UA81019C2 - Substituted p-diaminobenzene derivatives - Google Patents

Info

Publication number

UA81019C2

UA81019C2 UAA200509094A UA2005009094A UA81019C2 UA 81019 C2 UA81019 C2 UA 81019C2 UA A200509094 A UAA200509094 A UA A200509094A UA 2005009094 A UA2005009094 A UA 2005009094A UA 81019 C2 UA81019 C2 UA 81019C2

Authority

UA

Ukraine

Prior art keywords

amino

ylmethyl

carbamic acid

methyl

phenyl

Prior art date

2003-03-21

Links

• Espacenet
• Global Dossier
• Discuss

• CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical class NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 title claims description 5
• 150000003839 salts Chemical class 0.000 claims abstract description 66
• 150000001875 compounds Chemical class 0.000 claims description 497
• QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims description 258
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 252
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 223
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims description 221
• -1 en)yl Substances 0.000 claims description 212
• 125000004494 ethyl ester group Chemical group 0.000 claims description 166
• 239000001257 hydrogen Substances 0.000 claims description 51
• 229910052739 hydrogen Inorganic materials 0.000 claims description 51
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 43
• 206010010904 Convulsion Diseases 0.000 claims description 36
• 229920006395 saturated elastomer Polymers 0.000 claims description 35
• 229910052757 nitrogen Inorganic materials 0.000 claims description 33
• 125000005842 heteroatom Chemical group 0.000 claims description 32
• 239000002253 acid Substances 0.000 claims description 31
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
• 229910052736 halogen Inorganic materials 0.000 claims description 29
• 150000002367 halogens Chemical class 0.000 claims description 29
• 239000008194 pharmaceutical composition Substances 0.000 claims description 27
• 229910052799 carbon Inorganic materials 0.000 claims description 26
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
• 208000019901 Anxiety disease Diseases 0.000 claims description 23
• 125000002252 acyl group Chemical group 0.000 claims description 23
• 125000004432 carbon atom Chemical group C* 0.000 claims description 23
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 23
• 229910052709 silver Inorganic materials 0.000 claims description 23
• 206010015037 epilepsy Diseases 0.000 claims description 22
• 108020001213 potassium channel Proteins 0.000 claims description 21
• 102000004257 Potassium Channel Human genes 0.000 claims description 20
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 20
• JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 claims description 20
• 208000035475 disorder Diseases 0.000 claims description 20
• 230000000694 effects Effects 0.000 claims description 20
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 18
• 208000004296 neuralgia Diseases 0.000 claims description 17
• 208000021722 neuropathic pain Diseases 0.000 claims description 17
• 230000002265 prevention Effects 0.000 claims description 17
• YNTOKMNHRPSGFU-UHFFFAOYSA-N n-Propyl carbamate Chemical compound CCCOC(N)=O YNTOKMNHRPSGFU-UHFFFAOYSA-N 0.000 claims description 16
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 15
• 239000003937 drug carrier Substances 0.000 claims description 14
• 239000003085 diluting agent Substances 0.000 claims description 13
• 239000000126 substance Substances 0.000 claims description 13
• TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims description 11
• YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 11
• 230000005764 inhibitory process Effects 0.000 claims description 11
• 125000005605 benzo group Chemical group 0.000 claims description 10
• VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 10
• 150000002500 ions Chemical class 0.000 claims description 10
• 230000001537 neural effect Effects 0.000 claims description 10
• 230000001965 increasing effect Effects 0.000 claims description 9
• 230000004770 neurodegeneration Effects 0.000 claims description 9
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• 125000003118 aryl group Chemical group 0.000 claims description 8
• 230000036461 convulsion Effects 0.000 claims description 8
• 150000004702 methyl esters Chemical class 0.000 claims description 8
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 8
• 208000019695 Migraine disease Diseases 0.000 claims description 7
• 210000003169 central nervous system Anatomy 0.000 claims description 7
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
• PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 claims description 6
• 208000008811 Agoraphobia Diseases 0.000 claims description 6
• 229910002699 Ag–S Inorganic materials 0.000 claims description 6
• 208000014644 Brain disease Diseases 0.000 claims description 6
• 208000032274 Encephalopathy Diseases 0.000 claims description 6
• 208000002193 Pain Diseases 0.000 claims description 6
• 150000002148 esters Chemical class 0.000 claims description 6
• 206010027599 migraine Diseases 0.000 claims description 6
• 229940080818 propionamide Drugs 0.000 claims description 6
• 229910017982 Ag—Si Inorganic materials 0.000 claims description 5
• 206010020751 Hypersensitivity Diseases 0.000 claims description 5
• 206010034912 Phobia Diseases 0.000 claims description 5
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 5
• 208000026935 allergic disease Diseases 0.000 claims description 5
• 230000036506 anxiety Effects 0.000 claims description 5
• 230000009610 hypersensitivity Effects 0.000 claims description 5
