CZ301324B6 - Diazabicyklický derivát, farmaceutická kompozice s jeho obsahem a jeho použití - Google Patents

Info

Publication number

CZ301324B6

CZ301324B6 CZ20023765A CZ20023765A CZ301324B6 CZ 301324 B6 CZ301324 B6 CZ 301324B6 CZ 20023765 A CZ20023765 A CZ 20023765A CZ 20023765 A CZ20023765 A CZ 20023765A CZ 301324 B6 CZ301324 B6 CZ 301324B6

Authority

CZ

Czechia

Prior art keywords

pyridyl

pyrrole

mmol

octahydropyrrolo

give

Prior art date

2000-04-27

Links

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• Global Dossier
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• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
• 150000001875 compounds Chemical class 0.000 claims abstract description 425
• 239000003814 drug Substances 0.000 claims abstract description 41
• 241000124008 Mammalia Species 0.000 claims abstract description 27
• 230000003957 neurotransmitter release Effects 0.000 claims abstract 2
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 338
• -1 amino, amino Chemical group 0.000 claims description 252
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 90
• 125000000217 alkyl group Chemical group 0.000 claims description 59
• 229910052739 hydrogen Inorganic materials 0.000 claims description 44
• 239000001257 hydrogen Substances 0.000 claims description 43
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
• 208000002193 Pain Diseases 0.000 claims description 27
• 230000036407 pain Effects 0.000 claims description 27
• 150000003839 salts Chemical class 0.000 claims description 24
• 125000003545 alkoxy group Chemical group 0.000 claims description 22
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 21
• 208000035475 disorder Diseases 0.000 claims description 18
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
• 239000003937 drug carrier Substances 0.000 claims description 13
• 201000010099 disease Diseases 0.000 claims description 12
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 229960002715 nicotine Drugs 0.000 claims description 12
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 11
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 11
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
• 150000002367 halogens Chemical class 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 9
• 150000002431 hydrogen Chemical class 0.000 claims description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
• 125000000304 alkynyl group Chemical group 0.000 claims description 8
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 8
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 8
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims description 7
• 208000024827 Alzheimer disease Diseases 0.000 claims description 7
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 7
• 208000018737 Parkinson disease Diseases 0.000 claims description 7
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
• 125000004414 alkyl thio group Chemical group 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 6
• 208000000323 Tourette Syndrome Diseases 0.000 claims description 5
• 208000016620 Tourette disease Diseases 0.000 claims description 5
• 229940123445 Tricyclic antidepressant Drugs 0.000 claims description 5
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
• 201000000980 schizophrenia Diseases 0.000 claims description 5
• 208000011580 syndromic disease Diseases 0.000 claims description 5
• 239000003029 tricyclic antidepressant agent Substances 0.000 claims description 5
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 4
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 4
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
• 239000001961 anticonvulsive agent Substances 0.000 claims description 4
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 4
• 208000013403 hyperactivity Diseases 0.000 claims description 4
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 4
• 230000001773 anti-convulsant effect Effects 0.000 claims description 3
• 229960003965 antiepileptics Drugs 0.000 claims description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
• MBQYQLWSBRANKQ-IMTBSYHQSA-N (1s,5s)-3-(5,6-dichloropyridin-3-yl)-3,6-diazabicyclo[3.2.0]heptane Chemical compound N1=C(Cl)C(Cl)=CC(N2C[C@H]3NC[C@H]3C2)=C1 MBQYQLWSBRANKQ-IMTBSYHQSA-N 0.000 claims description 2
