IL185113A - Converted pyridine derivatives, pharmaceuticals containing it, and its use in drug preparation - Google Patents

Info

Publication number

IL185113A

IL185113A IL185113A IL18511307A IL185113A IL 185113 A IL185113 A IL 185113A IL 185113 A IL185113 A IL 185113A IL 18511307 A IL18511307 A IL 18511307A IL 185113 A IL185113 A IL 185113A

Authority

IL

Israel

Prior art keywords

alk

cycloalk

dimethyl

pyridin

morpholin

Prior art date

2005-03-03

Links

• Espacenet
• Global Dossier
• Discuss

• 239000008194 pharmaceutical composition Chemical class 0.000 title claims description 22
• 238000002360 preparation method Methods 0.000 title claims description 21
• 239000003814 drug Substances 0.000 title claims description 20
• 150000003222 pyridines Chemical class 0.000 title abstract description 4
• 238000011282 treatment Methods 0.000 claims abstract description 32
• 108020001213 potassium channel Proteins 0.000 claims abstract description 24
• 102000004257 Potassium Channel Human genes 0.000 claims abstract description 23
• 208000015114 central nervous system disease Diseases 0.000 claims abstract description 3
• 150000001875 compounds Chemical class 0.000 claims description 200
• -1 2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl Chemical group 0.000 claims description 46
• 206010010904 Convulsion Diseases 0.000 claims description 35
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 35
• 229910052736 halogen Inorganic materials 0.000 claims description 28
• 150000002367 halogens Chemical group 0.000 claims description 28
• 208000019901 Anxiety disease Diseases 0.000 claims description 27
• 150000003839 salts Chemical class 0.000 claims description 27
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
• 239000012458 free base Substances 0.000 claims description 24
• 125000001424 substituent group Chemical group 0.000 claims description 24
• 206010015037 epilepsy Diseases 0.000 claims description 21
• 208000004296 neuralgia Diseases 0.000 claims description 21
• 208000021722 neuropathic pain Diseases 0.000 claims description 21
• 201000010099 disease Diseases 0.000 claims description 20
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
• 208000035475 disorder Diseases 0.000 claims description 15
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 12
• 125000003107 substituted aryl group Chemical group 0.000 claims description 12
• 208000019695 Migraine disease Diseases 0.000 claims description 11
• 206010027599 migraine Diseases 0.000 claims description 11
• 239000000126 substance Substances 0.000 claims description 11
• 230000001537 neural effect Effects 0.000 claims description 10
• 239000003085 diluting agent Substances 0.000 claims description 9
• 208000027520 Somatoform disease Diseases 0.000 claims description 8
• 230000004770 neurodegeneration Effects 0.000 claims description 8
• 208000027753 pain disease Diseases 0.000 claims description 8
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 7
• 230000036506 anxiety Effects 0.000 claims description 7
• 125000003118 aryl group Chemical group 0.000 claims description 7
• 206010001497 Agitation Diseases 0.000 claims description 6
• 208000002193 Pain Diseases 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 239000001257 hydrogen Substances 0.000 claims description 6
• 229910052739 hydrogen Inorganic materials 0.000 claims description 6
• MHPUGCYGQWGLJL-UHFFFAOYSA-N 5-methyl-hexanoic acid Chemical compound CC(C)CCCC(O)=O MHPUGCYGQWGLJL-UHFFFAOYSA-N 0.000 claims description 5
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 5
• 208000008811 Agoraphobia Diseases 0.000 claims description 5
• 208000020925 Bipolar disease Diseases 0.000 claims description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 206010034912 Phobia Diseases 0.000 claims description 5
• FGKJLKRYENPLQH-UHFFFAOYSA-N isocaproic acid Chemical compound CC(C)CCC(O)=O FGKJLKRYENPLQH-UHFFFAOYSA-N 0.000 claims description 5
• 201000001716 specific phobia Diseases 0.000 claims description 5
• 208000006011 Stroke Diseases 0.000 claims description 4
• 208000019906 panic disease Diseases 0.000 claims description 4
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
• 208000030507 AIDS Diseases 0.000 claims description 3
• 208000024827 Alzheimer disease Diseases 0.000 claims description 3
• 241000589968 Borrelia Species 0.000 claims description 3
• 208000014644 Brain disease Diseases 0.000 claims description 3
• 208000022497 Cocaine-Related disease Diseases 0.000 claims description 3
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 3
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
• 206010013654 Drug abuse Diseases 0.000 claims description 3
• 208000032274 Encephalopathy Diseases 0.000 claims description 3
• 208000011688 Generalised anxiety disease Diseases 0.000 claims description 3
• 208000023105 Huntington disease Diseases 0.000 claims description 3
• 208000004454 Hyperalgesia Diseases 0.000 claims description 3
• 201000001916 Hypochondriasis Diseases 0.000 claims description 3
• 208000016604 Lyme disease Diseases 0.000 claims description 3
• 241000124008 Mammalia Species 0.000 claims description 3
• 206010029240 Neuritis Diseases 0.000 claims description 3
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 3
• 208000018737 Parkinson disease Diseases 0.000 claims description 3
• 208000004983 Phantom Limb Diseases 0.000 claims description 3