• 201000001716 specific phobia Diseases 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• 125000004434 sulfur atom Chemical group 0.000 claims description 5
• 208000030507 AIDS Diseases 0.000 claims description 4
• 208000024827 Alzheimer disease Diseases 0.000 claims description 4
• 241000589968 Borrelia Species 0.000 claims description 4
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 4
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 4
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 4
• 206010013754 Drug withdrawal syndrome Diseases 0.000 claims description 4
• 208000011688 Generalised anxiety disease Diseases 0.000 claims description 4
• 208000023105 Huntington disease Diseases 0.000 claims description 4
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 4
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 4
• 208000016604 Lyme disease Diseases 0.000 claims description 4
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
• 206010041250 Social phobia Diseases 0.000 claims description 4
• 206010070863 Toxicity to various agents Diseases 0.000 claims description 4
• 208000026345 acute stress disease Diseases 0.000 claims description 4
• 208000012826 adjustment disease Diseases 0.000 claims description 4
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
• 208000029364 generalized anxiety disease Diseases 0.000 claims description 4
• 208000015181 infectious disease Diseases 0.000 claims description 4
• 208000014674 injury Diseases 0.000 claims description 4
• 230000035987 intoxication Effects 0.000 claims description 4
• 231100000566 intoxication Toxicity 0.000 claims description 4
• 244000052769 pathogen Species 0.000 claims description 4
• 208000028173 post-traumatic stress disease Diseases 0.000 claims description 4
• 229910052710 silicon Inorganic materials 0.000 claims description 4
• 230000008733 trauma Effects 0.000 claims description 4
• 241001529453 unidentified herpesvirus Species 0.000 claims description 4
• YXYOLVAXVPOIMA-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2OCCC2=C1 YXYOLVAXVPOIMA-UHFFFAOYSA-N 0.000 claims description 3
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
• 208000004454 Hyperalgesia Diseases 0.000 claims description 3
• 201000001916 Hypochondriasis 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
• 241000710799 Rubella virus Species 0.000 claims description 3
• 208000000810 Separation Anxiety Diseases 0.000 claims description 3
• 206010053552 allodynia Diseases 0.000 claims description 3
• 230000036541 health Effects 0.000 claims description 3
• 208000005809 status epilepticus Diseases 0.000 claims description 3
• 239000005711 Benzoic acid Substances 0.000 claims description 2
• 241000124008 Mammalia Species 0.000 claims description 2
• 201000006417 multiple sclerosis Diseases 0.000 claims description 2
• 229910052720 vanadium Inorganic materials 0.000 claims description 2
• 241001397173 Kali <angiosperm> Species 0.000 claims 1
• 238000012876 topography Methods 0.000 claims 1
• 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 abstract 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 172
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 141
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 63
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 59
• 239000000203 mixture Substances 0.000 description 57
• 239000000243 solution Substances 0.000 description 51
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
• 239000002904 solvent Substances 0.000 description 44
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
• 238000000034 method Methods 0.000 description 37
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 36
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
• 239000007787 solid Substances 0.000 description 32
• 150000002431 hydrogen Chemical class 0.000 description 31
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 30
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 27
• 239000011541 reaction mixture Substances 0.000 description 27
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
• 108091006146 Channels Proteins 0.000 description 22
• 238000006243 chemical reaction Methods 0.000 description 22
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
• 125000001424 substituent group Chemical group 0.000 description 21
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 19
• 239000000047 product Substances 0.000 description 19
• 238000012360 testing method Methods 0.000 description 19
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
• 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 15
• 239000012074 organic phase Substances 0.000 description 15
• 229960003312 retigabine Drugs 0.000 description 15
• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
• 239000012043 crude product Substances 0.000 description 14
• 235000019441 ethanol Nutrition 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
• 235000017557 sodium bicarbonate Nutrition 0.000 description 14
• 238000000746 purification Methods 0.000 description 13
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 12
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
• 239000002585 base Substances 0.000 description 12
• 229910000027 potassium carbonate Inorganic materials 0.000 description 12
• 230000001773 anti-convulsant effect Effects 0.000 description 11
• DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 11
• 238000003818 flash chromatography Methods 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
• 150000001448 anilines Chemical class 0.000 description 10
• 239000001961 anticonvulsive agent Substances 0.000 description 10
