JP2008543915A - ２−（フェニルアミノ）ベンズイミダゾール誘導体及び低コンダクタンスカルシウム依存性カリウムチャネルのモジュレーターとしてのそれらの使用 - Google Patents
２−（フェニルアミノ）ベンズイミダゾール誘導体及び低コンダクタンスカルシウム依存性カリウムチャネルのモジュレーターとしてのそれらの使用 Download PDFInfo
- Publication number
- JP2008543915A JP2008543915A JP2008517496A JP2008517496A JP2008543915A JP 2008543915 A JP2008543915 A JP 2008543915A JP 2008517496 A JP2008517496 A JP 2008517496A JP 2008517496 A JP2008517496 A JP 2008517496A JP 2008543915 A JP2008543915 A JP 2008543915A
- Authority
- JP
- Japan
- Prior art keywords
- benzimidazol
- trifluoromethyl
- aniline
- disease
- alkyl
- 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.)
- Abandoned
Links
- 102000005702 Calcium-Activated Potassium Channels Human genes 0.000 title abstract description 4
- 108010045489 Calcium-Activated Potassium Channels Proteins 0.000 title abstract description 4
- OUAAURDVPDKVAK-UHFFFAOYSA-N n-phenyl-1h-benzimidazol-2-amine Chemical class N=1C2=CC=CC=C2NC=1NC1=CC=CC=C1 OUAAURDVPDKVAK-UHFFFAOYSA-N 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 123
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 206010010904 Convulsion Diseases 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 5
- 208000020925 Bipolar disease Diseases 0.000 claims description 4
- 241000282412 Homo Species 0.000 claims description 4
- GVORIUUNVSHUSR-UHFFFAOYSA-N n-[4-chloro-3-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(NC=2NC3=CC=CC=C3N=2)=C1 GVORIUUNVSHUSR-UHFFFAOYSA-N 0.000 claims description 4
- QNRAJGGNCAPFND-UHFFFAOYSA-N 3-(1h-benzimidazol-2-ylamino)benzonitrile Chemical compound N#CC1=CC=CC(NC=2NC3=CC=CC=C3N=2)=C1 QNRAJGGNCAPFND-UHFFFAOYSA-N 0.000 claims description 3
- 206010001497 Agitation Diseases 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 206010068871 Myotonic dystrophy Diseases 0.000 claims description 3
- 230000006735 deficit Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- BNEMVIZLWMJXMF-UHFFFAOYSA-N n-(2,3,4-trifluorophenyl)-1h-benzimidazol-2-amine Chemical compound FC1=C(F)C(F)=CC=C1NC1=NC2=CC=CC=C2N1 BNEMVIZLWMJXMF-UHFFFAOYSA-N 0.000 claims description 3
- CVIMPJVXTIFPDR-UHFFFAOYSA-N n-(2-phenylphenyl)-1h-benzimidazol-2-amine Chemical compound N=1C2=CC=CC=C2NC=1NC1=CC=CC=C1C1=CC=CC=C1 CVIMPJVXTIFPDR-UHFFFAOYSA-N 0.000 claims description 3
- WJMDSPCWFQLKIN-UHFFFAOYSA-N n-(3,4-dichlorophenyl)-1h-benzimidazol-2-amine Chemical compound C1=C(Cl)C(Cl)=CC=C1NC1=NC2=CC=CC=C2N1 WJMDSPCWFQLKIN-UHFFFAOYSA-N 0.000 claims description 3
- FICZTJWYAFBGBP-UHFFFAOYSA-N n-(3,4-dichlorophenyl)-n-methyl-1h-benzimidazol-2-amine Chemical compound N=1C2=CC=CC=C2NC=1N(C)C1=CC=C(Cl)C(Cl)=C1 FICZTJWYAFBGBP-UHFFFAOYSA-N 0.000 claims description 3
- WSZXVQQZOGCKDD-UHFFFAOYSA-N n-(3,4-difluorophenyl)-1h-benzimidazol-2-amine Chemical compound C1=C(F)C(F)=CC=C1NC1=NC2=CC=CC=C2N1 WSZXVQQZOGCKDD-UHFFFAOYSA-N 0.000 claims description 3
- XRWUVKRSWJWCFJ-UHFFFAOYSA-N n-(3,5-dichlorophenyl)-1h-benzimidazol-2-amine Chemical compound ClC1=CC(Cl)=CC(NC=2NC3=CC=CC=C3N=2)=C1 XRWUVKRSWJWCFJ-UHFFFAOYSA-N 0.000 claims description 3
- VDELLUVTWLBIHA-UHFFFAOYSA-N n-(3,5-difluorophenyl)-1h-benzimidazol-2-amine Chemical compound FC1=CC(F)=CC(NC=2NC3=CC=CC=C3N=2)=C1 VDELLUVTWLBIHA-UHFFFAOYSA-N 0.000 claims description 3
- DESWOWLTWCOBOI-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-1h-benzimidazol-2-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC2=CC=CC=C2N1 DESWOWLTWCOBOI-UHFFFAOYSA-N 0.000 claims description 3
