CA2660529C - Benzimidazole derivatives useful in treatment of vallinoid receptor trpv1 related disorders - Google Patents
Benzimidazole derivatives useful in treatment of vallinoid receptor trpv1 related disorders Download PDFInfo
- Publication number
- CA2660529C CA2660529C CA2660529A CA2660529A CA2660529C CA 2660529 C CA2660529 C CA 2660529C CA 2660529 A CA2660529 A CA 2660529A CA 2660529 A CA2660529 A CA 2660529A CA 2660529 C CA2660529 C CA 2660529C
- Authority
- CA
- Canada
- Prior art keywords
- cyano
- benzimidazol
- acetamide
- ethyl
- methylethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 56
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title abstract description 3
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 206
- 230000001684 chronic effect Effects 0.000 claims abstract description 23
- 208000002551 irritable bowel syndrome Diseases 0.000 claims abstract description 21
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims abstract description 20
- 208000000491 Tendinopathy Diseases 0.000 claims abstract description 15
- 206010043255 Tendonitis Diseases 0.000 claims abstract description 15
- 201000004415 tendinitis Diseases 0.000 claims abstract description 15
- 208000033808 peripheral neuropathy Diseases 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 206010020853 Hypertonic bladder Diseases 0.000 claims abstract description 10
- 208000000450 Pelvic Pain Diseases 0.000 claims abstract description 10
- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims abstract description 9
- 208000020629 overactive bladder Diseases 0.000 claims abstract description 9
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 8
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 172
- 150000003839 salts Chemical class 0.000 claims description 153
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 79
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 53
- -1 (+)-2-(7-chloro-6-fluoro-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)-fluorophenyl]ethyl}acetamide Chemical compound 0.000 claims description 45
- 239000000460 chlorine Substances 0.000 claims description 40
- 229910052801 chlorine Inorganic materials 0.000 claims description 30
- 239000011737 fluorine Chemical group 0.000 claims description 30
- 229910052731 fluorine Chemical group 0.000 claims description 30
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
- 208000035475 disorder Diseases 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 208000001294 Nociceptive Pain Diseases 0.000 claims description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 150000001721 carbon Chemical group 0.000 claims description 15
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 15
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 5
- JBMPULIBUHRVFV-UHFFFAOYSA-N n-[1-[4-(2-cyanopropan-2-yl)-3-fluorophenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=NC2=CC=C(F)C(F)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C(F)=C1 JBMPULIBUHRVFV-UHFFFAOYSA-N 0.000 claims description 3
- XFADJHQQUWGPMZ-AWEZNQCLSA-N 2-(7-chlorobenzimidazol-1-yl)-n-[(1s)-1-[4-(2-cyanopropan-2-yl)phenyl]ethyl]acetamide Chemical compound C1([C@@H](NC(=O)CN2C3=C(Cl)C=CC=C3N=C2)C)=CC=C(C(C)(C)C#N)C=C1 XFADJHQQUWGPMZ-AWEZNQCLSA-N 0.000 claims description 2
- SKAFVMHJNJDJAZ-ZDUSSCGKSA-N n-[(1s)-1-[4-(2-cyanopropan-2-yl)phenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1([C@@H](NC(=O)CN2C3=C(F)C(F)=CC=C3N=C2)C)=CC=C(C(C)(C)C#N)C=C1 SKAFVMHJNJDJAZ-ZDUSSCGKSA-N 0.000 claims description 2
- OOWYEILSUQLNPO-UHFFFAOYSA-N n-[1-[3-chloro-4-(2-cyanopropan-2-yl)phenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=NC2=CC=C(F)C(F)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C(Cl)=C1 OOWYEILSUQLNPO-UHFFFAOYSA-N 0.000 claims description 2
- LUEZBMHSXPIHCK-UHFFFAOYSA-N n-[1-[4-(2-cyanopropan-2-yl)-2-methylphenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=NC2=CC=C(F)C(F)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C=C1C LUEZBMHSXPIHCK-UHFFFAOYSA-N 0.000 claims 3
- WQUFPDDWRIAQFS-UHFFFAOYSA-N 2-(7-acetylbenzimidazol-1-yl)-n-[1-[4-(2-cyanopropan-2-yl)phenyl]ethyl]acetamide Chemical compound C1=NC2=CC=CC(C(C)=O)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C=C1 WQUFPDDWRIAQFS-UHFFFAOYSA-N 0.000 claims 2
- FMNGJTZLSAZEMM-UHFFFAOYSA-N 2-(7-chloro-6-fluorobenzimidazol-1-yl)-n-[1-[4-(2-cyanopropan-2-yl)-3-fluorophenyl]ethyl]acetamide Chemical compound C1=NC2=CC=C(F)C(Cl)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C(F)=C1 FMNGJTZLSAZEMM-UHFFFAOYSA-N 0.000 claims 2
- YAOGGQLFLBUIHI-HNNXBMFYSA-N 2-(7-cyanobenzimidazol-1-yl)-n-[(1s)-1-[4-(2-cyanopropan-2-yl)phenyl]ethyl]acetamide Chemical compound C1([C@@H](NC(=O)CN2C3=C(C#N)C=CC=C3N=C2)C)=CC=C(C(C)(C)C#N)C=C1 YAOGGQLFLBUIHI-HNNXBMFYSA-N 0.000 claims 2
- FTLWFHRFCYFDFU-UHFFFAOYSA-N 2-(7-cyanobenzimidazol-1-yl)-n-[1-[4-(1-cyanocyclohexyl)phenyl]ethyl]acetamide Chemical compound C1=NC2=CC=CC(C#N)=C2N1CC(=O)NC(C)C(C=C1)=CC=C1C1(C#N)CCCCC1 FTLWFHRFCYFDFU-UHFFFAOYSA-N 0.000 claims 2
- FJJBQVFDRWWMLA-UHFFFAOYSA-N n-[1-[4-(1-cyanocyclobutyl)phenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=NC2=CC=C(F)C(F)=C2N1CC(=O)NC(C)C(C=C1)=CC=C1C1(C#N)CCC1 FJJBQVFDRWWMLA-UHFFFAOYSA-N 0.000 claims 2
- MVWIHDIFVWICIP-UHFFFAOYSA-N n-[1-[4-(1-cyanocyclohexyl)phenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=NC2=CC=C(F)C(F)=C2N1CC(=O)NC(C)C(C=C1)=CC=C1C1(C#N)CCCCC1 MVWIHDIFVWICIP-UHFFFAOYSA-N 0.000 claims 2
- OBCHHQUXVCEXET-UHFFFAOYSA-N n-[1-[4-(4-cyanothian-4-yl)-2-methylphenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=NC2=CC=C(F)C(F)=C2N1CC(=O)NC(C)C(C(=C1)C)=CC=C1C1(C#N)CCSCC1 OBCHHQUXVCEXET-UHFFFAOYSA-N 0.000 claims 2
- QQISUOIDWCCYED-AWEZNQCLSA-N 2-(7-acetylbenzimidazol-1-yl)-n-[(1s)-1-[4-(2-cyanopropan-2-yl)-3-fluorophenyl]ethyl]acetamide Chemical compound C1([C@@H](NC(=O)CN2C3=C(C(C)=O)C=CC=C3N=C2)C)=CC=C(C(C)(C)C#N)C(F)=C1 QQISUOIDWCCYED-AWEZNQCLSA-N 0.000 claims 1
- QQISUOIDWCCYED-UHFFFAOYSA-N 2-(7-acetylbenzimidazol-1-yl)-n-[1-[4-(2-cyanopropan-2-yl)-3-fluorophenyl]ethyl]acetamide Chemical compound C1=NC2=CC=CC(C(C)=O)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C(F)=C1 QQISUOIDWCCYED-UHFFFAOYSA-N 0.000 claims 1