• 206010056238 Phantom pain Diseases 0.000 claims description 3
• 206010036105 Polyneuropathy Diseases 0.000 claims description 3
• 241000710799 Rubella virus Species 0.000 claims description 3
• 208000000810 Separation Anxiety Diseases 0.000 claims description 3
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 3
• 206010041250 Social phobia Diseases 0.000 claims description 3
• 208000009205 Tinnitus Diseases 0.000 claims description 3
• 208000012826 adjustment disease Diseases 0.000 claims description 3
• 206010053552 allodynia Diseases 0.000 claims description 3
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
• 201000001272 cocaine abuse Diseases 0.000 claims description 3
• 230000036461 convulsion Effects 0.000 claims description 3
• 208000029364 generalized anxiety disease Diseases 0.000 claims description 3
• 230000000917 hyperalgesic effect Effects 0.000 claims description 3
• 208000015181 infectious disease Diseases 0.000 claims description 3
• 208000014674 injury Diseases 0.000 claims description 3
• 206010022437 insomnia Diseases 0.000 claims description 3
• 230000035987 intoxication Effects 0.000 claims description 3
• 231100000566 intoxication Toxicity 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• 229960002715 nicotine Drugs 0.000 claims description 3
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 3
• 244000052769 pathogen Species 0.000 claims description 3
• 210000001428 peripheral nervous system Anatomy 0.000 claims description 3
• 230000007824 polyneuropathy Effects 0.000 claims description 3
• 208000028173 post-traumatic stress disease Diseases 0.000 claims description 3
• 208000020016 psychiatric disease Diseases 0.000 claims description 3
• 208000025874 separation anxiety disease Diseases 0.000 claims description 3
• 208000019116 sleep disease Diseases 0.000 claims description 3
• 208000005809 status epilepticus Diseases 0.000 claims description 3
• 231100000886 tinnitus Toxicity 0.000 claims description 3
• 230000008733 trauma Effects 0.000 claims description 3
• 241001529453 unidentified herpesvirus Species 0.000 claims description 3
• 208000002877 Epileptic Syndromes Diseases 0.000 claims description 2
• 208000012902 Nervous system disease Diseases 0.000 claims description 2
• 206010033664 Panic attack Diseases 0.000 claims description 2
• 206010052794 Panic disorder with agoraphobia Diseases 0.000 claims description 2
• 206010033668 Panic disorder without agoraphobia Diseases 0.000 claims description 2
• 208000031674 Traumatic Acute Stress disease Diseases 0.000 claims description 2
• 230000001154 acute effect Effects 0.000 claims description 2
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 2
• 150000002431 hydrogen Chemical group 0.000 claims description 2
• LOCRXXVELNBLQE-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-2-phenylacetamide Chemical compound CC1=CC(N2CCOCC2)=NC(C)=C1NC(=O)CC1=CC=CC=C1 LOCRXXVELNBLQE-UHFFFAOYSA-N 0.000 claims description 2
• MRNPWIWBKMYBTH-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-2-phenylcyclopropane-1-carboxamide Chemical compound CC1=CC(N2CCOCC2)=NC(C)=C1NC(=O)C1CC1C1=CC=CC=C1 MRNPWIWBKMYBTH-UHFFFAOYSA-N 0.000 claims description 2
• WVSKXMHDWLIKIR-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-3,5,5-trimethylhexanamide Chemical compound N1=C(C)C(NC(=O)CC(C)CC(C)(C)C)=C(C)C=C1N1CCOCC1 WVSKXMHDWLIKIR-UHFFFAOYSA-N 0.000 claims description 2
• RZPBJOUKSLGPAK-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)heptanamide Chemical compound N1=C(C)C(NC(=O)CCCCCC)=C(C)C=C1N1CCOCC1 RZPBJOUKSLGPAK-UHFFFAOYSA-N 0.000 claims description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
• 206010044652 trigeminal neuralgia Diseases 0.000 claims description 2
• 229940080818 propionamide Drugs 0.000 claims 4
• MEPMQOPXUQHOJD-UHFFFAOYSA-N 2-(cyclohexen-1-yl)-n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)acetamide Chemical compound CC1=CC(N2CCOCC2)=NC(C)=C1NC(=O)CC1=CCCCC1 MEPMQOPXUQHOJD-UHFFFAOYSA-N 0.000 claims 1
• NSXYSIRPQHZGRS-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-2-(3,4-dimethylphenyl)acetamide Chemical compound C1=C(C)C(C)=CC=C1CC(=O)NC1=C(C)C=C(N2CCOCC2)N=C1C NSXYSIRPQHZGRS-UHFFFAOYSA-N 0.000 claims 1
• QFXOZVHCESXJLE-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-2-(3,5-dimethylphenyl)acetamide Chemical compound CC1=CC(C)=CC(CC(=O)NC=2C(=NC(=CC=2C)N2CCOCC2)C)=C1 QFXOZVHCESXJLE-UHFFFAOYSA-N 0.000 claims 1
• LNHWKNMHQDEDHA-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-2-(3-fluorophenyl)acetamide Chemical compound CC1=CC(N2CCOCC2)=NC(C)=C1NC(=O)CC1=CC=CC(F)=C1 LNHWKNMHQDEDHA-UHFFFAOYSA-N 0.000 claims 1
• ZZQZQXDYSRXASP-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-2-(4-methylphenyl)acetamide Chemical compound C1=CC(C)=CC=C1CC(=O)NC1=C(C)C=C(N2CCOCC2)N=C1C ZZQZQXDYSRXASP-UHFFFAOYSA-N 0.000 claims 1
• OEMGVWLOWRPQLL-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-2-[3-(trifluoromethyl)phenyl]acetamide Chemical compound CC1=CC(N2CCOCC2)=NC(C)=C1NC(=O)CC1=CC=CC(C(F)(F)F)=C1 OEMGVWLOWRPQLL-UHFFFAOYSA-N 0.000 claims 1
• GKDVUJSUFGQXKA-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-2-naphthalen-2-ylacetamide Chemical compound N=1C(C)=C(NC(=O)CC=2C=C3C=CC=CC3=CC=2)C(C)=CC=1N1CCOCC1 GKDVUJSUFGQXKA-UHFFFAOYSA-N 0.000 claims 1
• 238000000105 evaporative light scattering detection Methods 0.000 description 51