- XSAWUTHHNIJKRI-UHFFFAOYSA-N n-(3-chlorophenyl)-1h-benzimidazol-2-amine Chemical compound ClC1=CC=CC(NC=2NC3=CC=CC=C3N=2)=C1 XSAWUTHHNIJKRI-UHFFFAOYSA-N 0.000 claims description 3
- ATZIHMHTBDVWPP-UHFFFAOYSA-N n-(4-chlorophenyl)-1h-benzimidazol-2-amine Chemical compound C1=CC(Cl)=CC=C1NC1=NC2=CC=CC=C2N1 ATZIHMHTBDVWPP-UHFFFAOYSA-N 0.000 claims description 3
- LLXCHOGIKFCMMS-UHFFFAOYSA-N n-(4-fluoro-3-methylphenyl)-1h-benzimidazol-2-amine Chemical compound C1=C(F)C(C)=CC(NC=2NC3=CC=CC=C3N=2)=C1 LLXCHOGIKFCMMS-UHFFFAOYSA-N 0.000 claims description 3
- JCPBVJDSLDBKSJ-UHFFFAOYSA-N n-(4-fluorophenyl)-1h-benzimidazol-2-amine Chemical compound C1=CC(F)=CC=C1NC1=NC2=CC=CC=C2N1 JCPBVJDSLDBKSJ-UHFFFAOYSA-N 0.000 claims description 3
- AWWPEZUTCHDUPP-UHFFFAOYSA-N n-(4-propan-2-ylphenyl)-1h-benzimidazol-2-amine Chemical compound C1=CC(C(C)C)=CC=C1NC1=NC2=CC=CC=C2N1 AWWPEZUTCHDUPP-UHFFFAOYSA-N 0.000 claims description 3
- TWDAYWOIVWKCFV-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound FC(F)(F)C1=CC=C(Cl)C(NC=2NC3=CC=CC=C3N=2)=C1 TWDAYWOIVWKCFV-UHFFFAOYSA-N 0.000 claims description 3
- IWQDFOADKFVOHQ-UHFFFAOYSA-N n-[2-fluoro-3-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound C1=CC=C(C(F)(F)F)C(F)=C1NC1=NC2=CC=CC=C2N1 IWQDFOADKFVOHQ-UHFFFAOYSA-N 0.000 claims description 3
- JTVYHMYOFWSBIR-UHFFFAOYSA-N n-[2-methyl-3-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound C1=CC=C(C(F)(F)F)C(C)=C1NC1=NC2=CC=CC=C2N1 JTVYHMYOFWSBIR-UHFFFAOYSA-N 0.000 claims description 3
- NNINUTMAMXDIMK-UHFFFAOYSA-N n-[2-methyl-5-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound CC1=CC=C(C(F)(F)F)C=C1NC1=NC2=CC=CC=C2N1 NNINUTMAMXDIMK-UHFFFAOYSA-N 0.000 claims description 3
- LPKCYASSIJNCKT-UHFFFAOYSA-N n-[3,5-bis(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(NC=2NC3=CC=CC=C3N=2)=C1 LPKCYASSIJNCKT-UHFFFAOYSA-N 0.000 claims description 3
- OZSXMCLVXAYZLJ-UHFFFAOYSA-N n-[3-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound FC(F)(F)C1=CC=CC(NC=2NC3=CC=CC=C3N=2)=C1 OZSXMCLVXAYZLJ-UHFFFAOYSA-N 0.000 claims description 3
- GEDXUWWRIKYXEH-UHFFFAOYSA-N n-[3-fluoro-5-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound FC(F)(F)C1=CC(F)=CC(NC=2NC3=CC=CC=C3N=2)=C1 GEDXUWWRIKYXEH-UHFFFAOYSA-N 0.000 claims description 3
- OHFXBBPZGSIOAQ-UHFFFAOYSA-N n-[3-methoxy-5-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound FC(F)(F)C1=CC(OC)=CC(NC=2NC3=CC=CC=C3N=2)=C1 OHFXBBPZGSIOAQ-UHFFFAOYSA-N 0.000 claims description 3
- PSCVLYRDOWNMOM-UHFFFAOYSA-N n-[4-(trifluoromethoxy)phenyl]-1h-benzimidazol-2-amine Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC1=NC2=CC=CC=C2N1 PSCVLYRDOWNMOM-UHFFFAOYSA-N 0.000 claims description 3
- FKOYGKNNSVQCPM-UHFFFAOYSA-N n-[4-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC2=CC=CC=C2N1 FKOYGKNNSVQCPM-UHFFFAOYSA-N 0.000 claims description 3
- JIUDYVPMTLQYPA-UHFFFAOYSA-N n-[4-bromo-3-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound C1=C(Br)C(C(F)(F)F)=CC(NC=2NC3=CC=CC=C3N=2)=C1 JIUDYVPMTLQYPA-UHFFFAOYSA-N 0.000 claims description 3
- SVBRYJZTSPUETP-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound C1=C(C(F)(F)F)C(F)=CC=C1NC1=NC2=CC=CC=C2N1 SVBRYJZTSPUETP-UHFFFAOYSA-N 0.000 claims description 3
- HORZXLXFCUFEOK-UHFFFAOYSA-N n-[4-methyl-3-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine Chemical compound C1=C(C(F)(F)F)C(C)=CC=C1NC1=NC2=CC=CC=C2N1 HORZXLXFCUFEOK-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 201000004384 Alopecia Diseases 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 206010003225 Arteriospasm coronary Diseases 0.000 claims description 2