• 238000001816 cooling Methods 0.000 description 10
• 201000010099 disease Diseases 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• 239000003814 drug Substances 0.000 description 10
• 125000001072 heteroaryl group Chemical group 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 229910052700 potassium Inorganic materials 0.000 description 10
• 238000002360 preparation method Methods 0.000 description 10
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 10
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
• 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 9
• 239000007864 aqueous solution Substances 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 125000006239 protecting group Chemical group 0.000 description 9
• 108090000623 proteins and genes Proteins 0.000 description 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
• 239000000741 silica gel Substances 0.000 description 9
• 229910002027 silica gel Inorganic materials 0.000 description 9
• 239000000377 silicon dioxide Substances 0.000 description 9
• 229940083542 sodium Drugs 0.000 description 9
• 241000699670 Mus sp. Species 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
• 150000001299 aldehydes Chemical class 0.000 description 8
• 239000000543 intermediate Substances 0.000 description 8
• 239000011591 potassium Substances 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• 229910052708 sodium Inorganic materials 0.000 description 8
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
• 241001465754 Metazoa Species 0.000 description 7
• 229960003965 antiepileptics Drugs 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• 239000011575 calcium Substances 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
• 235000019341 magnesium sulphate Nutrition 0.000 description 7
• 239000012044 organic layer Substances 0.000 description 7
• 239000006187 pill Substances 0.000 description 7
• 238000005932 reductive alkylation reaction Methods 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• TXYVWEKFPMFBDJ-UHFFFAOYSA-N (2-methoxy-4-nitrophenyl)carbamic acid Chemical compound COC1=CC([N+]([O-])=O)=CC=C1NC(O)=O TXYVWEKFPMFBDJ-UHFFFAOYSA-N 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 238000011161 development Methods 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 238000001704 evaporation Methods 0.000 description 6
• 230000008020 evaporation Effects 0.000 description 6
• 230000014509 gene expression Effects 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
• 230000003287 optical effect Effects 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 238000003786 synthesis reaction Methods 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
• TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical class NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 5
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 5
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 5
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-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
• 239000004480 active ingredient Substances 0.000 description 5
• 239000000654 additive Substances 0.000 description 5
• 125000000217 alkyl group Chemical group 0.000 description 5
• 150000001408 amides Chemical class 0.000 description 5
• 150000003863 ammonium salts Chemical class 0.000 description 5
• 229910052796 boron Inorganic materials 0.000 description 5
• 239000003638 chemical reducing agent Substances 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 230000004907 flux Effects 0.000 description 5
• 239000011521 glass Substances 0.000 description 5
• 125000005843 halogen group Chemical group 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• 229910052751 metal Inorganic materials 0.000 description 5
• 239000002184 metal Substances 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• 210000002569 neuron Anatomy 0.000 description 5
• 239000000546 pharmaceutical excipient Substances 0.000 description 5
• 229960001416 pilocarpine Drugs 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 238000000527 sonication Methods 0.000 description 5
• 230000000638 stimulation Effects 0.000 description 5
• 230000001629 suppression Effects 0.000 description 5
• 239000006188 syrup Substances 0.000 description 5
• 235000020357 syrup Nutrition 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 4
• 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 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 206010036105 Polyneuropathy Diseases 0.000 description 4
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
• 150000007513 acids Chemical class 0.000 description 4
• 230000004913 activation Effects 0.000 description 4
• 210000004727 amygdala Anatomy 0.000 description 4
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
• 210000004556 brain Anatomy 0.000 description 4
• 150000001805 chlorine compounds Chemical class 0.000 description 4
• 230000002920 convulsive effect Effects 0.000 description 4
• 230000001419 dependent effect Effects 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
• 238000001990 intravenous administration Methods 0.000 description 4
• 239000012948 isocyanate Substances 0.000 description 4
• 150000002513 isocyanates Chemical class 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 108020004999 messenger RNA Proteins 0.000 description 4
• 150000007522 mineralic acids Chemical class 0.000 description 4
• 230000035772 mutation Effects 0.000 description 4
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
• 150000007524 organic acids Chemical class 0.000 description 4
• 229910052763 palladium Inorganic materials 0.000 description 4
