MXPA05001592A - Oxadiazoles como moduladores de receptor-5 de glutamato metabotropico. - Google Patents
Oxadiazoles como moduladores de receptor-5 de glutamato metabotropico.Info
- Publication number
- MXPA05001592A MXPA05001592A MXPA05001592A MXPA05001592A MXPA05001592A MX PA05001592 A MXPA05001592 A MX PA05001592A MX PA05001592 A MXPA05001592 A MX PA05001592A MX PA05001592 A MXPA05001592 A MX PA05001592A MX PA05001592 A MXPA05001592 A MX PA05001592A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- piperazine
- carboxylic acid
- phenyl
- methyl
- Prior art date
Links
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 title claims description 23
- 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 title description 18
- 150000004866 oxadiazoles Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 228
- 238000000034 method Methods 0.000 claims abstract description 36
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 500
- -1 -propyl Chemical group 0.000 claims description 282
- 125000004494 ethyl ester group Chemical group 0.000 claims description 112
- 239000002253 acid Substances 0.000 claims description 106
- 229910052757 nitrogen Inorganic materials 0.000 claims description 60
- 229910052799 carbon Inorganic materials 0.000 claims description 57
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 49
- 125000004429 atom Chemical group 0.000 claims description 46
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 34
- 229910052717 sulfur Inorganic materials 0.000 claims description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
- 150000002148 esters Chemical class 0.000 claims description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical group 0.000 claims description 31
- 208000035475 disorder Diseases 0.000 claims description 29
- 238000011282 treatment Methods 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 26
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 claims description 25
- 125000001188 haloalkyl group Chemical group 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 125000004043 oxo group Chemical group O=* 0.000 claims description 23
- 230000002265 prevention Effects 0.000 claims description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 230000004913 activation Effects 0.000 claims description 20
- 102000005962 receptors Human genes 0.000 claims description 20
- 108020003175 receptors Proteins 0.000 claims description 20
- 208000002193 Pain Diseases 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 17
- XCARGDPHZYJCMU-UHFFFAOYSA-N 2-chloro-n'-hydroxyethanimidamide Chemical compound ClCC(N)=NO XCARGDPHZYJCMU-UHFFFAOYSA-N 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims description 6
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 6
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 208000000094 Chronic Pain Diseases 0.000 claims description 6
- 208000012902 Nervous system disease Diseases 0.000 claims description 6
- 208000025966 Neurological disease Diseases 0.000 claims description 6
- 208000005298 acute pain Diseases 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 208000020016 psychiatric disease Diseases 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 4
- RUTZHBJOSPBPDQ-UHFFFAOYSA-N 3-[3-(chloromethyl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound ClCC1=NOC(C=2C=C(C=CC=2)C#N)=N1 RUTZHBJOSPBPDQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 150000004702 methyl esters Chemical class 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- TUDMJGXXGOORCD-UHFFFAOYSA-N 3-(chloromethyl)-5-(3-chlorophenyl)-1,2,4-oxadiazole Chemical compound ClCC1=NOC(C=2C=C(Cl)C=CC=2)=N1 TUDMJGXXGOORCD-UHFFFAOYSA-N 0.000 claims description 3
- LFXFXJCRXBYQSX-UHFFFAOYSA-N 5-(3-methylphenyl)-3-(1-piperazin-1-ylethyl)-1,2,4-oxadiazole Chemical compound N=1OC(C=2C=C(C)C=CC=2)=NC=1C(C)N1CCNCC1 LFXFXJCRXBYQSX-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- HVHGZCLMBPGBGL-UHFFFAOYSA-N ethyl 4-[[5-(3-methoxyphenyl)-1,2-oxazol-3-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NOC(C=2C=C(OC)C=CC=2)=C1 HVHGZCLMBPGBGL-UHFFFAOYSA-N 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 239000003701 inert diluent Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- SHVRDJQIBDQSPK-UHFFFAOYSA-N 1-cyanoethylcarbamic acid Chemical compound N#CC(C)NC(O)=O SHVRDJQIBDQSPK-UHFFFAOYSA-N 0.000 claims description 2
- ZNRLMGFXSPUZNR-UHFFFAOYSA-N 2,2,4-trimethyl-1h-quinoline Chemical group C1=CC=C2C(C)=CC(C)(C)NC2=C1 ZNRLMGFXSPUZNR-UHFFFAOYSA-N 0.000 claims description 2
- PDOAHHIOZNFSOY-LBPRGKRZSA-N 4-[(1S)-1-[5-(3-methylphenyl)-1,2,4-oxadiazol-3-yl]ethyl]piperazine-1-carboxylic acid Chemical compound CC=1C=C(C=CC=1)C1=NC(=NO1)[C@H](C)N1CCN(CC1)C(=O)O PDOAHHIOZNFSOY-LBPRGKRZSA-N 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- BXSZMADWBGSREP-UHFFFAOYSA-N ethyl 2-[1-[5-(5-chloro-2-fluorophenyl)-1,2-oxazol-3-yl]-2,2,2-trifluoroethyl]piperazine-1-carboxylate Chemical compound C(C)OC(=O)N1C(CNCC1)C(C(F)(F)F)C1=NOC(=C1)C1=C(C=CC(=C1)Cl)F BXSZMADWBGSREP-UHFFFAOYSA-N 0.000 claims description 2