- 206010003591 Ataxia Diseases 0.000 claims description 2
- 206010048994 Bladder spasm Diseases 0.000 claims description 2
- 201000004569 Blindness Diseases 0.000 claims description 2
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010010774 Constipation Diseases 0.000 claims description 2
- 208000003890 Coronary Vasospasm Diseases 0.000 claims description 2
- 206010011878 Deafness Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 2
- 206010012735 Diarrhoea Diseases 0.000 claims description 2
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 2
- 206010013935 Dysmenorrhoea Diseases 0.000 claims description 2
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 206010062016 Immunosuppression Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 206010065390 Inflammatory pain Diseases 0.000 claims description 2
- 206010022562 Intermittent claudication Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000019022 Mood disease Diseases 0.000 claims description 2
- 208000026072 Motor neurone disease Diseases 0.000 claims description 2
- 208000008238 Muscle Spasticity Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 206010061876 Obstruction Diseases 0.000 claims description 2
- 208000002193 Pain Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 206010054048 Postoperative ileus Diseases 0.000 claims description 2
- 208000005107 Premature Birth Diseases 0.000 claims description 2
- 206010036590 Premature baby Diseases 0.000 claims description 2
- 208000028017 Psychotic disease Diseases 0.000 claims description 2
- 208000003782 Raynaud disease Diseases 0.000 claims description 2
- 208000012322 Raynaud phenomenon Diseases 0.000 claims description 2
- 208000036071 Rhinorrhea Diseases 0.000 claims description 2
- 206010039101 Rhinorrhoea Diseases 0.000 claims description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 2
- 206010046543 Urinary incontinence Diseases 0.000 claims description 2
- 206010047163 Vasospasm Diseases 0.000 claims description 2
- 208000028311 absence seizure Diseases 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 230000006793 arrhythmia Effects 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 208000028683 bipolar I disease Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- 206010009887 colitis Diseases 0.000 claims description 2
- 230000036461 convulsion Effects 0.000 claims description 2
- 208000029078 coronary artery disease Diseases 0.000 claims description 2
- 201000011634 coronary artery vasospasm Diseases 0.000 claims description 2
- 230000006866 deterioration Effects 0.000 claims description 2
- 206010013781 dry mouth Diseases 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 2
- 230000007160 gastrointestinal dysfunction Effects 0.000 claims description 2
- 230000003676 hair loss Effects 0.000 claims description 2
- 230000010370 hearing loss Effects 0.000 claims description 2
- 231100000888 hearing loss Toxicity 0.000 claims description 2
- 208000016354 hearing loss disease Diseases 0.000 claims description 2
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 2
- 201000008980 hyperinsulinism Diseases 0.000 claims description 2
- 230000001506 immunosuppresive effect Effects 0.000 claims description 2
- 201000001881 impotence Diseases 0.000 claims description 2