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
• LTKJAMNQTOSGOD-UHFFFAOYSA-N (2-chloro-4-nitrophenyl)carbamic acid Chemical compound OC(=O)NC1=CC=C([N+]([O-])=O)C=C1Cl LTKJAMNQTOSGOD-UHFFFAOYSA-N 0.000 description 3
• MOEXPBYTQDDUNU-UHFFFAOYSA-N (4-amino-2-methylphenyl)carbamic acid Chemical compound CC1=CC(N)=CC=C1NC(O)=O MOEXPBYTQDDUNU-UHFFFAOYSA-N 0.000 description 3
• CUCUKLJLRRAKFN-UHFFFAOYSA-N 7-Hydroxy-(S)-usnate Chemical compound CC12C(=O)C(C(=O)C)C(=O)C=C1OC1=C2C(O)=C(C)C(O)=C1C(C)=O CUCUKLJLRRAKFN-UHFFFAOYSA-N 0.000 description 3
• 206010001497 Agitation Diseases 0.000 description 3
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 229920002261 Corn starch Polymers 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• 208000002877 Epileptic Syndromes Diseases 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 238000010171 animal model Methods 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• 125000002619 bicyclic group Chemical group 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical compound C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 description 3
• 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 3
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 3
• 239000004927 clay Substances 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 239000008120 corn starch Substances 0.000 description 3
• 238000006880 cross-coupling reaction Methods 0.000 description 3
• 238000002425 crystallisation Methods 0.000 description 3
• 230000008025 crystallization Effects 0.000 description 3
• 125000004122 cyclic group Chemical group 0.000 description 3
• 239000012039 electrophile Substances 0.000 description 3
• 239000003480 eluent Substances 0.000 description 3
• 238000010828 elution Methods 0.000 description 3
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 230000001976 improved effect Effects 0.000 description 3
• 238000007918 intramuscular administration Methods 0.000 description 3
• 238000007912 intraperitoneal administration Methods 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 125000001624 naphthyl group Chemical group 0.000 description 3
• 235000005985 organic acids Nutrition 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 208000019906 panic disease Diseases 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• 229940002612 prodrug Drugs 0.000 description 3
• 239000000651 prodrug Substances 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 238000006722 reduction reaction Methods 0.000 description 3
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
• 159000000000 sodium salts Chemical class 0.000 description 3
• 231100001274 therapeutic index Toxicity 0.000 description 3
• AIWLDFXOLIMJEA-UHFFFAOYSA-N (2-methyl-4-nitrophenyl)carbamic acid Chemical compound CC1=CC([N+]([O-])=O)=CC=C1NC(O)=O AIWLDFXOLIMJEA-UHFFFAOYSA-N 0.000 description 2
• CABQBLHEESCKIP-UHFFFAOYSA-N (3-methyl-4-nitrophenyl)-[[4-(trifluoromethyl)phenyl]methyl]carbamic acid Chemical compound CC=1C=C(C=CC1[N+](=O)[O-])N(C(O)=O)CC1=CC=C(C=C1)C(F)(F)F CABQBLHEESCKIP-UHFFFAOYSA-N 0.000 description 2
• WHKVGIDSQKDXEE-UHFFFAOYSA-N (4-amino-2-chlorophenyl)carbamic acid Chemical compound NC1=CC=C(NC(O)=O)C(Cl)=C1 WHKVGIDSQKDXEE-UHFFFAOYSA-N 0.000 description 2
• TXQXBDFXTPQATN-UHFFFAOYSA-N (4-amino-3-chlorophenyl)-[(5-chlorothiophen-2-yl)methyl]carbamic acid Chemical compound NC1=C(C=C(C=C1)N(C(O)=O)CC=1SC(=CC1)Cl)Cl TXQXBDFXTPQATN-UHFFFAOYSA-N 0.000 description 2
• IQFUADQPSYSDIP-UHFFFAOYSA-N (4-aminophenyl)carbamic acid Chemical compound NC1=CC=C(NC(O)=O)C=C1 IQFUADQPSYSDIP-UHFFFAOYSA-N 0.000 description 2
• JAHSERRBNYOSLP-UHFFFAOYSA-N (4-nitrophenyl)carbamic acid Chemical compound OC(=O)NC1=CC=C([N+]([O-])=O)C=C1 JAHSERRBNYOSLP-UHFFFAOYSA-N 0.000 description 2
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
• 125000006552 (C3-C8) cycloalkyl group Chemical group 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
• SZJIQLSCDIEJFC-UHFFFAOYSA-N 1-(4-fluorophenyl)-n-methylmethanamine Chemical compound CNCC1=CC=C(F)C=C1 SZJIQLSCDIEJFC-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
• LOCWBQIWHWIRGN-UHFFFAOYSA-N 2-chloro-4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1Cl LOCWBQIWHWIRGN-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
• JUADTOTVJUYCRQ-UHFFFAOYSA-N 3-cyclohexylpropanoyl chloride Chemical compound ClC(=O)CCC1CCCCC1 JUADTOTVJUYCRQ-UHFFFAOYSA-N 0.000 description 2
• XPAYEWBTLKOEDA-UHFFFAOYSA-N 3-methyl-4-nitroaniline Chemical compound CC1=CC(N)=CC=C1[N+]([O-])=O XPAYEWBTLKOEDA-UHFFFAOYSA-N 0.000 description 2
• VWYFITBWBRVBSW-UHFFFAOYSA-N 5-chlorothiophene-2-carbaldehyde Chemical compound ClC1=CC=C(C=O)S1 VWYFITBWBRVBSW-UHFFFAOYSA-N 0.000 description 2
• QQURWFRNETXFTN-UHFFFAOYSA-N 5-fluoro-2-nitrophenol Chemical compound OC1=CC(F)=CC=C1[N+]([O-])=O QQURWFRNETXFTN-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 208000020925 Bipolar disease Diseases 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical class NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 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
• 206010011878 Deafness Diseases 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 102000004310 Ion Channels Human genes 0.000 description 2
• 108090000862 Ion Channels Proteins 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 101100498160 Mus musculus Dach1 gene Proteins 0.000 description 2
• 206010029240 Neuritis Diseases 0.000 description 2
• 206010033664 Panic attack Diseases 0.000 description 2
• 206010052794 Panic disorder with agoraphobia Diseases 0.000 description 2
• 206010033668 Panic disorder without agoraphobia Diseases 0.000 description 2