- NKJAPDVSHONLBX-ZDUSSCGKSA-N 2-(7-chloro-6-fluorobenzimidazol-1-yl)-n-[(1s)-1-[4-(2-cyanopropan-2-yl)phenyl]ethyl]acetamide Chemical compound C1([C@@H](NC(=O)CN2C3=C(Cl)C(F)=CC=C3N=C2)C)=CC=C(C(C)(C)C#N)C=C1 NKJAPDVSHONLBX-ZDUSSCGKSA-N 0.000 claims 1
- COPPOYCYVPJAKG-UHFFFAOYSA-N 2-(7-chlorobenzimidazol-1-yl)-n-[1-[4-(2-cyanopropan-2-yl)-3-fluorophenyl]ethyl]acetamide Chemical compound C1=NC2=CC=CC(Cl)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C(F)=C1 COPPOYCYVPJAKG-UHFFFAOYSA-N 0.000 claims 1
- JQEQXMUAJAWHFH-UHFFFAOYSA-N 2-(7-chlorobenzimidazol-1-yl)-n-[[4-(2-cyanopropan-2-yl)-3-fluorophenyl]methyl]acetamide Chemical compound C1=C(F)C(C(C)(C#N)C)=CC=C1CNC(=O)CN1C2=C(Cl)C=CC=C2N=C1 JQEQXMUAJAWHFH-UHFFFAOYSA-N 0.000 claims 1
- YAOGGQLFLBUIHI-OAHLLOKOSA-N 2-(7-cyanobenzimidazol-1-yl)-n-[(1r)-1-[4-(2-cyanopropan-2-yl)phenyl]ethyl]acetamide Chemical compound C1([C@H](NC(=O)CN2C3=C(C#N)C=CC=C3N=C2)C)=CC=C(C(C)(C)C#N)C=C1 YAOGGQLFLBUIHI-OAHLLOKOSA-N 0.000 claims 1
- JQEUJRARURCGDF-UHFFFAOYSA-N 2-(7-cyanobenzimidazol-1-yl)-n-[1-[4-(1-cyanocyclobutyl)phenyl]ethyl]acetamide Chemical compound C1=NC2=CC=CC(C#N)=C2N1CC(=O)NC(C)C(C=C1)=CC=C1C1(C#N)CCC1 JQEUJRARURCGDF-UHFFFAOYSA-N 0.000 claims 1
- KPRYMSHFAHNROT-UHFFFAOYSA-N 2-(7-cyanobenzimidazol-1-yl)-n-[1-[4-(2-cyanopropan-2-yl)-3-fluorophenyl]ethyl]acetamide Chemical compound C1=NC2=CC=CC(C#N)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C(F)=C1 KPRYMSHFAHNROT-UHFFFAOYSA-N 0.000 claims 1
- SKZQTBUGGJLXBA-UHFFFAOYSA-N 2-(7-cyanobenzimidazol-1-yl)-n-[1-[4-(2-cyanopropan-2-yl)-3-methylphenyl]ethyl]acetamide Chemical compound C1=NC2=CC=CC(C#N)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C(C)=C1 SKZQTBUGGJLXBA-UHFFFAOYSA-N 0.000 claims 1
- AQOZKGMSGBTFDO-UHFFFAOYSA-N 2-(7-cyanobenzimidazol-1-yl)-n-[[4-(2-cyanopropan-2-yl)-2-methylphenyl]methyl]acetamide Chemical compound CC1=CC(C(C)(C)C#N)=CC=C1CNC(=O)CN1C2=C(C#N)C=CC=C2N=C1 AQOZKGMSGBTFDO-UHFFFAOYSA-N 0.000 claims 1
- LBCQIXZBXXGGSG-UHFFFAOYSA-N 2-(7-cyanobenzimidazol-1-yl)-n-[[4-(2-cyanopropan-2-yl)-3-fluorophenyl]methyl]acetamide Chemical compound C1=C(F)C(C(C)(C#N)C)=CC=C1CNC(=O)CN1C2=C(C#N)C=CC=C2N=C1 LBCQIXZBXXGGSG-UHFFFAOYSA-N 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- SKAFVMHJNJDJAZ-CYBMUJFWSA-N n-[(1r)-1-[4-(2-cyanopropan-2-yl)phenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1([C@H](NC(=O)CN2C3=C(F)C(F)=CC=C3N=C2)C)=CC=C(C(C)(C)C#N)C=C1 SKAFVMHJNJDJAZ-CYBMUJFWSA-N 0.000 claims 1
- WPCWWLZADISOFB-OAHLLOKOSA-N n-[(1r)-1-[4-(3-cyanopentan-3-yl)phenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=CC(C(CC)(C#N)CC)=CC=C1[C@@H](C)NC(=O)CN1C2=C(F)C(F)=CC=C2N=C1 WPCWWLZADISOFB-OAHLLOKOSA-N 0.000 claims 1
- LESRBAHKNXNHPM-AWEZNQCLSA-N n-[(1s)-1-[4-(2-cyanopropan-2-yl)phenyl]ethyl]-2-(7-fluorobenzimidazol-1-yl)acetamide Chemical compound C1([C@@H](NC(=O)CN2C3=C(F)C=CC=C3N=C2)C)=CC=C(C(C)(C)C#N)C=C1 LESRBAHKNXNHPM-AWEZNQCLSA-N 0.000 claims 1
- WPCWWLZADISOFB-HNNXBMFYSA-N n-[(1s)-1-[4-(3-cyanopentan-3-yl)phenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=CC(C(CC)(C#N)CC)=CC=C1[C@H](C)NC(=O)CN1C2=C(F)C(F)=CC=C2N=C1 WPCWWLZADISOFB-HNNXBMFYSA-N 0.000 claims 1
- ITQDJAWGKNGDPH-UHFFFAOYSA-N n-[1-[3-chloro-4-(2-cyanopropan-2-yl)phenyl]ethyl]-2-(7-cyanobenzimidazol-1-yl)acetamide Chemical compound C1=NC2=CC=CC(C#N)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C(Cl)=C1 ITQDJAWGKNGDPH-UHFFFAOYSA-N 0.000 claims 1
- AAHBXZFWPVEASC-UHFFFAOYSA-N n-[1-[4-(2-cyanopropan-2-yl)-2-methylphenyl]ethyl]-2-(7-fluorobenzimidazol-1-yl)acetamide Chemical compound C1=NC2=CC=CC(F)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C=C1C AAHBXZFWPVEASC-UHFFFAOYSA-N 0.000 claims 1
- MNERVACTQDBZOP-UHFFFAOYSA-N n-[1-[4-(2-cyanopropan-2-yl)-3-methylphenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=NC2=CC=C(F)C(F)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C(C)=C1 MNERVACTQDBZOP-UHFFFAOYSA-N 0.000 claims 1
- GBACDVPSPPFDPL-UHFFFAOYSA-N n-[[4-(2-cyanopropan-2-yl)-2-methylphenyl]methyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound CC1=CC(C(C)(C)C#N)=CC=C1CNC(=O)CN1C2=C(F)C(F)=CC=C2N=C1 GBACDVPSPPFDPL-UHFFFAOYSA-N 0.000 claims 1
- FMKHQUDXZYJALB-UHFFFAOYSA-N n-[[4-(2-cyanopropan-2-yl)phenyl]methyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=CC(C(C)(C#N)C)=CC=C1CNC(=O)CN1C2=C(F)C(F)=CC=C2N=C1 FMKHQUDXZYJALB-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 62
- 238000002360 preparation method Methods 0.000 abstract description 11
- 239000005557 antagonist Substances 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 5
- 238000002560 therapeutic procedure Methods 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 159
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 135
- 239000000047 product Substances 0.000 description 117
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
- 239000000203 mixture Substances 0.000 description 105
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 102
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 99
- 239000000543 intermediate Substances 0.000 description 90
- 238000005160 1H NMR spectroscopy Methods 0.000 description 87
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 81
- 239000012071 phase Substances 0.000 description 68
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 67
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 66
- 239000011541 reaction mixture Substances 0.000 description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- 238000003786 synthesis reaction Methods 0.000 description 64
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- 230000015572 biosynthetic process Effects 0.000 description 63
- 239000007787 solid Substances 0.000 description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 54
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 46
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 40
- 235000019341 magnesium sulphate Nutrition 0.000 description 40
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 40
- 230000002829 reductive effect Effects 0.000 description 39