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 51
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
• 108010006746 KCNQ2 Potassium Channel Proteins 0.000 description 37
• 102000005453 KCNQ2 Potassium Channel Human genes 0.000 description 29
• 238000000034 method Methods 0.000 description 27
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 21
• 230000000694 effects Effects 0.000 description 21
• 238000012360 testing method Methods 0.000 description 19
• 108091006146 Channels Proteins 0.000 description 18
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 239000000243 solution Substances 0.000 description 18
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
• 238000005160 1H NMR spectroscopy Methods 0.000 description 17
• 239000000203 mixture Substances 0.000 description 17
• 239000002904 solvent Substances 0.000 description 17
• PCOBBVZJEWWZFR-UHFFFAOYSA-N ezogabine Chemical compound C1=C(N)C(NC(=O)OCC)=CC=C1NCC1=CC=C(F)C=C1 PCOBBVZJEWWZFR-UHFFFAOYSA-N 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• 229940093499 ethyl acetate Drugs 0.000 description 15
• 235000019439 ethyl acetate Nutrition 0.000 description 15
• 229960003312 retigabine Drugs 0.000 description 15
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
• 239000011541 reaction mixture Substances 0.000 description 13
• 239000007787 solid Substances 0.000 description 13
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• 108010038888 KCNQ3 Potassium Channel Proteins 0.000 description 11
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
• 238000005481 NMR spectroscopy Methods 0.000 description 11
• 229940079593 drug Drugs 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
• 102000015686 KCNQ3 Potassium Channel Human genes 0.000 description 10
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 10
• 125000004432 carbon atom Chemical group C* 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 10
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 239000012074 organic phase Substances 0.000 description 9
• 239000011591 potassium Substances 0.000 description 9
• 229910052700 potassium Inorganic materials 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• 101150041968 CDC13 gene Proteins 0.000 description 8
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 230000001773 anti-convulsant effect Effects 0.000 description 8
• 238000006880 cross-coupling reaction Methods 0.000 description 8
• 230000014509 gene expression Effects 0.000 description 8
• 239000007788 liquid Substances 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 235000011121 sodium hydroxide Nutrition 0.000 description 8
• 229940083608 sodium hydroxide Drugs 0.000 description 8
• 101000994656 Homo sapiens Potassium voltage-gated channel subfamily KQT member 5 Proteins 0.000 description 7
• 241000699670 Mus sp. Species 0.000 description 7
• 230000004913 activation Effects 0.000 description 7
• 239000001961 anticonvulsive agent Substances 0.000 description 7
• 229960003965 antiepileptics Drugs 0.000 description 7
• 210000004556 brain Anatomy 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 238000003818 flash chromatography Methods 0.000 description 7
• 239000012528 membrane Substances 0.000 description 7
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 7
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• 102100034365 Potassium voltage-gated channel subfamily KQT member 5 Human genes 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
• 239000004480 active ingredient Substances 0.000 description 6
• 229910052786 argon Inorganic materials 0.000 description 6
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
• 235000019341 magnesium sulphate Nutrition 0.000 description 6
• 125000002950 monocyclic group Chemical group 0.000 description 6
• 229910052757 nitrogen Inorganic materials 0.000 description 6
• 230000003287 optical effect Effects 0.000 description 6
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 5
• QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 5
• 229960000583 acetic acid Drugs 0.000 description 5
• 210000004727 amygdala Anatomy 0.000 description 5
• 230000002082 anti-convulsion Effects 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
• 239000012043 crude product Substances 0.000 description 5
• 238000007333 cyanation reaction Methods 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 230000000670 limiting effect Effects 0.000 description 5
• 238000002483 medication Methods 0.000 description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
• 238000006396 nitration reaction Methods 0.000 description 5
• 229960001416 pilocarpine Drugs 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 4
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 210000003169 central nervous system Anatomy 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 4
• 125000001072 heteroaryl group Chemical group 0.000 description 4
• 230000001535 kindling effect Effects 0.000 description 4
• WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
• 108020004999 messenger RNA Proteins 0.000 description 4
• 239000003921 oil Substances 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• 239000006188 syrup Substances 0.000 description 4
• 235000020357 syrup Nutrition 0.000 description 4
• 125000005270 trialkylamine group Chemical group 0.000 description 4