• YSAVCILVSULFGD-JOYOIKCWSA-N (3as,6as)-5-(5-methoxypyridin-3-yl)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[2,3-c]pyrrole Chemical compound COC1=CN=CC(N2C[C@H]3NCC[C@H]3C2)=C1 YSAVCILVSULFGD-JOYOIKCWSA-N 0.000 claims description 2
• YETODIXQMRZKEG-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropyrrolo[2,3-c]pyrrole Chemical compound C1NCC2NCCC21 YETODIXQMRZKEG-UHFFFAOYSA-N 0.000 claims description 2
• 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
• UYZGGVMCTYTMRJ-WCBMZHEXSA-N (1s,5s)-3-pyridin-3-yl-3,6-diazabicyclo[3.2.0]heptane Chemical compound C([C@H]1NC[C@H]1C1)N1C1=CC=CN=C1 UYZGGVMCTYTMRJ-WCBMZHEXSA-N 0.000 claims 1
• KWZWPEDWONELEI-YPMHNXCESA-N (3ar,6ar)-5-(5-ethylpyridin-3-yl)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[2,3-c]pyrrole Chemical compound CCC1=CN=CC(N2C[C@@H]3NCC[C@@H]3C2)=C1 KWZWPEDWONELEI-YPMHNXCESA-N 0.000 claims 1
• YSAVCILVSULFGD-SKDRFNHKSA-N (3ar,6ar)-5-(5-methoxypyridin-3-yl)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[2,3-c]pyrrole Chemical compound COC1=CN=CC(N2C[C@@H]3NCC[C@@H]3C2)=C1 YSAVCILVSULFGD-SKDRFNHKSA-N 0.000 claims 1
• ZCIPXINQRZWYCD-XCBNKYQSSA-N (3ar,6ar)-5-(6-bromo-5-chloropyridin-3-yl)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[2,3-c]pyrrole Chemical compound N1=C(Br)C(Cl)=CC(N2C[C@@H]3NCC[C@@H]3C2)=C1 ZCIPXINQRZWYCD-XCBNKYQSSA-N 0.000 claims 1
• GUZUKHDQICFNFX-PHIMTYICSA-N (3ar,6as)-5-(5-ethoxypyridin-3-yl)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole Chemical compound CCOC1=CN=CC(N2C[C@H]3CNC[C@H]3C2)=C1 GUZUKHDQICFNFX-PHIMTYICSA-N 0.000 claims 1
• OHWQUEIYHPZQPN-TXEJJXNPSA-N (3ar,6as)-5-(5-propoxypyridin-3-yl)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole Chemical compound CCCOC1=CN=CC(N2C[C@H]3CNC[C@H]3C2)=C1 OHWQUEIYHPZQPN-TXEJJXNPSA-N 0.000 claims 1
• VPFXUOCTXHVJCT-DTORHVGOSA-N (3as,6ar)-5-(6-chloro-5-methoxypyridin-3-yl)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole Chemical compound N1=C(Cl)C(OC)=CC(N2C[C@H]3CNC[C@H]3C2)=C1 VPFXUOCTXHVJCT-DTORHVGOSA-N 0.000 claims 1
• WNQHCICGYPNPJA-DTORHVGOSA-N (3as,6ar)-5-(6-chloropyridin-3-yl)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole Chemical compound C1=NC(Cl)=CC=C1N1C[C@H]2CNC[C@H]2C1 WNQHCICGYPNPJA-DTORHVGOSA-N 0.000 claims 1
• DQHQCRQWOJTKBG-WCBMZHEXSA-N (3as,6as)-5-(6-chloropyridin-3-yl)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[2,3-c]pyrrole Chemical compound C1=NC(Cl)=CC=C1N1C[C@H]2NCC[C@H]2C1 DQHQCRQWOJTKBG-WCBMZHEXSA-N 0.000 claims 1
• HMWDILXJWAOEJT-GXSJLCMTSA-N (3as,6as)-5-pyridin-3-yl-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[2,3-c]pyrrole Chemical compound C([C@@H]1CCN[C@@H]1C1)N1C1=CC=CN=C1 HMWDILXJWAOEJT-GXSJLCMTSA-N 0.000 claims 1
• KLNHDAVAIWEDTG-BETUJISGSA-N 3-[(3ar,6as)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrol-5-yl]quinoline Chemical compound C1=CC=CC2=CC(N3C[C@H]4CNC[C@H]4C3)=CN=C21 KLNHDAVAIWEDTG-BETUJISGSA-N 0.000 claims 1
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 1
• 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims 1
• 238000002360 preparation method Methods 0.000 abstract description 10
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 344
• CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 288
• 238000000034 method Methods 0.000 description 226
• 239000000047 product Substances 0.000 description 205
• 239000000203 mixture Substances 0.000 description 204
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 198
• 230000002829 reductive effect Effects 0.000 description 159
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 136
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 125
• 235000019439 ethyl acetate Nutrition 0.000 description 119
• 229910004298 SiO 2 Inorganic materials 0.000 description 117
• 238000004587 chromatography analysis Methods 0.000 description 117
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 108
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 86
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
• 239000007787 solid Substances 0.000 description 84
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 83
• 239000000243 solution Substances 0.000 description 75
• 235000019441 ethanol Nutrition 0.000 description 65
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 58
• 239000000706 filtrate Substances 0.000 description 57
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
• 239000003921 oil Substances 0.000 description 55
• 235000019198 oils Nutrition 0.000 description 55
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 48