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 206010027175 memory impairment Diseases 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 208000005264 motor neuron disease Diseases 0.000 claims description 2
- 208000031225 myocardial ischemia Diseases 0.000 claims description 2
- 201000003631 narcolepsy Diseases 0.000 claims description 2
- 208000004296 neuralgia Diseases 0.000 claims description 2
- 208000021722 neuropathic pain Diseases 0.000 claims description 2
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 2
- 208000020016 psychiatric disease Diseases 0.000 claims description 2
- 230000008085 renal dysfunction Effects 0.000 claims description 2
- 201000009881 secretory diarrhea Diseases 0.000 claims description 2
- 201000002859 sleep apnea Diseases 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 208000018198 spasticity Diseases 0.000 claims description 2
- 230000009529 traumatic brain injury Effects 0.000 claims description 2
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 9
- 238000004519 manufacturing process Methods 0.000 claims 2
- 201000003883 Cystic fibrosis Diseases 0.000 claims 1
- 208000005946 Xerostomia Diseases 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 claims 1
- 210000003205 muscle Anatomy 0.000 claims 1
- 208000020685 sleep-wake disease Diseases 0.000 claims 1
- 108091006146 Channels Proteins 0.000 abstract description 36
- 238000002360 preparation method Methods 0.000 abstract description 4
- AYPSHJCKSDNETA-UHFFFAOYSA-N 2-chloro-1h-benzimidazole Chemical compound C1=CC=C2NC(Cl)=NC2=C1 AYPSHJCKSDNETA-UHFFFAOYSA-N 0.000 description 29
- 239000000047 product Substances 0.000 description 29
- 125000005843 halogen group Chemical group 0.000 description 28
- 239000007787 solid Substances 0.000 description 27
- 238000001914 filtration Methods 0.000 description 24
- 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 18
- 239000011575 calcium Substances 0.000 description 13
- 125000001153 fluoro group Chemical group F* 0.000 description 13
- 239000012458 free base Substances 0.000 description 11
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 125000001309 chloro group Chemical group Cl* 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 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 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
- 239000008186 active pharmaceutical agent Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- -1 calcium-activated potassium Chemical class 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- CXUCKELNYMZTRT-UHFFFAOYSA-N 1-Ethyl-2-benzimidazolinone Chemical compound C1=CC=C2NC(=O)N(CC)C2=C1 CXUCKELNYMZTRT-UHFFFAOYSA-N 0.000 description 2
- 101710126338 Apamin Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 230000002102 hyperpolarization Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- YVIIHEKJCKCXOB-STYWVVQQSA-N molport-023-276-178 Chemical compound C([C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CSSC[C@H]2C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(N[C@@H](CSSC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N2)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)=O)CC(C)C)[C@@H](C)O)C(N)=O)C1=CNC=N1 YVIIHEKJCKCXOB-STYWVVQQSA-N 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- BWXCECYGGMGBHD-GRTNUQQKSA-M (6r)-6-[(5s)-6,6-dimethyl-7,8-dihydro-5h-[1,3]dioxolo[4,5-g]isoquinolin-6-ium-5-yl]-6h-furo[3,4-g][1,3]benzodioxol-8-one;bromide Chemical compound [Br-].O([C@H]1[C@@H]2C3=CC=4OCOC=4C=C3CC[N+]2(C)C)C(=O)C2=C1C=CC1=C2OCO1 BWXCECYGGMGBHD-GRTNUQQKSA-M 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical class C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- WRDGNXCXTDDYBZ-UHFFFAOYSA-N 2,3,4-trifluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1F WRDGNXCXTDDYBZ-UHFFFAOYSA-N 0.000 description 1