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• NILLIUYSJFTTRH-UHFFFAOYSA-N 2-cyclopentylacetyl chloride Chemical compound ClC(=O)CC1CCCC1 NILLIUYSJFTTRH-UHFFFAOYSA-N 0.000 description 3
• BRBUBVKGJRPRRD-UHFFFAOYSA-N 4,6-dimethylpyridin-2-amine Chemical compound CC1=CC(C)=NC(N)=C1 BRBUBVKGJRPRRD-UHFFFAOYSA-N 0.000 description 3
• NRPFNQUDKRYCNX-UHFFFAOYSA-N 4-methoxyphenylacetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1 NRPFNQUDKRYCNX-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
• ZNSMNVMLTJELDZ-UHFFFAOYSA-N Bis(2-chloroethyl)ether Chemical compound ClCCOCCCl ZNSMNVMLTJELDZ-UHFFFAOYSA-N 0.000 description 3
• 229920002261 Corn starch Polymers 0.000 description 3
• 206010011878 Deafness Diseases 0.000 description 3
• 239000001828 Gelatine Substances 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 101000801643 Homo sapiens Retinal-specific phospholipid-transporting ATPase ABCA4 Proteins 0.000 description 3
• 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 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 3
• NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 102100033617 Retinal-specific phospholipid-transporting ATPase ABCA4 Human genes 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 235000011054 acetic acid Nutrition 0.000 description 3
• 239000000654 additive Substances 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 238000010171 animal model Methods 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 229910052796 boron Inorganic materials 0.000 description 3
• 229910052794 bromium Inorganic materials 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 150000001721 carbon Chemical group 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• LJOODBDWMQKMFB-UHFFFAOYSA-N cyclohexylacetic acid Chemical compound OC(=O)CC1CCCCC1 LJOODBDWMQKMFB-UHFFFAOYSA-N 0.000 description 3
• 231100000895 deafness Toxicity 0.000 description 3
• 239000012039 electrophile Substances 0.000 description 3
• 238000010828 elution Methods 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 208000016354 hearing loss disease Diseases 0.000 description 3
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 230000006872 improvement Effects 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 238000007918 intramuscular administration Methods 0.000 description 3
• 238000007912 intraperitoneal administration Methods 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 3
• 229940011051 isopropyl acetate Drugs 0.000 description 3
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 239000000395 magnesium oxide Substances 0.000 description 3
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 3
• 230000035772 mutation Effects 0.000 description 3
• 235000019198 oils Nutrition 0.000 description 3
• 210000000287 oocyte Anatomy 0.000 description 3
• 229910052760 oxygen Inorganic materials 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• 229960005152 pentetrazol Drugs 0.000 description 3
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 235000019260 propionic acid Nutrition 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 229940083542 sodium Drugs 0.000 description 3
• 235000009518 sodium iodide Nutrition 0.000 description 3
• 235000010288 sodium nitrite Nutrition 0.000 description 3
• 231100001274 therapeutic index Toxicity 0.000 description 3
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 3
• 239000003643 water by type Substances 0.000 description 3
• FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
• GCCKNHYFOVQZRG-UHFFFAOYSA-N (2-chlorophenyl)methyl carbonochloridate Chemical compound ClC(=O)OCC1=CC=CC=C1Cl GCCKNHYFOVQZRG-UHFFFAOYSA-N 0.000 description 2
• GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• FJNNGKMAGDPVIU-UHFFFAOYSA-N 2,4,6-trichloropyridine Chemical compound ClC1=CC(Cl)=NC(Cl)=C1 FJNNGKMAGDPVIU-UHFFFAOYSA-N 0.000 description 2
• LPMZGLWTJXFVTO-UHFFFAOYSA-N 2,4-dimethyl-6-morpholin-4-ylpyridin-3-amine Chemical compound CC1=C(N)C(C)=CC(N2CCOCC2)=N1 LPMZGLWTJXFVTO-UHFFFAOYSA-N 0.000 description 2
• NNRZTJAACCRFRV-UHFFFAOYSA-N 2-(2-cyclopentenyl)-ethanoic acid Chemical compound OC(=O)CC1CCC=C1 NNRZTJAACCRFRV-UHFFFAOYSA-N 0.000 description 2
• YCAKYFIYUHHCKW-UHFFFAOYSA-N 2-(3,4-difluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(F)C(F)=C1 YCAKYFIYUHHCKW-UHFFFAOYSA-N 0.000 description 2
• OTTPBKINJOYJGW-UHFFFAOYSA-N 2-(3,4-dimethylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1C OTTPBKINJOYJGW-UHFFFAOYSA-N 0.000 description 2
• HDNBKTWQBJJYPD-UHFFFAOYSA-N 2-(3,5-dimethylphenyl)acetic acid Chemical compound CC1=CC(C)=CC(CC(O)=O)=C1 HDNBKTWQBJJYPD-UHFFFAOYSA-N 0.000 description 2
• KYNNBXCGXUOREX-UHFFFAOYSA-N 2-(3-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1 KYNNBXCGXUOREX-UHFFFAOYSA-N 0.000 description 2
• WFPMUFXQDKMVCO-UHFFFAOYSA-N 2-(3-chlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Cl)=C1 WFPMUFXQDKMVCO-UHFFFAOYSA-N 0.000 description 2
• YEAUYVGUXSZCFI-UHFFFAOYSA-N 2-(3-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(F)=C1 YEAUYVGUXSZCFI-UHFFFAOYSA-N 0.000 description 2
• UMQUIRYNOVNYPA-UHFFFAOYSA-N 2-(4-chlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Cl)C=C1 UMQUIRYNOVNYPA-UHFFFAOYSA-N 0.000 description 2
• MGKPFALCNDRSQD-UHFFFAOYSA-N 2-(4-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(F)C=C1 MGKPFALCNDRSQD-UHFFFAOYSA-N 0.000 description 2
