NZ564253A - Novel oxadiazole derivatives and their use as positive allosteric modulators of metabotropic glutamate receptors - Google Patents

Info

Publication number

NZ564253A

NZ564253A NZ564253A NZ56425306A NZ564253A NZ 564253 A NZ564253 A NZ 564253A NZ 564253 A NZ564253 A NZ 564253A NZ 56425306 A NZ56425306 A NZ 56425306A NZ 564253 A NZ564253 A NZ 564253A

Authority

NZ

New Zealand

Prior art keywords

phenyl

fluoro

oxadiazol

piperidin

methanone

Prior art date

2005-05-18

Links

• Espacenet
• Global Dossier
• Discuss

• 230000003281 allosteric effect Effects 0.000 title abstract description 22
• 102000016193 Metabotropic glutamate receptors Human genes 0.000 title description 12
• 108010010914 Metabotropic glutamate receptors Proteins 0.000 title description 12
• 150000004866 oxadiazoles Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 235
• -1 Di-fluoro-phenyl Chemical group 0.000 claims abstract description 48
• 239000000203 mixture Substances 0.000 claims abstract description 33
• 208000015114 central nervous system disease Diseases 0.000 claims abstract description 24
• 201000000980 schizophrenia Diseases 0.000 claims abstract description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
• 150000003839 salts Chemical class 0.000 claims abstract description 11
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
• 208000010877 cognitive disease Diseases 0.000 claims abstract description 8
• 239000012453 solvate Substances 0.000 claims abstract description 7
• 125000001207 fluorophenyl group Chemical group 0.000 claims abstract description 4
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
• 239000003814 drug Substances 0.000 claims description 23
• 238000002360 preparation method Methods 0.000 claims description 23
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 13
• 229940025084 amphetamine Drugs 0.000 claims description 12
• 208000028017 Psychotic disease Diseases 0.000 claims description 11
• 206010012289 Dementia Diseases 0.000 claims description 10
• 208000035475 disorder Diseases 0.000 claims description 9
• 208000019901 Anxiety disease Diseases 0.000 claims description 7
• 208000007118 chronic progressive multiple sclerosis Diseases 0.000 claims description 6
• WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 208000011117 substance-related disease Diseases 0.000 claims description 5
• 208000007848 Alcoholism Diseases 0.000 claims description 4
• 206010012218 Delirium Diseases 0.000 claims description 4
• 208000011688 Generalised anxiety disease Diseases 0.000 claims description 4
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 4
• 208000029364 generalized anxiety disease Diseases 0.000 claims description 4
• 201000006417 multiple sclerosis Diseases 0.000 claims description 4
• 230000002085 persistent effect Effects 0.000 claims description 4
• 208000028173 post-traumatic stress disease Diseases 0.000 claims description 4
• 208000030814 Eating disease Diseases 0.000 claims description 3
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 3
• 208000019022 Mood disease Diseases 0.000 claims description 3
• QFMMOKDCOXWAJZ-AWEZNQCLSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-fluoropyridin-4-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)N=CC=2)=N1 QFMMOKDCOXWAJZ-AWEZNQCLSA-N 0.000 claims description 3
• SPENSVJLZHTTRH-AWEZNQCLSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(6-fluoropyridin-3-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=NC(F)=CC=2)=N1 SPENSVJLZHTTRH-AWEZNQCLSA-N 0.000 claims description 3
• 235000014632 disordered eating Nutrition 0.000 claims description 3
• 206010013663 drug dependence Diseases 0.000 claims description 3
• 230000002757 inflammatory effect Effects 0.000 claims description 3
• 208000022821 personality disease Diseases 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 239000000126 substance Substances 0.000 claims description 3
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 2
• IJIAFQNUTJPDOD-ZDUSSCGKSA-N (3,4-difluorophenyl)-[(3s)-3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=C(F)C(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2N=CC=CC=2)CCC1 IJIAFQNUTJPDOD-ZDUSSCGKSA-N 0.000 claims description 2
• VNKSJCLXZWQXFV-HNNXBMFYSA-N (6-fluoropyridin-3-yl)-[(3s)-3-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=NC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC=CC=2)CCC1 VNKSJCLXZWQXFV-HNNXBMFYSA-N 0.000 claims description 2
• 206010065040 AIDS dementia complex Diseases 0.000 claims description 2
• 208000008811 Agoraphobia Diseases 0.000 claims description 2
• 208000029197 Amphetamine-Related disease Diseases 0.000 claims description 2
• 208000000103 Anorexia Nervosa Diseases 0.000 claims description 2
• 208000020925 Bipolar disease Diseases 0.000 claims description 2
• 206010006550 Bulimia nervosa Diseases 0.000 claims description 2
• 208000022497 Cocaine-Related disease Diseases 0.000 claims description 2
• 206010012225 Delirium tremens Diseases 0.000 claims description 2
• 208000024254 Delusional disease Diseases 0.000 claims description 2
• 206010057852 Nicotine dependence Diseases 0.000 claims description 2
• 208000026251 Opioid-Related disease Diseases 0.000 claims description 2
• 206010067063 Progressive relapsing multiple sclerosis Diseases 0.000 claims description 2
• 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 claims description 2
• 208000020186 Schizophreniform disease Diseases 0.000 claims description 2
• 206010041250 Social phobia Diseases 0.000 claims description 2
• 208000011962 Substance-induced mood disease Diseases 0.000 claims description 2
• 231100000395 Substance-induced mood disorder Toxicity 0.000 claims description 2
• 208000011963 Substance-induced psychotic disease Diseases 0.000 claims description 2
• 231100000393 Substance-induced psychotic disorder Toxicity 0.000 claims description 2
• 208000025569 Tobacco Use disease Diseases 0.000 claims description 2
• 206010001584 alcohol abuse Diseases 0.000 claims description 2
• 201000007930 alcohol dependence Diseases 0.000 claims description 2
• 208000025746 alcohol use disease Diseases 0.000 claims description 2
• 208000029650 alcohol withdrawal Diseases 0.000 claims description 2
• 208000006246 alcohol withdrawal delirium Diseases 0.000 claims description 2
• 229960003920 cocaine Drugs 0.000 claims description 2
• 201000006145 cocaine dependence Diseases 0.000 claims description 2
• 208000026725 cyclothymic disease Diseases 0.000 claims description 2
• 230000006735 deficit Effects 0.000 claims description 2
• 208000024732 dysthymic disease Diseases 0.000 claims description 2
• 208000024714 major depressive disease Diseases 0.000 claims description 2
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 2
• 229960002715 nicotine Drugs 0.000 claims description 2
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 2
• 208000030459 obsessive-compulsive personality disease Diseases 0.000 claims description 2
• 201000005040 opiate dependence Diseases 0.000 claims description 2
• 208000002851 paranoid schizophrenia Diseases 0.000 claims description 2
• 208000019899 phobic disease Diseases 0.000 claims description 2
• 206010063401 primary progressive multiple sclerosis Diseases 0.000 claims description 2
• 208000022610 schizoaffective disease Diseases 0.000 claims description 2
• 201000008628 secondary progressive multiple sclerosis Diseases 0.000 claims description 2
• 208000013403 hyperactivity Diseases 0.000 claims 1
• 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 abstract description 56
• 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 abstract description 56
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 abstract description 24
• 229930195712 glutamate Natural products 0.000 abstract description 24
• 230000002265 prevention Effects 0.000 abstract description 7