- 238000003756 stirring Methods 0.000 description 37
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 34
- 235000019439 ethyl acetate Nutrition 0.000 description 34
- 239000007821 HATU Substances 0.000 description 32
- 239000012074 organic phase Substances 0.000 description 32
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 31
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- 239000012267 brine Substances 0.000 description 29
- 239000003921 oil Substances 0.000 description 29
- 235000019198 oils Nutrition 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 239000002253 acid Substances 0.000 description 26
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 26
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 22
- 239000008346 aqueous phase Substances 0.000 description 22
- 238000004296 chiral HPLC Methods 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 238000007792 addition Methods 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- 238000004128 high performance liquid chromatography Methods 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 description 17
- 108050004388 Transient receptor potential cation channel subfamily V member 1 Proteins 0.000 description 17
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 239000007832 Na2SO4 Substances 0.000 description 16
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 16
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 15
- 239000012043 crude product Substances 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 238000002156 mixing Methods 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 15
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- 235000019253 formic acid Nutrition 0.000 description 14
- 125000000623 heterocyclic group Chemical group 0.000 description 14
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 239000012279 sodium borohydride Substances 0.000 description 13
- 229910000033 sodium borohydride Inorganic materials 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 229960001866 silicon dioxide Drugs 0.000 description 12
- 238000001851 vibrational circular dichroism spectroscopy Methods 0.000 description 12
- CTMUOPMCEIJFPH-UHFFFAOYSA-N 2-(7-cyanobenzimidazol-1-yl)acetic acid Chemical compound C1=CC(C#N)=C2N(CC(=O)O)C=NC2=C1 CTMUOPMCEIJFPH-UHFFFAOYSA-N 0.000 description 11
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 11
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 238000013019 agitation Methods 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000001228 spectrum Methods 0.000 description 9
- 239000003643 water by type Substances 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 208000002193 Pain Diseases 0.000 description 8
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 8
- 235000017663 capsaicin Nutrition 0.000 description 8
- 229960002504 capsaicin Drugs 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 229940031098 ethanolamine Drugs 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000011369 resultant mixture Substances 0.000 description 7
- 239000012047 saturated solution Substances 0.000 description 7
- AIVDGNMSAJOGES-UHFFFAOYSA-N 2-(6,7-difluorobenzimidazol-1-yl)acetic acid Chemical compound C1=C(F)C(F)=C2N(CC(=O)O)C=NC2=C1 AIVDGNMSAJOGES-UHFFFAOYSA-N 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000007844 bleaching agent Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 208000004296 neuralgia Diseases 0.000 description 6
- 208000021722 neuropathic pain Diseases 0.000 description 6
- 230000036407 pain Effects 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 125000001010 sulfinic acid amide group Chemical group 0.000 description 6
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 6
- 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 6
- WKHRGYGWUZSFLP-UHFFFAOYSA-N 2-(7-chlorobenzimidazol-1-yl)acetic acid Chemical compound C1=CC(Cl)=C2N(CC(=O)O)C=NC2=C1 WKHRGYGWUZSFLP-UHFFFAOYSA-N 0.000 description 5
- 241000349731 Afzelia bipindensis Species 0.000 description 5
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- 238000003775 Density Functional Theory Methods 0.000 description 5
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000013058 crude material Substances 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- OYVXVLSZQHSNDK-UHFFFAOYSA-N n-methoxy-n-methylacetamide Chemical compound CON(C)C(C)=O OYVXVLSZQHSNDK-UHFFFAOYSA-N 0.000 description 5
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 239000012064 sodium phosphate buffer Substances 0.000 description 5
- DQKVZWAEWJUKAX-UHFFFAOYSA-N thiane-4-carbonitrile Chemical compound N#CC1CCSCC1 DQKVZWAEWJUKAX-UHFFFAOYSA-N 0.000 description 5
- 241000283724 Bison bonasus Species 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 229950005228 bromoform Drugs 0.000 description 4
- 238000004364 calculation method Methods 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 239000006196 drop Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- PAQVZCDJJABVMB-UHFFFAOYSA-N (4-bromo-2-chlorophenyl)methanol Chemical compound OCC1=CC=C(Br)C=C1Cl PAQVZCDJJABVMB-UHFFFAOYSA-N 0.000 description 3
- JIUJDPYXIMYHKM-UHFFFAOYSA-N 1-(4-acetylphenyl)cyclobutane-1-carbonitrile Chemical compound C1=CC(C(=O)C)=CC=C1C1(C#N)CCC1 JIUJDPYXIMYHKM-UHFFFAOYSA-N 0.000 description 3
- DZWFVACFASLQKS-UHFFFAOYSA-N 1-(4-bromophenyl)cyclobutane-1-carbonitrile Chemical compound C1=CC(Br)=CC=C1C1(C#N)CCC1 DZWFVACFASLQKS-UHFFFAOYSA-N 0.000 description 3
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 3
- MXZBZBHXAMJWMY-UHFFFAOYSA-N 2-(4-bromo-2-chlorophenyl)acetonitrile Chemical compound ClC1=CC(Br)=CC=C1CC#N MXZBZBHXAMJWMY-UHFFFAOYSA-N 0.000 description 3
- QLASQEZPJFNZQC-UHFFFAOYSA-N 2-(4-bromo-2-fluorophenyl)acetonitrile Chemical compound FC1=CC(Br)=CC=C1CC#N QLASQEZPJFNZQC-UHFFFAOYSA-N 0.000 description 3
- DGUMUVFOYZCEAZ-UHFFFAOYSA-N 2-(7-chloro-6-fluorobenzimidazol-1-yl)acetic acid Chemical compound C1=C(F)C(Cl)=C2N(CC(=O)O)C=NC2=C1 DGUMUVFOYZCEAZ-UHFFFAOYSA-N 0.000 description 3
- CESUXLKAADQNTB-ZETCQYMHSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](N)=O CESUXLKAADQNTB-ZETCQYMHSA-N 0.000 description 3