• GYBWDAKGSPTODN-UHFFFAOYSA-N 2-(4-methoxy-3-methylphenyl)acetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1C GYBWDAKGSPTODN-UHFFFAOYSA-N 0.000 description 2
• KDFBPHXESBPHTK-UHFFFAOYSA-N 2-(cyclohexen-1-yl)acetic acid Chemical compound OC(=O)CC1=CCCCC1 KDFBPHXESBPHTK-UHFFFAOYSA-N 0.000 description 2
• BLXXCCIBGGBDHI-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(F)(F)F)=C1 BLXXCCIBGGBDHI-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
• VIBOGIYPPWLDTI-UHFFFAOYSA-N 2-naphthylacetic acid Chemical compound C1=CC=CC2=CC(CC(=O)O)=CC=C21 VIBOGIYPPWLDTI-UHFFFAOYSA-N 0.000 description 2
• RCNOGGGBSSVMAS-UHFFFAOYSA-N 2-thiophen-3-ylacetic acid Chemical compound OC(=O)CC=1C=CSC=1 RCNOGGGBSSVMAS-UHFFFAOYSA-N 0.000 description 2
• OILUAKBAMVLXGF-UHFFFAOYSA-N 3,5,5-trimethyl-hexanoic acid Chemical compound OC(=O)CC(C)CC(C)(C)C OILUAKBAMVLXGF-UHFFFAOYSA-N 0.000 description 2
• CLTDVBQNUHHYCA-UHFFFAOYSA-N 3-(3-chlorophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC(Cl)=C1 CLTDVBQNUHHYCA-UHFFFAOYSA-N 0.000 description 2
• JUADTOTVJUYCRQ-UHFFFAOYSA-N 3-cyclohexylpropanoyl chloride Chemical compound ClC(=O)CCC1CCCCC1 JUADTOTVJUYCRQ-UHFFFAOYSA-N 0.000 description 2
• SZQVEGOXJYTLLB-UHFFFAOYSA-N 3-cyclopentylpropanoyl chloride Chemical compound ClC(=O)CCC1CCCC1 SZQVEGOXJYTLLB-UHFFFAOYSA-N 0.000 description 2
• GJMPSRSMBJLKKB-UHFFFAOYSA-N 3-methylphenylacetic acid Chemical compound CC1=CC=CC(CC(O)=O)=C1 GJMPSRSMBJLKKB-UHFFFAOYSA-N 0.000 description 2
• BIESNLWMYKMSOC-UHFFFAOYSA-N 4-(4,6-dichloro-5-nitropyridin-2-yl)morpholine Chemical compound N1=C(Cl)C([N+](=O)[O-])=C(Cl)C=C1N1CCOCC1 BIESNLWMYKMSOC-UHFFFAOYSA-N 0.000 description 2
• ZINNHCARUJQQRJ-UHFFFAOYSA-N 4-(4,6-dimethylpyridin-2-yl)morpholine Chemical compound CC1=CC(C)=NC(N2CCOCC2)=C1 ZINNHCARUJQQRJ-UHFFFAOYSA-N 0.000 description 2
• XDMRHYVTLFVRSW-UHFFFAOYSA-N 4-(4-chloro-6-methoxy-5-nitropyridin-2-yl)morpholine Chemical compound ClC1=C([N+]([O-])=O)C(OC)=NC(N2CCOCC2)=C1 XDMRHYVTLFVRSW-UHFFFAOYSA-N 0.000 description 2
• 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 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 2
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 2
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• 239000012981 Hank's balanced salt solution Substances 0.000 description 2
• 101000994648 Homo sapiens Potassium voltage-gated channel subfamily KQT member 4 Proteins 0.000 description 2
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
• 102000004310 Ion Channels Human genes 0.000 description 2
• 108090000862 Ion Channels Proteins 0.000 description 2
• 102000012359 KCNQ Potassium Channels Human genes 0.000 description 2
• 108010022282 KCNQ Potassium Channels Proteins 0.000 description 2
• 235000019759 Maize starch Nutrition 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
• 235000019483 Peanut oil Nutrition 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
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
• 208000008409 Romano-Ward Syndrome Diseases 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
• PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 2
• 230000036982 action potential Effects 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 125000003342 alkenyl group Chemical group 0.000 description 2
• 150000001345 alkine derivatives Chemical class 0.000 description 2
• 125000000217 alkyl group Chemical group 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
• 230000002059 anti-epileptogenic effect Effects 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• 230000001977 ataxic effect Effects 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 230000006399 behavior Effects 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 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 2
• 229940049706 benzodiazepine Drugs 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 2
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 2
• 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 2
• 150000001735 carboxylic acids Chemical class 0.000 description 2
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 230000001276 controlling effect Effects 0.000 description 2
• 229910000365 copper sulfate Inorganic materials 0.000 description 2
• ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
• 229960003368 croscarmellose sodium type a Drugs 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 150000002170 ethers Chemical class 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 229960002870 gabapentin Drugs 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 125000000623 heterocyclic group Chemical group 0.000 description 2
• YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 2
• 210000001320 hippocampus Anatomy 0.000 description 2
• 238000005984 hydrogenation reaction Methods 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
• 230000002631 hypothermal effect Effects 0.000 description 2
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 230000010354 integration Effects 0.000 description 2
• 238000007913 intrathecal administration Methods 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 229910000103 lithium hydride Inorganic materials 0.000 description 2
• 229940006116 lithium hydroxide Drugs 0.000 description 2
• 230000006742 locomotor activity Effects 0.000 description 2
• 201000006908 long QT syndrome 1 Diseases 0.000 description 2