• 208000024891 symptom Diseases 0.000 abstract description 5
• 201000010099 disease Diseases 0.000 abstract description 4
• 102000006239 metabotropic receptors Human genes 0.000 abstract description 4
• 108020004083 metabotropic receptors Proteins 0.000 abstract description 4
• 230000006999 cognitive decline Effects 0.000 abstract description 3
• 208000027232 peripheral nervous system disease Diseases 0.000 abstract description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 264
• 238000000034 method Methods 0.000 description 251
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 180
• 238000002514 liquid chromatography mass spectrum Methods 0.000 description 119
• 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 116
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 76
• 239000000741 silica gel Substances 0.000 description 76
• 229910002027 silica gel Inorganic materials 0.000 description 76
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 68
• 125000000217 alkyl group Chemical group 0.000 description 65
• 238000005160 1H NMR spectroscopy Methods 0.000 description 63
• 239000003480 eluent Substances 0.000 description 61
• 239000002253 acid Substances 0.000 description 56
• 239000007787 solid Substances 0.000 description 54
• 238000003818 flash chromatography Methods 0.000 description 51
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
• 238000000746 purification Methods 0.000 description 36
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
• 125000003118 aryl group Chemical group 0.000 description 33
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 30
• 125000001072 heteroaryl group Chemical group 0.000 description 27
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
• 238000006243 chemical reaction Methods 0.000 description 24
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
• 238000005481 NMR spectroscopy Methods 0.000 description 22
• 239000002904 solvent Substances 0.000 description 22
• 101150041968 CDC13 gene Proteins 0.000 description 20
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
• 102220079670 rs759826252 Human genes 0.000 description 20
• 210000004027 cell Anatomy 0.000 description 17
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 16
• 230000000694 effects Effects 0.000 description 16
• 230000002829 reductive effect Effects 0.000 description 16
• 239000003643 water by type Substances 0.000 description 16
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 15
• 235000011114 ammonium hydroxide Nutrition 0.000 description 15
• 229910052736 halogen Inorganic materials 0.000 description 14
• 150000002367 halogens Chemical class 0.000 description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
• 239000000243 solution Substances 0.000 description 13
• 125000001424 substituent group Chemical group 0.000 description 13
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• 241000699670 Mus sp. Species 0.000 description 12
• 125000003710 aryl alkyl group Chemical group 0.000 description 12
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• 238000001665 trituration Methods 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
• KTHGOGJDJNSQDK-PPHPATTJSA-N 3-(4-fluorophenyl)-5-[(3s)-piperidin-3-yl]-1,2,4-oxadiazole;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1=NOC([C@@H]2CNCCC2)=N1 KTHGOGJDJNSQDK-PPHPATTJSA-N 0.000 description 11
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
• 239000011541 reaction mixture Substances 0.000 description 11
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• 230000004913 activation Effects 0.000 description 10
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 10
• 229910052739 hydrogen Inorganic materials 0.000 description 10
• 239000001257 hydrogen Substances 0.000 description 10
• 238000002953 preparative HPLC Methods 0.000 description 10
• 230000008569 process Effects 0.000 description 10
• 238000003786 synthesis reaction Methods 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 9
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
• 239000000556 agonist Substances 0.000 description 8
• 210000004556 brain Anatomy 0.000 description 8
• 125000004122 cyclic group Chemical group 0.000 description 8
• 229960004132 diethyl ether Drugs 0.000 description 8
• 238000002474 experimental method Methods 0.000 description 8
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
• 230000006742 locomotor activity Effects 0.000 description 8
• 239000012044 organic layer Substances 0.000 description 8
• AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
• 239000011780 sodium chloride Substances 0.000 description 8
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 7
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
• 230000027455 binding Effects 0.000 description 7
• 230000001054 cortical effect Effects 0.000 description 7
• 125000000753 cycloalkyl group Chemical group 0.000 description 7
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 7
• 239000003208 petroleum Substances 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 230000004044 response Effects 0.000 description 7
• 238000010561 standard procedure Methods 0.000 description 7
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 6
• RPQWXGVZELKOEU-UHFFFAOYSA-N 3,4-difluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1F RPQWXGVZELKOEU-UHFFFAOYSA-N 0.000 description 6
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
• 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 6
• 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• 101001032838 Rattus norvegicus Metabotropic glutamate receptor 5 Proteins 0.000 description 6
• 125000002877 alkyl aryl group Chemical group 0.000 description 6
• 125000005213 alkyl heteroaryl group Chemical group 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 239000012131 assay buffer Substances 0.000 description 6
• 238000005859 coupling reaction Methods 0.000 description 6
• 230000006870 function Effects 0.000 description 6
• 230000003834 intracellular effect Effects 0.000 description 6
• 239000012299 nitrogen atmosphere Substances 0.000 description 6
• 208000020016 psychiatric disease Diseases 0.000 description 6
• 238000000825 ultraviolet detection Methods 0.000 description 6
• 239000003981 vehicle Substances 0.000 description 6
• JSWRVDNTKPAJLB-UHFFFAOYSA-N 2,4-difluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C(F)=C1 JSWRVDNTKPAJLB-UHFFFAOYSA-N 0.000 description 5
• KDXOONIQRUZGSY-UHFFFAOYSA-N 4-fluoro-2-methylbenzoic acid Chemical compound CC1=CC(F)=CC=C1C(O)=O KDXOONIQRUZGSY-UHFFFAOYSA-N 0.000 description 5
• VQBXUKGMJCPBMF-UHFFFAOYSA-N 5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC=1ON=CC=1C(O)=O VQBXUKGMJCPBMF-UHFFFAOYSA-N 0.000 description 5
• UJDLCTNVHJEBDG-UHFFFAOYSA-N 6-fluoropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(F)N=C1 UJDLCTNVHJEBDG-UHFFFAOYSA-N 0.000 description 5
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
• 210000001130 astrocyte Anatomy 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 235000019441 ethanol Nutrition 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 230000003137 locomotive effect Effects 0.000 description 5
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• 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 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
• 208000012902 Nervous system disease Diseases 0.000 description 4
• 208000025966 Neurological disease Diseases 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 230000003185 calcium uptake Effects 0.000 description 4
• 239000003795 chemical substances by application Substances 0.000 description 4
• 239000012091 fetal bovine serum Substances 0.000 description 4
• 239000008103 glucose Substances 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 102000005962 receptors Human genes 0.000 description 4
• 108020003175 receptors Proteins 0.000 description 4