- VKTTYIXIDXWHKW-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)aniline Chemical compound NC1=CC(C(F)(F)F)=CC=C1Cl VKTTYIXIDXWHKW-UHFFFAOYSA-N 0.000 description 1
- YKPDYPPZLUZONK-UHFFFAOYSA-N 2-fluoro-3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1F YKPDYPPZLUZONK-UHFFFAOYSA-N 0.000 description 1
- TWLDBACVSHADLI-UHFFFAOYSA-N 2-methyl-3-(trifluoromethyl)aniline Chemical compound CC1=C(N)C=CC=C1C(F)(F)F TWLDBACVSHADLI-UHFFFAOYSA-N 0.000 description 1
- BCLCKENDTZITFB-UHFFFAOYSA-N 2-methyl-5-(trifluoromethyl)aniline Chemical compound CC1=CC=C(C(F)(F)F)C=C1N BCLCKENDTZITFB-UHFFFAOYSA-N 0.000 description 1
- DRMYLINAGHHBNG-UHFFFAOYSA-N 2-oxo-3h-furan-4-carboxylic acid Chemical class OC(=O)C1=COC(=O)C1 DRMYLINAGHHBNG-UHFFFAOYSA-N 0.000 description 1
- TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical group NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 description 1
- DUSNCFKVMGTTFK-UHFFFAOYSA-N 3,4-dichloro-n-methylaniline Chemical compound CNC1=CC=C(Cl)C(Cl)=C1 DUSNCFKVMGTTFK-UHFFFAOYSA-N 0.000 description 1
- SDYWXFYBZPNOFX-UHFFFAOYSA-N 3,4-dichloroaniline Chemical compound NC1=CC=C(Cl)C(Cl)=C1 SDYWXFYBZPNOFX-UHFFFAOYSA-N 0.000 description 1
- AXNUZKSSQHTNPZ-UHFFFAOYSA-N 3,4-difluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1 AXNUZKSSQHTNPZ-UHFFFAOYSA-N 0.000 description 1
- CDIDGWDGQGVCIB-UHFFFAOYSA-N 3,5-bis(trifluoromethyl)aniline Chemical compound NC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CDIDGWDGQGVCIB-UHFFFAOYSA-N 0.000 description 1
- UQRLKWGPEVNVHT-UHFFFAOYSA-N 3,5-dichloroaniline Chemical compound NC1=CC(Cl)=CC(Cl)=C1 UQRLKWGPEVNVHT-UHFFFAOYSA-N 0.000 description 1
- KQOIBXZRCYFZSO-UHFFFAOYSA-N 3,5-difluoroaniline Chemical compound NC1=CC(F)=CC(F)=C1 KQOIBXZRCYFZSO-UHFFFAOYSA-N 0.000 description 1
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 1
- NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 description 1
- YSEMCVGMNUUNRK-UHFFFAOYSA-N 3-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Cl)=C1 YSEMCVGMNUUNRK-UHFFFAOYSA-N 0.000 description 1
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
- WQKQODZOQAFYPR-UHFFFAOYSA-N 3-fluoro-5-(trifluoromethyl)aniline Chemical compound NC1=CC(F)=CC(C(F)(F)F)=C1 WQKQODZOQAFYPR-UHFFFAOYSA-N 0.000 description 1
- VTFGJEYZCUWSAM-UHFFFAOYSA-N 3-methoxy-5-(trifluoromethyl)aniline Chemical compound COC1=CC(N)=CC(C(F)(F)F)=C1 VTFGJEYZCUWSAM-UHFFFAOYSA-N 0.000 description 1
- XUJFOSLZQITUOI-UHFFFAOYSA-N 4-(trifluoromethoxy)aniline Chemical compound NC1=CC=C(OC(F)(F)F)C=C1 XUJFOSLZQITUOI-UHFFFAOYSA-N 0.000 description 1
- YGNISOAUPSJDJE-UHFFFAOYSA-N 4-bromo-3-(trifluoromethyl)aniline Chemical compound NC1=CC=C(Br)C(C(F)(F)F)=C1 YGNISOAUPSJDJE-UHFFFAOYSA-N 0.000 description 1
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
- PGFQDLOMDIBAPY-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)aniline Chemical compound NC1=CC=C(F)C(C(F)(F)F)=C1 PGFQDLOMDIBAPY-UHFFFAOYSA-N 0.000 description 1
- NYMDPDNETOLVBS-UHFFFAOYSA-N 4-fluoro-3-methylaniline Chemical compound CC1=CC(N)=CC=C1F NYMDPDNETOLVBS-UHFFFAOYSA-N 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