- DYPSDTOQOSPYOT-UHFFFAOYSA-N 4-bromo-1-(bromomethyl)-2-chlorobenzene Chemical compound ClC1=CC(Br)=CC=C1CBr DYPSDTOQOSPYOT-UHFFFAOYSA-N 0.000 description 3
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 101150041968 CDC13 gene Proteins 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
- 206010065390 Inflammatory pain Diseases 0.000 description 3
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- VBWIZSYFQSOUFQ-UHFFFAOYSA-N cyclohexanecarbonitrile Chemical compound N#CC1CCCCC1 VBWIZSYFQSOUFQ-UHFFFAOYSA-N 0.000 description 3
- 239000002274 desiccant Substances 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000004678 hydrides Chemical class 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 238000000324 molecular mechanic Methods 0.000 description 3
- 210000000929 nociceptor Anatomy 0.000 description 3
- 108091008700 nociceptors Proteins 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- CWOKZNRRLJXSAA-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)-2-methylbenzene Chemical compound CC1=CC(CBr)=CC=C1Br CWOKZNRRLJXSAA-UHFFFAOYSA-N 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
- WAHHSJLFAFREMV-UHFFFAOYSA-N 2-(2-chloro-3-fluoro-6-nitroanilino)ethanol Chemical compound OCCNC1=C(Cl)C(F)=CC=C1[N+]([O-])=O WAHHSJLFAFREMV-UHFFFAOYSA-N 0.000 description 2
- OIBRFAUQTMYQLB-UHFFFAOYSA-N 2-(4-bromo-3-methylphenyl)acetonitrile Chemical compound CC1=CC(CC#N)=CC=C1Br OIBRFAUQTMYQLB-UHFFFAOYSA-N 0.000 description 2
- PCPMYBCGWOKLRK-UHFFFAOYSA-N 2-(6-chloro-7-fluorobenzimidazol-1-yl)acetic acid Chemical compound C1=C(Cl)C(F)=C2N(CC(=O)O)C=NC2=C1 PCPMYBCGWOKLRK-UHFFFAOYSA-N 0.000 description 2
- LVVHTRTZAYLIMQ-UHFFFAOYSA-N 2-(7-acetylbenzimidazol-1-yl)acetic acid Chemical compound CC(=O)C1=CC=CC2=C1N(CC(O)=O)C=N2 LVVHTRTZAYLIMQ-UHFFFAOYSA-N 0.000 description 2
- QOTWWGPYJMHWTB-UHFFFAOYSA-N 2-(7-fluorobenzimidazol-1-yl)acetic acid Chemical compound C1=CC(F)=C2N(CC(=O)O)C=NC2=C1 QOTWWGPYJMHWTB-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- CTVBVNKEMCGZDF-UHFFFAOYSA-N 2-chloro-1,3-difluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(Cl)=C1F CTVBVNKEMCGZDF-UHFFFAOYSA-N 0.000 description 2
- PMUNIMVZCACZBB-UHFFFAOYSA-N 2-hydroxyethylazanium;chloride Chemical compound Cl.NCCO PMUNIMVZCACZBB-UHFFFAOYSA-N 0.000 description 2
- LYDZBCFIIYATHV-UHFFFAOYSA-N 3-(2-hydroxyethyl)benzimidazole-4-carbonitrile Chemical compound C1=CC(C#N)=C2N(CCO)C=NC2=C1 LYDZBCFIIYATHV-UHFFFAOYSA-N 0.000 description 2
- QRMTTYZXARWZOY-UHFFFAOYSA-N 4-(1-cyanocyclobutyl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1(C#N)CCC1 QRMTTYZXARWZOY-UHFFFAOYSA-N 0.000 description 2
- SYUPLHKPEJZFPN-UHFFFAOYSA-N 4-(1-cyanocyclohexyl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1(C#N)CCCCC1 SYUPLHKPEJZFPN-UHFFFAOYSA-N 0.000 description 2
- QIMXISBDADQDFU-UHFFFAOYSA-N 4-(1-cyanocyclopropyl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1(C#N)CC1 QIMXISBDADQDFU-UHFFFAOYSA-N 0.000 description 2
- OPBCREVVWZUMLN-UHFFFAOYSA-N 4-(3-cyanopentan-3-yl)benzonitrile Chemical compound CCC(CC)(C#N)C1=CC=C(C#N)C=C1 OPBCREVVWZUMLN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 208000005615 Interstitial Cystitis Diseases 0.000 description 2
- 239000003810 Jones reagent Substances 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
- 206010029350 Neurotoxicity Diseases 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 102000003566 TRPV1 Human genes 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 206010044221 Toxic encephalopathy Diseases 0.000 description 2
- 101150016206 Trpv1 gene Proteins 0.000 description 2
- 206010046543 Urinary incontinence Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 239000012455 biphasic mixture Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- GFBLFDSCAKHHGX-UHFFFAOYSA-N cyclobutanecarbonitrile Chemical compound N#CC1CCC1 GFBLFDSCAKHHGX-UHFFFAOYSA-N 0.000 description 2
- AUQDITHEDVOTCU-UHFFFAOYSA-N cyclopropyl cyanide Chemical compound N#CC1CC1 AUQDITHEDVOTCU-UHFFFAOYSA-N 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 230000007135 neurotoxicity Effects 0.000 description 2
- 231100000228 neurotoxicity Toxicity 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000008058 pain sensation Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 235000019633 pungent taste Nutrition 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000004576 sand Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 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 2
- 238000012360 testing method Methods 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 2
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 2
- AGJAUFUNZWHLKE-UHFFFAOYSA-N (2E,4E)-N-isobutyl-2,4-tetradecadienamide Natural products CCCCCCCCCC=CC=CC(=O)NCC(C)C AGJAUFUNZWHLKE-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical class O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- IFKWLKCPUIQXPU-UHFFFAOYSA-N (4-bromo-2-methylphenyl)methanol Chemical compound CC1=CC(Br)=CC=C1CO IFKWLKCPUIQXPU-UHFFFAOYSA-N 0.000 description 1
- HBSHHYYUASJVCG-UHFFFAOYSA-N (4-bromo-3-methylphenyl)methanol Chemical compound CC1=CC(CO)=CC=C1Br HBSHHYYUASJVCG-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- ARCACZWMYGILNI-UHFFFAOYSA-N 1,2,3-trifluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(F)=C1F ARCACZWMYGILNI-UHFFFAOYSA-N 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- AVGHIQUXSVAJBC-UHFFFAOYSA-N 1,2-diazabicyclo[2.2.1]heptane Chemical compound C1C2CCN1NC2 AVGHIQUXSVAJBC-UHFFFAOYSA-N 0.000 description 1
- IXIJRPBFPLESEI-UHFFFAOYSA-N 1,2-difluoro-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(F)=C1F IXIJRPBFPLESEI-UHFFFAOYSA-N 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- CZLMRJZAHXYRIX-UHFFFAOYSA-N 1,3-dioxepane Chemical compound C1CCOCOC1 CZLMRJZAHXYRIX-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- IAYSDKUKIIYRRA-UHFFFAOYSA-N 1-(isocyanatomethylsulfonyl)-4-methylbenzene Chemical compound CC1=CC=C(S(=O)(=O)CN=C=O)C=C1 IAYSDKUKIIYRRA-UHFFFAOYSA-N 0.000 description 1
