UA75871C2 - 1,2,4-oxadiazole derivatives and use thereof as antagonists at metabotropic glutamate receptors - Google Patents

1,2,4-oxadiazole derivatives and use thereof as antagonists at metabotropic glutamate receptors Download PDF

Info

Publication number: UA75871C2
Authority: UA; Ukraine
Prior art keywords: oxadiazole; pyridyl; group; cyanophenyl; chloro
Prior art date: 1999-08-19

Application number

UA2002032079A

Other languages

English (en)

Ukrainian (uk)

Inventor

Methvin Benjamin Isaac

Original Assignee

Nps Pharma Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-08-19

Filing date

2000-08-18

Publication date

2006-06-15

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22530400&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=UA75871(C2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2000-08-18 Application filed by Nps Pharma Inc filed Critical Nps Pharma Inc

2006-06-15 Publication of UA75871C2 publication Critical patent/UA75871C2/uk

Links

102000016193 Metabotropic glutamate receptors Human genes 0.000 title claims abstract description 13
108010010914 Metabotropic glutamate receptors Proteins 0.000 title claims abstract description 13
150000005071 1,2,4-oxadiazoles Chemical class 0.000 title claims description 33
239000005557 antagonist Substances 0.000 title abstract description 21
150000001875 compounds Chemical class 0.000 claims abstract description 55
208000012902 Nervous system disease Diseases 0.000 claims abstract description 13
208000025966 Neurological disease Diseases 0.000 claims abstract description 12
125000003118 aryl group Chemical group 0.000 claims abstract description 11
229910052799 carbon Inorganic materials 0.000 claims abstract description 7
102000005962 receptors Human genes 0.000 claims description 32
108020003175 receptors Proteins 0.000 claims description 32
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
201000010099 disease Diseases 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 11
208000035475 disorder Diseases 0.000 claims description 11
229930195712 glutamate Natural products 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 10
229910052700 potassium Inorganic materials 0.000 claims description 8
OTAZWJWYCGCZPY-UHFFFAOYSA-N 3-pyridin-2-yl-5-(2,3,6-trifluorophenyl)-1,2,4-oxadiazole Chemical compound FC1=CC=C(F)C(C=2ON=C(N=2)C=2N=CC=CC=2)=C1F OTAZWJWYCGCZPY-UHFFFAOYSA-N 0.000 claims description 7
125000002877 alkyl aryl group Chemical group 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
KZOBYFBUONCLFZ-UHFFFAOYSA-N 3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 KZOBYFBUONCLFZ-UHFFFAOYSA-N 0.000 claims description 6
JWGWZTPLPSOQLP-UHFFFAOYSA-N 5-(2,5-difluorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound FC1=CC=C(F)C(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 JWGWZTPLPSOQLP-UHFFFAOYSA-N 0.000 claims description 6
NGKWCJCCZGCLID-UHFFFAOYSA-N 5-(2-chlorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound ClC1=CC=CC=C1C1=NC(C=2N=CC=CC=2)=NO1 NGKWCJCCZGCLID-UHFFFAOYSA-N 0.000 claims description 6
QAWYDHMYEBUWOI-UHFFFAOYSA-N 5-(3-chloro-5-fluorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound FC1=CC(Cl)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 QAWYDHMYEBUWOI-UHFFFAOYSA-N 0.000 claims description 6
230000006378 damage Effects 0.000 claims description 6
GELAFISMURFRCA-UHFFFAOYSA-N 3-fluoro-5-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound FC1=CC(C#N)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 GELAFISMURFRCA-UHFFFAOYSA-N 0.000 claims description 5
IBIPNEKWIOPNFP-UHFFFAOYSA-N 5-(2,3-dichlorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound ClC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1Cl IBIPNEKWIOPNFP-UHFFFAOYSA-N 0.000 claims description 5
HSLAPYCDJGEODS-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound ClC1=CC(Cl)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 HSLAPYCDJGEODS-UHFFFAOYSA-N 0.000 claims description 5
PREUPKHXEHMSKI-UHFFFAOYSA-N 5-(5-chloro-2-methoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC=C(Cl)C=C1C1=NC(C=2N=CC=CC=2)=NO1 PREUPKHXEHMSKI-UHFFFAOYSA-N 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
208000020016 psychiatric disease Diseases 0.000 claims description 5
ACEMLHPTBCVQEO-UHFFFAOYSA-N 3-[3-(3-fluoropyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound FC1=CC=CN=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 ACEMLHPTBCVQEO-UHFFFAOYSA-N 0.000 claims description 4
JTCHHBMKZRITLW-UHFFFAOYSA-N 3-[3-(5-fluoropyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound N1=CC(F)=CC=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 JTCHHBMKZRITLW-UHFFFAOYSA-N 0.000 claims description 4
BRSJLLPXGUAIGO-UHFFFAOYSA-N 3-[3-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound ClC1=CC(C(F)(F)F)=CN=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 BRSJLLPXGUAIGO-UHFFFAOYSA-N 0.000 claims description 4
NEBUBOGLNXERLF-UHFFFAOYSA-N 3-chloro-5-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound ClC1=CC(C#N)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 NEBUBOGLNXERLF-UHFFFAOYSA-N 0.000 claims description 4
RBSPCALDSNXWEP-UHFFFAOYSA-N 3-fluoro-5-[3-(5-fluoropyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound N1=CC(F)=CC=C1C1=NOC(C=2C=C(C=C(F)C=2)C#N)=N1 RBSPCALDSNXWEP-UHFFFAOYSA-N 0.000 claims description 4
MWFUWMAFXIIDOK-UHFFFAOYSA-N 5-(3,5-difluorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound FC1=CC(F)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 MWFUWMAFXIIDOK-UHFFFAOYSA-N 0.000 claims description 4
208000024827 Alzheimer disease Diseases 0.000 claims description 4
206010019196 Head injury Diseases 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
206010015037 epilepsy Diseases 0.000 claims description 4
YWSNJWSAQDJCBJ-UHFFFAOYSA-N 5-(3-bromophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound BrC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 YWSNJWSAQDJCBJ-UHFFFAOYSA-N 0.000 claims description 3
IMLLSKDXLVDFRH-UHFFFAOYSA-N 5-(3-chlorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound ClC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 IMLLSKDXLVDFRH-UHFFFAOYSA-N 0.000 claims description 3
206010012289 Dementia Diseases 0.000 claims description 3
208000019695 Migraine disease Diseases 0.000 claims description 3
208000002193 Pain Diseases 0.000 claims description 3
208000018737 Parkinson disease Diseases 0.000 claims description 3
230000036407 pain Effects 0.000 claims description 3
201000000980 schizophrenia Diseases 0.000 claims description 3
NPHDXXRKYHPQLD-UHFFFAOYSA-N 5-(3-methylphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound CC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 NPHDXXRKYHPQLD-UHFFFAOYSA-N 0.000 claims description 2
208000013016 Hypoglycemia Diseases 0.000 claims description 2
230000002218 hypoglycaemic effect Effects 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
VMDCHMHYENMYCK-UHFFFAOYSA-N 5-phenyl-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound C1=CC=CC=C1C1=NC(C=2N=CC=CC=2)=NO1 VMDCHMHYENMYCK-UHFFFAOYSA-N 0.000 claims 2
208000020401 Depressive disease Diseases 0.000 claims 1
208000023105 Huntington disease Diseases 0.000 claims 1
208000027418 Wounds and injury Diseases 0.000 claims 1
208000014674 injury Diseases 0.000 claims 1
208000037906 ischaemic injury Diseases 0.000 claims 1
229940126601 medicinal product Drugs 0.000 claims 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
125000000623 heterocyclic group Chemical group 0.000 abstract description 15
125000005842 heteroatom Chemical group 0.000 abstract description 8
229910002091 carbon monoxide Inorganic materials 0.000 abstract description 3
229910052757 nitrogen Inorganic materials 0.000 abstract description 2
229910052760 oxygen Inorganic materials 0.000 abstract description 2
229910052717 sulfur Inorganic materials 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 82
238000000034 method Methods 0.000 description 68
230000015572 biosynthetic process Effects 0.000 description 57
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 56
239000000243 solution Substances 0.000 description 52
238000003786 synthesis reaction Methods 0.000 description 48
-1 2-oxazole Chemical compound 0.000 description 45
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 41
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
239000011541 reaction mixture Substances 0.000 description 31
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
230000004913 activation Effects 0.000 description 28
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
239000000203 mixture Substances 0.000 description 27
238000010992 reflux Methods 0.000 description 27
210000004027 cell Anatomy 0.000 description 25
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
238000010898 silica gel chromatography Methods 0.000 description 20
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
238000012360 testing method Methods 0.000 description 19
239000000556 agonist Substances 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 16
239000007787 solid Substances 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 14
238000001953 recrystallisation Methods 0.000 description 14
230000003197 catalytic effect Effects 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 13
239000003826 tablet Substances 0.000 description 13
239000002904 solvent Substances 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
210000002569 neuron Anatomy 0.000 description 11
230000004044 response Effects 0.000 description 11
239000000872 buffer Substances 0.000 description 9
230000005284 excitation Effects 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
239000012267 brine Substances 0.000 description 8
239000011575 calcium Substances 0.000 description 8
238000001816 cooling Methods 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 7
RPESZQVUWMFBEO-UHFFFAOYSA-N 3-cyanobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(C#N)=C1 RPESZQVUWMFBEO-UHFFFAOYSA-N 0.000 description 7
230000000694 effects Effects 0.000 description 7