• 210000003141 lower extremity Anatomy 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 238000006263 metalation reaction Methods 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 210000002569 neuron Anatomy 0.000 description 2
• 230000008587 neuronal excitability Effects 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 239000000312 peanut oil Substances 0.000 description 2
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
• 230000035479 physiological effects, processes and functions Effects 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 239000004036 potassium channel stimulating agent Substances 0.000 description 2
• NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
• 229910000105 potassium hydride Inorganic materials 0.000 description 2
• 229940093932 potassium hydroxide Drugs 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 2
• 229940085605 saccharin sodium Drugs 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 230000002459 sustained effect Effects 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
• 150000003536 tetrazoles Chemical class 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• 230000001256 tonic effect Effects 0.000 description 2
• 150000003852 triazoles Chemical class 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• FHZUOZWUOXJEHV-UHFFFAOYSA-N (2-chlorophenyl)methyl n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)carbamate Chemical compound CC1=CC(N2CCOCC2)=NC(C)=C1NC(=O)OCC1=CC=CC=C1Cl FHZUOZWUOXJEHV-UHFFFAOYSA-N 0.000 description 1
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
• OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 1
• JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
• CKYXLLATWNDTOC-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)acetamide Chemical compound CC1=CC(N2CCOCC2)=NC(C)=C1NC(=O)CC1=CC=C(Cl)C(Cl)=C1 CKYXLLATWNDTOC-UHFFFAOYSA-N 0.000 description 1
• AQBIYGJLUAYHKV-UHFFFAOYSA-N 2-(3-bicyclo[2.2.1]heptanyl)-n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)acetamide Chemical compound N=1C(C)=C(NC(=O)CC2C3CCC(C3)C2)C(C)=CC=1N1CCOCC1 AQBIYGJLUAYHKV-UHFFFAOYSA-N 0.000 description 1
• IWPAOTPPULTUIR-UHFFFAOYSA-N 2-(3-chlorophenyl)-n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)acetamide Chemical compound CC1=CC(N2CCOCC2)=NC(C)=C1NC(=O)CC1=CC=CC(Cl)=C1 IWPAOTPPULTUIR-UHFFFAOYSA-N 0.000 description 1
• QEDVSHKCKCPZJX-UHFFFAOYSA-N 2-chloro-4-methoxy-6-morpholin-4-ylpyridin-3-amine Chemical compound ClC1=C(N)C(OC)=CC(N2CCOCC2)=N1 QEDVSHKCKCPZJX-UHFFFAOYSA-N 0.000 description 1
• NNJPKMLLSQRIQX-UHFFFAOYSA-N 2-methylpropyl n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)carbamate Chemical compound N1=C(C)C(NC(=O)OCC(C)C)=C(C)C=C1N1CCOCC1 NNJPKMLLSQRIQX-UHFFFAOYSA-N 0.000 description 1
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
• DEAXCAUYSPNKPN-UHFFFAOYSA-N 4-(4,6-dichloropyridin-2-yl)morpholine Chemical compound ClC1=CC(Cl)=NC(N2CCOCC2)=C1 DEAXCAUYSPNKPN-UHFFFAOYSA-N 0.000 description 1
• NGMNFXMTMMZYOG-UHFFFAOYSA-N 4-(4,6-dimethyl-5-nitropyridin-2-yl)morpholine Chemical compound CC1=C([N+]([O-])=O)C(C)=CC(N2CCOCC2)=N1 NGMNFXMTMMZYOG-UHFFFAOYSA-N 0.000 description 1
• CJGYIHZNIXBLMM-UHFFFAOYSA-N 4-(6-chloro-4-methoxy-5-nitropyridin-2-yl)morpholine Chemical compound ClC1=C([N+]([O-])=O)C(OC)=CC(N2CCOCC2)=N1 CJGYIHZNIXBLMM-UHFFFAOYSA-N 0.000 description 1
• PXSPLZGLKGQCIU-UHFFFAOYSA-N 4-chloro-2-methoxy-6-morpholin-4-ylpyridin-3-amine Chemical compound ClC1=C(N)C(OC)=NC(N2CCOCC2)=C1 PXSPLZGLKGQCIU-UHFFFAOYSA-N 0.000 description 1
• SKTFQHRVFFOHTQ-UHFFFAOYSA-N 8-bromo-1,3-dimethyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Br)=N2 SKTFQHRVFFOHTQ-UHFFFAOYSA-N 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 208000008882 Benign Neonatal Epilepsy Diseases 0.000 description 1
• 206010067866 Benign familial neonatal convulsions Diseases 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 108090000312 Calcium Channels Proteins 0.000 description 1
• 102000003922 Calcium Channels Human genes 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• PCLITLDOTJTVDJ-UHFFFAOYSA-N Chlormethiazole Chemical compound CC=1N=CSC=1CCCl PCLITLDOTJTVDJ-UHFFFAOYSA-N 0.000 description 1
• 206010053398 Clonic convulsion Diseases 0.000 description 1
• 208000033001 Complex partial seizures Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• 238000011765 DBA/2 mouse Methods 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• 206010016173 Fall Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
• 241000282412 Homo Species 0.000 description 1
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 101150118846 MKT1 gene Proteins 0.000 description 1
• 101150106280 Mchr1 gene Proteins 0.000 description 1
• 108700036626 Melanin-concentrating hormone receptor 1 Proteins 0.000 description 1
• 102100027375 Melanin-concentrating hormone receptor 1 Human genes 0.000 description 1
• 238000006751 Mitsunobu reaction Methods 0.000 description 1
• 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
• 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
• PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
• 150000001204 N-oxides Chemical class 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 238000006411 Negishi coupling reaction Methods 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical class ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• LHNKBXRFNPMIBR-UHFFFAOYSA-N Picrotoxin Natural products CC(C)(O)C1(O)C2OC(=O)C1C3(O)C4OC4C5C(=O)OC2C35C LHNKBXRFNPMIBR-UHFFFAOYSA-N 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 102100034363 Potassium voltage-gated channel subfamily KQT member 4 Human genes 0.000 description 1