- JBCDCYFEJQHTTA-UHFFFAOYSA-N 4-methyl-3-(trifluoromethyl)aniline Chemical compound CC1=CC=C(N)C=C1C(F)(F)F JBCDCYFEJQHTTA-UHFFFAOYSA-N 0.000 description 1
- ODGIMMLDVSWADK-UHFFFAOYSA-N 4-trifluoromethylaniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1 ODGIMMLDVSWADK-UHFFFAOYSA-N 0.000 description 1
- ASPDJZINBYYZRU-UHFFFAOYSA-N 5-amino-2-chlorobenzotrifluoride Chemical compound NC1=CC=C(Cl)C(C(F)(F)F)=C1 ASPDJZINBYYZRU-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical class CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000004381 Choline salt Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical class OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 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
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical class OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical class OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000032683 aging Effects 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
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 235000019417 choline salt Nutrition 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 210000000627 locus coeruleus Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000001730 monoaminergic effect Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 230000003274 myotonic effect Effects 0.000 description 1
- KXHORCXSQZTQQI-UHFFFAOYSA-N n-(fluoromethyl)aniline Chemical compound FCNC1=CC=CC=C1 KXHORCXSQZTQQI-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 210000000478 neocortex Anatomy 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- LRTFPLFDLJYEKT-UHFFFAOYSA-N para-isopropylaniline Chemical compound CC(C)C1=CC=C(N)C=C1 LRTFPLFDLJYEKT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 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
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 210000001609 raphe nuclei Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004181 riluzole Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940075554 sorbate Drugs 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000004685 tetrahydrates Chemical class 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- JFJZZMVDLULRGK-URLMMPGGSA-O tubocurarine Chemical compound C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CCN3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 JFJZZMVDLULRGK-URLMMPGGSA-O 0.000 description 1
- 229960001844 tubocurarine Drugs 0.000 description 1
- HZWVJPDDZQOYGA-UHFFFAOYSA-P ucl 1684 Chemical compound C1C(C=2)=CC=CC=2C[N+](C2=CC=CC=C22)=CC=C2NCC(C=C2)=CC=C2CNC2=CC=[N+]1C1=CC=CC=C21 HZWVJPDDZQOYGA-UHFFFAOYSA-P 0.000 description 1
- 210000004515 ventral tegmental area Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
-
- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- 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
- A61P1/10—Laxatives
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Gynecology & Obstetrics (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Psychology (AREA)
- Hematology (AREA)
- Pregnancy & Childbirth (AREA)
- Dermatology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US69225205P | 2005-06-21 | 2005-06-21 | |
| DKPA200500910 | 2005-06-21 | ||
| PCT/EP2006/063405 WO2006136580A2 (en) | 2005-06-21 | 2006-06-21 | 2-(phenylamino)benzimidazole derivatives and their use as modulators of small-conductance calcium-activated potassium channels |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008543915A true JP2008543915A (ja) | 2008-12-04 |