• 229910052938 sodium sulfate Inorganic materials 0.000 description 4
• 235000011152 sodium sulphate Nutrition 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
• PSEHPTJSVAZKRB-LBPRGKRZSA-N (2,4-difluorophenyl)-[(3s)-3-[3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound FC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C(=CC=CC=2)F)CCC1 PSEHPTJSVAZKRB-LBPRGKRZSA-N 0.000 description 3
• WWPISKFGYAYDHO-ZDUSSCGKSA-N (5-ethyl-1,2-oxazol-4-yl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1CC WWPISKFGYAYDHO-ZDUSSCGKSA-N 0.000 description 3
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
• CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 3
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 239000007995 HEPES buffer Substances 0.000 description 3
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
• 150000001204 N-oxides Chemical class 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
• KFXKGPXJQLMBMW-ZDUSSCGKSA-N [(3s)-3-[3-(2,4-difluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-fluoro-2-methylphenyl)methanone Chemical compound CC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C(=CC(F)=CC=2)F)CCC1 KFXKGPXJQLMBMW-ZDUSSCGKSA-N 0.000 description 3
• JWGJNZULNIBAFQ-LBPRGKRZSA-N [(3s)-3-[3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(5-methyl-1,2-oxazol-4-yl)methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C(=CC=CC=2)F)=C1C JWGJNZULNIBAFQ-LBPRGKRZSA-N 0.000 description 3
• HTVYMGIJIXWRFY-ZDUSSCGKSA-N [(3s)-3-[3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(6-fluoropyridin-3-yl)methanone Chemical compound C1=NC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C(=CC=CC=2)F)CCC1 HTVYMGIJIXWRFY-ZDUSSCGKSA-N 0.000 description 3
• 125000000304 alkynyl group Chemical group 0.000 description 3
• 239000005557 antagonist Substances 0.000 description 3
• 239000000164 antipsychotic agent Substances 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000011575 calcium Substances 0.000 description 3
• 239000001110 calcium chloride Substances 0.000 description 3
• 235000011148 calcium chloride Nutrition 0.000 description 3
• 229910001628 calcium chloride Inorganic materials 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• 210000003169 central nervous system Anatomy 0.000 description 3
• 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 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 239000007822 coupling agent Substances 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 229940035423 ethyl ether Drugs 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 150000004677 hydrates Chemical class 0.000 description 3
• 150000002431 hydrogen Chemical class 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 238000003384 imaging method Methods 0.000 description 3
• 230000001965 increasing effect Effects 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 238000007912 intraperitoneal administration Methods 0.000 description 3
• 238000011068 loading method Methods 0.000 description 3
• 230000027928 long-term synaptic potentiation Effects 0.000 description 3
• 230000015654 memory Effects 0.000 description 3
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
• 230000000926 neurological effect Effects 0.000 description 3
• 229910052757 nitrogen Inorganic materials 0.000 description 3
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 3
• 150000003906 phosphoinositides Chemical class 0.000 description 3
• 239000000047 product Substances 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• ZNJHFNUEQDVFCJ-UHFFFAOYSA-M sodium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[Na+].OCCN1CCN(CCS(O)(=O)=O)CC1 ZNJHFNUEQDVFCJ-UHFFFAOYSA-M 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 3
• HRWCCIUWNWQMHX-AWEZNQCLSA-N (2,4-difluorophenyl)-[(3s)-3-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound FC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC=CC=2)CCC1 HRWCCIUWNWQMHX-AWEZNQCLSA-N 0.000 description 2
• MLTBZEPGVPQYGS-LBPRGKRZSA-N (2,4-difluorophenyl)-[(3s)-3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound FC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2N=CC=CC=2)CCC1 MLTBZEPGVPQYGS-LBPRGKRZSA-N 0.000 description 2
• BYFSESWIBYKSKJ-NSHDSACASA-N (2,4-difluorophenyl)-[(3s)-3-[3-(2,4-difluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound FC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C(=CC(F)=CC=2)F)CCC1 BYFSESWIBYKSKJ-NSHDSACASA-N 0.000 description 2
• XIPCASJRKSGLMT-LBPRGKRZSA-N (3,4-difluorophenyl)-[(3s)-3-(3-thiophen-3-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=C(F)C(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C2=CSC=C2)CCC1 XIPCASJRKSGLMT-LBPRGKRZSA-N 0.000 description 2
• XHIHRABWCMQDKK-NSHDSACASA-N (3,4-difluorophenyl)-[(3s)-3-[3-(1,3-thiazol-4-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=C(F)C(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2N=CSC=2)CCC1 XHIHRABWCMQDKK-NSHDSACASA-N 0.000 description 2
• LUQDMFURIUHGRN-LBPRGKRZSA-N (3,4-difluorophenyl)-[(3s)-3-[3-(2,4-difluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound FC1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)C(F)=CC=2)=N1 LUQDMFURIUHGRN-LBPRGKRZSA-N 0.000 description 2
• UUSRUAGBLVVASE-HNNXBMFYSA-N (4-fluoro-2-methylphenyl)-[(3s)-3-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound CC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CN=CC=2)CCC1 UUSRUAGBLVVASE-HNNXBMFYSA-N 0.000 description 2
• BDWLILFPLXVQLM-ZDUSSCGKSA-N (4-fluorophenyl)-[(3s)-3-(3-thiophen-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2SC=CC=2)CCC1 BDWLILFPLXVQLM-ZDUSSCGKSA-N 0.000 description 2
• LDUDEDVAKPQDJR-ZDUSSCGKSA-N (4-fluorophenyl)-[(3s)-3-(3-thiophen-3-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C2=CSC=C2)CCC1 LDUDEDVAKPQDJR-ZDUSSCGKSA-N 0.000 description 2
• YKSCFSZDWWZLEF-HNNXBMFYSA-N (4-fluorophenyl)-[(3s)-3-[3-(3-methylpyridin-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CC1=CC=CN=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 YKSCFSZDWWZLEF-HNNXBMFYSA-N 0.000 description 2
• SCCWPLNCLATLGT-UHFFFAOYSA-N (4-fluorophenyl)-[5-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]-3,6-dihydro-2h-pyridin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CC(C=2ON=C(N=2)C=2C=CC(F)=CC=2)=CCC1 SCCWPLNCLATLGT-UHFFFAOYSA-N 0.000 description 2
• LGMVMAZHYUIXOA-DJZRFWRSSA-N (5-fluoro-2,3-dihydro-1h-inden-1-yl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C2C3=CC=C(F)C=C3CC2)=N1 LGMVMAZHYUIXOA-DJZRFWRSSA-N 0.000 description 2
• OWHVTMNWZKUIPA-NSHDSACASA-N (5-methyl-1,2-oxazol-4-yl)-[(3s)-3-(3-thiophen-3-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C2=CSC=C2)=C1C OWHVTMNWZKUIPA-NSHDSACASA-N 0.000 description 2
• YYMCVDNIIFNDJK-XFQWXJFMSA-N (z)-1-(3-fluorophenyl)-n-[(z)-(3-fluorophenyl)methylideneamino]methanimine Chemical compound FC1=CC=CC(\C=N/N=C\C=2C=C(F)C=CC=2)=C1 YYMCVDNIIFNDJK-XFQWXJFMSA-N 0.000 description 2
• 150000005071 1,2,4-oxadiazoles Chemical class 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
• JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 2
• NEWKHUASLBMWRE-UHFFFAOYSA-N 2-methyl-6-(phenylethynyl)pyridine Chemical compound CC1=CC=CC(C#CC=2C=CC=CC=2)=N1 NEWKHUASLBMWRE-UHFFFAOYSA-N 0.000 description 2
• NWPNXBQSRGKSJB-UHFFFAOYSA-N 2-methylbenzonitrile Chemical compound CC1=CC=CC=C1C#N NWPNXBQSRGKSJB-UHFFFAOYSA-N 0.000 description 2
• BKUIZWILNWHFHD-UHFFFAOYSA-N 3-cyano-n-(2,5-diphenylpyrazol-3-yl)benzamide Chemical compound C=1C=CC(C#N)=CC=1C(=O)NC1=CC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 BKUIZWILNWHFHD-UHFFFAOYSA-N 0.000 description 2
• IHCCAYCGZOLTEU-UHFFFAOYSA-N 3-furoic acid Chemical compound OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 description 2
• ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 2