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 description 1
- ZFSLZDZLRHXNKE-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)-2-methylbenzene (4-bromo-3-methylphenyl)methanol Chemical compound BrC1=C(C=C(C=C1)CO)C.BrC1=C(C=C(C=C1)CBr)C ZFSLZDZLRHXNKE-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- YHCUZRJTNSWYCY-UHFFFAOYSA-N 2,3,4,7-tetrahydro-1h-azepine Chemical compound C1CNCC=CC1 YHCUZRJTNSWYCY-UHFFFAOYSA-N 0.000 description 1
- OZIJESHLNXSUNE-UHFFFAOYSA-N 2,3-dihydrofuran;thiolane 1,1-dioxide Chemical compound C1CC=CO1.O=S1(=O)CCCC1 OZIJESHLNXSUNE-UHFFFAOYSA-N 0.000 description 1
- GSUPYHWEFVSXBA-UHFFFAOYSA-N 2,5-dihydrofuran;oxolane Chemical compound C1CCOC1.C1OCC=C1 GSUPYHWEFVSXBA-UHFFFAOYSA-N 0.000 description 1
- WCCDTLCLGOIWAR-UHFFFAOYSA-N 2-(2-amino-6-chloroanilino)ethanol Chemical compound NC1=CC=CC(Cl)=C1NCCO WCCDTLCLGOIWAR-UHFFFAOYSA-N 0.000 description 1
- KHCVOCRTIRGKJP-UHFFFAOYSA-N 2-(2-chloro-6-nitroanilino)ethanol N-(2,3-dichlorophenyl)nitramide Chemical compound ClC1=C(N[N+](=O)[O-])C=CC=C1Cl.ClC1=C(C(=CC=C1)[N+](=O)[O-])NCCO KHCVOCRTIRGKJP-UHFFFAOYSA-N 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- QLEHYIIVXAQKSS-UHFFFAOYSA-N 2-(4-acetyl-3-methylphenyl)-2-methylpropanenitrile Chemical compound CC(=O)C1=CC=C(C(C)(C)C#N)C=C1C QLEHYIIVXAQKSS-UHFFFAOYSA-N 0.000 description 1
- JVPNKXZIJKBMDH-UHFFFAOYSA-N 2-(4-bromo-2-methylphenyl)acetonitrile Chemical compound CC1=CC(Br)=CC=C1CC#N JVPNKXZIJKBMDH-UHFFFAOYSA-N 0.000 description 1
- MFHFWRBXPQDZSA-UHFFFAOYSA-N 2-(4-bromophenyl)acetonitrile Chemical compound BrC1=CC=C(CC#N)C=C1 MFHFWRBXPQDZSA-UHFFFAOYSA-N 0.000 description 1
- MXZKEULCPQUUFK-UHFFFAOYSA-N 2-(6,7-difluorobenzimidazol-1-yl)ethanol Chemical compound C1=C(F)C(F)=C2N(CCO)C=NC2=C1 MXZKEULCPQUUFK-UHFFFAOYSA-N 0.000 description 1
- FUCXOIWSEFJHCP-UHFFFAOYSA-N 2-(6-amino-2,3-difluoroanilino)ethanol Chemical compound NC1=CC=C(F)C(F)=C1NCCO FUCXOIWSEFJHCP-UHFFFAOYSA-N 0.000 description 1
- DBFUZSITYSEOJG-UHFFFAOYSA-N 2-(6-amino-2-chloro-3-fluoroanilino)ethanol Chemical compound NC1=CC=C(F)C(Cl)=C1NCCO DBFUZSITYSEOJG-UHFFFAOYSA-N 0.000 description 1
- HAAWVWZJMFGZOU-UHFFFAOYSA-N 2-(6-chloro-7-fluorobenzimidazol-1-yl)ethanol Chemical compound C1=C(Cl)C(F)=C2N(CCO)C=NC2=C1 HAAWVWZJMFGZOU-UHFFFAOYSA-N 0.000 description 1
- CZGIGHYDEJBFDQ-UHFFFAOYSA-N 2-(7-chloro-6-fluorobenzimidazol-1-yl)ethanol Chemical compound C1=C(F)C(Cl)=C2N(CCO)C=NC2=C1 CZGIGHYDEJBFDQ-UHFFFAOYSA-N 0.000 description 1
- SBPHCNNHDIQASA-UHFFFAOYSA-N 2-(7-chlorobenzimidazol-1-yl)ethanol Chemical compound C1=CC(Cl)=C2N(CCO)C=NC2=C1 SBPHCNNHDIQASA-UHFFFAOYSA-N 0.000 description 1
- KUUUIUJSKYPFJX-UHFFFAOYSA-N 2-(7-fluorobenzimidazol-1-yl)ethanol Chemical compound C1=CC(F)=C2N(CCO)C=NC2=C1 KUUUIUJSKYPFJX-UHFFFAOYSA-N 0.000 description 1
- BMJIYFNMIOIMPD-UHFFFAOYSA-N 2-[4-(aminomethyl)-3-methylphenyl]-2-methylpropanenitrile Chemical compound CC1=CC(C(C)(C)C#N)=CC=C1CN BMJIYFNMIOIMPD-UHFFFAOYSA-N 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- VMUXSMXIQBNMGZ-UHFFFAOYSA-N 3,4-dihydrocoumarin Chemical compound C1=CC=C2OC(=O)CCC2=C1 VMUXSMXIQBNMGZ-UHFFFAOYSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- IDESKDBOALJDLH-UHFFFAOYSA-N 3-[4-(2-cyanopropan-2-yl)phenyl]-2-(6,7-difluorobenzimidazol-1-yl)butanamide Chemical compound C(#N)C(C)(C)C1=CC=C(C=C1)C(C)C(C(=O)N)N1C=NC2=C1C(=C(C=C2)F)F IDESKDBOALJDLH-UHFFFAOYSA-N 0.000 description 1
- QYDKSTIFIVWJDP-UHFFFAOYSA-N 3-amino-2-(2-hydroxyethylamino)benzonitrile methanol Chemical compound CO.NC=1C(=C(C#N)C=CC1)NCCO QYDKSTIFIVWJDP-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
- BAKUAUDFCNFLBX-UHFFFAOYSA-N 4,7-dihydro-1,3-dioxepine Chemical compound C1OCC=CCO1 BAKUAUDFCNFLBX-UHFFFAOYSA-N 0.000 description 1
- CGYQBNYSADLBEI-UHFFFAOYSA-N 4-(4-cyano-3-methylphenyl)thiane-4-carbonitrile Chemical compound C1=C(C#N)C(C)=CC(C2(CCSCC2)C#N)=C1 CGYQBNYSADLBEI-UHFFFAOYSA-N 0.000 description 1
- QILKKAFYAFEWGU-UHFFFAOYSA-N 4-(cyanomethyl)benzonitrile Chemical compound N#CCC1=CC=C(C#N)C=C1 QILKKAFYAFEWGU-UHFFFAOYSA-N 0.000 description 1
- RRBOULIORCZELO-UHFFFAOYSA-N 4-bromo-1-(bromomethyl)-2-methylbenzene Chemical compound CC1=CC(Br)=CC=C1CBr RRBOULIORCZELO-UHFFFAOYSA-N 0.000 description 1
- LHBDUAQGNSVGGV-UHFFFAOYSA-N 4-bromo-1-(bromomethyl)-2-methylbenzene (4-bromo-2-methylphenyl)methanol Chemical compound BrC1=CC(=C(C=C1)CO)C.BrC1=CC(=C(C=C1)CBr)C LHBDUAQGNSVGGV-UHFFFAOYSA-N 0.000 description 1
- UNVUTWAGCWSEND-UHFFFAOYSA-N 4-bromo-1-(bromomethyl)-2-methylbenzene 2-(4-bromo-2-methylphenyl)acetonitrile Chemical compound BrC1=CC(=C(C=C1)CBr)C.BrC1=CC(=C(C=C1)CC#N)C UNVUTWAGCWSEND-UHFFFAOYSA-N 0.000 description 1
- JAVZWSOFJKYSDY-UHFFFAOYSA-N 4-bromo-2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1Cl JAVZWSOFJKYSDY-UHFFFAOYSA-N 0.000 description 1
- BJBXUIUJKPOZLV-UHFFFAOYSA-N 4-fluoro-2-methylbenzonitrile Chemical compound CC1=CC(F)=CC=C1C#N BJBXUIUJKPOZLV-UHFFFAOYSA-N 0.000 description 1
- YPWFNLSXQIGJCK-UHFFFAOYSA-N 7-oxabicyclo[2.2.1]heptane Chemical compound C1CC2CCC1O2 YPWFNLSXQIGJCK-UHFFFAOYSA-N 0.000 description 1
- PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical compound C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- QOXLQVXWVZHPBG-UHFFFAOYSA-N BrC1=C(C=C(C(=O)OC)C=C1)C.BrC1=C(C=C(C=C1)CO)C Chemical compound BrC1=C(C=C(C(=O)OC)C=C1)C.BrC1=C(C=C(C=C1)CO)C QOXLQVXWVZHPBG-UHFFFAOYSA-N 0.000 description 1
- RPXDPWMYLCAYSD-UHFFFAOYSA-N BrC1=CC(=C(C(=O)O)C=C1)C.BrC1=CC(=C(C=C1)CO)C Chemical compound BrC1=CC(=C(C(=O)O)C=C1)C.BrC1=CC(=C(C=C1)CO)C RPXDPWMYLCAYSD-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- PQJQIWKHNCUEMH-UHFFFAOYSA-N CC(C#N)(C)C1=CC=C(C=C1)C.C(#N)C(C)(C)C1=CC=C(C#N)C=C1 Chemical compound CC(C#N)(C)C1=CC=C(C=C1)C.C(#N)C(C)(C)C1=CC=C(C#N)C=C1 PQJQIWKHNCUEMH-UHFFFAOYSA-N 0.000 description 1
- 235000002568 Capsicum frutescens Nutrition 0.000 description 1
- 240000008574 Capsicum frutescens Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- CLYOIXCDXCLJOU-UHFFFAOYSA-N ClC1=C(C#N)C=CC=C1[N+](=O)[O-].OCCNC1=C(C#N)C=CC=C1[N+](=O)[O-] Chemical compound ClC1=C(C#N)C=CC=C1[N+](=O)[O-].OCCNC1=C(C#N)C=CC=C1[N+](=O)[O-] CLYOIXCDXCLJOU-UHFFFAOYSA-N 0.000 description 1