| JP2008543915A5 JP2008543915A5 (enExample) | 2009-07-23 |
Family
ID=37526982
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008517496A Abandoned JP2008543915A (ja) | 2005-06-21 | 2006-06-21 | ２−（フェニルアミノ）ベンズイミダゾール誘導体及び低コンダクタンスカルシウム依存性カリウムチャネルのモジュレーターとしてのそれらの使用 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US7960561B2 (enExample) |
| EP (1) | EP1896427A2 (enExample) |
| JP (1) | JP2008543915A (enExample) |
| CA (1) | CA2612922A1 (enExample) |
| MX (1) | MX2007015689A (enExample) |
| WO (1) | WO2006136580A2 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0715103D0 (en) * | 2007-08-03 | 2007-09-12 | Lectus Therapeutics Ltd | Calcium ion channel modulators and uses thereof |
| US11427600B2 (en) | 2014-06-27 | 2022-08-30 | Nogra Pharma Limited | Aryl receptor modulators and methods of making and using the same |
| CN108283000B (zh) | 2015-09-23 | 2021-04-13 | 凯瑞康宁生物工程（武汉）有限公司 | γ-羟基丁酸的前药及其组合物和用途 |
| CN109153667B (zh) * | 2016-02-24 | 2021-04-02 | 阿塞西翁制药公司 | 新型钾通道抑制剂 |
| US10653681B2 (en) | 2016-03-16 | 2020-05-19 | Recurium Ip Holdings, Llc | Analgesic compounds |
| KR102510784B1 (ko) | 2017-03-30 | 2023-03-15 | 엑스더블유파마 리미티드 | 이환형 헤테로아릴 유도체 및 이의 제조 및 용도 |
| EP3672953B1 (en) * | 2017-08-23 | 2021-07-28 | Acesion Pharma ApS | Benzimidazole derivatives useful as potassium channel inhibitors |
| CN114042070A (zh) | 2018-09-30 | 2022-02-15 | 凯瑞康宁生物工程（武汉）有限公司 | 作为神经元组胺受体-3拮抗剂的化合物及其用途 |
| WO2021127461A1 (en) | 2019-12-20 | 2021-06-24 | Xw Laboratories Limited | Methods of synthesizing 4-valyloxybutyric acid |
| AU2021292406B2 (en) | 2020-06-18 | 2024-03-14 | XWPharma Ltd. | Controlled release granulations of water-soluble active pharmaceutical ingredients |
| KR102982616B1 (ko) | 2020-06-18 | 2026-06-26 | 엑스더블유파마 리미티드 | 수용성 원료의약품의 약학적 과립화제 |
| WO2022020621A1 (en) | 2020-07-24 | 2022-01-27 | XWPharma Ltd. | Pharmaceutical compositions and pharmacokinetics of a gamma-hydroxybutyric acid derivative |
| AU2021357705B2 (en) | 2020-10-05 | 2024-09-26 | XWPharma Ltd. | Modified release compositions of a gamma-hydroxybutyric acid derivative |
| DK4308086T3 (da) | 2021-03-19 | 2025-11-17 | Xwpharma Ltd | Farmakokinetik af formuleringer med kombineret frigivelse af et gamma-hydroxysmørsyrederivat |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE632578A (enExample) * | 1963-05-22 | |||
| GB1171904A (en) * | 1965-10-21 | 1969-11-26 | Unilever Ltd | Anilinobenzimidazoles having Antibacterial Properties |
| JP2869561B2 (ja) * | 1989-05-22 | 1999-03-10 | 大塚製薬株式会社 | 血小板粘着抑制剤 |
| ATE244717T1 (de) * | 1997-03-14 | 2003-07-15 | Vertex Pharma | Inhibitoren des impdh-enzyms |
| WO2001021160A2 (en) * | 1999-09-23 | 2001-03-29 | Axxima Pharmaceuticals Aktiengesellschaft | Carboxymide and aniline derivatives as selective inhibitors of pathogens |
| DE10060292A1 (de) * | 2000-12-05 | 2002-06-20 | Aventis Pharma Gmbh | Verwendung substituierter Benzimidazole zur Herstellung eines Medikaments zur Behandlung von Krankheiten, welche durch Inhibierung des Na+/H+-Austauschers beeinflusst werden können und sie enthaltendes Medikament |
| WO2003043345A1 (fr) | 2001-11-16 | 2003-05-22 | Ntt Docomo, Inc. | Procede de codage d'image, procede de decodage d'image, codeur et decodeur d'image, programme, signal de donnees informatiques et systeme d'emission d'image |