• 235000019483 Peanut oil Nutrition 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• 208000034189 Sclerosis Diseases 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• 208000031674 Traumatic Acute Stress disease Diseases 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• 241000700605 Viruses Species 0.000 description 2
• 230000036982 action potential Effects 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 125000002877 alkyl aryl group Chemical group 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 230000002059 anti-epileptogenic effect Effects 0.000 description 2
• 229940125681 anticonvulsant agent Drugs 0.000 description 2
• 125000005418 aryl aryl group Chemical group 0.000 description 2
• 230000001977 ataxic effect Effects 0.000 description 2
• 229940049706 benzodiazepine Drugs 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 2
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
• 150000001718 carbodiimides Chemical class 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 150000001735 carboxylic acids Chemical class 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 150000001793 charged compounds Chemical class 0.000 description 2
• 239000000460 chlorine Substances 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 description 2
• 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 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 231100000895 deafness Toxicity 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
• XDKSFHCRKBLVPN-UHFFFAOYSA-N ethyl n-[4-[(2,4-difluorophenyl)methylamino]-2-methoxyphenyl]carbamate Chemical compound C1=C(OC)C(NC(=O)OCC)=CC=C1NCC1=CC=C(F)C=C1F XDKSFHCRKBLVPN-UHFFFAOYSA-N 0.000 description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 229960002870 gabapentin Drugs 0.000 description 2
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 210000002768 hair cell Anatomy 0.000 description 2
• 208000016354 hearing loss disease Diseases 0.000 description 2
• 210000001320 hippocampus Anatomy 0.000 description 2
• YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 2
• 230000002631 hypothermal effect Effects 0.000 description 2
• 150000002466 imines Chemical class 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 238000007913 intrathecal administration Methods 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 239000000395 magnesium oxide Substances 0.000 description 2
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 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
• 230000037023 motor activity Effects 0.000 description 2
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
• YTKTYLWVFKOLBX-UHFFFAOYSA-N n-[(5-chlorothiophen-2-yl)methyl]-n,3-dimethyl-4-nitroaniline Chemical compound C=1C=C([N+]([O-])=O)C(C)=CC=1N(C)CC1=CC=C(Cl)S1 YTKTYLWVFKOLBX-UHFFFAOYSA-N 0.000 description 2
• WLIJYSBELWAITG-UHFFFAOYSA-N n-[2-(4-fluorophenyl)ethyl]-4-nitro-3-phenylmethoxyaniline Chemical compound C1=C(OCC=2C=CC=CC=2)C([N+](=O)[O-])=CC=C1NCCC1=CC=C(F)C=C1 WLIJYSBELWAITG-UHFFFAOYSA-N 0.000 description 2
• 230000000626 neurodegenerative effect Effects 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• 229940078552 o-xylene Drugs 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
• 239000000312 peanut oil Substances 0.000 description 2
• 230000008447 perception Effects 0.000 description 2
• 210000001428 peripheral nervous system Anatomy 0.000 description 2
• 150000002989 phenols Chemical class 0.000 description 2
• 208000019629 polyneuritis Diseases 0.000 description 2
• 230000007824 polyneuropathy Effects 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 2
• QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 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
• 102000004169 proteins and genes Human genes 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
• 229940081974 saccharin Drugs 0.000 description 2
• 235000019204 saccharin Nutrition 0.000 description 2
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 125000003107 substituted aryl group Chemical group 0.000 description 2
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 230000001256 tonic effect Effects 0.000 description 2
• 125000005270 trialkylamine group Chemical group 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 238000002604 ultrasonography Methods 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
• DBLSJJAIARSHKC-UHFFFAOYSA-N (2-methoxyphenyl)carbamic acid Chemical compound COC1=CC=CC=C1NC(O)=O DBLSJJAIARSHKC-UHFFFAOYSA-N 0.000 description 1
• NMSGCHVJZPSBBV-UHFFFAOYSA-N (4-amino-3-methylphenyl)-[[4-(trifluoromethyl)phenyl]methyl]carbamic acid Chemical compound NC1=C(C=C(C=C1)N(C(O)=O)CC1=CC=C(C=C1)C(F)(F)F)C NMSGCHVJZPSBBV-UHFFFAOYSA-N 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• AQOSPGCCTHGZFL-UHFFFAOYSA-N 1-(3a-hydroxy-7-methoxy-1,2,4,8b-tetrahydropyrrolo[2,3-b]indol-3-yl)ethanone Chemical compound COC1=CC=C2NC3(O)N(C(C)=O)CCC3C2=C1 AQOSPGCCTHGZFL-UHFFFAOYSA-N 0.000 description 1
• CIHQPXPTFQJZKN-UHFFFAOYSA-N 1-[4-[(4-fluorophenyl)methyl]-2-propan-2-yloxyphenyl]-1-methylhydrazine Chemical compound C1=C(N(C)N)C(OC(C)C)=CC(CC=2C=CC(F)=CC=2)=C1 CIHQPXPTFQJZKN-UHFFFAOYSA-N 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
• ODXSASFYKQUPFL-UHFFFAOYSA-N 2,2-dimethyl-n-(2-methyl-4-nitrophenyl)propanamide Chemical compound CC1=CC([N+]([O-])=O)=CC=C1NC(=O)C(C)(C)C ODXSASFYKQUPFL-UHFFFAOYSA-N 0.000 description 1
• PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 1
• UMQUIRYNOVNYPA-UHFFFAOYSA-N 2-(4-chlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Cl)C=C1 UMQUIRYNOVNYPA-UHFFFAOYSA-N 0.000 description 1