• 102100040125 Prokineticin-2 Human genes 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• 244000000231 Sesamum indicum Species 0.000 description 1
• 108010052164 Sodium Channels Proteins 0.000 description 1
• 102000018674 Sodium Channels Human genes 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
• KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
• 229930003427 Vitamin E Natural products 0.000 description 1
• 206010048010 Withdrawal syndrome Diseases 0.000 description 1
• 241000269370 Xenopus <genus> Species 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 208000026345 acute stress disease Diseases 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 150000001347 alkyl bromides Chemical class 0.000 description 1
• 150000001348 alkyl chlorides Chemical class 0.000 description 1
• 150000005215 alkyl ethers Chemical class 0.000 description 1
• 125000005233 alkylalcohol group Chemical group 0.000 description 1
• VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 210000004102 animal cell Anatomy 0.000 description 1
• 230000000573 anti-seizure effect Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 230000006400 anxiety behaviour Effects 0.000 description 1
• 230000007529 anxiety like behavior Effects 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 238000007080 aromatic substitution reaction Methods 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 210000001130 astrocyte Anatomy 0.000 description 1
• 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 1
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical class O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
• 201000003452 benign familial neonatal epilepsy Diseases 0.000 description 1
• 201000010295 benign neonatal seizures Diseases 0.000 description 1
• 150000001557 benzodiazepines Chemical class 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• KAEMILXLUFFLSU-UHFFFAOYSA-N benzyl n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)carbamate Chemical compound CC1=CC(N2CCOCC2)=NC(C)=C1NC(=O)OCC1=CC=CC=C1 KAEMILXLUFFLSU-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
• FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
• 229960000623 carbamazepine Drugs 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical class BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 1
• 239000012159 carrier gas Substances 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical class ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• VEZNCHDBSQWUHQ-UHFFFAOYSA-N chlorocyclopropane Chemical compound ClC1CC1 VEZNCHDBSQWUHQ-UHFFFAOYSA-N 0.000 description 1
• 230000001713 cholinergic effect Effects 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 229960004414 clomethiazole Drugs 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 210000003477 cochlea Anatomy 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 230000036757 core body temperature Effects 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• ARUKYTASOALXFG-UHFFFAOYSA-N cycloheptylcycloheptane Chemical group C1CCCCCC1C1CCCCCC1 ARUKYTASOALXFG-UHFFFAOYSA-N 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• HTKZGRKHUPOTPF-UHFFFAOYSA-N cyclopropanecarbonyl chloride zinc Chemical compound [Zn].C1(CC1)C(=O)Cl HTKZGRKHUPOTPF-UHFFFAOYSA-N 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 239000007933 dermal patch Substances 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 208000037765 diseases and disorders Diseases 0.000 description 1
• 230000003291 dopaminomimetic effect Effects 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 210000003027 ear inner Anatomy 0.000 description 1
• 230000003804 effect on potassium Effects 0.000 description 1
• 238000000537 electroencephalography Methods 0.000 description 1
• 238000007345 electrophilic aromatic substitution reaction Methods 0.000 description 1
• 230000008918 emotional behaviour Effects 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 230000001037 epileptic effect Effects 0.000 description 1
• HAPOVYFOVVWLRS-UHFFFAOYSA-N ethosuximide Chemical compound CCC1(C)CC(=O)NC1=O HAPOVYFOVVWLRS-UHFFFAOYSA-N 0.000 description 1
• 229960002767 ethosuximide Drugs 0.000 description 1
• 230000002461 excitatory amino acid Effects 0.000 description 1
• 239000003257 excitatory amino acid Substances 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 238000011686 genetic mapping animal model Methods 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 210000002768 hair cell Anatomy 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 239000001307 helium Substances 0.000 description 1
• 229910052734 helium Inorganic materials 0.000 description 1
• SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
• 238000009904 heterogeneous catalytic hydrogenation reaction Methods 0.000 description 1
• VHHHONWQHHHLTI-UHFFFAOYSA-N hexachloroethane Chemical compound ClC(Cl)(Cl)C(Cl)(Cl)Cl VHHHONWQHHHLTI-UHFFFAOYSA-N 0.000 description 1