238000005160 1H NMR spectroscopy Methods 0.000 description 6
JKPMWUHRDUMXKK-UHFFFAOYSA-N 2-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)aniline Chemical compound NC1=CC=CC=C1C1=NC(C=2N=CC=CC=2)=NO1 JKPMWUHRDUMXKK-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 6
210000003169 central nervous system Anatomy 0.000 description 6
SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
238000001914 filtration Methods 0.000 description 6
239000003102 growth factor Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
230000004048 modification Effects 0.000 description 6
238000012986 modification Methods 0.000 description 6
239000008194 pharmaceutical composition Substances 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
239000000126 substance Substances 0.000 description 6
GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 6
FKZJTFVDFGPXSB-UHFFFAOYSA-N 3-(3-quinolin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2ON=C(N=2)C=2N=C3C=CC=CC3=CC=2)=C1 FKZJTFVDFGPXSB-UHFFFAOYSA-N 0.000 description 5
XKZXZXODZDSMKN-UHFFFAOYSA-N 3-[3-(5-methoxypyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound N1=CC(OC)=CC=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 XKZXZXODZDSMKN-UHFFFAOYSA-N 0.000 description 5
GIHMKZCHBTWVSO-UHFFFAOYSA-N 5-(2,3-difluorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound FC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1F GIHMKZCHBTWVSO-UHFFFAOYSA-N 0.000 description 5
UTVLFQJTGRGDDM-UHFFFAOYSA-N 5-(3-methoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 UTVLFQJTGRGDDM-UHFFFAOYSA-N 0.000 description 5
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 5
125000004429 atom Chemical group 0.000 description 5
229910052791 calcium Inorganic materials 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000000428 dust Substances 0.000 description 5
230000003834 intracellular effect Effects 0.000 description 5
239000002609 medium Substances 0.000 description 5
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
230000009466 transformation Effects 0.000 description 5
229910052725 zinc Inorganic materials 0.000 description 5
239000011701 zinc Substances 0.000 description 5
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 4
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 4
SQUAEZRORGDMPG-UHFFFAOYSA-N 3-[3-(5-chloropyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound N1=CC(Cl)=CC=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 SQUAEZRORGDMPG-UHFFFAOYSA-N 0.000 description 4
FPYLVHWPDOYNOI-UHFFFAOYSA-N 4-pyridin-2-yl-2-(2,3,6-trifluorophenyl)-1,3-oxazole Chemical compound FC1=CC=C(F)C(C=2OC=C(N=2)C=2N=CC=CC=2)=C1F FPYLVHWPDOYNOI-UHFFFAOYSA-N 0.000 description 4
XUZXZGGCOASVTJ-UHFFFAOYSA-N 5-(2-bromo-5-methoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC=C(Br)C(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 XUZXZGGCOASVTJ-UHFFFAOYSA-N 0.000 description 4
PBVARAUVAZZUHN-UHFFFAOYSA-N 5-(3,5-dimethoxyphenyl)-3-(5-fluoropyridin-2-yl)-1,2,4-oxadiazole Chemical compound COC1=CC(OC)=CC(C=2ON=C(N=2)C=2N=CC(F)=CC=2)=C1 PBVARAUVAZZUHN-UHFFFAOYSA-N 0.000 description 4
NFNZGNPPPSUBSN-UHFFFAOYSA-N 5-(3,5-dimethoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC(OC)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 NFNZGNPPPSUBSN-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 4
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
239000004472 Lysine Substances 0.000 description 4
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 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
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
238000003556 assay Methods 0.000 description 4
210000001130 astrocyte Anatomy 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
230000037396 body weight Effects 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
150000001805 chlorine compounds Chemical class 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
125000004122 cyclic group Chemical group 0.000 description 4
ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 4
231100000673 dose–response relationship Toxicity 0.000 description 4
239000008298 dragée Substances 0.000 description 4
230000002964 excitative effect Effects 0.000 description 4
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
208000004296 neuralgia Diseases 0.000 description 4
238000002414 normal-phase solid-phase extraction Methods 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
229910052709 silver Inorganic materials 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
LOOGPKFISVEXCP-UHFFFAOYSA-N 2-[3-(3-chlorophenyl)-1h-1,2,4-triazol-5-yl]pyridine Chemical compound ClC1=CC=CC(C=2NN=C(N=2)C=2N=CC=CC=2)=C1 LOOGPKFISVEXCP-UHFFFAOYSA-N 0.000 description 3
FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 3
KKCMPWWHEFYPCT-UHFFFAOYSA-N 3-(3-methoxyphenyl)-5-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC=CC(C=2N=C(ON=2)C=2N=CC=CC=2)=C1 KKCMPWWHEFYPCT-UHFFFAOYSA-N 0.000 description 3
HADZSOZVTCEMNP-UHFFFAOYSA-N 3-cyano-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC(C#N)=C1 HADZSOZVTCEMNP-UHFFFAOYSA-N 0.000 description 3
BUOOPPZRKFHIRP-UHFFFAOYSA-N 3-pyridin-2-yl-5-(3,4,5-trifluorophenyl)-1,2,4-oxadiazole Chemical compound FC1=C(F)C(F)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 BUOOPPZRKFHIRP-UHFFFAOYSA-N 0.000 description 3
HCFSVVMXJRUPET-UHFFFAOYSA-N 4-chloro-2-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)phenol Chemical compound OC1=CC=C(Cl)C=C1C1=NC(C=2N=CC=CC=2)=NO1 HCFSVVMXJRUPET-UHFFFAOYSA-N 0.000 description 3
HJMPRAZONMDZOD-UHFFFAOYSA-N 5-(2,3-dimethoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1OC HJMPRAZONMDZOD-UHFFFAOYSA-N 0.000 description 3
BAHKRFBCZDXBRK-UHFFFAOYSA-N 5-(2-chloro-5-methylsulfanylphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound CSC1=CC=C(Cl)C(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 BAHKRFBCZDXBRK-UHFFFAOYSA-N 0.000 description 3
KKOMUMXAHMIGQB-UHFFFAOYSA-N 5-(3-fluorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound FC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 KKOMUMXAHMIGQB-UHFFFAOYSA-N 0.000 description 3
CLJZFDWXGGBINO-UHFFFAOYSA-N 5-(3-phenoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound C=1C=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=CC=1OC1=CC=CC=C1 CLJZFDWXGGBINO-UHFFFAOYSA-N 0.000 description 3
WTHODOKFSYPTKA-UHFFFAOYSA-N 5-chloropyridine-2-carbonitrile Chemical compound ClC1=CC=C(C#N)N=C1 WTHODOKFSYPTKA-UHFFFAOYSA-N 0.000 description 3
BHXHRMVSUUPOLX-UHFFFAOYSA-N 5-fluoropyridine-2-carbonitrile Chemical compound FC1=CC=C(C#N)N=C1 BHXHRMVSUUPOLX-UHFFFAOYSA-N 0.000 description 3
YGUDIHOQAIXIFH-UHFFFAOYSA-N 5-naphthalen-1-yl-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound N1=CC=CC=C1C1=NOC(C=2C3=CC=CC=C3C=CC=2)=N1 YGUDIHOQAIXIFH-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
241000700159 Rattus Species 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
229940114079 arachidonic acid Drugs 0.000 description 3
235000021342 arachidonic acid Nutrition 0.000 description 3
239000012131 assay buffer Substances 0.000 description 3
125000002619 bicyclic group Chemical group 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
229940014259 gelatin Drugs 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
125000001072 heteroaryl group Chemical group 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
125000002950 monocyclic group Chemical group 0.000 description 3
150000002825 nitriles Chemical class 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 3
PQEZLFXQUJSYLI-UHFFFAOYSA-N phenyl-[3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)phenyl]methanone Chemical compound C=1C=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=CC=1C(=O)C1=CC=CC=C1 PQEZLFXQUJSYLI-UHFFFAOYSA-N 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
230000001242 postsynaptic effect Effects 0.000 description 3
239000002243 precursor Substances 0.000 description 3
230000003518 presynaptic effect Effects 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
125000005493 quinolyl group Chemical group 0.000 description 3
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
230000005062 synaptic transmission Effects 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 2
HTJMXYRLEDBSLT-UHFFFAOYSA-N 1,2,4,5-tetrazine Chemical compound C1=NN=CN=N1 HTJMXYRLEDBSLT-UHFFFAOYSA-N 0.000 description 2
YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 2
FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 2
UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 description 2
FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 2
YYUIROVDIXDEKU-UHFFFAOYSA-N 1,3,4-oxathiazole Chemical compound C1OC=NS1 YYUIROVDIXDEKU-UHFFFAOYSA-N 0.000 description 2
MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 2
JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 2
AICIYIDUYNFPRY-UHFFFAOYSA-N 1,3-dihydro-2H-imidazol-2-one Chemical compound O=C1NC=CN1 AICIYIDUYNFPRY-UHFFFAOYSA-N 0.000 description 2
ZWEGOVJVJZJDQJ-UHFFFAOYSA-N 1,4,2-dioxazole Chemical compound C1OC=NO1 ZWEGOVJVJZJDQJ-UHFFFAOYSA-N 0.000 description 2
CEBAFUFWRQAHJL-UHFFFAOYSA-N 1,4,2-oxathiazole Chemical compound C1ON=CS1 CEBAFUFWRQAHJL-UHFFFAOYSA-N 0.000 description 2
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 2
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 description 2
DMUGJQMADYEWSQ-UHFFFAOYSA-N 2,3,6-trifluorobenzoyl chloride Chemical compound FC1=CC=C(F)C(C(Cl)=O)=C1F DMUGJQMADYEWSQ-UHFFFAOYSA-N 0.000 description 2
LWTIGYSPAXKMDG-UHFFFAOYSA-N 2,3-dihydro-1h-imidazole Chemical compound C1NC=CN1 LWTIGYSPAXKMDG-UHFFFAOYSA-N 0.000 description 2
VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 2
JQNBCSPQVSUBSR-UHFFFAOYSA-N 2,3-dimethoxybenzoyl chloride Chemical compound COC1=CC=CC(C(Cl)=O)=C1OC JQNBCSPQVSUBSR-UHFFFAOYSA-N 0.000 description 2
FFMBYMANYCDCMK-UHFFFAOYSA-N 2,5-dihydro-1h-imidazole Chemical compound C1NCN=C1 FFMBYMANYCDCMK-UHFFFAOYSA-N 0.000 description 2
AAWCNLJAPJLNKK-UHFFFAOYSA-N 2-(2,3-dichlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1Cl AAWCNLJAPJLNKK-UHFFFAOYSA-N 0.000 description 2
RJOREFFZIBPFKY-UHFFFAOYSA-N 2-(2,3-difluorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound FC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1F RJOREFFZIBPFKY-UHFFFAOYSA-N 0.000 description 2
LRFMDDYKWJYVBK-UHFFFAOYSA-N 2-(2,5-difluorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound FC1=CC=C(F)C(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 LRFMDDYKWJYVBK-UHFFFAOYSA-N 0.000 description 2
ZLPWRJCQPWCDGU-UHFFFAOYSA-N 2-(2-bromo-5-methoxyphenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound COC1=CC=C(Br)C(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 ZLPWRJCQPWCDGU-UHFFFAOYSA-N 0.000 description 2
YXDVCVJVOFDWQF-UHFFFAOYSA-N 2-(2-chlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC=CC=C1C1=NC(C=2N=CC=CC=2)=CO1 YXDVCVJVOFDWQF-UHFFFAOYSA-N 0.000 description 2
ASQZRZJOTGTSSV-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC(Cl)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 ASQZRZJOTGTSSV-UHFFFAOYSA-N 0.000 description 2
YHRDDEHPQTZUOC-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound FC1=CC(F)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 YHRDDEHPQTZUOC-UHFFFAOYSA-N 0.000 description 2
IUSLSOMMUPIHNA-UHFFFAOYSA-N 2-(3,5-dimethoxyphenyl)-4-(5-fluoropyridin-2-yl)-1,3-oxazole Chemical compound COC1=CC(OC)=CC(C=2OC=C(N=2)C=2N=CC(F)=CC=2)=C1 IUSLSOMMUPIHNA-UHFFFAOYSA-N 0.000 description 2
LPMYOKHUPLYHGH-UHFFFAOYSA-N 2-(3,5-dimethoxyphenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound COC1=CC(OC)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 LPMYOKHUPLYHGH-UHFFFAOYSA-N 0.000 description 2
HFGWLRAJYOVQAY-UHFFFAOYSA-N 2-(3-bromophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound BrC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 HFGWLRAJYOVQAY-UHFFFAOYSA-N 0.000 description 2
DVWPIPCIVDZTFL-UHFFFAOYSA-N 2-(3-chloro-5-fluorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound FC1=CC(Cl)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 DVWPIPCIVDZTFL-UHFFFAOYSA-N 0.000 description 2
CQXOVXIKDZNZMV-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 CQXOVXIKDZNZMV-UHFFFAOYSA-N 0.000 description 2
SIWHIGOKGZLPDD-UHFFFAOYSA-N 2-(3-methoxyphenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound COC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 SIWHIGOKGZLPDD-UHFFFAOYSA-N 0.000 description 2
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 2
PMOQVFICQPOUQU-UHFFFAOYSA-N 2-[3-(3-iodophenyl)-1h-1,2,4-triazol-5-yl]pyridine Chemical compound IC1=CC=CC(C=2NN=C(N=2)C=2N=CC=CC=2)=C1 PMOQVFICQPOUQU-UHFFFAOYSA-N 0.000 description 2
DNPMOGQMEOPVNT-UHFFFAOYSA-N 2-bromo-1-pyridin-2-ylethanone Chemical compound BrCC(=O)C1=CC=CC=N1 DNPMOGQMEOPVNT-UHFFFAOYSA-N 0.000 description 2
RZCQJXVXRYIJQE-UHFFFAOYSA-N 2-bromo-5-methoxybenzoyl chloride Chemical compound COC1=CC=C(Br)C(C(Cl)=O)=C1 RZCQJXVXRYIJQE-UHFFFAOYSA-N 0.000 description 2
NDONJURDFYQATR-UHFFFAOYSA-N 2-chloro-5-methylbenzenecarbothioyl chloride Chemical compound CC1=CC=C(Cl)C(C(Cl)=S)=C1 NDONJURDFYQATR-UHFFFAOYSA-N 0.000 description 2
DTCUYJPWUOVEAD-UHFFFAOYSA-N 2-naphthalen-1-yl-4-pyridin-2-yl-1,3-oxazole Chemical compound C=1OC(C=2C3=CC=CC=C3C=CC=2)=NC=1C1=CC=CC=N1 DTCUYJPWUOVEAD-UHFFFAOYSA-N 0.000 description 2
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 2
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 2
YRUNCQNKZIQTEO-UHFFFAOYSA-N 3,4,5-trifluorobenzoyl chloride Chemical compound FC1=CC(C(Cl)=O)=CC(F)=C1F YRUNCQNKZIQTEO-UHFFFAOYSA-N 0.000 description 2
XZDUVAVPEQYRJT-UHFFFAOYSA-N 3-(4-pyridin-2-yl-1,3-oxazol-2-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 XZDUVAVPEQYRJT-UHFFFAOYSA-N 0.000 description 2
WILMXYZSNMNDTC-UHFFFAOYSA-N 3-(4-quinolin-2-yl-1,3-oxazol-2-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2OC=C(N=2)C=2N=C3C=CC=CC3=CC=2)=C1 WILMXYZSNMNDTC-UHFFFAOYSA-N 0.000 description 2
LTWCNRAEKVTUGX-UHFFFAOYSA-N 3-[4-(5-chloropyridin-2-yl)-1,3-oxazol-2-yl]benzonitrile Chemical compound N1=CC(Cl)=CC=C1C1=COC(C=2C=C(C=CC=2)C#N)=N1 LTWCNRAEKVTUGX-UHFFFAOYSA-N 0.000 description 2
FQISOUJORHQCKI-UHFFFAOYSA-N 3-[4-(5-fluoropyridin-2-yl)-1,3-oxazol-2-yl]benzonitrile Chemical compound N1=CC(F)=CC=C1C1=COC(C=2C=C(C=CC=2)C#N)=N1 FQISOUJORHQCKI-UHFFFAOYSA-N 0.000 description 2
ROQYQCOWQVBTHR-UHFFFAOYSA-N 3-[4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-1,3-oxazol-2-yl]benzonitrile Chemical compound ClC1=CC(C(F)(F)F)=CN=C1C1=COC(C=2C=C(C=CC=2)C#N)=N1 ROQYQCOWQVBTHR-UHFFFAOYSA-N 0.000 description 2
RBBMPXMOUHLZIO-UHFFFAOYSA-N 3-benzoylbenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 RBBMPXMOUHLZIO-UHFFFAOYSA-N 0.000 description 2
YWIPSYPWKZNEDJ-UHFFFAOYSA-N 3-chloro-5-cyanobenzoyl chloride Chemical compound ClC(=O)C1=CC(Cl)=CC(C#N)=C1 YWIPSYPWKZNEDJ-UHFFFAOYSA-N 0.000 description 2
CQQPZYVMGWYJOO-UHFFFAOYSA-N 3-chloro-5-fluorobenzoyl chloride Chemical compound FC1=CC(Cl)=CC(C(Cl)=O)=C1 CQQPZYVMGWYJOO-UHFFFAOYSA-N 0.000 description 2
LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
YDPLFBIGFQFIDB-UHFFFAOYSA-N 3-chloropyridine-2-carbonitrile Chemical compound ClC1=CC=CN=C1C#N YDPLFBIGFQFIDB-UHFFFAOYSA-N 0.000 description 2
WLBLIJUBANCKOH-UHFFFAOYSA-N 3-cyano-5-fluorobenzoyl chloride Chemical compound FC1=CC(C#N)=CC(C(Cl)=O)=C1 WLBLIJUBANCKOH-UHFFFAOYSA-N 0.000 description 2
LARWPXDSCLBOFH-UHFFFAOYSA-N 3-fluoro-5-[4-(5-fluoropyridin-2-yl)-1,3-oxazol-2-yl]benzonitrile Chemical compound N1=CC(F)=CC=C1C1=COC(C=2C=C(C=C(F)C=2)C#N)=N1 LARWPXDSCLBOFH-UHFFFAOYSA-N 0.000 description 2
TTZXIWBOKOZOPL-UHFFFAOYSA-N 3-phenoxybenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(OC=2C=CC=CC=2)=C1 TTZXIWBOKOZOPL-UHFFFAOYSA-N 0.000 description 2
GTUAPLZFNZVARE-UHFFFAOYSA-N 3h-1,2,4-oxathiazole Chemical compound C1SOC=N1 GTUAPLZFNZVARE-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
IOQSPWXNEANOEM-UHFFFAOYSA-N 4-pyridin-2-yl-2-[3-(trifluoromethoxy)phenyl]-1,3-oxazole Chemical compound FC(F)(F)OC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 IOQSPWXNEANOEM-UHFFFAOYSA-N 0.000 description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
MRUWJENAYHTDQG-UHFFFAOYSA-N 4H-pyran Chemical compound C1C=COC=C1 MRUWJENAYHTDQG-UHFFFAOYSA-N 0.000 description 2
STBGWNRZMPCVTG-UHFFFAOYSA-N 4h-thiopyran Chemical compound C1C=CSC=C1 STBGWNRZMPCVTG-UHFFFAOYSA-N 0.000 description 2
YYKRPCBJFTUNFZ-UHFFFAOYSA-N 5-(3-nitrophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound [O-][N+](=O)C1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 YYKRPCBJFTUNFZ-UHFFFAOYSA-N 0.000 description 2
JVLUMHRASWENRU-UHFFFAOYSA-N 5-chloro-2-methoxybenzoyl chloride Chemical compound COC1=CC=C(Cl)C=C1C(Cl)=O JVLUMHRASWENRU-UHFFFAOYSA-N 0.000 description 2
XUGRSPXJFBZQSS-UHFFFAOYSA-N 5-methoxypyridine-2-carbonitrile Chemical compound COC1=CC=C(C#N)N=C1 XUGRSPXJFBZQSS-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
241000772991 Aira Species 0.000 description 2
208000019901 Anxiety disease Diseases 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
206010008748 Chorea Diseases 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-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
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
ASNFTDCKZKHJSW-UHFFFAOYSA-N DL-Quisqualic acid Natural products OC(=O)C(N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
208000032131 Diabetic Neuropathies Diseases 0.000 description 2
206010012667 Diabetic glaucoma Diseases 0.000 description 2
206010012689 Diabetic retinopathy Diseases 0.000 description 2
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 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 2
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 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
ASNFTDCKZKHJSW-REOHCLBHSA-N Quisqualic acid Chemical compound OC(=O)[C@@H](N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-REOHCLBHSA-N 0.000 description 2
206010038923 Retinopathy Diseases 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 2
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
208000009205 Tinnitus Diseases 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
102000014384 Type C Phospholipases Human genes 0.000 description 2
108010079194 Type C Phospholipases Proteins 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000000654 additive Substances 0.000 description 2
125000005213 alkyl heteroaryl group Chemical group 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
230000036506 anxiety Effects 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
238000009835 boiling Methods 0.000 description 2
125000002837 carbocyclic group Chemical group 0.000 description 2
150000003857 carboxamides Chemical class 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
238000002512 chemotherapy Methods 0.000 description 2
208000012601 choreatic disease Diseases 0.000 description 2
238000000576 coating method Methods 0.000 description 2
ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 2
BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
239000000975 dye Substances 0.000 description 2
229950005627 embonate Drugs 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
238000000605 extraction Methods 0.000 description 2
239000012894 fetal calf serum Substances 0.000 description 2
239000000945 filler Substances 0.000 description 2
230000005714 functional activity Effects 0.000 description 2
JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
239000000499 gel Substances 0.000 description 2
229940050410 gluconate Drugs 0.000 description 2
239000008103 glucose Substances 0.000 description 2
125000005283 haloketone group Chemical group 0.000 description 2
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 2
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 2
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
125000001041 indolyl group Chemical group 0.000 description 2
230000001057 ionotropic effect Effects 0.000 description 2
230000000302 ischemic effect Effects 0.000 description 2
125000005956 isoquinolyl group Chemical group 0.000 description 2
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
102000006239 metabotropic receptors Human genes 0.000 description 2
108020004083 metabotropic receptors Proteins 0.000 description 2
JCOFSHLLQXPNDX-UHFFFAOYSA-N methyl 3-chloro-5-cyanobenzoate Chemical compound COC(=O)C1=CC(Cl)=CC(C#N)=C1 JCOFSHLLQXPNDX-UHFFFAOYSA-N 0.000 description 2
206010027599 migraine Diseases 0.000 description 2
CEHMGZTZNNEADY-UHFFFAOYSA-N n'-hydroxy-3-methoxybenzenecarboximidamide Chemical compound COC1=CC=CC(C(N)=NO)=C1 CEHMGZTZNNEADY-UHFFFAOYSA-N 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
230000000926 neurological effect Effects 0.000 description 2
230000003961 neuronal insult Effects 0.000 description 2
230000002981 neuropathic effect Effects 0.000 description 2
208000021722 neuropathic pain Diseases 0.000 description 2
201000001119 neuropathy Diseases 0.000 description 2
230000007823 neuropathy Effects 0.000 description 2
230000000324 neuroprotective effect Effects 0.000 description 2
210000000287 oocyte Anatomy 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 2
150000004866 oxadiazoles Chemical class 0.000 description 2
230000007170 pathology Effects 0.000 description 2
230000035778 pathophysiological process Effects 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
150000003906 phosphoinositides Chemical class 0.000 description 2
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
235000003270 potassium fluoride Nutrition 0.000 description 2
239000011698 potassium fluoride Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
230000008569 process Effects 0.000 description 2
238000012545 processing Methods 0.000 description 2
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
125000003373 pyrazinyl group Chemical group 0.000 description 2
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 2
DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 2
125000005412 pyrazyl group Chemical group 0.000 description 2
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
125000002098 pyridazinyl group Chemical group 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
125000000714 pyrimidinyl group Chemical group 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
229960001860 salicylate Drugs 0.000 description 2
238000005070 sampling Methods 0.000 description 2
238000012216 screening Methods 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
229940095064 tartrate Drugs 0.000 description 2
125000000335 thiazolyl group Chemical group 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
231100000886 tinnitus Toxicity 0.000 description 2
238000000844 transformation Methods 0.000 description 2
238000005406 washing Methods 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
IICQXOJPUDICND-UHFFFAOYSA-N 1,2,4-triazole-3,5-dione Chemical compound O=C1NC(=O)N=N1 IICQXOJPUDICND-UHFFFAOYSA-N 0.000 description 1
CDCHBOQVXIGZHA-UHFFFAOYSA-N 1,2-dihydropyrrol-5-one Chemical compound O=C1NCC=C1 CDCHBOQVXIGZHA-UHFFFAOYSA-N 0.000 description 1
KCOPAESEGCGTKM-UHFFFAOYSA-N 1,3-oxazol-4-one Chemical compound O=C1COC=N1 KCOPAESEGCGTKM-UHFFFAOYSA-N 0.000 description 1
GGMDFPMASIXEIR-UHFFFAOYSA-N 1-bromo-3-chloro-5-fluorobenzene Chemical compound FC1=CC(Cl)=CC(Br)=C1 GGMDFPMASIXEIR-UHFFFAOYSA-N 0.000 description 1
FKHVWXNPDWQSIT-UHFFFAOYSA-N 1-chloro-3-fluoro-5-methylbenzene Chemical compound CC1=CC(F)=CC(Cl)=C1 FKHVWXNPDWQSIT-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
OPOJRMTZHYUKLY-UHFFFAOYSA-N 1h-1,3,5-triazin-2-one Chemical compound O=C1N=CN=CN1 OPOJRMTZHYUKLY-UHFFFAOYSA-N 0.000 description 1
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
HFAYWAUCHUMJMH-UHFFFAOYSA-N 1h-pyrimidine-4,6-dione Chemical compound O=C1CC(=O)N=CN1 HFAYWAUCHUMJMH-UHFFFAOYSA-N 0.000 description 1
YBONBWJSFMTXLE-UHFFFAOYSA-N 2,3-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Cl)=C1Cl YBONBWJSFMTXLE-UHFFFAOYSA-N 0.000 description 1
MAKFMOSBBNKPMS-UHFFFAOYSA-N 2,3-dichloropyridine Chemical compound ClC1=CC=CN=C1Cl MAKFMOSBBNKPMS-UHFFFAOYSA-N 0.000 description 1
CDCFERWURRNLLA-UHFFFAOYSA-N 2,3-difluorobenzoyl chloride Chemical compound FC1=CC=CC(C(Cl)=O)=C1F CDCFERWURRNLLA-UHFFFAOYSA-N 0.000 description 1
ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
GCTFDMFLLBCLPF-UHFFFAOYSA-N 2,5-dichloropyridine Chemical compound ClC1=CC=C(Cl)N=C1 GCTFDMFLLBCLPF-UHFFFAOYSA-N 0.000 description 1
RLRUKKDFNWXXRT-UHFFFAOYSA-N 2,5-difluorobenzoyl chloride Chemical compound FC1=CC=C(F)C(C(Cl)=O)=C1 RLRUKKDFNWXXRT-UHFFFAOYSA-N 0.000 description 1
DEMSILUPLXBKQE-UHFFFAOYSA-N 2-(2-chloro-5-methylsulfanylphenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound CSC1=CC=C(Cl)C(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 DEMSILUPLXBKQE-UHFFFAOYSA-N 0.000 description 1
MMOZNJWTGXWZAK-UHFFFAOYSA-N 2-(3-methylphenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound CC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 MMOZNJWTGXWZAK-UHFFFAOYSA-N 0.000 description 1
VVAAKNGCCMGISN-UHFFFAOYSA-N 2-(3-nitrophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound [O-][N+](=O)C1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 VVAAKNGCCMGISN-UHFFFAOYSA-N 0.000 description 1
BWGHUEIUTYJJMM-UHFFFAOYSA-N 2-(5-chloro-2-methoxyphenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound COC1=CC=C(Cl)C=C1C1=NC(C=2N=CC=CC=2)=CO1 BWGHUEIUTYJJMM-UHFFFAOYSA-N 0.000 description 1
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
ODHJOROUCITYNF-UHFFFAOYSA-N 2-bromo-5-methoxybenzoic acid Chemical compound COC1=CC=C(Br)C(C(O)=O)=C1 ODHJOROUCITYNF-UHFFFAOYSA-N 0.000 description 1
FRARPACTAFPNNL-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=C(Cl)C(C(Cl)=O)=C1 FRARPACTAFPNNL-UHFFFAOYSA-N 0.000 description 1
OZNRJPYVSBAJLX-UHFFFAOYSA-N 2-chloro-5-cyanobenzoic acid Chemical compound OC(=O)C1=CC(C#N)=CC=C1Cl OZNRJPYVSBAJLX-UHFFFAOYSA-N 0.000 description 1
XJYUBDLTMBGWTP-UHFFFAOYSA-N 2-chloro-5-methylbenzenecarbothioic s-acid Chemical compound CC1=CC=C(Cl)C(C(O)=S)=C1 XJYUBDLTMBGWTP-UHFFFAOYSA-N 0.000 description 1
HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical compound O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 description 1
QMDFJHAAWUGVKQ-UHFFFAOYSA-N 2h-thiopyran Chemical compound C1SC=CC=C1 QMDFJHAAWUGVKQ-UHFFFAOYSA-N 0.000 description 1
VJMYKESYFHYUEQ-UHFFFAOYSA-N 3,4,5-trifluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(F)=C1 VJMYKESYFHYUEQ-UHFFFAOYSA-N 0.000 description 1
GGHLXLVPNZMBQR-UHFFFAOYSA-N 3,5-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC(Cl)=CC(Cl)=C1 GGHLXLVPNZMBQR-UHFFFAOYSA-N 0.000 description 1
OYZWEOORLJBPMA-UHFFFAOYSA-N 3,5-difluorobenzoyl chloride Chemical compound FC1=CC(F)=CC(C(Cl)=O)=C1 OYZWEOORLJBPMA-UHFFFAOYSA-N 0.000 description 1
FTHPLWDYWAKYCY-UHFFFAOYSA-N 3,5-dimethoxybenzoyl chloride Chemical compound COC1=CC(OC)=CC(C(Cl)=O)=C1 FTHPLWDYWAKYCY-UHFFFAOYSA-N 0.000 description 1
RUJYJCANMOTJMO-UHFFFAOYSA-N 3-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC(C(Cl)=O)=C1 RUJYJCANMOTJMO-UHFFFAOYSA-N 0.000 description 1
WOTTVHZQQOFUGF-UHFFFAOYSA-N 3-[4-(5-methoxypyridin-2-yl)-1,3-oxazol-2-yl]benzonitrile Chemical compound N1=CC(OC)=CC=C1C1=COC(C=2C=C(C=CC=2)C#N)=N1 WOTTVHZQQOFUGF-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
BCWHYTSDRPOETF-UHFFFAOYSA-N 3-chloro-5-(4-pyridin-2-yl-1,3-oxazol-2-yl)benzonitrile Chemical compound ClC1=CC(C#N)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 BCWHYTSDRPOETF-UHFFFAOYSA-N 0.000 description 1
CAZBPYYWJAVBMY-UHFFFAOYSA-N 3-chloro-5-cyanobenzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC(C#N)=C1 CAZBPYYWJAVBMY-UHFFFAOYSA-N 0.000 description 1
QFMRANWPGGSNHS-UHFFFAOYSA-N 3-chloro-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC(Cl)=C1 QFMRANWPGGSNHS-UHFFFAOYSA-N 0.000 description 1
GIKLRWNRBOLRDV-UHFFFAOYSA-N 3-chloro-5-fluorobenzonitrile Chemical compound FC1=CC(Cl)=CC(C#N)=C1 GIKLRWNRBOLRDV-UHFFFAOYSA-N 0.000 description 1
PHRDZSRVSVNQRN-UHFFFAOYSA-N 3-chlorobenzohydrazide Chemical compound NNC(=O)C1=CC=CC(Cl)=C1 PHRDZSRVSVNQRN-UHFFFAOYSA-N 0.000 description 1
WHIHIKVIWVIIER-UHFFFAOYSA-N 3-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Cl)=C1 WHIHIKVIWVIIER-UHFFFAOYSA-N 0.000 description 1
AODMJIOEGCBUQL-UHFFFAOYSA-N 3-ethynylphenol Chemical group OC1=CC=CC(C#C)=C1 AODMJIOEGCBUQL-UHFFFAOYSA-N 0.000 description 1
PURMTHHDJDASBS-UHFFFAOYSA-N 3-fluoro-5-(4-pyridin-2-yl-1,3-oxazol-2-yl)benzonitrile Chemical compound FC1=CC(C#N)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 PURMTHHDJDASBS-UHFFFAOYSA-N 0.000 description 1
SYVNVEGIRVXRQH-UHFFFAOYSA-N 3-fluorobenzoyl chloride Chemical compound FC1=CC=CC(C(Cl)=O)=C1 SYVNVEGIRVXRQH-UHFFFAOYSA-N 0.000 description 1
VZFPSCNTFBJZHB-UHFFFAOYSA-N 3-fluoropyridine-2-carbonitrile Chemical compound FC1=CC=CN=C1C#N VZFPSCNTFBJZHB-UHFFFAOYSA-N 0.000 description 1
RXXCIBALSKQCAE-UHFFFAOYSA-N 3-methylbutoxymethylbenzene Chemical compound CC(C)CCOCC1=CC=CC=C1 RXXCIBALSKQCAE-UHFFFAOYSA-N 0.000 description 1
NXTDJHZGHOFSQG-UHFFFAOYSA-N 3-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC(OC=2C=CC=CC=2)=C1 NXTDJHZGHOFSQG-UHFFFAOYSA-N 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
DNCAZYRLRMTVSF-UHFFFAOYSA-N 4-(1-amino-1-carboxyethyl)benzoic acid Chemical compound OC(=O)C(N)(C)C1=CC=C(C(O)=O)C=C1 DNCAZYRLRMTVSF-UHFFFAOYSA-N 0.000 description 1
NIGOFAVNIBBNJV-UHFFFAOYSA-N 5-chloro-1h-3,1-benzoxazine-2,4-dione Chemical compound N1C(=O)OC(=O)C2=C1C=CC=C2Cl NIGOFAVNIBBNJV-UHFFFAOYSA-N 0.000 description 1
HULDRQRKKXRXBI-UHFFFAOYSA-N 5-chloro-2-methoxybenzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(O)=O HULDRQRKKXRXBI-UHFFFAOYSA-N 0.000 description 1
102000003678 AMPA Receptors Human genes 0.000 description 1
108090000078 AMPA Receptors Proteins 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
101500020117 Aedes aegypti Sialokinin Proteins 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
206010001497 Agitation Diseases 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
239000005711 Benzoic acid Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
101000616562 Danio rerio Sonic hedgehog protein A Proteins 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 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
102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
102000018899 Glutamate Receptors Human genes 0.000 description 1
108010027915 Glutamate Receptors Proteins 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
108010078321 Guanylate Cyclase Proteins 0.000 description 1
102000014469 Guanylate cyclase Human genes 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
101000939500 Homo sapiens UBX domain-containing protein 11 Proteins 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical compound O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 description 1
102000006541 Ionotropic Glutamate Receptors Human genes 0.000 description 1
108010008812 Ionotropic Glutamate Receptors Proteins 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
102100037611 Lysophospholipase Human genes 0.000 description 1
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-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
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
USNVBPORCHVKNZ-PREAGGAWSA-H N[C@@H](CCC(=O)[O-])C(=O)[O-].[B+3].N[C@@H](CCC(=O)[O-])C(=O)[O-].N[C@@H](CCC(=O)[O-])C(=O)[O-].[B+3] Chemical compound N[C@@H](CCC(=O)[O-])C(=O)[O-].[B+3].N[C@@H](CCC(=O)[O-])C(=O)[O-].N[C@@H](CCC(=O)[O-])C(=O)[O-].[B+3] USNVBPORCHVKNZ-PREAGGAWSA-H 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
241000282320 Panthera leo Species 0.000 description 1
240000001090 Papaver somniferum Species 0.000 description 1
235000008753 Papaver somniferum Nutrition 0.000 description 1
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical class ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
102000015439 Phospholipases Human genes 0.000 description 1
108010064785 Phospholipases Proteins 0.000 description 1
108010058864 Phospholipases A2 Proteins 0.000 description 1
206010062519 Poor quality sleep Diseases 0.000 description 1
206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
229930006000 Sucrose Natural products 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
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
229920002253 Tannate Polymers 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102100029645 UBX domain-containing protein 11 Human genes 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
230000009471 action Effects 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
239000012190 activator Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
150000001263 acyl chlorides Chemical class 0.000 description 1
102000030621 adenylate cyclase Human genes 0.000 description 1
108060000200 adenylate cyclase Proteins 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
229940040563 agaric acid Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001409 amidines Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
150000003862 amino acid derivatives Chemical class 0.000 description 1
230000036592 analgesia Effects 0.000 description 1
229940035676 analgesics Drugs 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
239000000730 antalgic agent Substances 0.000 description 1
229940125681 anticonvulsant agent Drugs 0.000 description 1
239000001961 anticonvulsive agent Substances 0.000 description 1
230000001640 apoptogenic effect Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000000305 astragalus gummifer gum Substances 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
230000008901 benefit Effects 0.000 description 1
150000001555 benzenes Chemical group 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
238000010876 biochemical test Methods 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
238000003965 capillary gas chromatography Methods 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
210000001638 cerebellum Anatomy 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
229940099112 cornstarch Drugs 0.000 description 1
GCUVBACNBHGZRS-UHFFFAOYSA-N cyclopenta-1,3-diene cyclopenta-2,4-dien-1-yl(diphenyl)phosphane iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.c1cc[c-](c1)P(c1ccccc1)c1ccccc1 GCUVBACNBHGZRS-UHFFFAOYSA-N 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
230000029087 digestion Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
239000001177 diphosphate Substances 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003596 drug target Substances 0.000 description 1
229940009662 edetate Drugs 0.000 description 1
230000001037 epileptic effect Effects 0.000 description 1
229950000206 estolate Drugs 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
238000002481 ethanol extraction Methods 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000010685 fatty oil Substances 0.000 description 1
229940126864 fibroblast growth factor Drugs 0.000 description 1
239000006260 foam Substances 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
229960001731 gluceptate Drugs 0.000 description 1
KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
229940049906 glutamate Drugs 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000000227 grinding Methods 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 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
125000004446 heteroarylalkyl group Chemical group 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
230000000971 hippocampal effect Effects 0.000 description 1
210000004295 hippocampal neuron Anatomy 0.000 description 1
210000001320 hippocampus Anatomy 0.000 description 1
WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
229940091173 hydantoin Drugs 0.000 description 1
XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
239000005457 ice water Substances 0.000 description 1
DWRDBJCTLDOPFZ-UHFFFAOYSA-N imidazole-2,4-dione Chemical compound O=C1NC(=O)N=C1 DWRDBJCTLDOPFZ-UHFFFAOYSA-N 0.000 description 1
YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
238000007914 intraventricular administration Methods 0.000 description 1
230000007654 ischemic lesion Effects 0.000 description 1
229950000886 isetionate Drugs 0.000 description 1
125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
238000011068 loading method Methods 0.000 description 1
230000027928 long-term synaptic potentiation Effects 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
MJTGQALMWUUPQM-UHFFFAOYSA-N m-Chlorobenzamide Chemical compound NC(=O)C1=CC=CC(Cl)=C1 MJTGQALMWUUPQM-UHFFFAOYSA-N 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
RGLQGCVEXOWXEK-UHFFFAOYSA-N methyl 2-chloro-5-cyanobenzoate Chemical compound COC(=O)C1=CC(C#N)=CC=C1Cl RGLQGCVEXOWXEK-UHFFFAOYSA-N 0.000 description 1
BTEVDFJXGLQUDS-UHFFFAOYSA-N methyl 3,5-dichlorobenzoate Chemical compound COC(=O)C1=CC(Cl)=CC(Cl)=C1 BTEVDFJXGLQUDS-UHFFFAOYSA-N 0.000 description 1
DOZOMYSFEVYLAU-UHFFFAOYSA-N methyl 3-chloro-5-fluorobenzoate Chemical compound COC(=O)C1=CC(F)=CC(Cl)=C1 DOZOMYSFEVYLAU-UHFFFAOYSA-N 0.000 description 1
KJWHRMZKJXOWFC-UHFFFAOYSA-N methyl 5-chloro-2-hydroxybenzoate Chemical compound COC(=O)C1=CC(Cl)=CC=C1O KJWHRMZKJXOWFC-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
NSNPSJGHTQIXDO-UHFFFAOYSA-N naphthalene-1-carbonyl chloride Chemical compound C1=CC=C2C(C(=O)Cl)=CC=CC2=C1 NSNPSJGHTQIXDO-UHFFFAOYSA-N 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
230000007472 neurodevelopment Effects 0.000 description 1
230000016273 neuron death Effects 0.000 description 1
239000004090 neuroprotective agent Substances 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
230000003957 neurotransmitter release Effects 0.000 description 1
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003791 organic solvent mixture Substances 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
210000004681 ovum Anatomy 0.000 description 1
COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 description 1
QOWOXBFFQOXPHM-UHFFFAOYSA-O oxo-[[1-[[4-(oxoazaniumylmethylidene)pyridin-1-yl]methyl]pyridin-4-ylidene]methyl]azanium;chloride Chemical compound [Cl-].C1=CC(=C[NH+]=O)C=CN1CN1C=CC(=C[NH+]=O)C=C1 QOWOXBFFQOXPHM-UHFFFAOYSA-O 0.000 description 1
229940014662 pantothenate Drugs 0.000 description 1
235000019161 pantothenic acid Nutrition 0.000 description 1
239000011713 pantothenic acid Substances 0.000 description 1
230000008447 perception Effects 0.000 description 1
150000005331 phenylglycines Chemical class 0.000 description 1
230000035479 physiological effects, processes and functions Effects 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
229940081066 picolinic acid Drugs 0.000 description 1
239000000049 pigment Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
KNCYXPMJDCCGSJ-UHFFFAOYSA-N piperidine-2,6-dione Chemical compound O=C1CCCC(=O)N1 KNCYXPMJDCCGSJ-UHFFFAOYSA-N 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
229940116317 potato starch Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
229940069328 povidone Drugs 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
WDXARTMCIRVMAE-UHFFFAOYSA-N quinoline-2-carbonitrile Chemical compound C1=CC=CC2=NC(C#N)=CC=C21 WDXARTMCIRVMAE-UHFFFAOYSA-N 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
238000011160 research Methods 0.000 description 1
229940100486 rice starch Drugs 0.000 description 1
230000020341 sensory perception of pain Effects 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
229910000342 sodium bisulfate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
239000007921 spray Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000003956 synaptic plasticity Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
210000001103 thalamus Anatomy 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
239000003104 tissue culture media Substances 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
210000003901 trigeminal nerve Anatomy 0.000 description 1
206010044652 trigeminal neuralgia Diseases 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
239000002966 varnish Substances 0.000 description 1
230000004462 vestibulo-ocular reflex Effects 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Heart & Thoracic Surgery (AREA)
Psychology (AREA)
Rheumatology (AREA)
Diabetes (AREA)
Cardiology (AREA)
Obesity (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Hematology (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Thiazole And Isothizaole Compounds (AREA)

UA2002032079A 1999-08-19 2000-08-18 1,2,4-oxadiazole derivatives and use thereof as antagonists at metabotropic glutamate receptors UA75871C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US14946499P	1999-08-19	1999-08-19
PCT/US2000/022618 WO2001012627A1 (en)	1999-08-19	2000-08-18	Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists

Publications (1)

Publication Number	Publication Date
UA75871C2 true UA75871C2 (en)	2006-06-15

Family

ID=22530400

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2002032079A UA75871C2 (en)	1999-08-19	2000-08-18	1,2,4-oxadiazole derivatives and use thereof as antagonists at metabotropic glutamate receptors

Country Status (28)

Country	Link
EP (1)	EP1210344B1 (zh)
JP (2)	JP3790472B2 (zh)
KR (1)	KR100875222B1 (zh)
CN (1)	CN1313465C (zh)
AT (1)	ATE307129T1 (zh)
AU (1)	AU780191B2 (zh)
BG (1)	BG65586B1 (zh)
BR (1)	BR0013427A (zh)
CA (1)	CA2381975A1 (zh)
CY (1)	CY1105253T1 (zh)
CZ (1)	CZ2002599A3 (zh)
DE (1)	DE60023318T2 (zh)
DK (1)	DK1210344T3 (zh)
EE (1)	EE200200079A (zh)
ES (1)	ES2250177T3 (zh)
HK (1)	HK1047929A1 (zh)
HU (1)	HUP0202757A3 (zh)
IL (2)	IL148157A0 (zh)
IS (1)	IS6275A (zh)
MX (1)	MXPA02001764A (zh)
NO (1)	NO322460B1 (zh)
NZ (1)	NZ517221A (zh)
PL (1)	PL353825A1 (zh)
RU (1)	RU2296127C9 (zh)
SK (1)	SK2512002A3 (zh)
UA (1)	UA75871C2 (zh)
WO (1)	WO2001012627A1 (zh)
ZA (1)	ZA200201358B (zh)