• OSUPWUQRPLIJKX-UHFFFAOYSA-N 4-fluoro-n'-hydroxybenzenecarboximidamide Chemical compound ON=C(N)C1=CC=C(F)C=C1 OSUPWUQRPLIJKX-UHFFFAOYSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 2
• 229910014585 C2-Ce Inorganic materials 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 2
• OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 2
• 206010065390 Inflammatory pain Diseases 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• QUPYTYBQMROHSV-UHFFFAOYSA-N N'-hydroxy-6-methylpyridine-2-carboximidamide Chemical compound CC1=CC=CC(C(N)=NO)=N1 QUPYTYBQMROHSV-UHFFFAOYSA-N 0.000 description 2
• WVMBPWMAQDVZCM-UHFFFAOYSA-N N-methylanthranilic acid Chemical compound CNC1=CC=CC=C1C(O)=O WVMBPWMAQDVZCM-UHFFFAOYSA-N 0.000 description 2
• 229930182555 Penicillin Natural products 0.000 description 2
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• INEGTVJXINDDTL-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(3-methyl-1,2-oxazol-4-yl)methanone Chemical compound CC1=NOC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 INEGTVJXINDDTL-ZDUSSCGKSA-N 0.000 description 2
• FDJIUZIDMFYKFS-AWEZNQCLSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(3-methylfuran-2-yl)methanone Chemical compound C1=COC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C FDJIUZIDMFYKFS-AWEZNQCLSA-N 0.000 description 2
• BLCPGJHACBOEBK-HNNXBMFYSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(oxan-4-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C2CCOCC2)=N1 BLCPGJHACBOEBK-HNNXBMFYSA-N 0.000 description 2
• UOLHJLVCCDQPQT-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-[5-(methoxymethyl)-1,2-oxazol-4-yl]methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1COC UOLHJLVCCDQPQT-ZDUSSCGKSA-N 0.000 description 2
• ZDDWOJJRUCFGAZ-NSHDSACASA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-[5-(trifluoromethyl)-1h-pyrazol-4-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C(=NNC=2)C(F)(F)F)=N1 ZDDWOJJRUCFGAZ-NSHDSACASA-N 0.000 description 2
• JBDANKZNQJIQJN-KRWDZBQOSA-N [(3s)-3-[3-[4-(dimethylamino)phenyl]-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(N(C)C)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 JBDANKZNQJIQJN-KRWDZBQOSA-N 0.000 description 2
• MOVYFTBROQGAAF-QFIPXVFZSA-N [3-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidine-1-carbonyl]phenyl]-phenylmethanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(C=CC=2)C(=O)C=2C=CC=CC=2)=N1 MOVYFTBROQGAAF-QFIPXVFZSA-N 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
• 125000003342 alkenyl group Chemical group 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 125000004103 aminoalkyl group Chemical group 0.000 description 2
• 230000036506 anxiety Effects 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 230000002238 attenuated effect Effects 0.000 description 2
• 125000005605 benzo group Chemical group 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 125000004432 carbon atom Chemical group C* 0.000 description 2
• 239000003426 co-catalyst Substances 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
• SOWWXUOAKQFNCQ-INIZCTEOSA-N cyclohexyl-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C2CCCCC2)=N1 SOWWXUOAKQFNCQ-INIZCTEOSA-N 0.000 description 2
• NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• 238000004821 distillation Methods 0.000 description 2
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 230000004064 dysfunction Effects 0.000 description 2
• 238000000132 electrospray ionisation Methods 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 230000002964 excitative effect Effects 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• 125000000623 heterocyclic group Chemical group 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 239000010410 layer Substances 0.000 description 2
• 230000013016 learning Effects 0.000 description 2
• 239000006210 lotion 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
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 238000012544 monitoring process Methods 0.000 description 2
• 208000004296 neuralgia Diseases 0.000 description 2
• 230000003227 neuromodulating effect Effects 0.000 description 2
• 208000021722 neuropathic pain Diseases 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 2
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 229940049954 penicillin Drugs 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
• 150000004885 piperazines Chemical group 0.000 description 2
• 230000001242 postsynaptic effect Effects 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Chemical compound OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 2
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical group N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 238000012453 sprague-dawley rat model Methods 0.000 description 2
• 238000007619 statistical method Methods 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• MBGGBVCUIVRRBF-UHFFFAOYSA-N sulfinpyrazone Chemical compound O=C1N(C=2C=CC=CC=2)N(C=2C=CC=CC=2)C(=O)C1CCS(=O)C1=CC=CC=C1 MBGGBVCUIVRRBF-UHFFFAOYSA-N 0.000 description 2
• 229960003329 sulfinpyrazone Drugs 0.000 description 2
• 230000000946 synaptic effect Effects 0.000 description 2
• 230000005062 synaptic transmission Effects 0.000 description 2
• 230000024587 synaptic transmission, glutamatergic Effects 0.000 description 2
• QLAIHIIPBKOTBI-LBPRGKRZSA-N tert-butyl (3s)-3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC[C@@H]1C1=NC(C=2N=CC=CC=2)=NO1 QLAIHIIPBKOTBI-LBPRGKRZSA-N 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
• QOWKSCUAOVQCBQ-AWEZNQCLSA-N (1,5-dimethylpyrazol-4-yl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=NN(C)C(C)=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 QOWKSCUAOVQCBQ-AWEZNQCLSA-N 0.000 description 1
• LUQQNCFMWZZQLI-NSHDSACASA-N (2,4-difluorophenyl)-[(3s)-3-[3-(2-methyl-1,3-thiazol-5-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound S1C(C)=NC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C(=CC(F)=CC=2)F)=N1 LUQQNCFMWZZQLI-NSHDSACASA-N 0.000 description 1
• YBPRZKRBGFRJDK-ZDUSSCGKSA-N (2,4-difluorophenyl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C(=CC(F)=CC=2)F)=N1 YBPRZKRBGFRJDK-ZDUSSCGKSA-N 0.000 description 1
• SZHOQEARQQGNRI-AWEZNQCLSA-N (2,4-dimethyl-1,3-thiazol-5-yl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound S1C(C)=NC(C)=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 SZHOQEARQQGNRI-AWEZNQCLSA-N 0.000 description 1
• ZXSHTZBELHXACW-UHFFFAOYSA-N (2-ethylphenyl)-[3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CCC1=CC=CC=C1C(=O)N1CC(C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 ZXSHTZBELHXACW-UHFFFAOYSA-N 0.000 description 1
• AVTDNPLZFDEFRU-HNNXBMFYSA-N (3,4-difluorophenyl)-[(3s)-3-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=C(F)C(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC=CC=2)CCC1 AVTDNPLZFDEFRU-HNNXBMFYSA-N 0.000 description 1
• OMQIYLVWYJRRJT-AWEZNQCLSA-N (3,4-difluorophenyl)-[(3s)-3-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=C(F)C(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CN=CC=2)CCC1 OMQIYLVWYJRRJT-AWEZNQCLSA-N 0.000 description 1
• PFGNSMGKXMEDJQ-LBPRGKRZSA-N (3,4-difluorophenyl)-[(3s)-3-[3-(2-methyl-1,3-thiazol-5-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound S1C(C)=NC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)C(F)=CC=2)=N1 PFGNSMGKXMEDJQ-LBPRGKRZSA-N 0.000 description 1
• IBSDJBSJEWVTOR-AWEZNQCLSA-N (3,4-difluorophenyl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)C(F)=CC=2)=N1 IBSDJBSJEWVTOR-AWEZNQCLSA-N 0.000 description 1
• XNUMYFLOQVCEKO-AWEZNQCLSA-N (3,4-difluorophenyl)-[(3s)-3-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)C(F)=CC=2)=N1 XNUMYFLOQVCEKO-AWEZNQCLSA-N 0.000 description 1
• ZQNKSWZPJZRQSJ-UHFFFAOYSA-N (3-fluorophenyl)-[3-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound FC1=CC=CC(C(=O)N2CC(CCC2)C=2ON=C(N=2)C=2C=CC=CC=2)=C1 ZQNKSWZPJZRQSJ-UHFFFAOYSA-N 0.000 description 1