- OISXGWXRLGGZSY-UHFFFAOYSA-N ClC1=C(C(=C(C=C1)[N+](=O)[O-])Cl)F.C(=O)OCC Chemical compound ClC1=C(C(=C(C=C1)[N+](=O)[O-])Cl)F.C(=O)OCC OISXGWXRLGGZSY-UHFFFAOYSA-N 0.000 description 1
- MPRJQXJHKCWBIK-UHFFFAOYSA-N ClC1=C(C(=O)N)C=CC=C1[N+](=O)[O-].ClC1=C(C#N)C=CC=C1[N+](=O)[O-] Chemical compound ClC1=C(C(=O)N)C=CC=C1[N+](=O)[O-].ClC1=C(C#N)C=CC=C1[N+](=O)[O-] MPRJQXJHKCWBIK-UHFFFAOYSA-N 0.000 description 1
- NEJSBYHWPPFNBX-UHFFFAOYSA-N ClC1=C(C(=O)O)C=CC=C1[N+](=O)[O-].ClC1=C(C(=O)N)C=CC=C1[N+](=O)[O-] Chemical compound ClC1=C(C(=O)O)C=CC=C1[N+](=O)[O-].ClC1=C(C(=O)N)C=CC=C1[N+](=O)[O-] NEJSBYHWPPFNBX-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- 238000004057 DFT-B3LYP calculation Methods 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- XIQVNETUBQGFHX-UHFFFAOYSA-N Ditropan Chemical compound C=1C=CC=CC=1C(O)(C(=O)OCC#CCN(CC)CC)C1CCCCC1 XIQVNETUBQGFHX-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 241000982822 Ficus obtusifolia Species 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 101000633069 Homo sapiens Transient receptor potential cation channel subfamily V member 1 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- QPCVHQBVMYCJOM-UHFFFAOYSA-N Propiverine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OCCC)C(=O)OC1CCN(C)CC1 QPCVHQBVMYCJOM-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
- 108010025083 TRPV1 receptor Proteins 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 108010084455 Zeocin Proteins 0.000 description 1
- FYJKEHKQUPSJDH-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;potassium Chemical compound [K].C[Si](C)(C)N[Si](C)(C)C FYJKEHKQUPSJDH-UHFFFAOYSA-N 0.000 description 1
- QOMNQGZXFYNBNG-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-difluoro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(F)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(F)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O QOMNQGZXFYNBNG-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 229910001632 barium fluoride Inorganic materials 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- JFIOVJDNOJYLKP-UHFFFAOYSA-N bithionol Chemical compound OC1=C(Cl)C=C(Cl)C=C1SC1=CC(Cl)=CC(Cl)=C1O JFIOVJDNOJYLKP-UHFFFAOYSA-N 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960002677 darifenacin Drugs 0.000 description 1
- HXGBXQDTNZMWGS-RUZDIDTESA-N darifenacin Chemical compound C=1C=CC=CC=1C([C@H]1CN(CCC=2C=C3CCOC3=CC=2)CC1)(C(=O)N)C1=CC=CC=C1 HXGBXQDTNZMWGS-RUZDIDTESA-N 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- RNOJZAYWQCKGRK-UHFFFAOYSA-N diazene hydrochloride Chemical compound Cl.N=N RNOJZAYWQCKGRK-UHFFFAOYSA-N 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- DMSHWWDRAYHEBS-UHFFFAOYSA-N dihydrocoumarin Natural products C1CC(=O)OC2=C1C=C(OC)C(OC)=C2 DMSHWWDRAYHEBS-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 229960004945 etoricoxib Drugs 0.000 description 1
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000012909 foetal bovine serum Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 102000045756 human TRPV1 Human genes 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002197 infrared dichroism spectroscopy Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000004658 ketimines Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940060977 lidoderm Drugs 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229960002373 loxoprofen Drugs 0.000 description 1
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 229960000994 lumiracoxib Drugs 0.000 description 1
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- FGNGTWFJQFTFGN-UHFFFAOYSA-N n,n,n',n'-tetramethylethane-1,2-diamine Chemical compound CN(C)CCN(C)C.CN(C)CCN(C)C FGNGTWFJQFTFGN-UHFFFAOYSA-N 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- WHWRXFLOPJUZDK-UHFFFAOYSA-N n-methoxy-n-methylformamide Chemical compound CON(C)C=O WHWRXFLOPJUZDK-UHFFFAOYSA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- UHHKSVZZTYJVEG-UHFFFAOYSA-N oxepane Chemical compound C1CCCOCC1 UHHKSVZZTYJVEG-UHFFFAOYSA-N 0.000 description 1
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229960005434 oxybutynin Drugs 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 238000000711 polarimetry Methods 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920001992 poloxamer 407 Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 125000004585 polycyclic heterocycle group Chemical group 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229960003510 propiverine Drugs 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- LJPZHJUSICYOIX-UHFFFAOYSA-N quinolizidine Chemical compound C1CCCC2CCCCN21 LJPZHJUSICYOIX-UHFFFAOYSA-N 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
- 229950003023 robalzotan Drugs 0.000 description 1
- MQTUXRKNJYPMCG-CYBMUJFWSA-N robalzotan Chemical compound C1CCC1N([C@H]1COC=2C(F)=CC=C(C=2C1)C(=O)N)C1CCC1 MQTUXRKNJYPMCG-CYBMUJFWSA-N 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 229960003855 solifenacin Drugs 0.000 description 1
- FBOUYBDGKBSUES-VXKWHMMOSA-N solifenacin Chemical compound C1([C@H]2C3=CC=CC=C3CCN2C(O[C@@H]2C3CCN(CC3)C2)=O)=CC=CC=C1 FBOUYBDGKBSUES-VXKWHMMOSA-N 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000003491 tear gas Substances 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- OVRJVKCZJCNSOW-UHFFFAOYSA-N thian-4-one Chemical compound O=C1CCSCC1 OVRJVKCZJCNSOW-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
- VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 229960004045 tolterodine Drugs 0.000 description 1
- OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 229920000685 trimethylsilyl polyphosphate Polymers 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- BDIAUFOIMFAIPU-UHFFFAOYSA-N valepotriate Natural products CC(C)CC(=O)OC1C=C(C(=COC2OC(=O)CC(C)C)COC(C)=O)C2C11CO1 BDIAUFOIMFAIPU-UHFFFAOYSA-N 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000003868 zero point energy Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83724906P | 2006-08-11 | 2006-08-11 | |
| US60/837,249 | 2006-08-11 | ||