• 238000003756 stirring Methods 0.000 description 40
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 37
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 36
• 235000011087 fumaric acid Nutrition 0.000 description 35
• 239000001530 fumaric acid Substances 0.000 description 34
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 31
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 31
• 239000011734 sodium Substances 0.000 description 29
• 239000012267 brine Substances 0.000 description 28
• 229940079593 drug Drugs 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• 238000001914 filtration Methods 0.000 description 26
• 229910052763 palladium Inorganic materials 0.000 description 25
• 239000012043 crude product Substances 0.000 description 24
• 239000012074 organic phase Substances 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 24
• 238000006243 chemical reaction Methods 0.000 description 23
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
• 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 21
• 239000012298 atmosphere Substances 0.000 description 21
• 230000000694 effects Effects 0.000 description 21
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 21
• 239000000126 substance Substances 0.000 description 21
• 239000012458 free base Substances 0.000 description 20
• 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 19
• 239000002858 neurotransmitter agent Substances 0.000 description 19
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
• 239000002244 precipitate Substances 0.000 description 17
• NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 16
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 16
• 229910052799 carbon Inorganic materials 0.000 description 16
• 238000010992 reflux Methods 0.000 description 16
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 15
• 239000003054 catalyst Substances 0.000 description 15
• 239000000284 extract Substances 0.000 description 15
• RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 15
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 15
• 239000012230 colorless oil Substances 0.000 description 14
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 14
• 239000010410 layer Substances 0.000 description 14
• JRKBTFBZMOGASJ-UHFFFAOYSA-N 1h-pyrrole;dihydrochloride Chemical compound Cl.Cl.C=1C=CNC=1 JRKBTFBZMOGASJ-UHFFFAOYSA-N 0.000 description 13
• 239000012044 organic layer Substances 0.000 description 13
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 13
• PEAOEIWYQVXZMB-UHFFFAOYSA-N 5-bromo-2-chloropyridine Chemical compound ClC1=CC=C(Br)C=N1 PEAOEIWYQVXZMB-UHFFFAOYSA-N 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 12
• 238000010438 heat treatment Methods 0.000 description 12
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• FTFFHWWIPOQCBC-UHFFFAOYSA-N 5-bromopyridine-3-carbonitrile Chemical compound BrC1=CN=CC(C#N)=C1 FTFFHWWIPOQCBC-UHFFFAOYSA-N 0.000 description 11
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 11
• 125000003118 aryl group Chemical group 0.000 description 11
• 210000004027 cell Anatomy 0.000 description 11
• 210000003169 central nervous system Anatomy 0.000 description 11
• 229910052757 nitrogen Inorganic materials 0.000 description 11
• 230000001242 postsynaptic effect Effects 0.000 description 11
• 150000001412 amines Chemical class 0.000 description 10
• 150000001649 bromium compounds Chemical class 0.000 description 10
• 125000004432 carbon atom Chemical group C* 0.000 description 10
• 150000007942 carboxylates Chemical class 0.000 description 10
• 239000012528 membrane Substances 0.000 description 10
• 230000005062 synaptic transmission Effects 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 9
• SOSPMXMEOFGPIM-UHFFFAOYSA-N 3,5-dibromopyridine Chemical compound BrC1=CN=CC(Br)=C1 SOSPMXMEOFGPIM-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 9
• LFDGRWDETVOGDT-UHFFFAOYSA-N 1h-pyrrole;hydrochloride Chemical compound Cl.C=1C=CNC=1 LFDGRWDETVOGDT-UHFFFAOYSA-N 0.000 description 8
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 8
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 8
• 229960004373 acetylcholine Drugs 0.000 description 8
• 125000003342 alkenyl group Chemical group 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 8
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
• 125000001424 substituent group Chemical group 0.000 description 8
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