• AYMVIZABQIOQEK-UHFFFAOYSA-N (3-fluorophenyl)-[3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC(C2CN(CCC2)C(=O)C=2C=C(F)C=CC=2)=N1 AYMVIZABQIOQEK-UHFFFAOYSA-N 0.000 description 1
• WSFJHBITGSMFKP-INIZCTEOSA-N (4-fluoro-2-methylphenyl)-[(3s)-3-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound CC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC=CC=2)CCC1 WSFJHBITGSMFKP-INIZCTEOSA-N 0.000 description 1
• JSVZRUOSIODDMU-AWEZNQCLSA-N (4-fluoro-2-methylphenyl)-[(3s)-3-[3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C(=CC=CC=2)F)CCC1 JSVZRUOSIODDMU-AWEZNQCLSA-N 0.000 description 1
• SOWBLJMJSODIFI-SFHVURJKSA-N (4-fluorophenyl)-[(3s)-3-(3-naphthalen-1-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C3=CC=CC=C3C=CC=2)CCC1 SOWBLJMJSODIFI-SFHVURJKSA-N 0.000 description 1
• XXWXHIOXVHKIQD-INIZCTEOSA-N (4-fluorophenyl)-[(3s)-3-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC=CC=2)CCC1 XXWXHIOXVHKIQD-INIZCTEOSA-N 0.000 description 1
• OUSXYAFJPPAAJF-ZDUSSCGKSA-N (4-fluorophenyl)-[(3s)-3-(3-pyrazin-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2N=CC=NC=2)CCC1 OUSXYAFJPPAAJF-ZDUSSCGKSA-N 0.000 description 1
• PKOCQAVNDBHVSN-LBPRGKRZSA-N (4-fluorophenyl)-[(3s)-3-[3-(1,3-thiazol-4-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2N=CSC=2)CCC1 PKOCQAVNDBHVSN-LBPRGKRZSA-N 0.000 description 1
• SQPDXEMVOFZYRN-AWEZNQCLSA-N (4-fluorophenyl)-[(3s)-3-[3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C(=CC=CC=2)F)CCC1 SQPDXEMVOFZYRN-AWEZNQCLSA-N 0.000 description 1
• XTALYXOQCLWHAX-INIZCTEOSA-N (4-fluorophenyl)-[(3s)-3-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CC1=CC=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 XTALYXOQCLWHAX-INIZCTEOSA-N 0.000 description 1
• LOQRBMDMBVNLAA-KRWDZBQOSA-N (4-fluorophenyl)-[(3s)-3-[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(C)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 LOQRBMDMBVNLAA-KRWDZBQOSA-N 0.000 description 1
• QCEZQFAPIXPJNK-AWEZNQCLSA-N (4-fluorophenyl)-[(3s)-3-[3-(5-methylfuran-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound O1C(C)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 QCEZQFAPIXPJNK-AWEZNQCLSA-N 0.000 description 1
• RWFCKJHNXMCJDE-HNNXBMFYSA-N (4-fluorophenyl)-[(3s)-3-[3-(6-methylpyridin-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CC1=CC=CC(C=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 RWFCKJHNXMCJDE-HNNXBMFYSA-N 0.000 description 1
• NHOFNYNXSRPXCX-ZDUSSCGKSA-N (4-fluorophenyl)-[(3s)-3-[3-(furan-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2OC=CC=2)CCC1 NHOFNYNXSRPXCX-ZDUSSCGKSA-N 0.000 description 1
• BKWGSBXXTFACMW-UHFFFAOYSA-N (4-fluorophenyl)-[3-[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CC(C=2ON=C(N=2)C=2C=C(F)C=CC=2)CCC1 BKWGSBXXTFACMW-UHFFFAOYSA-N 0.000 description 1
• VXQCCZHCFBHTTD-UHFFFAOYSA-N (4-fluorophenyl)-[3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CC(C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 VXQCCZHCFBHTTD-UHFFFAOYSA-N 0.000 description 1
• HPWJUUGBBSSRQS-AWEZNQCLSA-N (5-methyl-1,2-oxazol-4-yl)-[(3s)-3-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC=CC=2)=C1C HPWJUUGBBSSRQS-AWEZNQCLSA-N 0.000 description 1
• XDFWUDHCDXZYMV-LBPRGKRZSA-N (6-fluoropyridin-3-yl)-[(3s)-3-[3-(2-methyl-1,3-thiazol-5-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound S1C(C)=NC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=NC(F)=CC=2)=N1 XDFWUDHCDXZYMV-LBPRGKRZSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000006718 (C3-C7) heterocycloalkenyl group Chemical group 0.000 description 1
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 1
• QMDFHZOGAYONLN-UHFFFAOYSA-N 1,2,3,4-tetrahydropyridine-3-carboxylic acid Chemical compound OC(=O)C1CNC=CC1 QMDFHZOGAYONLN-UHFFFAOYSA-N 0.000 description 1
• HAKSOKWVNPZVNM-UHFFFAOYSA-N 1,2,3,4-tetrahydropyridine;hydrochloride Chemical compound Cl.C1CNC=CC1 HAKSOKWVNPZVNM-UHFFFAOYSA-N 0.000 description 1
• PIINXYKJQGMIOZ-UHFFFAOYSA-N 1,2-dipyridin-2-ylethane-1,2-dione Chemical compound C=1C=CC=NC=1C(=O)C(=O)C1=CC=CC=N1 PIINXYKJQGMIOZ-UHFFFAOYSA-N 0.000 description 1
• FNWICKMGOBZJRL-AWEZNQCLSA-N 1,3-benzothiazol-2-yl-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2SC3=CC=CC=C3N=2)=N1 FNWICKMGOBZJRL-AWEZNQCLSA-N 0.000 description 1
• SBQLFYRKTQSROX-HNNXBMFYSA-N 1,3-benzothiazol-6-yl-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C3SC=NC3=CC=2)=N1 SBQLFYRKTQSROX-HNNXBMFYSA-N 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical group C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• PNAFRZGWUVQUKH-UHFFFAOYSA-N 1,3-thiazole-4-carbonitrile Chemical compound N#CC1=CSC=N1 PNAFRZGWUVQUKH-UHFFFAOYSA-N 0.000 description 1
• SKTIXLZNJZTGRT-UHFFFAOYSA-N 1,5-dimethylpyrazole-4-carboxylic acid Chemical compound CC1=C(C(O)=O)C=NN1C SKTIXLZNJZTGRT-UHFFFAOYSA-N 0.000 description 1
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 1
• KKHQYUPHBPYITH-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]-3,6-dihydro-2h-pyridine-5-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC=C(C(O)=O)C1 KKHQYUPHBPYITH-UHFFFAOYSA-N 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• JRQSGIQEBOZPHK-UHFFFAOYSA-N 1-methylpyrrole-2-carbonitrile Chemical compound CN1C=CC=C1C#N JRQSGIQEBOZPHK-UHFFFAOYSA-N 0.000 description 1
• 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• VCLSWKVAHAJSFL-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=CC=C2C(=O)O VCLSWKVAHAJSFL-UHFFFAOYSA-N 0.000 description 1
• SJZATRRXUILGHH-UHFFFAOYSA-N 2,4,6-trifluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=C(F)C=C1F SJZATRRXUILGHH-UHFFFAOYSA-N 0.000 description 1
• LJFDXXUKKMEQKE-UHFFFAOYSA-N 2,4-difluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(F)=C1 LJFDXXUKKMEQKE-UHFFFAOYSA-N 0.000 description 1
• MQGBARXPCXAFRZ-UHFFFAOYSA-N 2,4-dimethyl-1,3-thiazole-5-carboxylic acid Chemical compound CC1=NC(C)=C(C(O)=O)S1 MQGBARXPCXAFRZ-UHFFFAOYSA-N 0.000 description 1
• CNTHHNPBADVTRY-UHFFFAOYSA-N 2,5-dimethylfuran-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=C(C)O1 CNTHHNPBADVTRY-UHFFFAOYSA-N 0.000 description 1
• JGQKORRBYIBYOF-UHFFFAOYSA-N 2-(benzylamino)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NCC1=CC=CC=C1 JGQKORRBYIBYOF-UHFFFAOYSA-N 0.000 description 1
• UNIDAFCQFPGYJJ-UHFFFAOYSA-N 2-amino-2-(2-chloro-5-hydroxyphenyl)acetic acid Chemical compound OC(=O)C(N)C1=CC(O)=CC=C1Cl UNIDAFCQFPGYJJ-UHFFFAOYSA-N 0.000 description 1
• RVSXMPCELBYUSF-UHFFFAOYSA-N 2-bromothiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1Br RVSXMPCELBYUSF-UHFFFAOYSA-N 0.000 description 1
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
• CGMMPMYKMDITEA-UHFFFAOYSA-N 2-ethylbenzoic acid Chemical compound CCC1=CC=CC=C1C(O)=O CGMMPMYKMDITEA-UHFFFAOYSA-N 0.000 description 1
• GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 1
• LLLVHTWJGWNRBD-UHFFFAOYSA-N 2-fluoropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1F LLLVHTWJGWNRBD-UHFFFAOYSA-N 0.000 description 1
• JMPFWDWYGOWUFP-UHFFFAOYSA-N 2-fluoropyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(F)=C1 JMPFWDWYGOWUFP-UHFFFAOYSA-N 0.000 description 1
• YXDXXGXWFJCXEB-UHFFFAOYSA-N 2-furonitrile Chemical compound N#CC1=CC=CO1 YXDXXGXWFJCXEB-UHFFFAOYSA-N 0.000 description 1
• YQLHOMLLEOCIOH-UHFFFAOYSA-N 2-methyl-1,3-thiazole-5-carbonitrile Chemical compound CC1=NC=C(C#N)S1 YQLHOMLLEOCIOH-UHFFFAOYSA-N 0.000 description 1
• CFGQZVOVFIZRMN-UHFFFAOYSA-N 2-methylfuran-3-carboxylic acid Chemical compound CC=1OC=CC=1C(O)=O CFGQZVOVFIZRMN-UHFFFAOYSA-N 0.000 description 1
• HNTZKNJGAFJMHQ-UHFFFAOYSA-N 2-methylpyridine-3-carboxylic acid Chemical compound CC1=NC=CC=C1C(O)=O HNTZKNJGAFJMHQ-UHFFFAOYSA-N 0.000 description 1