• ADDZHRRCUWNSCS-UHFFFAOYSA-N 2-Benzofurancarboxaldehyde Chemical compound C1=CC=C2OC(C=O)=CC2=C1 ADDZHRRCUWNSCS-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• IVQFFODLTVTZCX-UHFFFAOYSA-N 2-cyclopentyloxy-4-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1OC1CCCC1 IVQFFODLTVTZCX-UHFFFAOYSA-N 0.000 description 1
• LOLSEMNGXKAZBZ-UHFFFAOYSA-N 2-iodo-4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1I LOLSEMNGXKAZBZ-UHFFFAOYSA-N 0.000 description 1
• GVBHRNIWBGTNQA-UHFFFAOYSA-N 2-methoxy-4-nitroaniline Chemical compound COC1=CC([N+]([O-])=O)=CC=C1N GVBHRNIWBGTNQA-UHFFFAOYSA-N 0.000 description 1
• XTTIQGSLJBWVIV-UHFFFAOYSA-N 2-methyl-4-nitroaniline Chemical compound CC1=CC([N+]([O-])=O)=CC=C1N XTTIQGSLJBWVIV-UHFFFAOYSA-N 0.000 description 1
• VRDBIJCCXDEZJN-UHFFFAOYSA-N 2-piperidin-1-ylacetic acid Chemical compound OC(=O)CN1CCCCC1 VRDBIJCCXDEZJN-UHFFFAOYSA-N 0.000 description 1
• NIMYJJLXJWPXHX-UHFFFAOYSA-N 3,3-dimethyl-n-(2-methyl-4-nitrophenyl)butanamide Chemical compound CC1=CC([N+]([O-])=O)=CC=C1NC(=O)CC(C)(C)C NIMYJJLXJWPXHX-UHFFFAOYSA-N 0.000 description 1
• BUTKIHRNYUEGKB-UHFFFAOYSA-N 3,3-dimethylbutanoyl chloride Chemical compound CC(C)(C)CC(Cl)=O BUTKIHRNYUEGKB-UHFFFAOYSA-N 0.000 description 1
• KBRSJPHSCOAFDR-UHFFFAOYSA-N 3-chloro-6-methyl-5,5-dioxo-11h-benzo[c][2,1]benzothiazepin-11-ol Chemical compound O=S1(=O)N(C)C2=CC=CC=C2C(O)C2=CC=C(Cl)C=C21 KBRSJPHSCOAFDR-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• PIKNVEVCWAAOMJ-UHFFFAOYSA-N 3-fluorobenzaldehyde Chemical compound FC1=CC=CC(C=O)=C1 PIKNVEVCWAAOMJ-UHFFFAOYSA-N 0.000 description 1
• BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
• 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 1
• FOYQTDKPDAJMPF-UHFFFAOYSA-N 4-fluoro-1-nitro-2-phenylmethoxybenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1OCC1=CC=CC=C1 FOYQTDKPDAJMPF-UHFFFAOYSA-N 0.000 description 1
• SLRNETDLLJMLMR-UHFFFAOYSA-N 4-fluoro-1-nitro-2-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC(F)=CC=C1[N+]([O-])=O SLRNETDLLJMLMR-UHFFFAOYSA-N 0.000 description 1
• PRADKNLOTXNLSM-UHFFFAOYSA-N 4-fluoro-1-nitro-2-propan-2-yloxybenzene;n-[(4-fluorophenyl)methyl]-n-methyl-4-nitro-3-propan-2-yloxyaniline Chemical compound CC(C)OC1=CC(F)=CC=C1[N+]([O-])=O.C1=C([N+]([O-])=O)C(OC(C)C)=CC(N(C)CC=2C=CC(F)=CC=2)=C1 PRADKNLOTXNLSM-UHFFFAOYSA-N 0.000 description 1
• UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
• UNBMPKNTYKDYCG-UHFFFAOYSA-N 4-methylpentan-2-amine Chemical compound CC(C)CC(C)N UNBMPKNTYKDYCG-UHFFFAOYSA-N 0.000 description 1
• IYPAPVDFYYEDPJ-UHFFFAOYSA-N 5-(4-chlorophenoxy)-1,3-dimethylpyrazole-4-carbaldehyde Chemical compound CC1=NN(C)C(OC=2C=CC(Cl)=CC=2)=C1C=O IYPAPVDFYYEDPJ-UHFFFAOYSA-N 0.000 description 1
• IJJWOSAXNHWBPR-HUBLWGQQSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-(6-hydrazinyl-6-oxohexyl)pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCCCCC(=O)NN)SC[C@@H]21 IJJWOSAXNHWBPR-HUBLWGQQSA-N 0.000 description 1
• 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 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
• 244000215068 Acacia senegal Species 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 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 1
• PNZXMIKHJXIPEK-UHFFFAOYSA-N Amide-Cyclohexanecarboxylic acid Natural products NC(=O)C1CCCCC1 PNZXMIKHJXIPEK-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• HGNWMWKOPMPLKL-UHFFFAOYSA-N C1=CC(=C(C=C1N)Br)NC(=O)O Chemical compound C1=CC(=C(C=C1N)Br)NC(=O)O HGNWMWKOPMPLKL-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 102000003922 Calcium Channels Human genes 0.000 description 1
• 108090000312 Calcium Channels Proteins 0.000 description 1
• 244000224127 Camellia kissi Species 0.000 description 1
• 235000014016 Camellia kissi Nutrition 0.000 description 1
• 102000034573 Channels Human genes 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
• 208000032065 Convulsion neonatal Diseases 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
• 206010011882 Deafness congenital Diseases 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
• 101000985278 Escherichia coli 5-carboxymethyl-2-hydroxymuconate Delta-isomerase Proteins 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 108010010803 Gelatin Proteins 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
• 229920000084 Gum arabic Polymers 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000939500 Homo sapiens UBX domain-containing protein 11 Proteins 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 102100040448 Leukocyte cell-derived chemotaxin 1 Human genes 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 201000005505 Measles Diseases 0.000 description 1
• 238000006751 Mitsunobu reaction Methods 0.000 description 1
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
• NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
• KKCBUQHMOMHUOY-UHFFFAOYSA-N Na2O Inorganic materials [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
• 239000001888 Peptone Substances 0.000 description 1
• 108010080698 Peptones Proteins 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
• 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
• 241000287531 Psittacidae Species 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 244000000231 Sesamum indicum Species 0.000 description 1
• 229910004298 SiO 2 Inorganic materials 0.000 description 1
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
• 102000018674 Sodium Channels Human genes 0.000 description 1
• 108010052164 Sodium Channels Proteins 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 238000006619 Stille reaction Methods 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