| PCT/SE2007/000720 WO2008018827A1 (en) | 2006-08-11 | 2007-08-10 | Benzimidazole derivatives useful in treatment of vallinoid receptor trpv1 related disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2660529A1 CA2660529A1 (en) | 2008-02-14 |
| CA2660529C true CA2660529C (en) | 2014-10-21 |
Family
ID=39033277
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2660529A Active CA2660529C (en) | 2006-08-11 | 2007-08-10 | Benzimidazole derivatives useful in treatment of vallinoid receptor trpv1 related disorders |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US7906654B2 (enExample) |
| EP (1) | EP2051967B1 (enExample) |
| JP (1) | JP5140077B2 (enExample) |
| KR (1) | KR101412881B1 (enExample) |
| CN (2) | CN101522637A (enExample) |
| AR (1) | AR062299A1 (enExample) |
| AU (1) | AU2007282186B2 (enExample) |
| BR (1) | BRPI0715746B8 (enExample) |
| CA (1) | CA2660529C (enExample) |
| CL (1) | CL2007002343A1 (enExample) |
| CO (1) | CO6150176A2 (enExample) |
| ES (1) | ES2533971T3 (enExample) |
| IL (1) | IL196672A0 (enExample) |
| MX (1) | MX2009001496A (enExample) |
| MY (1) | MY147649A (enExample) |
| NO (1) | NO20091054L (enExample) |
| NZ (1) | NZ575416A (enExample) |
| PE (1) | PE20081315A1 (enExample) |
| RU (1) | RU2458055C2 (enExample) |
| SG (1) | SG173360A1 (enExample) |
| TW (1) | TWI433839B (enExample) |
| UA (1) | UA96764C2 (enExample) |
| UY (1) | UY30533A1 (enExample) |
| WO (1) | WO2008018827A1 (enExample) |
| ZA (1) | ZA200900961B (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0301446D0 (sv) | 2003-05-16 | 2003-05-16 | Astrazeneca Ab | New Compounds |
| UY30048A1 (es) | 2005-12-23 | 2007-07-31 | Astrazeneca Ab | Derivados sustituidos de la n,2-(1h-benzimidazol-1-il) acetamida, composiciones farmacéuticas conteniéndolos, procesos de preparación y aplicaciones |
| TWI433839B (zh) * | 2006-08-11 | 2014-04-11 | Neomed Inst | 新穎的苯并咪唑衍生物290 |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| NZ587771A (en) | 2008-04-18 | 2011-05-27 | Dae Woong Pharma | Novel benzoxazine benzimidazole derivatives, pharmaceutical composition comprising same, and a use thereof |
| KR101293384B1 (ko) | 2010-10-13 | 2013-08-05 | 주식회사 대웅제약 | 신규 피리딜 벤조옥사진 유도체, 이를 포함하는 약학 조성물 및 이의 용도 |
| US8716226B2 (en) | 2012-07-18 | 2014-05-06 | Saint Louis University | 3,5 phenyl-substituted beta amino acid derivatives as integrin antagonists |
| CA2878469A1 (en) | 2012-07-18 | 2014-01-23 | Saint Louis University | Beta amino acid derivatives as integrin antagonists |
| JO3719B1 (ar) | 2014-11-20 | 2021-01-31 | Takeda Pharmaceuticals Co | 4- أوكسو-4،3- داي هيدرو-3،2،1- بنزوترايازينات كمواد ضابطة لأجل gpr139 |
| JP6853778B2 (ja) | 2014-12-08 | 2021-03-31 | ローム アンド ハース カンパニーＲｏｈｍ Ａｎｄ Ｈａａｓ Ｃｏｍｐａｎｙ | ポリオレフィン添加剤、耐垂下性ポリオレフィン、及びその調製方法 |
| JP2018052817A (ja) * | 2015-01-21 | 2018-04-05 | 大日本住友製薬株式会社 | 新規ベンズイミダゾール誘導体およびその医薬用途 |
| CN108779077A (zh) | 2015-12-30 | 2018-11-09 | 圣路易斯大学 | 作为pan整合素拮抗剂的间位氮杂环氨基苯甲酸衍生物 |
| KR20210148081A (ko) * | 2019-01-08 | 2021-12-07 | 네오메드 인스티튜트 | (s)-2-(7-시아노-1h-벤즈이미다졸-1 일)-n-(1-(4-(1-시아노-1-메틸에틸)페닐)에틸)아세트아미드의 결정 형태 |
| WO2021055326A1 (en) | 2019-09-16 | 2021-03-25 | Takeda Pharmaceutical Company Limited | Azole-fused pyridazin-3(2h)-one derivatives |
| RU2755206C1 (ru) | 2020-05-20 | 2021-09-14 | Федеральное государственное бюджетное учреждение науки Тихоокеанский институт биоорганической химии им. Г.Б. Елякова Дальневосточного отделения Российской академии наук (ТИБОХ ДВО РАН) | Средство пролонгированного анальгетического действия и лекарственный препарат на его основе |
| CN117623972A (zh) * | 2022-08-17 | 2024-03-01 | 上海慧聚药业有限公司 | 非离子型造影剂中间体的合成 |
Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1186504A (en) | 1966-10-15 | 1970-04-02 | Fisons Pest Control Ltd | Substituted Heterocyclic Compounds |
| IT1036004B (it) * | 1968-05-21 | 1979-10-30 | Abc Ist Biolog Chem Spa | Acidt 3 indolil adetoidrossamici |
| BE793718A (fr) * | 1972-01-07 | 1973-07-05 | Merck & Co Inc | Aminobenzimidazoles |
| DE3347290A1 (de) * | 1983-12-28 | 1985-07-11 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue 2-phenyl-imidazole, ihre herstellung und diese verbindungen enthaltende arzneimittel |
| US4738981A (en) * | 1984-11-13 | 1988-04-19 | Warner-Lambert | Substituted trans-1,2-diaminocyclohexyl amide compounds |
| JP2639000B2 (ja) | 1988-09-30 | 1997-08-06 | スズキ株式会社 | 酸素富化エンジンの酸素富化空気制御装置 |
| JPH0295767A (ja) | 1988-09-30 | 1990-04-06 | Showa Alum Corp | 吸気マニホルド |
| JPH06759B2 (ja) | 1989-09-22 | 1994-01-05 | ファイザー製薬株式会社 | 新規なベンゾイミダゾール化合物 |
| DE4309969A1 (de) | 1993-03-26 | 1994-09-29 | Bayer Ag | Substituierte heteroanellierte Imidazole |
| US5403851A (en) | 1994-04-05 | 1995-04-04 | Interneuron Pharmaceuticals, Inc. | Substituted tryptamines, phenalkylamines and related compounds |
| EA002357B1 (ru) | 1995-12-28 | 2002-04-25 | Фудзисава Фармасьютикал Ко., Лтд. | Производные бензимидазола |
| GB9713484D0 (en) | 1997-06-27 | 1997-09-03 | Smithkline Beecham Plc | Neuroprotective vanilloid compounds |
| JP2000095767A (ja) | 1998-09-28 | 2000-04-04 | Takeda Chem Ind Ltd | 性腺刺激ホルモン放出ホルモン拮抗剤 |
| AP2002002442A0 (en) | 1999-08-12 | 2002-03-31 | Pharmacia Italia Spa | 3(5)-Amino-pyrazole derivatives, process for their preparation and their preparation and their use as antitumor agents. |
| US6534651B2 (en) * | 2000-04-06 | 2003-03-18 | Inotek Pharmaceuticals Corp. | 7-Substituted isoindolinone inhibitors of inflammation and reperfusion injury and methods of use thereof |
| EP1278744A1 (en) | 2000-05-05 | 2003-01-29 | Millenium Pharmaceuticals, Inc. | Heterobicyclic sulfonamides and their use as platelet adp receptor inhibitors |
| MXPA02010763A (es) | 2000-06-14 | 2003-03-10 | Warner Lambert Co | Heterociclicos biciclos-6,5 fusionados. |
| US6448281B1 (en) * | 2000-07-06 | 2002-09-10 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| EP1312601A4 (en) | 2000-08-22 | 2005-09-21 | Ono Pharmaceutical Co | CARBOXYLENE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, AND MEDICAMENTS CONTAINING THEM AS AN ACTIVE SUBSTANCE |
| GB0031315D0 (en) * | 2000-12-21 | 2001-02-07 | Glaxo Group Ltd | Indole derivatives |