• YJZOPBSZDIBXBG-UHFFFAOYSA-N 2-methylthiophene-3-carboxylic acid Chemical compound CC=1SC=CC=1C(O)=O YJZOPBSZDIBXBG-UHFFFAOYSA-N 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical group C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• LBZUGBMJRBSYGH-QRPNPIFTSA-N 3-(2,4-difluorophenyl)-5-[(3s)-piperidin-3-yl]-1,2,4-oxadiazole;hydrochloride Chemical compound Cl.FC1=CC(F)=CC=C1C1=NOC([C@@H]2CNCCC2)=N1 LBZUGBMJRBSYGH-QRPNPIFTSA-N 0.000 description 1
• XVYOUZOKKZECJK-FVGYRXGTSA-N 3-(2-fluorophenyl)-5-[(3s)-piperidin-3-yl]-1,2,4-oxadiazole;hydrochloride Chemical compound Cl.FC1=CC=CC=C1C1=NOC([C@@H]2CNCCC2)=N1 XVYOUZOKKZECJK-FVGYRXGTSA-N 0.000 description 1
• RGAZJVQJKJHPJH-QRPNPIFTSA-N 3-(2-methyl-1,3-thiazol-5-yl)-5-[(3s)-piperidin-3-yl]-1,2,4-oxadiazole;hydrochloride Chemical compound Cl.S1C(C)=NC=C1C1=NOC([C@@H]2CNCCC2)=N1 RGAZJVQJKJHPJH-QRPNPIFTSA-N 0.000 description 1
• JZOFIKWPHMMQES-KRWDZBQOSA-N 3-(4-fluorophenyl)-1-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]propan-1-one Chemical compound C1=CC(F)=CC=C1CCC(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 JZOFIKWPHMMQES-KRWDZBQOSA-N 0.000 description 1
• KTHGOGJDJNSQDK-UHFFFAOYSA-N 3-(4-fluorophenyl)-5-piperidin-3-yl-1,2,4-oxadiazole;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1=NOC(C2CNCCC2)=N1 KTHGOGJDJNSQDK-UHFFFAOYSA-N 0.000 description 1
• URLYREZIPSJJQU-UHFFFAOYSA-N 3-(phenoxymethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(COC=2C=CC=CC=2)=C1 URLYREZIPSJJQU-UHFFFAOYSA-N 0.000 description 1
• AXJXRLHTQQONQR-UHFFFAOYSA-N 3-benzoylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 AXJXRLHTQQONQR-UHFFFAOYSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• JMHGATOBRPWPBZ-UHFFFAOYSA-N 3-cyano-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(C#N)=C1 JMHGATOBRPWPBZ-UHFFFAOYSA-N 0.000 description 1
• POLXLLIQWDBJMD-UHFFFAOYSA-N 3-fluoropyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC=C1F POLXLLIQWDBJMD-UHFFFAOYSA-N 0.000 description 1
• YBLSBWHFPXDRHC-UHFFFAOYSA-N 3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC=C1C(O)=O YBLSBWHFPXDRHC-UHFFFAOYSA-N 0.000 description 1
• BNYIQEFWGSXIKQ-UHFFFAOYSA-N 3-methylfuran-2-carboxylic acid Chemical compound CC=1C=COC=1C(O)=O BNYIQEFWGSXIKQ-UHFFFAOYSA-N 0.000 description 1
• WBXZCDIZXWDPBL-UHFFFAOYSA-N 3-methylpyridine-2-carbonitrile Chemical compound CC1=CC=CN=C1C#N WBXZCDIZXWDPBL-UHFFFAOYSA-N 0.000 description 1
• OSMAGAVKVRGYGR-UHFFFAOYSA-N 3-methylpyridine-4-carboxylic acid Chemical compound CC1=CN=CC=C1C(O)=O OSMAGAVKVRGYGR-UHFFFAOYSA-N 0.000 description 1
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• NHGWUMGOMGQTIT-HNNXBMFYSA-N 3h-benzimidazol-5-yl-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C3N=CNC3=CC=2)=N1 NHGWUMGOMGQTIT-HNNXBMFYSA-N 0.000 description 1
• JYMNQRQQBJIMCV-UHFFFAOYSA-N 4-(dimethylamino)benzonitrile Chemical compound CN(C)C1=CC=C(C#N)C=C1 JYMNQRQQBJIMCV-UHFFFAOYSA-N 0.000 description 1
• RATSANVPHHXDCT-UHFFFAOYSA-N 4-(trifluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=C(OC(F)(F)F)C=C1 RATSANVPHHXDCT-UHFFFAOYSA-N 0.000 description 1
• NKTZRZBSADJAJL-UHFFFAOYSA-N 4-fluoro-2-(methylamino)benzoic acid Chemical compound CNC1=CC(F)=CC=C1C(O)=O NKTZRZBSADJAJL-UHFFFAOYSA-N 0.000 description 1
• LWGCZCMLPRMKIZ-UHFFFAOYSA-N 4-fluoro-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1F LWGCZCMLPRMKIZ-UHFFFAOYSA-N 0.000 description 1
• AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
• FXPOCCDGHHTZAO-UHFFFAOYSA-N 4-methyl-1h-pyrrole-3-carboxylic acid Chemical compound CC1=CNC=C1C(O)=O FXPOCCDGHHTZAO-UHFFFAOYSA-N 0.000 description 1
• NHHQOYLPBUYHQU-UHFFFAOYSA-N 4-methylthiadiazole-5-carboxylic acid Chemical compound CC=1N=NSC=1C(O)=O NHHQOYLPBUYHQU-UHFFFAOYSA-N 0.000 description 1
• TUSLAEPZELMPGR-UHFFFAOYSA-N 4-piperidin-4-yloxadiazole Chemical compound C1CNCCC1C1=CON=N1 TUSLAEPZELMPGR-UHFFFAOYSA-N 0.000 description 1
• VKYAVCXPZKRQAJ-UHFFFAOYSA-N 5-(methoxymethyl)-1,2-oxazole-4-carboxylic acid Chemical compound COCC=1ON=CC=1C(O)=O VKYAVCXPZKRQAJ-UHFFFAOYSA-N 0.000 description 1
• VHKMTORCXXPIFI-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NNC=1C(F)(F)F VHKMTORCXXPIFI-UHFFFAOYSA-N 0.000 description 1
• UJKIYNCVTRNAFB-KLXURFKVSA-N 5-[(3s)-piperidin-3-yl]-3-(1,3-thiazol-4-yl)-1,2,4-oxadiazole;dihydrochloride Chemical compound Cl.Cl.C1CCNC[C@H]1C1=NC(C=2N=CSC=2)=NO1 UJKIYNCVTRNAFB-KLXURFKVSA-N 0.000 description 1
• WBGYIIJTFUGNTO-FJXQXJEOSA-N 5-[(3s)-piperidin-3-yl]-3-(1,3-thiazol-4-yl)-1,2,4-oxadiazole;hydrochloride Chemical compound Cl.C1CCNC[C@H]1C1=NC(C=2N=CSC=2)=NO1 WBGYIIJTFUGNTO-FJXQXJEOSA-N 0.000 description 1
• YGUUMRJFLRVBOD-UHFFFAOYSA-N 5-ethyl-1,2-oxazole-4-carboxylic acid Chemical compound CCC=1ON=CC=1C(O)=O YGUUMRJFLRVBOD-UHFFFAOYSA-N 0.000 description 1
• AXUVBHSQWRRJSD-UHFFFAOYSA-N 5-fluoro-2,3-dihydro-1h-indene-1-carboxylic acid Chemical compound FC1=CC=C2C(C(=O)O)CCC2=C1 AXUVBHSQWRRJSD-UHFFFAOYSA-N 0.000 description 1
• XGCRBVWSFYTMEC-UHFFFAOYSA-N 5-methylfuran-2-carbonitrile Chemical compound CC1=CC=C(C#N)O1 XGCRBVWSFYTMEC-UHFFFAOYSA-N 0.000 description 1
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
• CMADFEQMYFNYCF-UHFFFAOYSA-N 6-methylpyridine-2-carbonitrile Chemical compound CC1=CC=CC(C#N)=N1 CMADFEQMYFNYCF-UHFFFAOYSA-N 0.000 description 1
• WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
• 238000009010 Bradford assay Methods 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 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 1
• ASNFTDCKZKHJSW-UHFFFAOYSA-N DL-Quisqualic acid Natural products OC(=O)C(N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-UHFFFAOYSA-N 0.000 description 1
• 206010012335 Dependence Diseases 0.000 description 1
• 206010013654 Drug abuse Diseases 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
• 101800003838 Epidermal growth factor Proteins 0.000 description 1
• 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 108091006027 G proteins Proteins 0.000 description 1
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
• 102000030782 GTP binding Human genes 0.000 description 1
• 108091000058 GTP-Binding Proteins 0.000 description 1
• 102000018899 Glutamate Receptors Human genes 0.000 description 1
• 108010027915 Glutamate Receptors Proteins 0.000 description 1
• 206010019196 Head injury Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-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
• VLSMHEGGTFMBBZ-OOZYFLPDSA-M Kainate Chemical compound CC(=C)[C@H]1C[NH2+][C@H](C([O-])=O)[C@H]1CC([O-])=O VLSMHEGGTFMBBZ-OOZYFLPDSA-M 0.000 description 1
• ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
• 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 1
• 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 1
• 102100038354 Metabotropic glutamate receptor 4 Human genes 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 208000016285 Movement disease Diseases 0.000 description 1
• HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
• 229910017974 NH40H Inorganic materials 0.000 description 1
• 229940123730 Orexin receptor antagonist Drugs 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• ASNFTDCKZKHJSW-REOHCLBHSA-N Quisqualic acid Chemical compound OC(=O)[C@@H](N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-REOHCLBHSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 239000005864 Sulphur Chemical group 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 102000014384 Type C Phospholipases Human genes 0.000 description 1
• 108010079194 Type C Phospholipases Proteins 0.000 description 1
• DHTJJOSBYXRGQT-ZDUSSCGKSA-N [(3s)-3-[3-(2,4-difluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C(=CC(F)=CC=2)F)CCC1 DHTJJOSBYXRGQT-ZDUSSCGKSA-N 0.000 description 1
• PYUPTXHFQPNYMS-NSHDSACASA-N [(3s)-3-[3-(2,4-difluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(5-methyl-1,2-oxazol-4-yl)methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C(=CC(F)=CC=2)F)=C1C PYUPTXHFQPNYMS-NSHDSACASA-N 0.000 description 1