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• 206010042953 Systemic sclerosis Diseases 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
• 102100029645 UBX domain-containing protein 11 Human genes 0.000 description 1
• 229930003427 Vitamin E Natural products 0.000 description 1
• 102000003734 Voltage-Gated Potassium Channels Human genes 0.000 description 1
• 108090000013 Voltage-Gated Potassium Channels Proteins 0.000 description 1
• 206010048010 Withdrawal syndrome Diseases 0.000 description 1
• RIIPFHVHLXPMHQ-UHFFFAOYSA-N [4-(dimethylamino)phenyl]boronic acid Chemical compound CN(C)C1=CC=C(B(O)O)C=C1 RIIPFHVHLXPMHQ-UHFFFAOYSA-N 0.000 description 1
• AOBADABBJXLXLD-UHFFFAOYSA-N [4-[(4-methylsulfanylphenyl)methylamino]-2-(trifluoromethyl)phenyl]carbamic acid Chemical compound CSC1=CC=C(CNC2=CC(=C(C=C2)NC(O)=O)C(F)(F)F)C=C1 AOBADABBJXLXLD-UHFFFAOYSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
• PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000012190 activator Substances 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
• 150000001347 alkyl bromides Chemical class 0.000 description 1
• 229920013820 alkyl cellulose Polymers 0.000 description 1
• 150000001348 alkyl chlorides Chemical class 0.000 description 1
• 150000001351 alkyl iodides Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 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
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
• 210000004102 animal cell Anatomy 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
• 206010003119 arrhythmia Diseases 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 210000001130 astrocyte Anatomy 0.000 description 1
• METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 1
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
• 229940125717 barbiturate Drugs 0.000 description 1
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 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
• SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical class BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 150000005524 benzylchlorides Chemical class 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
• 230000033228 biological regulation Effects 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 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
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 210000001159 caudate nucleus Anatomy 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 210000003710 cerebral cortex Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 238000004140 cleaning Methods 0.000 description 1
• 229960004414 clomethiazole Drugs 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 230000002594 corticospinal effect Effects 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 229960005168 croscarmellose Drugs 0.000 description 1
• 229960003368 croscarmellose sodium type a Drugs 0.000 description 1
• 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
• 239000013078 crystal Substances 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
• 230000007423 decrease Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 239000007933 dermal patch Substances 0.000 description 1
• 238000001514 detection method 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
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
• HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
• 208000037765 diseases and disorders Diseases 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 229920001971 elastomer Polymers 0.000 description 1
• 238000007336 electrophilic 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
• 150000002170 ethers Chemical class 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
• SNQCCZLFQJDEHG-UHFFFAOYSA-N ethyl n-(2-cyclopentyloxy-4-nitrophenyl)carbamate Chemical compound CCOC(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1CCCC1 SNQCCZLFQJDEHG-UHFFFAOYSA-N 0.000 description 1
• NZEXUOZLXSEWRF-UHFFFAOYSA-N ethyl n-(2-hydroxy-4-nitrophenyl)carbamate Chemical compound CCOC(=O)NC1=CC=C([N+]([O-])=O)C=C1O NZEXUOZLXSEWRF-UHFFFAOYSA-N 0.000 description 1
• INDLHHFLOFBUDD-UHFFFAOYSA-N ethyl n-(2-methoxy-4-nitrophenyl)carbamate;2-methoxy-4-nitroaniline Chemical compound COC1=CC([N+]([O-])=O)=CC=C1N.CCOC(=O)NC1=CC=C([N+]([O-])=O)C=C1OC INDLHHFLOFBUDD-UHFFFAOYSA-N 0.000 description 1
• CEYYPEQLAGSIMS-UHFFFAOYSA-N ethyl n-(4-amino-2-iodophenyl)carbamate Chemical compound CCOC(=O)NC1=CC=C(N)C=C1I CEYYPEQLAGSIMS-UHFFFAOYSA-N 0.000 description 1
• WYCVJCXQNWVQJY-UHFFFAOYSA-N ethyl n-(4-amino-2-methoxyphenyl)carbamate Chemical compound CCOC(=O)NC1=CC=C(N)C=C1OC WYCVJCXQNWVQJY-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 230000003203 everyday effect Effects 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 230000002461 excitatory amino acid Effects 0.000 description 1
• 239000003257 excitatory amino acid Substances 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 210000003414 extremity Anatomy 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000000796 flavoring agent Substances 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
• 150000002222 fluorine compounds Chemical class 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 1
• 150000002240 furans Chemical class 0.000 description 1
• 108700039708 galantide Proteins 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
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 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
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 230000000917 hyperalgesic effect Effects 0.000 description 1
