JP5667934B2

JP5667934B2 - 新規２環性複素環化合物からなる医薬

新規２環性複素環化合物からなる医薬 Download PDF

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Publication number: JP5667934B2
Authority: JP; Japan
Prior art keywords: group; substituted; unsubstituted; methyl; benzimidazol
Prior art date: 2010-06-28
Legal status : Active

Application number

JP2011141877A

Other languages

English (en)

Japanese (ja)

Other versions

JP2012031152A (ja

JP2012031152A5 (enExample

Inventor

克憲坪井

悠介山井

渡辺　仁

仁渡辺

博紀木下

Current Assignee

Sumitomo Pharma Co Ltd

Original Assignee

Sumitomo Dainippon Pharma Co Ltd

Priority date

2010-06-28

Filing date

2011-06-27

Publication date

2015-02-12

2011-06-27 Application filed by Sumitomo Dainippon Pharma Co Ltd filed Critical Sumitomo Dainippon Pharma Co Ltd

2011-06-27 Priority to JP2011141877A priority Critical patent/JP5667934B2/ja

2012-02-16 Publication of JP2012031152A publication Critical patent/JP2012031152A/ja

2014-06-19 Publication of JP2012031152A5 publication Critical patent/JP2012031152A5/ja

2015-02-12 Application granted granted Critical

2015-02-12 Publication of JP5667934B2 publication Critical patent/JP5667934B2/ja

Status Active legal-status Critical Current

2031-06-27 Anticipated expiration legal-status Critical

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239000003814 drug Substances 0.000 title claims description 29
125000002618 bicyclic heterocycle group Chemical group 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims description 258
-1 unsaturated nitrogen-containing aliphatic compounds Chemical class 0.000 claims description 180
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 133
125000000217 alkyl group Chemical group 0.000 claims description 117
125000004432 carbon atom Chemical group C* 0.000 claims description 102
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 90
125000000623 heterocyclic group Chemical group 0.000 claims description 78
125000001931 aliphatic group Chemical group 0.000 claims description 77
125000003545 alkoxy group Chemical group 0.000 claims description 76
125000005843 halogen group Chemical group 0.000 claims description 67
150000003839 salts Chemical class 0.000 claims description 65
125000004438 haloalkoxy group Chemical group 0.000 claims description 54
125000003118 aryl group Chemical group 0.000 claims description 41
125000004433 nitrogen atom Chemical group N* 0.000 claims description 35
229910052757 nitrogen Chemical group 0.000 claims description 33
125000000753 cycloalkyl group Chemical group 0.000 claims description 32
QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 31
125000001188 haloalkyl group Chemical group 0.000 claims description 27
229910052799 carbon Inorganic materials 0.000 claims description 26
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
229920006395 saturated elastomer Polymers 0.000 claims description 23
150000001721 carbon Chemical class 0.000 claims description 22
208000004296 neuralgia Diseases 0.000 claims description 19
208000021722 neuropathic pain Diseases 0.000 claims description 17
125000004430 oxygen atom Chemical group O* 0.000 claims description 17
125000004434 sulfur atom Chemical group 0.000 claims description 16
208000001294 Nociceptive Pain Diseases 0.000 claims description 15
239000003795 chemical substances by application Substances 0.000 claims description 15
125000000392 cycloalkenyl group Chemical group 0.000 claims description 15
201000006417 multiple sclerosis Diseases 0.000 claims description 15
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 14
206010013990 dysuria Diseases 0.000 claims description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 13
125000000304 alkynyl group Chemical group 0.000 claims description 13
210000005036 nerve Anatomy 0.000 claims description 13
125000005842 heteroatom Chemical group 0.000 claims description 12
239000003112 inhibitor Substances 0.000 claims description 12
229910052717 sulfur Inorganic materials 0.000 claims description 8
125000006618 5- to 10-membered aromatic heterocyclic group Chemical group 0.000 claims description 7
230000001953 sensory effect Effects 0.000 claims description 7
239000004480 active ingredient Substances 0.000 claims description 6
229940124597 therapeutic agent Drugs 0.000 claims description 6
230000003449 preventive effect Effects 0.000 claims description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
ZYUAASICHDTDEK-AWEZNQCLSA-N (2s)-2-[[1-ethyl-6-(4-methylphenoxy)benzimidazol-2-yl]methylamino]propanamide Chemical compound C1=C2N(CC)C(CN[C@@H](C)C(N)=O)=NC2=CC=C1OC1=CC=C(C)C=C1 ZYUAASICHDTDEK-AWEZNQCLSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
239000000047 product Substances 0.000 description 97
125000001424 substituent group Chemical group 0.000 description 91
238000005160 1H NMR spectroscopy Methods 0.000 description 86
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 80
239000000243 solution Substances 0.000 description 78
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
125000002887 hydroxy group Chemical group [H]O* 0.000 description 64
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
238000000034 method Methods 0.000 description 60
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
238000006243 chemical reaction Methods 0.000 description 57
125000006615 aromatic heterocyclic group Chemical group 0.000 description 51
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
239000002904 solvent Substances 0.000 description 47
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
239000000203 mixture Substances 0.000 description 42
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 40
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 39
230000003647 oxidation Effects 0.000 description 39
238000007254 oxidation reaction Methods 0.000 description 39
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
125000004453 alkoxycarbonyl group Chemical group 0.000 description 38
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 35
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 32
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
125000003277 amino group Chemical group 0.000 description 27
125000004093 cyano group Chemical group *C#N 0.000 description 27
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
239000000741 silica gel Substances 0.000 description 26
229910002027 silica gel Inorganic materials 0.000 description 26
239000012044 organic layer Substances 0.000 description 25
229910052938 sodium sulfate Inorganic materials 0.000 description 25
235000011152 sodium sulphate Nutrition 0.000 description 25
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 24
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 24
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
239000002585 base Substances 0.000 description 23
230000002829 reductive effect Effects 0.000 description 23
108091006146 Channels Proteins 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
239000011734 sodium Substances 0.000 description 21
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 20