- SZBWDTUBTCZQFP-UHFFFAOYSA-N ethyl 4-[1-[5-(3-methylphenyl)-1,2-oxazol-3-yl]ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(C)C1=NOC(C=2C=C(C)C=CC=2)=C1 SZBWDTUBTCZQFP-UHFFFAOYSA-N 0.000 claims description 2
- WCOPPSVBQXBIFX-UHFFFAOYSA-N ethyl 4-[[5-(3-chlorophenyl)-1,3-oxazol-2-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NC=C(C=2C=C(Cl)C=CC=2)O1 WCOPPSVBQXBIFX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims 5
- YTNYGYFGDMDRLH-NSHDSACASA-N (3S)-4-[[5-(3-chlorophenyl)-1,2-oxazol-3-yl]methyl]-3-methylpiperazine-1-carboxylic acid Chemical compound ClC=1C=C(C=CC1)C1=CC(=NO1)CN1[C@H](CN(CC1)C(=O)O)C YTNYGYFGDMDRLH-NSHDSACASA-N 0.000 claims 1
- MMIWDPMBWOTICQ-UHFFFAOYSA-N 2-methylpiperazine-1-carboxylic acid Chemical compound CC1CNCCN1C(O)=O MMIWDPMBWOTICQ-UHFFFAOYSA-N 0.000 claims 1
- JVLFMTZUPSBCNJ-UHFFFAOYSA-N 3,5-difluoropyridin-2-amine Chemical compound NC1=NC=C(F)C=C1F JVLFMTZUPSBCNJ-UHFFFAOYSA-N 0.000 claims 1
- 241001103870 Adia Species 0.000 claims 1
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims 1
- MKVHQMLKKPKZSY-UHFFFAOYSA-N ethyl 4-[[5-(3-iodophenyl)-1,2,4-oxadiazol-3-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NOC(C=2C=C(I)C=CC=2)=N1 MKVHQMLKKPKZSY-UHFFFAOYSA-N 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 15
- 230000008569 process Effects 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 375
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 246
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 234
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 195
- 238000005481 NMR spectroscopy Methods 0.000 description 159
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 107
- 239000000203 mixture Substances 0.000 description 95
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
- 101150041968 CDC13 gene Proteins 0.000 description 91
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 91
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 91
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 90
- 239000011541 reaction mixture Substances 0.000 description 89
- 239000007787 solid Substances 0.000 description 81
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 80
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 74
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 73
- 239000003921 oil Substances 0.000 description 71
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 67
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 65
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 63
- 238000000746 purification Methods 0.000 description 63
- 239000000741 silica gel Substances 0.000 description 61
- 229910002027 silica gel Inorganic materials 0.000 description 61
- 229910000027 potassium carbonate Inorganic materials 0.000 description 57
- 239000000243 solution Substances 0.000 description 56
- 239000012267 brine Substances 0.000 description 52
- 238000003756 stirring Methods 0.000 description 51
- 235000011181 potassium carbonates Nutrition 0.000 description 47
- 238000004587 chromatography analysis Methods 0.000 description 45
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 238000003818 flash chromatography Methods 0.000 description 38
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 35
- 229910052938 sodium sulfate Inorganic materials 0.000 description 35
- 235000011152 sodium sulphate Nutrition 0.000 description 35
- 239000002904 solvent Substances 0.000 description 32
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 31
- 239000012074 organic phase Substances 0.000 description 30
- 239000012230 colorless oil Substances 0.000 description 28
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 27
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
- 229940086542 triethylamine Drugs 0.000 description 27
- 150000002431 hydrogen Chemical group 0.000 description 25
- LNOQURRKNJKKBU-UHFFFAOYSA-N ethyl piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCNCC1 LNOQURRKNJKKBU-UHFFFAOYSA-N 0.000 description 24
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 24
- 229940098779 methanesulfonic acid Drugs 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 238000007792 addition Methods 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 15
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 15
- 238000007363 ring formation reaction Methods 0.000 description 15
- 229920006395 saturated elastomer Chemical group 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 125000001424 substituent group Chemical group 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 239000000556 agonist Substances 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- 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 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000007995 HEPES buffer Substances 0.000 description 9