• 230000001771 impaired effect 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
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 150000002475 indoles Chemical class 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 206010022437 insomnia Diseases 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical class ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 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
• 238000002955 isolation Methods 0.000 description 1
• 230000000155 isotopic effect Effects 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
• 229910052744 lithium Inorganic materials 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 210000003141 lower extremity Anatomy 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• CGJMROBVSBIBKP-UHFFFAOYSA-N malonamic acid Chemical compound NC(=O)CC(O)=O CGJMROBVSBIBKP-UHFFFAOYSA-N 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000017813 membrane repolarization 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
• WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 239000010413 mother solution Substances 0.000 description 1
• 230000004118 muscle contraction Effects 0.000 description 1
• 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 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
• 238000006396 nitration reaction Methods 0.000 description 1
• 150000002828 nitro derivatives Chemical class 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• 239000012038 nucleophile Substances 0.000 description 1
• 238000007339 nucleophilic aromatic substitution reaction Methods 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
• 239000003960 organic solvent Substances 0.000 description 1
• 150000002916 oxazoles Chemical class 0.000 description 1
• 125000005489 p-toluenesulfonic acid group Chemical class 0.000 description 1
• 210000002741 palatine tonsil Anatomy 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 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
• XGISHOFUAFNYQF-UHFFFAOYSA-N pentanoyl chloride Chemical compound CCCCC(Cl)=O XGISHOFUAFNYQF-UHFFFAOYSA-N 0.000 description 1
• 235000019319 peptone Nutrition 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
• 229960002036 phenytoin Drugs 0.000 description 1
• 150000003904 phospholipids Chemical class 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
• 210000002381 plasma Anatomy 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 229940069328 povidone Drugs 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000001556 precipitation Methods 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
• 230000008569 process Effects 0.000 description 1
• 210000001176 projection neuron Anatomy 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
• LBXOQOAKKNEZKV-UHFFFAOYSA-N propyl n-(4-amino-2-methylphenyl)carbamate Chemical compound CCCOC(=O)NC1=CC=C(N)C=C1C LBXOQOAKKNEZKV-UHFFFAOYSA-N 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 208000020016 psychiatric disease Diseases 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• YGDICLRMNDWZAK-UHFFFAOYSA-N quinolin-3-ylboronic acid Chemical compound C1=CC=CC2=CC(B(O)O)=CN=C21 YGDICLRMNDWZAK-UHFFFAOYSA-N 0.000 description 1
• 150000003248 quinolines Chemical class 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000012827 research and development Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000000284 resting effect Effects 0.000 description 1
• 201000005404 rubella Diseases 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
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 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
• 208000025874 separation anxiety disease Diseases 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 229910052814 silicon oxide Inorganic materials 0.000 description 1
• 208000019116 sleep disease Diseases 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
• 229910001415 sodium ion Inorganic materials 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
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000007909 solid dosage form 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
• 238000011105 stabilization Methods 0.000 description 1
• 230000010473 stable expression Effects 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000001119 stannous chloride Substances 0.000 description 1
• 235000011150 stannous chloride Nutrition 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 239000012258 stirred mixture Substances 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
• 238000011477 surgical intervention Methods 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 230000000946 synaptic effect Effects 0.000 description 1
• 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003892 tartrate salts Chemical class 0.000 description 1
• JSYWSJCDQZOEDY-UHFFFAOYSA-N tert-butyl n-(4-amino-3-methylphenyl)-n-[[4-(trifluoromethyl)phenyl]methyl]carbamate Chemical compound C1=C(N)C(C)=CC(N(CC=2C=CC(=CC=2)C(F)(F)F)C(=O)OC(C)(C)C)=C1 JSYWSJCDQZOEDY-UHFFFAOYSA-N 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 238000009210 therapy by ultrasound Methods 0.000 description 1
• 150000003557 thiazoles Chemical class 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 150000003577 thiophenes Chemical class 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
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 210000000427 trigeminal ganglion Anatomy 0.000 description 1
• 210000003462 vein 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
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 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
• 150000003952 β-lactams Chemical class 0.000 description 1