Families Citing this family (70)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6660753B2 (en)	1999-08-19	2003-12-09	Nps Pharmaceuticals, Inc.	Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
ATE375340T1 (de) *	2001-02-21	2007-10-15	Nps Pharma Inc	Heteropolycyclische verbindungen und deren verwendung als metabotrope glutamatrezeptorantagonisten
US6916821B2 (en)	2001-04-02	2005-07-12	Brown University	Methods of treating disorders with Group I mGluR antagonists
EP1392363B1 (en)	2001-04-02	2006-09-20	Brown University Research Foundation	Use of mGLuR5 antagonists in the manufacture of a medicament in the treatment of Fragile X syndrome, Autism and Mental Retardation
WO2003051833A2 (en) *	2001-12-18	2003-06-26	Merck & Co., Inc.	Heteroaryl substituted pyrazole modulators of metabotropic glutamate receptor-5
ES2292854T3 (es) *	2001-12-18	2008-03-16	MERCK & CO., INC.	Moduladores triazol sustituidos con heteroarilo del receptor-5 metabotropico de glumatamato.
US20040259917A1 (en) *	2001-12-19	2004-12-23	Cosford Nicholas D.P.	Heteroaryl substituted imidazole modulators of metabotropic glutamate receptor-5
AU2003213783B2 (en) *	2002-03-12	2007-01-25	Merck Sharp & Dohme Corp.	Di-aryl substituted tetrazole modulators of metabotropic glutamate receptor-5
SE0201943D0 (sv) *	2002-06-20	2002-06-20	Astrazeneca Ab	New use
US7964609B2 (en)	2002-06-20	2011-06-21	Astrazeneca Ab	Use of mGluR5 antagonists for the treatment of gerd
EP1529045A2 (en)	2002-08-09	2005-05-11	Astra Zeneca AB	New compounds
AR041508A1 (es) *	2002-08-09	2005-05-18	Astra Ab	Compuestos con actividad en los receptores de glutamato metabotropicos
AU2003264018A1 (en) *	2002-08-09	2004-02-25	Astrazeneca Ab	Compounds having an activity at metabotropic glutamate receptors
GB0303503D0 (en) *	2003-02-14	2003-03-19	Novartis Ag	Organic compounds
AU2004227833B2 (en) *	2003-04-04	2009-10-01	Merck & Co., Inc.	Di-aryl substituted triazole modulators of metabotropic glutamate receptor-5
EP1625123A4 (en) *	2003-05-15	2007-08-29	Merck & Co Inc	3- (2-AMINO-1-AZACYCLYL) -5-ARYL-1,2,4-OXADIAZOLE AS S1P RECEPTOR AGONISTS
WO2005060961A2 (en) *	2003-12-18	2005-07-07	Astrazeneca Ab	Treatment of transient lower esophageal sphincter relaxations (tlesrs) and gastro-esophageal reflux disease (gerd)
US8207147B2 (en)	2003-12-24	2012-06-26	Prosidion Limited	Heterocyclic derivatives as GPCR receptor agonists
AU2005214380A1 (en)	2004-02-18	2005-09-01	Astrazeneca Ab	Fused hetrocyclic compounds and their use as metabotropic receptor antagonists for the treatment of gastrointestinal disorders
US7585881B2 (en) *	2004-02-18	2009-09-08	Astrazeneca Ab	Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
ES2309718T3 (es) *	2004-02-18	2008-12-16	Astrazeneca Ab	Compuestos heterociclicos condensados y su uso como antagonistas de los receptores metabotropicos para el tratamiento de trastornos gastrointestinales.
CA2570318A1 (en) *	2004-06-30	2006-01-12	Banyu Pharmaceutical Co., Ltd.	Biaryl derivatives
KR100621192B1 (ko) *	2004-10-13	2006-09-19	한국화학연구원	무스카린 수용체 작용물질로서 작용하는1,2,3,4-테트라하이드로피리미디닐-1,2,4-옥사다이아졸유도체와 이의 제조방법
JP4557685B2 (ja)	2004-11-15	2010-10-06	独立行政法人理化学研究所	蛍光蛋白質
EP1844044B1 (en)	2005-01-14	2010-07-21	F.Hoffmann-La Roche Ag	Thiazole-4-carboxamide derivatives as mglur5 antagonists
GB0510142D0 (en) *	2005-05-18	2005-06-22	Addex Pharmaceuticals Sa	Novel compounds A1
WO2007001973A1 (en) *	2005-06-28	2007-01-04	Astrazeneca Ab	New use
PT1907382E (pt)	2005-07-26	2015-09-25	Bial Portela & Ca Sa	Derivados de nitrocatecol como inibidores de comt
UY29796A1 (es)	2005-09-29	2007-04-30	Astrazeneca Ab	Nuevos compuestos para el tratamiento de trastornos neurológicos, psiquiátricos o del dolor
RU2425834C2 (ru)	2005-11-08	2011-08-10	Ф. Хоффманн-Ля Рош Аг	ПРОИЗВОДНЫЕ ТИАЗОЛО[4,5-c]ПИРИДИНА В КАЧЕСТВЕ АНТАГОНИСТОВ РЕЦЕПТОРОВ mGluR5
US7951824B2 (en)	2006-02-17	2011-05-31	Hoffman-La Roche Inc.	4-aryl-pyridine-2-carboxyamide derivatives
TWI382984B (zh) *	2006-04-03	2013-01-21	Astellas Pharma Inc	雜環化合物
EP1845097A1 (en)	2006-04-10	2007-10-17	Portela & Ca., S.A.	Oxadiazole derivatives as COMT inhibitors
EP2255848A3 (en) *	2006-09-04	2011-04-06	NeuroSearch AS	Pharmaceutical combinations of a nicotine receptor modulator and a cognitive enhancer
JP5253401B2 (ja)	2006-09-07	2013-07-31	アクテリオンファーマシューティカルズリミテッド	免疫調節薬としてのピリジン−４−イル誘導体
RU2454413C2 (ru)	2006-09-08	2012-06-27	Актелион Фармасьютиклз Лтд	Производные пиридин-3-ила в качестве иммуномодулирующих агентов
CN101522645B (zh)	2006-09-21	2013-01-09	埃科特莱茵药品有限公司	苯衍生物及其免疫调节剂的用途
DK2481410T3 (en)	2007-01-31	2016-10-24	Bial - Portela & Ca S A	Nitrocatecholderivater as COMT inhibitors administered in a specific dosage regimen
JP2010521450A (ja)	2007-03-16	2010-06-24	アクテリオンファーマシューティカルズリミテッド	Ｓ１ｐ１／ｅｄｇ１受容体アゴニストとしてのアミノ−ピリジン誘導体
BRPI0815190A2 (pt)	2007-08-17	2015-03-31	Actelion Pharmaceuticals Ltd	Composto derivado de piridina, composição farmacêutica que o compreende e uso do mesmo
WO2009058298A1 (en)	2007-10-31	2009-05-07	Merck & Co., Inc.	P2x3, receptor antagonists for treatment of pain
US8299086B2 (en)	2007-11-01	2012-10-30	Actelion Pharmaceuticals Ltd.	Pyrimidine derivatives
KR101649381B1 (ko) *	2007-12-20	2016-08-19	바이엘 인텔렉쳐 프로퍼티 게엠베하	４-(４-시아노-２-티오아릴)디히드로피리미디논 및 그의 용도
EP2732819B1 (en)	2008-02-07	2019-10-16	Massachusetts Eye & Ear Infirmary	Compounds that enhance Atoh-1 expression
CN102007107B (zh)	2008-03-07	2014-07-23	埃科特莱茵药品有限公司	氨甲基苯衍生物
TW200942531A (en)	2008-03-17	2009-10-16	Bial Portela & Companhia S A	Crystal forms of a nitrocatechol
MX2011004570A (es)	2008-10-31	2011-06-17	Merck Sharp & Dohme	Antagonistas del receptor p2x3 para el tratamiento del dolor.
DE102008057364A1 (de)	2008-11-14	2010-05-20	Bayer Schering Pharma Aktiengesellschaft	Substituierte Aryl-Verbindungen und ihre Verwendung
DE102008057344A1 (de)	2008-11-14	2010-05-20	Bayer Schering Pharma Aktiengesellschaft	Aminoalkyl-substituierte Aryl-Verbindungen und ihre Verwendung
DE102009041242A1 (de)	2009-09-11	2011-12-15	Bayer Schering Pharma Aktiengesellschaft	Heterocyclisch substituierte Aryl-Verbindungen und ihre Verwendung
DE102009041241A1 (de)	2009-09-11	2011-08-04	Bayer Schering Pharma Aktiengesellschaft, 13353	Substituierte Aryl-Verbindungen und ihre Verwendung
DE102008057343A1 (de)	2008-11-14	2010-05-20	Bayer Schering Pharma Aktiengesellschaft	Heterocyclisch substituierte Aryl-Verbindungen und ihre Verwendung
US8946231B2 (en)	2009-03-23	2015-02-03	Merck Sharp & Dohme Corp.	P2X3, receptor antagonists for treatment of pain
EP2410857B1 (en)	2009-03-23	2014-01-29	Merck Sharp & Dohme Corp.	P2x3, receptor antagonists for treatment of pain
CA2755768A1 (en)	2009-03-23	2010-09-30	Merck Sharp & Dohme Corp.	P2x3, receptor antagonists for treatment of pain
AU2010231961B2 (en)	2009-04-01	2015-05-21	Bial - Portela & Ca., S.A.	Pharmaceutical formulations comprising nitrocatechol derivatives and methods of making thereof
BRPI1014453A2 (pt) *	2009-04-13	2016-04-05	Irm Llc	composições e métodos para modular ligação de retinol a proteína de ligação ao retinol 4 (rbp4)
SI2454255T1 (sl)	2009-07-16	2014-01-31	Actelion Pharmaceuticals Ltd.	Derivati piridin-4-ila kot agonisti s1p1/edg1
US20130058915A1 (en)	2010-03-02	2013-03-07	Children's Medica Center Corporation	Methods and compositions for treatment of angelman syndrome and autism spectrum disorders
PT2665720E (pt)	2011-01-19	2015-09-16	Actelion Pharmaceuticals Ltd	Derivados de 2-metoxi-piridin-4-ilo
US20140045900A1 (en)	2011-02-11	2014-02-13	Bial-Portela & Ca, S.A.	Administration regime for nitrocatechols
BR112014014341A2 (pt)	2011-12-13	2017-08-22	Bial Portela & Ca Sa	Intermediário metilado, seu método de preparação e seus usos, e composição farmacêutica
JP5946288B2 (ja) *	2012-02-24	2016-07-06	公立大学法人名古屋市立大学	新規ヒドロキサム酸誘導体及びその用途
US9232800B2 (en)	2013-02-15	2016-01-12	Monsanto Technology Llc	3,5-disubstituted-4,5-dihydro-1,2,4-oxadiazoles and compositions and methods for controlling nematode pests
EP2853532B1 (en) *	2013-09-28	2020-12-09	Instytut Farmakologii Polskiej Akademii Nauk	1,2,4-oxadiazole derivatives as allosteric modulators of metabotropic glutamate receptors belonging to group III
JP2018500300A (ja)	2014-11-28	2018-01-11	ノヴィファーマ，エス．アー．	パーキンソン病を遅延させるための医薬
KR20200044155A (ko)	2015-05-20	2020-04-28	이도르시아 파마슈티컬스 리미티드	화합물 (s)-3-｛4-[5-(2-시클로펜틸-6-메톡시-피리딘-4-일)-[1,2,4]옥사디아졸-3-일]-2-에틸-6-메틸-페녹시｝-프로판-1,2-디올의 결정형
MX2017016876A (es)	2015-06-23	2018-04-10	Kissei Pharmaceutical	Derivado de pirazol o sal farmaceuticamente aceptable del mismo.
WO2017171594A1 (en) *	2016-03-30	2017-10-05	Tadeusz Wieloch	Negative allosteric modulators of mglur5 for use in the treatment of mature brain damages.
KR102276327B1 (ko) *	2019-06-25	2021-07-12	연세대학교 산학협력단	신규 옥사다이아졸 화합물 및 이를 포함하는 당뇨 예방 또는 치료용 조성물