| ITTO20010110A1 (it) | 2001-02-08 | 2002-08-08 | Rotta Research Lab | Nuovi derivati benzamidinici dotati di attivita' anti-infiammatoria ed immunosoppressiva. |
| GB0105895D0 (en) | 2001-03-09 | 2001-04-25 | Smithkline Beecham Plc | Novel compounds |
| SE0101387D0 (sv) | 2001-04-20 | 2001-04-20 | Astrazeneca Ab | Novel compounds |
| GB0110901D0 (en) | 2001-05-02 | 2001-06-27 | Smithkline Beecham Plc | Novel Compounds |
| TWI239942B (en) * | 2001-06-11 | 2005-09-21 | Dainippon Pharmaceutical Co | N-arylphenylacetamide derivative and pharmaceutical composition containing the same |
| EA008476B1 (ru) | 2001-06-11 | 2007-06-29 | Биовитрум Аб | Замещенные сульфонамиды, способ их получения и их применение в качестве лечебного средства для лечения расстройств цнс, ожирения и диабета типа ii |
| WO2003014064A1 (en) | 2001-07-31 | 2003-02-20 | Bayer Healthcare Ag | Naphthylurea and naphthylacetamide derivatives as vanilloid receptor 1 (vr1) antagonists |
| JP4059473B2 (ja) | 2001-08-09 | 2008-03-12 | 株式会社ルネサステクノロジ | メモリカード及びメモリコントローラ |
| TWI283665B (en) | 2001-09-13 | 2007-07-11 | Smithkline Beecham Plc | Novel urea compound, pharmaceutical composition containing the same and its use |
| TWI231757B (en) | 2001-09-21 | 2005-05-01 | Solvay Pharm Bv | 1H-Imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity |
| US7582657B2 (en) | 2001-12-10 | 2009-09-01 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| GB0130550D0 (en) | 2001-12-20 | 2002-02-06 | Smithkline Beecham Plc | Novel compounds |
| EP2033953A1 (en) | 2002-02-15 | 2009-03-11 | Glaxo Group Limited | Vanilloid receptor modulators |
| US20030158188A1 (en) * | 2002-02-20 | 2003-08-21 | Chih-Hung Lee | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
| EP1513828A1 (en) | 2002-06-20 | 2005-03-16 | Biovitrum AB | New compounds useful for the treatment of obesity, type ii diabetes and cns disorders |
| FR2842069B1 (fr) | 2002-07-12 | 2004-09-10 | Pellenc Sa | Effeuilleuse, plus specialement destinee a l'effeuillage selectif de la vigne |
| GB0221157D0 (en) | 2002-09-12 | 2002-10-23 | Glaxo Group Ltd | Novel treatment |
| AU2003270199A1 (en) | 2002-09-13 | 2004-04-30 | Glaxo Group Limited | Urea compounds active as vanilloid receptor antagonists for the treatment of pain |
| MXPA05003948A (es) * | 2002-10-17 | 2005-06-17 | Amgen Inc | Derivados de bencimidazol y su uso como ligandos de receptor vaniloide. |
| SE0301446D0 (sv) * | 2003-05-16 | 2003-05-16 | Astrazeneca Ab | New Compounds |
| SE0301701D0 (sv) * | 2003-06-10 | 2003-06-10 | Astrazeneca Ab | Benzimidazole derivatives, compositions containing them, preparation thereof and uses thereof |
| BRPI0414105B8 (pt) | 2003-09-03 | 2021-05-25 | Askat Inc | compostos de benzimidazolona com atividade agonista do receptor 5-ht4 |
| JP4775259B2 (ja) * | 2004-03-31 | 2011-09-21 | 味の素株式会社 | アニリン誘導体 |
| SE0402284D0 (sv) * | 2004-09-21 | 2004-09-21 | Astrazeneca Ab | New heterocyclic amides |
| UY30048A1 (es) | 2005-12-23 | 2007-07-31 | Astrazeneca Ab | Derivados sustituidos de la n,2-(1h-benzimidazol-1-il) acetamida, composiciones farmacéuticas conteniéndolos, procesos de preparación y aplicaciones |
| TWI433839B (zh) | 2006-08-11 | 2014-04-11 | Neomed Inst | 新穎的苯并咪唑衍生物290 |
-
2007
- 2007-08-07 TW TW096129068A patent/TWI433839B/zh not_active IP Right Cessation
- 2007-08-09 US US11/836,221 patent/US7906654B2/en active Active
- 2007-08-09 AR ARP070103520A patent/AR062299A1/es not_active Application Discontinuation
- 2007-08-10 NZ NZ575416A patent/NZ575416A/en not_active IP Right Cessation
- 2007-08-10 CA CA2660529A patent/CA2660529C/en active Active
- 2007-08-10 AU AU2007282186A patent/AU2007282186B2/en not_active Ceased
- 2007-08-10 EP EP07794109.4A patent/EP2051967B1/en active Active
- 2007-08-10 SG SG2011049962A patent/SG173360A1/en unknown
- 2007-08-10 UY UY30533A patent/UY30533A1/es not_active Application Discontinuation
- 2007-08-10 CN CNA2007800380988A patent/CN101522637A/zh active Pending
- 2007-08-10 CN CN201010003679A patent/CN101792436A/zh active Pending
- 2007-08-10 MY MYPI20090512A patent/MY147649A/en unknown
- 2007-08-10 UA UAA200900383A patent/UA96764C2/ru unknown
- 2007-08-10 CL CL200702343A patent/CL2007002343A1/es unknown
- 2007-08-10 MX MX2009001496A patent/MX2009001496A/es active IP Right Grant
- 2007-08-10 BR BRPI0715746A patent/BRPI0715746B8/pt not_active IP Right Cessation
- 2007-08-10 ES ES07794109.4T patent/ES2533971T3/es active Active
- 2007-08-10 KR KR1020097002681A patent/KR101412881B1/ko not_active Expired - Fee Related
- 2007-08-10 JP JP2009523746A patent/JP5140077B2/ja not_active Expired - Fee Related
- 2007-08-10 WO PCT/SE2007/000720 patent/WO2008018827A1/en not_active Ceased
- 2007-08-10 PE PE2007001076A patent/PE20081315A1/es not_active Application Discontinuation
- 2007-08-10 RU RU2009103675/04A patent/RU2458055C2/ru active
-
2009
- 2009-01-22 IL IL196672A patent/IL196672A0/en unknown
- 2009-01-29 CO CO09008297A patent/CO6150176A2/es unknown
- 2009-02-10 ZA ZA200900961A patent/ZA200900961B/xx unknown
- 2009-03-09 NO NO20091054A patent/NO20091054L/no not_active Application Discontinuation
-
2011
- 2011-02-08 US US13/023,112 patent/US8093402B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2660529C (en) | Benzimidazole derivatives useful in treatment of vallinoid receptor trpv1 related disorders | |
| CA2525628C (en) | New benzimidazole derivatives | |
| BRPI0709803B1 (pt) | compostos moduladores de benzimidazol de vr1, sais, processo de preparação do mesmo, seu uso e composição farmacêutica que os compreende | |
| WO2008021849A2 (en) | Novel compounds as antagonists or inverse agonists at opioid receptors | |
| CA3035999C (en) | Benzene fused heterocyclic derivatives and pharmaceutical composition comprising the same | |
| AU2005285656A1 (en) | New heterocyclic amides | |
| KR20190126525A (ko) | 신규 소듐채널 저해 화합물, 이의 제조방법, 및 이를 포함하는 소듐채널 관련 질환의 예방 또는 치료용 약학적 조성물 | |
| TW202102469A (zh) | 具有側鏈烷基與烯基延伸的苯基衍生物及包括有其的藥學組合物 | |
| HK1128475A (en) | Benzimidazole derivatives as vanilloid receptor antagonists | |
| HK1085735B (en) | New benzimidazole derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |