description 3
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- WHWGPUNVTOQEIM-UHFFFAOYSA-N 11-aza-tricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-6-ol Chemical compound C1C2CNCC1CC1=C2C=CC=C1O WHWGPUNVTOQEIM-UHFFFAOYSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- DICOOVAUGLVWQN-UHFFFAOYSA-N chembl363791 Chemical compound C1NCC2C3=CC(O)=CC=C3CC1C2 DICOOVAUGLVWQN-UHFFFAOYSA-N 0.000 claims description 2
- 230000006999 cognitive decline Effects 0.000 claims description 2
- UEUSVFILMLMQMI-UHFFFAOYSA-N ctk0j4562 Chemical compound C1NCC2CC3=CC(O)=CC=C3C1C2 UEUSVFILMLMQMI-UHFFFAOYSA-N 0.000 claims description 2
- HYDLTSOVXCUHPA-UHFFFAOYSA-N ctk0j4563 Chemical compound C1NCC2CC3=C(F)C(F)=CC=C3C1C2 HYDLTSOVXCUHPA-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 150000003457 sulfones Chemical class 0.000 claims description 2
- 150000003462 sulfoxides Chemical class 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 206010013663 drug dependence Diseases 0.000 claims 1
- 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims 1
- 208000022925 sleep disturbance Diseases 0.000 claims 1
- 208000011117 substance-related disease Diseases 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 177
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 144
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 103
- 238000006243 chemical reaction Methods 0.000 description 103
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 84
- 239000000243 solution Substances 0.000 description 83
- 235000019439 ethyl acetate Nutrition 0.000 description 71
- 239000000203 mixture Substances 0.000 description 71
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 70
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
- 238000005160 1H NMR spectroscopy Methods 0.000 description 57
- 238000004809 thin layer chromatography Methods 0.000 description 56
- 229910001868 water Inorganic materials 0.000 description 56
- 239000003921 oil Substances 0.000 description 49
- 235000019198 oils Nutrition 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- 239000012044 organic layer Substances 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
- 239000002904 solvent Substances 0.000 description 32
- 239000007787 solid Substances 0.000 description 31
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- 239000010410 layer Substances 0.000 description 26
- 239000012267 brine Substances 0.000 description 25
- 239000000047 product Substances 0.000 description 25
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000002585 base Substances 0.000 description 24
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 24
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- 238000010992 reflux Methods 0.000 description 19
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
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- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 14
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- 239000002253 acid Substances 0.000 description 14
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- FAMLQSCGIQGDPV-UHFFFAOYSA-N 3,4-dihydroxy-6-[4-hydroxy-5-(hydroxymethyl)-2-(sulfooxymethyl)oxolan-3-yl]oxy-5-sulfooxyoxane-2-carboxylic acid Chemical compound OC1C(CO)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(O)C(C(O)=O)O1 FAMLQSCGIQGDPV-UHFFFAOYSA-N 0.000 description 12
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- 230000015572 biosynthetic process Effects 0.000 description 12
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- 238000006722 reduction reaction Methods 0.000 description 12
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 11
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- 125000006239 protecting group Chemical group 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 9
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- 239000000543 intermediate Substances 0.000 description 9
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- 229910000069 nitrogen hydride Inorganic materials 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 235000017550 sodium carbonate Nutrition 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 238000010511 deprotection reaction Methods 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 229910052763 palladium Inorganic materials 0.000 description 8
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 8
- 235000011056 potassium acetate Nutrition 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 8
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 7
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- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
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- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
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- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical group CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- DYFFAVRFJWYYQO-UHFFFAOYSA-N n-methyl-n-phenylaniline Chemical compound C=1C=CC=CC=1N(C)C1=CC=CC=C1 DYFFAVRFJWYYQO-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
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- 235000011181 potassium carbonates Nutrition 0.000 description 1
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- 125000004076 pyridyl group Chemical group 0.000 description 1
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- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- GZHPURDUBITIAR-UHFFFAOYSA-M sodium;hydrogen sulfite;oxaldehyde Chemical compound [Na+].OS([O-])=O.O=CC=O GZHPURDUBITIAR-UHFFFAOYSA-M 0.000 description 1
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- PJYXVICYYHGLSW-UHFFFAOYSA-J tetrachloroplumbane Chemical compound Cl[Pb](Cl)(Cl)Cl PJYXVICYYHGLSW-UHFFFAOYSA-J 0.000 description 1
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- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8355698P | 1998-04-29 | 1998-04-29 | |
| PCT/IB1999/000617 WO1999055680A1 (en) | 1998-04-29 | 1999-04-08 | Aryl fused azapolycyclic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20000731A2 true HRP20000731A2 (en) | 2001-06-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20000731A HRP20000731A2 (en) | 1998-04-29 | 2000-10-27 | Aryl fused azapolycyclic compounds |
Country Status (42)
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|---|---|
| US (3) | US6462035B1 (zh) |
| EP (1) | EP1076650B1 (zh) |
| JP (1) | JP2002513007A (zh) |
| KR (1) | KR100420423B1 (zh) |
| CN (1) | CN1144787C (zh) |
| AP (1) | AP1154A (zh) |
| AR (1) | AR018596A1 (zh) |
| AT (1) | ATE258921T1 (zh) |
| AU (1) | AU749831B2 (zh) |
| BG (1) | BG64556B1 (zh) |
| BR (1) | BR9910058A (zh) |
| CA (1) | CA2330576A1 (zh) |
| CO (1) | CO5021124A1 (zh) |
| DE (1) | DE69914594T2 (zh) |
| DK (1) | DK1076650T3 (zh) |
| DZ (1) | DZ2778A1 (zh) |
| EA (1) | EA003669B1 (zh) |
| ES (1) | ES2213354T3 (zh) |
| GT (1) | GT199900059A (zh) |
| HK (1) | HK1036453A1 (zh) |
| HR (1) | HRP20000731A2 (zh) |
| HU (1) | HUP0103340A3 (zh) |
| ID (1) | ID26700A (zh) |
| IL (1) | IL138917A0 (zh) |
| IS (1) | IS5649A (zh) |
| MA (1) | MA26623A1 (zh) |
| MY (1) | MY133474A (zh) |
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| PA (1) | PA8471301A1 (zh) |
| PE (1) | PE20000435A1 (zh) |
| PL (1) | PL344010A1 (zh) |
| PT (1) | PT1076650E (zh) |
| SK (1) | SK15952000A3 (zh) |
| TN (1) | TNSN99080A1 (zh) |
| TR (1) | TR200003122T2 (zh) |
| UA (1) | UA61991C2 (zh) |
| UY (1) | UY25636A1 (zh) |
| WO (1) | WO1999055680A1 (zh) |
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|---|---|---|---|---|
| DE122008000038I1 (de) * | 1997-12-31 | 2008-11-13 | Pfizer Prod Inc | Arylkondensierte azapolycyclische derivate |
| US6605610B1 (en) * | 1997-12-31 | 2003-08-12 | Pfizer Inc | Aryl fused azapolycyclic compounds |
| US20010036943A1 (en) * | 2000-04-07 | 2001-11-01 | Coe Jotham W. | Pharmaceutical composition for treatment of acute, chronic pain and/or neuropathic pain and migraines |
| KR100551183B1 (ko) | 2001-04-20 | 2006-02-13 | 화이자 프로덕츠 인크. | 1,3-치환 인덴 및 아릴-융합 아자폴리시클릭 화합물의제조 방법 |
| BR0213696A (pt) * | 2001-10-31 | 2004-10-26 | Pfizer Prod Inc | Agonistas do receptor de acetilcolina nicotìnicos no tratamento da sìndrome de pernas inquietas |
| RU2004116320A (ru) | 2001-11-30 | 2005-10-10 | Пфайзер Продактс Инк. (Us) | Арилконденсированные азаполициклические соединения |
| AU2003233228A1 (en) * | 2002-05-03 | 2003-11-17 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Novel spiro ketone and carboxylic acid derivatives as specific inhibitors for (po3h2) ser/(po3h2)thr-pro-specific peptidyl-prolyl-cis/trans-isomerases |
| US20040224962A1 (en) * | 2003-05-09 | 2004-11-11 | Pfizer Inc | Pharmaceutical composition for the treatment of obesity or to facilitate or promote weight loss |
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| DE602004023299D1 (de) * | 2003-07-21 | 2009-11-05 | Pfizer Prod Inc | Nikotin abhängigkeit reduzierende heteroaryl kondensierte azapolycyclische verbindungen |
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| US3687937A (en) * | 1970-06-23 | 1972-08-29 | Us Of America The | 1,5-methano-3-benzazocine derivatives |
| JPS4914473A (zh) * | 1972-06-09 | 1974-02-07 | ||
| JPS4924968A (zh) * | 1972-07-01 | 1974-03-05 |
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