• 230000000971 hippocampal effect Effects 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• 230000002102 hyperpolarization Effects 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 230000000415 inactivating effect Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• 150000004694 iodide salts Chemical class 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 238000005040 ion trap Methods 0.000 description 1
• VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 1
• 229950006874 kainic acid Drugs 0.000 description 1
• 229960001848 lamotrigine Drugs 0.000 description 1
• PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 1
• 229960004002 levetiracetam Drugs 0.000 description 1
• HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 description 1
• 230000002197 limbic effect Effects 0.000 description 1
• 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
• 239000008297 liquid dosage form Substances 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 108010093708 mamba intestinal toxin 1 Proteins 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• UNFUYWDGSFDHCW-UHFFFAOYSA-N monochlorocyclohexane Chemical compound ClC1CCCCC1 UNFUYWDGSFDHCW-UHFFFAOYSA-N 0.000 description 1
• 230000004118 muscle contraction Effects 0.000 description 1
• BKFDFCVASNKPOA-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-3,3-dimethylbutanamide Chemical compound CC1=C(NC(=O)CC(C)(C)C)C(C)=CC(N2CCOCC2)=N1 BKFDFCVASNKPOA-UHFFFAOYSA-N 0.000 description 1
• BLESCNKLEXGCBO-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-4-methylpentanamide Chemical compound N1=C(C)C(NC(=O)CCC(C)C)=C(C)C=C1N1CCOCC1 BLESCNKLEXGCBO-UHFFFAOYSA-N 0.000 description 1
• LRPPLNWCCXUMIQ-UHFFFAOYSA-N n-(2,4-dimethyl-6-morpholin-4-ylpyridin-3-yl)-5-methylhexanamide Chemical compound N1=C(C)C(NC(=O)CCCC(C)C)=C(C)C=C1N1CCOCC1 LRPPLNWCCXUMIQ-UHFFFAOYSA-N 0.000 description 1
• 230000036403 neuro physiology Effects 0.000 description 1
• 230000000626 neurodegenerative effect Effects 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 230000008555 neuronal activation Effects 0.000 description 1
• 230000003961 neuronal insult Effects 0.000 description 1
• 230000000324 neuroprotective effect Effects 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 125000005489 p-toluenesulfonic acid group Chemical class 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• 229960002036 phenytoin Drugs 0.000 description 1
• 229940067631 phospholipid Drugs 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• PZHNNJXWQYFUTD-UHFFFAOYSA-N phosphorus triiodide Chemical compound IP(I)I PZHNNJXWQYFUTD-UHFFFAOYSA-N 0.000 description 1
• VJKUPQSHOVKBCO-AHMKVGDJSA-N picrotoxin Chemical compound O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(=C)C)[C@@H]1C(=O)O2.O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(C)(O)C)[C@@H]1C(=O)O2 VJKUPQSHOVKBCO-AHMKVGDJSA-N 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 238000007747 plating Methods 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 229940069328 povidone Drugs 0.000 description 1
• 229960001233 pregabalin Drugs 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
• 230000002265 prevention Effects 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 210000001176 projection neuron Anatomy 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000036390 resting membrane potential Effects 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 230000018448 secretion by cell Effects 0.000 description 1
• 239000000932 sedative agent Substances 0.000 description 1
• 230000001624 sedative effect Effects 0.000 description 1
• 230000031893 sensory processing Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000002356 single layer Substances 0.000 description 1
• ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
• 235000010344 sodium nitrate Nutrition 0.000 description 1
• 239000004317 sodium nitrate Substances 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
• 229940084026 sodium valproate Drugs 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 210000003594 spinal ganglia Anatomy 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 230000010473 stable expression Effects 0.000 description 1
• 235000011150 stannous chloride Nutrition 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 230000000946 synaptic effect Effects 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• 229960000278 theophylline Drugs 0.000 description 1
• PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 description 1
• 229960001918 tiagabine Drugs 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229960004394 topiramate Drugs 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 125000004665 trialkylsilyl group Chemical group 0.000 description 1
• 125000005106 triarylsilyl group Chemical group 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 210000000427 trigeminal ganglion Anatomy 0.000 description 1
• 210000000836 trigeminal nuclei Anatomy 0.000 description 1
• 210000004496 type 1 vestibular hair cell Anatomy 0.000 description 1
• 231100000691 up-and-down procedure Toxicity 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 210000004515 ventral tegmental area Anatomy 0.000 description 1
• 210000001213 vestibule labyrinth Anatomy 0.000 description 1
• 235000019165 vitamin E Nutrition 0.000 description 1
• 229940046009 vitamin E Drugs 0.000 description 1
• 239000011709 vitamin E Substances 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
• 229960002911 zonisamide Drugs 0.000 description 1
• UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 1