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1149011B (de) *	1960-04-05	1963-05-22	Hoechst Ag	Verfahren zur Herstellung von 3, 5-disubstituierten 1, 2, 4-Oxdiazolen
IL31990A (en) *	1968-04-26	1974-05-16	Chinoin Gyogyszer Es Vegyeszet	Pyridyl 1,2,4-oxadiazole derivatives,process for the preparation thereof and pharmaceutical compositions containing same
US4003909A (en) *	1974-07-22	1977-01-18	E. R. Squibb & Sons, Inc.	[(1,2,4-Oxadiazol-3-yl)phenyl]carbamic or thiocarbamic acid esters
US4022901A (en) *	1975-03-05	1977-05-10	E. R. Squibb & Sons, Inc.	3-Pyridinyl-5-isothiocyanophenyl oxadiazoles
AU675484B2 (en) *	1993-03-24	1997-02-06	Neurosearch A/S	Benzimidazole compounds, their use and preparation
US5554630A (en) *	1993-03-24	1996-09-10	Neurosearch A/S	Benzimidazole compounds
WO1994022846A1 (en) *	1993-03-30	1994-10-13	Pfizer Inc.	Compounds enhancing antitumor activity of other cytotoxic agents
US5922724A (en) *	1995-04-21	1999-07-13	Neurosearch A/S	Benzimidazole compounds and their use as modulators of the GABA a receptor complex
AU6526896A (en) *	1995-07-22	1997-02-18	Rhone-Poulenc Rorer Limited	Substituted aromatic compounds and their pharmaceutical use
DE19643037A1 (de) *	1996-10-18	1998-04-23	Boehringer Ingelheim Kg	Neue Oxadiazole, Verfahren zu ihrer Herstellung sowie deren Verwendung als Arzneimittel
EP1037878A2 (en) *	1997-11-21	2000-09-27	Nps Pharmaceuticals, Inc.	Metabotropic glutamate receptor antagonists for treating central nervous system diseases

2000
- 2000-08-18 NZ NZ517221A patent/NZ517221A/en not_active IP Right Cessation
- 2000-08-18 EP EP00955657A patent/EP1210344B1/en not_active Expired - Lifetime
- 2000-08-18 HU HU0202757A patent/HUP0202757A3/hu unknown
- 2000-08-18 CA CA002381975A patent/CA2381975A1/en not_active Abandoned
- 2000-08-18 IL IL14815700A patent/IL148157A0/xx active IP Right Grant
- 2000-08-18 MX MXPA02001764A patent/MXPA02001764A/es active IP Right Grant
- 2000-08-18 EE EEP200200079A patent/EE200200079A/xx unknown
- 2000-08-18 UA UA2002032079A patent/UA75871C2/uk unknown
- 2000-08-18 JP JP2001517525A patent/JP3790472B2/ja not_active Expired - Fee Related
- 2000-08-18 PL PL00353825A patent/PL353825A1/xx not_active Application Discontinuation
- 2000-08-18 BR BR0013427-9A patent/BR0013427A/pt not_active Application Discontinuation
- 2000-08-18 AU AU67824/00A patent/AU780191B2/en not_active Ceased
- 2000-08-18 SK SK251-2002A patent/SK2512002A3/sk unknown
- 2000-08-18 KR KR1020027002120A patent/KR100875222B1/ko not_active IP Right Cessation
- 2000-08-18 DE DE60023318T patent/DE60023318T2/de not_active Expired - Lifetime
- 2000-08-18 CN CNB008145024A patent/CN1313465C/zh not_active Expired - Fee Related
- 2000-08-18 CZ CZ2002599A patent/CZ2002599A3/cs unknown
- 2000-08-18 ES ES00955657T patent/ES2250177T3/es not_active Expired - Lifetime
- 2000-08-18 DK DK00955657T patent/DK1210344T3/da active
- 2000-08-18 WO PCT/US2000/022618 patent/WO2001012627A1/en active IP Right Grant
- 2000-08-18 RU RU2002107201/04A patent/RU2296127C9/ru not_active IP Right Cessation
- 2000-08-18 AT AT00955657T patent/ATE307129T1/de active
2002
- 2002-02-14 IL IL148157A patent/IL148157A/en not_active IP Right Cessation
- 2002-02-18 ZA ZA200201358A patent/ZA200201358B/xx unknown
- 2002-02-18 IS IS6275A patent/IS6275A/is unknown
- 2002-02-19 NO NO20020823A patent/NO322460B1/no not_active IP Right Cessation
- 2002-03-07 BG BG106493A patent/BG65586B1/bg unknown
- 2002-12-05 HK HK02108861A patent/HK1047929A1/xx not_active IP Right Cessation
2005
- 2005-12-09 CY CY20051101521T patent/CY1105253T1/el unknown
2006
- 2006-01-25 JP JP2006016914A patent/JP2006143746A/ja active Pending

Also Published As

Publication number	Publication date
CN1313465C (zh)	2007-05-02
BR0013427A (pt)	2002-07-30
SK2512002A3 (en)	2002-07-02
KR100875222B1 (ko)	2008-12-19
HUP0202757A2 (hu)	2002-12-28
HK1047929A1 (en)	2003-03-14
PL353825A1 (en)	2003-12-01
ZA200201358B (en)	2003-07-30
ES2250177T3 (es)	2006-04-16
CZ2002599A3 (cs)	2002-06-12
DE60023318T2 (de)	2006-07-20
EP1210344B1 (en)	2005-10-19
IS6275A (is)	2002-02-18
AU6782400A (en)	2001-03-13
CY1105253T1 (el)	2010-03-03
RU2296127C9 (ru)	2007-08-27
IL148157A (en)	2007-07-04
JP3790472B2 (ja)	2006-06-28
NO322460B1 (no)	2006-10-09
BG106493A (en)	2003-01-31
RU2296127C2 (ru)	2007-03-27
EE200200079A (et)	2003-06-16
ATE307129T1 (de)	2005-11-15
MXPA02001764A (es)	2004-03-19
EP1210344A1 (en)	2002-06-05
DK1210344T3 (da)	2006-03-06
CN1379775A (zh)	2002-11-13
NO20020823D0 (no)	2002-02-19
JP2006143746A (ja)	2006-06-08
IL148157A0 (en)	2002-09-12
CA2381975A1 (en)	2001-02-22
KR20020038731A (ko)	2002-05-23
DE60023318D1 (de)	2006-03-02
BG65586B1 (bg)	2009-01-30
JP2003507378A (ja)	2003-02-25
HUP0202757A3 (en)	2006-03-28
WO2001012627A1 (en)	2001-02-22
NO20020823L (no)	2002-04-17
AU780191B2 (en)	2005-03-03
NZ517221A (en)	2004-01-30

Publication	Publication Date	Title
UA75871C2 (en)	2006-06-15	1,2,4-oxadiazole derivatives and use thereof as antagonists at metabotropic glutamate receptors
DE60221098T2 (de)	2008-01-24	Kondensierte heterocyclische derivate
TWI344955B (en)	2011-07-11	Heterocyclic rinf having nitrogen atom derivatives and medicament containing the derivatives as active ingredient
EA037257B1 (ru)	2021-02-26	Новые агонисты рецептора апелина и способы применения
KR101458007B1 (ko)	2014-11-04	사이클로프로판 화합물
KR101666729B1 (ko)	2016-10-17	Mgat2 억제제로서의 아릴 디히드로피리디논 및 피페리디논
JP5587246B2 (ja)	2014-09-10	レニン阻害剤としての３，４−置換ピペリジン誘導体
US10717727B2 (en)	2020-07-21	Pyridinium compounds
JP2008508307A (ja)	2008-03-21	カリウムチャンネル阻害剤
KR20050109583A (ko)	2005-11-21	나트륨 채널 차단제로서의 바이아릴 치환된 트리아졸
US20030181472A1 (en)	2003-09-25	Inflammation modulators
JP2009514865A (ja)	2009-04-09	有糸分裂キネシン阻害剤
WO2017008681A1 (zh)	2017-01-19	酰胺类衍生物、其制备方法及其在医药上的用途
EP1582519A2 (en)	2005-10-05	Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
TW202440553A (zh)	2024-10-16	作為at2r拮抗劑的雜環化合物
TW201742857A (zh)	2017-12-16	醯胺類衍生物、其製備方法、其藥物組合物及其在醫藥上的用途