• QNFBKFBGEBITCP-LBPRGKRZSA-N [(3s)-3-[3-(2,4-difluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(6-fluoropyridin-3-yl)methanone Chemical compound FC1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=NC(F)=CC=2)=N1 QNFBKFBGEBITCP-LBPRGKRZSA-N 0.000 description 1
• QRRNOELOFVMJSB-INIZCTEOSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(1,2,5-trimethylpyrrol-3-yl)methanone Chemical compound CN1C(C)=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C QRRNOELOFVMJSB-INIZCTEOSA-N 0.000 description 1
• DJEVSCMJCSBCPI-LBPRGKRZSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2,4,6-trifluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C(=CC(F)=CC=2F)F)=N1 DJEVSCMJCSBCPI-LBPRGKRZSA-N 0.000 description 1
• BJJNRFMRISOXPD-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-fluoropyridin-3-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C(=NC=CC=2)F)=N1 BJJNRFMRISOXPD-ZDUSSCGKSA-N 0.000 description 1
• USXAKDIHSQAMFA-INIZCTEOSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 USXAKDIHSQAMFA-INIZCTEOSA-N 0.000 description 1
• LLLWZUZTYBTHKY-AWEZNQCLSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-methylthiophen-3-yl)methanone Chemical compound S1C=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C LLLWZUZTYBTHKY-AWEZNQCLSA-N 0.000 description 1
• KRHSIUQSPWXSFM-KRWDZBQOSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-phenylpyrazol-3-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2N(N=CC=2)C=2C=CC=CC=2)=N1 KRHSIUQSPWXSFM-KRWDZBQOSA-N 0.000 description 1
• IBWFEJNHMHBTBS-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(3-fluoropyridin-4-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C(=CN=CC=2)F)=N1 IBWFEJNHMHBTBS-ZDUSSCGKSA-N 0.000 description 1
• DCLPVKFRLZPBCW-HNNXBMFYSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(3-methylpyridin-4-yl)methanone Chemical compound CC1=CN=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 DCLPVKFRLZPBCW-HNNXBMFYSA-N 0.000 description 1
• SZAIFOWFJJIPFW-AWEZNQCLSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(3-methylthiophen-2-yl)methanone Chemical compound C1=CSC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C SZAIFOWFJJIPFW-AWEZNQCLSA-N 0.000 description 1
• SXGLZFNQHQDZSH-SFHVURJKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-imidazol-1-ylphenyl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(=CC=2)N2C=NC=C2)=N1 SXGLZFNQHQDZSH-SFHVURJKSA-N 0.000 description 1
• CYWXVEVPUWQCCE-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-methyl-1,3-thiazol-5-yl)methanone Chemical compound N1=CSC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C CYWXVEVPUWQCCE-ZDUSSCGKSA-N 0.000 description 1
• JBMYRAUIFUWLCQ-AWEZNQCLSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-methyl-1h-pyrrol-3-yl)methanone Chemical compound CC1=CNC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 JBMYRAUIFUWLCQ-AWEZNQCLSA-N 0.000 description 1
• VYKNVFUTELGSOR-HNNXBMFYSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-methyl-2-pyrazin-2-yl-1,3-thiazol-5-yl)methanone Chemical compound N=1OC([C@H]2CCCN(C2)C(=O)C=2SC(=NC=2C)C=2N=CC=NC=2)=NC=1C1=CC=C(F)C=C1 VYKNVFUTELGSOR-HNNXBMFYSA-N 0.000 description 1
• YGNFIZHFAPPOIR-LBPRGKRZSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-methylthiadiazol-5-yl)methanone Chemical compound N1=NSC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C YGNFIZHFAPPOIR-LBPRGKRZSA-N 0.000 description 1
• ZUMONWCRAGUXED-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(5-methyl-1,2-oxazol-3-yl)methanone Chemical compound O1C(C)=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=N1 ZUMONWCRAGUXED-ZDUSSCGKSA-N 0.000 description 1
• FKMGYJOXJPJOHR-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(5-methyl-1,2-oxazol-4-yl)methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C FKMGYJOXJPJOHR-ZDUSSCGKSA-N 0.000 description 1
• BAFOZTRIMVNTHI-INIZCTEOSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(5-pyridin-2-ylthiophen-2-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2SC(=CC=2)C=2N=CC=CC=2)=N1 BAFOZTRIMVNTHI-INIZCTEOSA-N 0.000 description 1
• WPXAVYSKTIOGKI-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(furan-3-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C2=COC=C2)=N1 WPXAVYSKTIOGKI-ZDUSSCGKSA-N 0.000 description 1
• VKJZVLBDNQPKRA-NSHDSACASA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(thiadiazol-4-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2N=NSC=2)=N1 VKJZVLBDNQPKRA-NSHDSACASA-N 0.000 description 1
• IKHYAWIWACYCNL-HNNXBMFYSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(thian-4-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C2CCSCC2)=N1 IKHYAWIWACYCNL-HNNXBMFYSA-N 0.000 description 1
• FNYQFUSDAGYVCH-QFIPXVFZSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-[3-(phenoxymethyl)phenyl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(COC=3C=CC=CC=3)C=CC=2)=N1 FNYQFUSDAGYVCH-QFIPXVFZSA-N 0.000 description 1
• YUMVLNSSMKOWOU-HNNXBMFYSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-[4-(trifluoromethyl)phenyl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(=CC=2)C(F)(F)F)=N1 YUMVLNSSMKOWOU-HNNXBMFYSA-N 0.000 description 1
• CXIBEVBSQCBRSY-UQKRIMTDSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-pyridin-2-ylmethanone;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2N=CC=CC=2)=N1 CXIBEVBSQCBRSY-UQKRIMTDSA-N 0.000 description 1
• QFADMZQACXNHLE-INIZCTEOSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-quinoxalin-6-ylmethanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C3N=CC=NC3=CC=2)=N1 QFADMZQACXNHLE-INIZCTEOSA-N 0.000 description 1
• MIWXWTMHANIIFK-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-thiophen-2-ylmethanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2SC=CC=2)=N1 MIWXWTMHANIIFK-ZDUSSCGKSA-N 0.000 description 1
• RHBWREIUJZJYMB-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-thiophen-3-ylmethanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C2=CSC=C2)=N1 RHBWREIUJZJYMB-ZDUSSCGKSA-N 0.000 description 1
• YYXGJEWUAPJCFZ-NRFANRHFSA-N [2-(benzylamino)phenyl]-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C(=CC=CC=2)NCC=2C=CC=CC=2)=N1 YYXGJEWUAPJCFZ-NRFANRHFSA-N 0.000 description 1
• MKGRRQCMPAMPJS-UHFFFAOYSA-N [3-[3-(4-butoxyphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-chloropyridin-4-yl)methanone Chemical compound C1=CC(OCCCC)=CC=C1C1=NOC(C2CN(CCC2)C(=O)C=2C=C(Cl)N=CC=2)=N1 MKGRRQCMPAMPJS-UHFFFAOYSA-N 0.000 description 1
• FLBKKZSEIFCLTL-UHFFFAOYSA-N [3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-phenylmethanone Chemical compound C1=CC(F)=CC=C1C1=NOC(C2CN(CCC2)C(=O)C=2C=CC=CC=2)=N1 FLBKKZSEIFCLTL-UHFFFAOYSA-N 0.000 description 1
• WKZGPTRKMXRGDT-AWEZNQCLSA-N [4-fluoro-2-(methylamino)phenyl]-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CNC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 WKZGPTRKMXRGDT-AWEZNQCLSA-N 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
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229940125516 allosteric modulator Drugs 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• PYHRZPFZZDCOPH-UHFFFAOYSA-N amphetamine sulfate Chemical compound OS(O)(=O)=O.CC(N)CC1=CC=CC=C1.CC(N)CC1=CC=CC=C1 PYHRZPFZZDCOPH-UHFFFAOYSA-N 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 230000000507 anthelmentic effect Effects 0.000 description 1
• 229940124339 anthelmintic agent Drugs 0.000 description 1
• 239000000921 anthelmintic agent Substances 0.000 description 1
• 229940005529 antipsychotics Drugs 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 101150024767 arnT gene Proteins 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