229910000027 potassium carbonate Inorganic materials 0.000 description 20
238000003756 stirring Methods 0.000 description 20
229910052731 fluorine Inorganic materials 0.000 description 19
238000010992 reflux Methods 0.000 description 19
125000001153 fluoro group Chemical group F* 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
125000001412 tetrahydropyranyl group Chemical group 0.000 description 17
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 16
229910000024 caesium carbonate Inorganic materials 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
210000004027 cell Anatomy 0.000 description 15
229910052801 chlorine Inorganic materials 0.000 description 15
125000001309 chloro group Chemical group Cl* 0.000 description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 15
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
FIAINKIUSZGVGX-DKWTVANSSA-N [(2s)-1-amino-1-oxopropan-2-yl]azanium;chloride Chemical compound Cl.C[C@H](N)C(N)=O FIAINKIUSZGVGX-DKWTVANSSA-N 0.000 description 14
229910052943 magnesium sulfate Inorganic materials 0.000 description 14
235000019341 magnesium sulphate Nutrition 0.000 description 14
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 14
208000002193 Pain Diseases 0.000 description 13
230000000069 prophylactic effect Effects 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 13
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 12
125000004448 alkyl carbonyl group Chemical group 0.000 description 12
239000007810 chemical reaction solvent Substances 0.000 description 12
229940079593 drug Drugs 0.000 description 12
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
108090000623 proteins and genes Proteins 0.000 description 12
125000003107 substituted aryl group Chemical group 0.000 description 12
230000001225 therapeutic effect Effects 0.000 description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 12
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 11
125000004390 alkyl sulfonyl group Chemical group 0.000 description 11
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 11
229910052736 halogen Inorganic materials 0.000 description 11
150000002367 halogens Chemical class 0.000 description 11
229910052751 metal Inorganic materials 0.000 description 11
239000002184 metal Substances 0.000 description 11
230000009467 reduction Effects 0.000 description 11
238000006722 reduction reaction Methods 0.000 description 11
CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 11
229950010357 tetrodotoxin Drugs 0.000 description 11
CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 11
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 11
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 10
229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
235000017557 sodium bicarbonate Nutrition 0.000 description 10
238000001816 cooling Methods 0.000 description 9
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 9
239000007800 oxidant agent Substances 0.000 description 9
125000004043 oxo group Chemical group O=* 0.000 description 9
125000000547 substituted alkyl group Chemical group 0.000 description 9
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
210000001170 unmyelinated nerve fiber Anatomy 0.000 description 9
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 8
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
125000004414 alkyl thio group Chemical group 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 8
229910000105 potassium hydride Inorganic materials 0.000 description 8
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
239000012312 sodium hydride Substances 0.000 description 8
229910000104 sodium hydride Inorganic materials 0.000 description 8
RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 description 7
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
201000010099 disease Diseases 0.000 description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
230000002401 inhibitory effect Effects 0.000 description 7
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 7
125000002950 monocyclic group Chemical group 0.000 description 7
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 6
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
125000004104 aryloxy group Chemical group 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
229910052742 iron Inorganic materials 0.000 description 6
239000003446 ligand Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
238000004519 manufacturing process Methods 0.000 description 6
230000001537 neural effect Effects 0.000 description 6
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 6
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
125000004193 piperazinyl group Chemical group 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
210000001519 tissue Anatomy 0.000 description 6
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 5
239000002253 acid Substances 0.000 description 5
125000005129 aryl carbonyl group Chemical group 0.000 description 5
125000004391 aryl sulfonyl group Chemical group 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
125000002883 imidazolyl group Chemical group 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
125000003386 piperidinyl group Chemical group 0.000 description 5
125000005936 piperidyl group Chemical group 0.000 description 5
239000000843 powder Substances 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
230000000638 stimulation Effects 0.000 description 5
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 5
238000012360 testing method Methods 0.000 description 5
125000000464 thioxo group Chemical group S=* 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
FVECELJHCSPHKY-UHFFFAOYSA-N Veratridine Natural products C1=C(OC)C(OC)=CC=C1C(=O)OC1C2(O)OC34CC5(O)C(CN6C(CCC(C)C6)C6(C)O)C6(O)C(O)CC5(O)C4CCC2C3(C)CC1 FVECELJHCSPHKY-UHFFFAOYSA-N 0.000 description 4
125000005196 alkyl carbonyloxy group Chemical group 0.000 description 4
230000000202 analgesic effect Effects 0.000 description 4
125000002619 bicyclic group Chemical group 0.000 description 4
239000004210 ether based solvent Substances 0.000 description 4
238000011156 evaluation Methods 0.000 description 4
125000002541 furyl group Chemical group 0.000 description 4
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 4
230000027939 micturition Effects 0.000 description 4
239000011259 mixed solution Substances 0.000 description 4
125000002757 morpholinyl group Chemical group 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
230000001575 pathological effect Effects 0.000 description 4
125000004076 pyridyl group Chemical group 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 4
FVECELJHCSPHKY-JLSHOZRYSA-N veratridine Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)O[C@@H]1[C@@]2(O)O[C@]34C[C@@]5(O)[C@H](CN6[C@@H](CC[C@H](C)C6)[C@@]6(C)O)[C@]6(O)[C@@H](O)C[C@@]5(O)[C@@H]4CC[C@H]2[C@]3(C)CC1 FVECELJHCSPHKY-JLSHOZRYSA-N 0.000 description 4
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 3
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
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