| DE10304294A1 (de) | 2003-02-04 | 2004-08-12 | Aventis Pharma Deutschland Gmbh | N-Substituierte(Benzoimidazol-2-yl)-phenyl, Verfahren zu ihrer Herstellung , ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| US20050054705A1 (en) | 2003-02-04 | 2005-03-10 | Aventis Pharma Deutschland Gmbh | N-substituted (benzoimidazol-2-yl) phenylamines, process for their preparation, their use as medicament or diagnostic aid, and medicament comprising them |
| WO2004098494A2 (en) * | 2003-04-30 | 2004-11-18 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| US7714009B2 (en) | 2003-10-31 | 2010-05-11 | Takeda Pharmaceutical Company Limited | Nitrogen-containing fused heterocyclic compounds |
-
2006
- 2006-06-21 JP JP2008517496A patent/JP2008543915A/ja not_active Abandoned
- 2006-06-21 WO PCT/EP2006/063405 patent/WO2006136580A2/en not_active Ceased
- 2006-06-21 US US11/919,708 patent/US7960561B2/en not_active Expired - Fee Related
- 2006-06-21 EP EP06777399A patent/EP1896427A2/en not_active Withdrawn
- 2006-06-21 MX MX2007015689A patent/MX2007015689A/es not_active Application Discontinuation
- 2006-06-21 CA CA002612922A patent/CA2612922A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US7960561B2 (en) | 2011-06-14 |
| CA2612922A1 (en) | 2006-12-28 |
| MX2007015689A (es) | 2008-02-21 |
| WO2006136580A3 (en) | 2007-04-12 |
| EP1896427A2 (en) | 2008-03-12 |
| WO2006136580A2 (en) | 2006-12-28 |
| US20090076106A1 (en) | 2009-03-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20100280087A1 (en) | Novel 2-amino benzimidazole derivatives and their use as modulators of small-conductance calcium-activated potassium channels | |
| SK382004A3 (en) | 5-halo-tryptamine derivatives used as ligands of the 5-HT6 and/or 5-HT7 serotonin receptors | |
| US7960561B2 (en) | 2-(phenylamino) benzimidazole derivatives and their use as modulators of small-conductance calcium-activated potassium channels | |
| JP2011516561A (ja) | 抗葉酸化合物の結晶塩形およびその製造方法 | |
| US8895602B1 (en) | 6-pyrazolylamido-3-substituted azabicyclo[3.1.0]hexane compounds as calcium channel inhibitors | |
| US20110318266A1 (en) | Phthalimide derivative metabotropic glutamate r4 ligands | |
| JPWO2006028161A1 (ja) | セロトニン５−ｈｔ３受容体作動薬 | |
| US8048877B2 (en) | Guanidine derivatives and their medical use | |
| US8039632B2 (en) | 2-aminio-pyridine derivatives and their use as potassium channel modulators | |
| JP2009542602A (ja) | ２−アミノベンズイミダゾール誘導体及び小コンダクタンスカルシウム依存性カリウムチャネルの調節剤としてのそれらの使用 | |
| JP2010509249A (ja) | 新規な４−アミノ−ピリジン誘導体及びカリウムチャネルモジュレーターとしてのその使用 | |
| MX2007001325A (es) | Nuevos derivados de bencimidazol 2-amino y su uso como moduladores de canales de potasio activados con calcio, de baja conductancia. | |
| JP2009511548A (ja) | 新規ピリミジン−２，４−ジアミン誘導体及び小コンダクタンスのカルシウム依存性カリウムチャネルのモジュレーターとしてのこれらの使用 | |
| CN101180276A (zh) | 2-（苯基氨基）苯并咪唑衍生物及其作为小电导钙激活的钾通道调节剂的用途 | |
| JP2002538154A (ja) | セロトニン作動活性を有するｎ−置換イミド誘導体 | |
| US20090048278A1 (en) | Novel Quinazoline-2,4-Diamine Derivatives and Their Use as Modulators of Small-Conductance Calcium-Activated Potassium Channels | |
| JP2009518359A (ja) | 新規なキナゾリン−２，４−ジアミン誘導体及び小コンダクタンスカルシウム依存性カリウムチャネルの調節剤としてのそれらの使用 | |
| WO2024137968A1 (en) | Androgen receptor modulators and methods for their use | |
| HK1101581A (en) | 2-amino benzimidazole derivatives and their use as modulators of small-conductance calcium-activated potassium channels |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090608 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090608 |
|
| A762 | Written abandonment of application |
Free format text: JAPANESE INTERMEDIATE CODE: A762 Effective date: 20110721 |