• SJSWRKNSCWKNIR-UHFFFAOYSA-N azane;dihydrochloride Chemical compound N.Cl.Cl SJSWRKNSCWKNIR-UHFFFAOYSA-N 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• 150000003936 benzamides Chemical class 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 239000012148 binding buffer Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 230000001275 ca(2+)-mobilization Effects 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 235000019993 champagne Nutrition 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000010568 chiral column chromatography Methods 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical group N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
• 125000005390 cinnolyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 230000037411 cognitive enhancing Effects 0.000 description 1
• 230000003920 cognitive function Effects 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• PMSVVUSIPKHUMT-UHFFFAOYSA-N cyanopyrazine Chemical compound N#CC1=CN=CC=N1 PMSVVUSIPKHUMT-UHFFFAOYSA-N 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 238000007405 data analysis Methods 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 238000009795 derivation Methods 0.000 description 1
• 229960000632 dexamfetamine Drugs 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• 229960003638 dopamine Drugs 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 210000002257 embryonic structure Anatomy 0.000 description 1
• 230000008451 emotion Effects 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 229940116977 epidermal growth factor Drugs 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical group C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 230000002518 glial effect Effects 0.000 description 1
• 230000000848 glutamatergic effect Effects 0.000 description 1
• 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 125000005253 heteroarylacyl group Chemical group 0.000 description 1
• 150000002391 heterocyclic compounds Chemical class 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
• 229940097277 hygromycin b Drugs 0.000 description 1
• 230000002296 hyperlocomotor Effects 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical group C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 206010027175 memory impairment Diseases 0.000 description 1
• 108010038421 metabotropic glutamate receptor 2 Proteins 0.000 description 1
• 108010038422 metabotropic glutamate receptor 4 Proteins 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
• 150000002780 morpholines Chemical class 0.000 description 1
• IXRNQIKIVWWFBH-UHFFFAOYSA-N n-(1-phenylethenyl)acetamide Chemical compound CC(=O)NC(=C)C1=CC=CC=C1 IXRNQIKIVWWFBH-UHFFFAOYSA-N 0.000 description 1
• UFOUABRZSDGGAZ-UHFFFAOYSA-N n-[4-chloro-2-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]-2-hydroxybenzamide Chemical compound OC1=CC=CC=C1C(=O)NC1=CC=C(Cl)C=C1CN1C(=O)C2=CC=CC=C2C1=O UFOUABRZSDGGAZ-UHFFFAOYSA-N 0.000 description 1
• GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
• 229940126662 negative allosteric modulator Drugs 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 230000002981 neuropathic effect Effects 0.000 description 1
• 230000004112 neuroprotection Effects 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 230000003957 neurotransmitter release Effects 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• 210000001009 nucleus accumben Anatomy 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 238000001543 one-way ANOVA Methods 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• AVPKHOTUOHDTLW-UHFFFAOYSA-N oxane-4-carboxylic acid Chemical compound OC(=O)C1CCOCC1 AVPKHOTUOHDTLW-UHFFFAOYSA-N 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 208000019906 panic disease Diseases 0.000 description 1
• 230000007310 pathophysiology Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 125000005981 pentynyl group Chemical group 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 150000003020 phtalazines Chemical group 0.000 description 1
• 125000002265 phtalazinyl group Chemical group 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 229940081066 picolinic acid Drugs 0.000 description 1
• JSSXHAMIXJGYCS-UHFFFAOYSA-N piperazin-4-ium-2-carboxylate Chemical compound OC(=O)C1CNCCN1 JSSXHAMIXJGYCS-UHFFFAOYSA-N 0.000 description 1
• 150000003053 piperidines Chemical class 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 229920000053 polysorbate 80 Polymers 0.000 description 1
• 229940126027 positive allosteric modulator Drugs 0.000 description 1
• 210000003538 post-synaptic density Anatomy 0.000 description 1
• 108010092804 postsynaptic density proteins Proteins 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 230000006977 prepulse inhibition Effects 0.000 description 1
• 230000003518 presynaptic effect Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 238000002731 protein assay Methods 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical group N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 210000002763 pyramidal cell Anatomy 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 239000002287 radioligand Substances 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 238000003757 reverse transcription PCR Methods 0.000 description 1
• 230000000698 schizophrenic effect Effects 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000021317 sensory perception Effects 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 230000006886 spatial memory Effects 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 229910001220 stainless steel Inorganic materials 0.000 description 1
• 239000010935 stainless steel Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 230000002739 subcortical effect Effects 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 230000009469 supplementation Effects 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000003956 synaptic plasticity Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• DEVHBWSVFHUUED-ZDUSSCGKSA-N tert-butyl (3s)-3-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC[C@@H]1C1=NC(C=2C=CN=CC=2)=NO1 DEVHBWSVFHUUED-ZDUSSCGKSA-N 0.000 description 1
• HRQJCFCSYHSTNR-JTQLQIEISA-N tert-butyl (3s)-3-[3-(1,3-thiazol-4-yl)-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC[C@@H]1C1=NC(C=2N=CSC=2)=NO1 HRQJCFCSYHSTNR-JTQLQIEISA-N 0.000 description 1
• YQFIZFAVRFYLPI-NSHDSACASA-N tert-butyl (3s)-3-[3-(2-methyl-1,3-thiazol-5-yl)-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate Chemical compound S1C(C)=NC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)OC(C)(C)C)=N1 YQFIZFAVRFYLPI-NSHDSACASA-N 0.000 description 1
• JLLNNPJTXFQSEC-ZDUSSCGKSA-N tert-butyl (3s)-3-[3-(3-methylpyridin-2-yl)-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate Chemical compound CC1=CC=CN=C1C1=NOC([C@@H]2CN(CCC2)C(=O)OC(C)(C)C)=N1 JLLNNPJTXFQSEC-ZDUSSCGKSA-N 0.000 description 1
• JMWQPTNKOJVFGF-ZDUSSCGKSA-N tert-butyl (3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC[C@@H]1C1=NC(C=2C=CC(F)=CC=2)=NO1 JMWQPTNKOJVFGF-ZDUSSCGKSA-N 0.000 description 1
• BHDPJQPSOGJYSM-ZDUSSCGKSA-N tert-butyl (3s)-3-[3-(6-methylpyridin-2-yl)-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate Chemical compound CC1=CC=CC(C=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)OC(C)(C)C)=N1 BHDPJQPSOGJYSM-ZDUSSCGKSA-N 0.000 description 1
• XTDXZSGSIMLARD-UHFFFAOYSA-N tert-butyl 2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC=CC=C1 XTDXZSGSIMLARD-UHFFFAOYSA-N 0.000 description 1
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
• 150000003536 tetrazoles Chemical group 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• SCKSQOIXSGPVJS-UHFFFAOYSA-N thiane-4-carboxylic acid Chemical compound OC(=O)C1CCSCC1 SCKSQOIXSGPVJS-UHFFFAOYSA-N 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 description 1
• QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
• GSXCEVHRIVLFJV-UHFFFAOYSA-N thiophene-3-carbonitrile Chemical compound N#CC=1C=CSC=1 GSXCEVHRIVLFJV-UHFFFAOYSA-N 0.000 description 1
• 150000003852 triazoles Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000031836 visual learning Effects 0.000 description 1
• 239000002699 waste material Substances 0.000 description 1