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229930195712 glutamate Natural products 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 9
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 229910021529 ammonia Inorganic materials 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 150000002825 nitriles Chemical class 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 230000001154 acute effect Effects 0.000 description 7
- 210000003169 central nervous system Anatomy 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 230000036407 pain Effects 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- MTVWFVDWRVYDOR-UHFFFAOYSA-N 3,4-Dihydroxyphenylglycol Chemical compound OCC(O)C1=CC=C(O)C(O)=C1 MTVWFVDWRVYDOR-UHFFFAOYSA-N 0.000 description 6
- 208000019695 Migraine disease Diseases 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 6
- 230000005284 excitation Effects 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 206010027599 migraine Diseases 0.000 description 6
- 235000015320 potassium carbonate Nutrition 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017550 sodium carbonate Nutrition 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- XYOLTWLVHYEZIA-UHFFFAOYSA-N 3-(chloromethyl)-5-(2-fluoro-5-methylphenyl)-1,2,4-oxadiazole Chemical compound CC1=CC=C(F)C(C=2ON=C(CCl)N=2)=C1 XYOLTWLVHYEZIA-UHFFFAOYSA-N 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 150000008064 anhydrides Chemical class 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 206010015037 epilepsy Diseases 0.000 description 5
- BCRCNSBMXWWOJT-SSDOTTSWSA-N ethyl (3r)-3-methylpiperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN[C@H](C)C1 BCRCNSBMXWWOJT-SSDOTTSWSA-N 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 125000002541 furyl group Chemical group 0.000 description 5
- 229960000367 inositol Drugs 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- RABRSXCOXPUJMJ-UHFFFAOYSA-N methyl 5-(2-fluoro-5-methylphenyl)-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OC)C=C1C1=CC(C)=CC=C1F RABRSXCOXPUJMJ-UHFFFAOYSA-N 0.000 description 5
- 239000012038 nucleophile Substances 0.000 description 5
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 4
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 description 4
- PZGADOOBMVLBJE-UHFFFAOYSA-N 3-methylsulfanylbenzoic acid Chemical compound CSC1=CC=CC(C(O)=O)=C1 PZGADOOBMVLBJE-UHFFFAOYSA-N 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 4
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 4
- HOOWCUZPEFNHDT-UHFFFAOYSA-N DHPG Natural products OC(=O)C(N)C1=CC(O)=CC(O)=C1 HOOWCUZPEFNHDT-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000036506 anxiety Effects 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 235000008504 concentrate Nutrition 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 4
- BCRCNSBMXWWOJT-ZETCQYMHSA-N ethyl (3s)-3-methylpiperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN[C@@H](C)C1 BCRCNSBMXWWOJT-ZETCQYMHSA-N 0.000 description 4
- CJJMZZQGSJKNJH-AWEZNQCLSA-N ethyl 4-[(1s)-1-[5-(3-methylphenyl)-1,2,4-oxadiazol-3-yl]ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1[C@@H](C)C1=NOC(C=2C=C(C)C=CC=2)=N1 CJJMZZQGSJKNJH-AWEZNQCLSA-N 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 238000005342 ion exchange Methods 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 4
- 235000021317 phosphate Nutrition 0.000 description 4
- 125000004193 piperazinyl group Chemical group 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- 239000000126 substance Chemical group 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- YCOKTYBAJSXBTK-UHFFFAOYSA-N 3-(chloromethyl)-5-(3-fluorophenyl)-1,2,4-oxadiazole Chemical compound FC1=CC=CC(C=2ON=C(CCl)N=2)=C1 YCOKTYBAJSXBTK-UHFFFAOYSA-N 0.000 description 3
- XQUARYVCTXYWLA-UHFFFAOYSA-N 3-(chloromethyl)-5-(3-iodophenyl)-1,2,4-oxadiazole Chemical compound ClCC1=NOC(C=2C=C(I)C=CC=2)=N1 XQUARYVCTXYWLA-UHFFFAOYSA-N 0.000 description 3
- PHKTWKSTBQFLSM-UHFFFAOYSA-N 3-(chloromethyl)-5-(3-methylphenyl)-1,2,4-oxadiazole Chemical compound CC1=CC=CC(C=2ON=C(CCl)N=2)=C1 PHKTWKSTBQFLSM-UHFFFAOYSA-N 0.000 description 3
- XVCOYXNZFBSKBF-UHFFFAOYSA-N 5-(3-chlorophenyl)-1,2,4-oxadiazole-3-carbaldehyde Chemical compound ClC1=CC=CC(C=2ON=C(C=O)N=2)=C1 XVCOYXNZFBSKBF-UHFFFAOYSA-N 0.000 description 3
- ITHLUXJRCDKRBP-UHFFFAOYSA-N 5-(3-methylphenyl)-3-(piperazin-1-ylmethyl)-1,2,4-oxadiazole Chemical compound CC1=CC=CC(C=2ON=C(CN3CCNCC3)N=2)=C1 ITHLUXJRCDKRBP-UHFFFAOYSA-N 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 102000018899 Glutamate Receptors Human genes 0.000 description 3
- 108010027915 Glutamate Receptors Proteins 0.000 description 3
- 208000013016 Hypoglycemia Diseases 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 102000014384 Type C Phospholipases Human genes 0.000 description 3
- 108010079194 Type C Phospholipases Proteins 0.000 description 3
- INAPMGSXUVUWAF-GCVPSNMTSA-N [(2r,3s,5r,6r)-2,3,4,5,6-pentahydroxycyclohexyl] dihydrogen phosphate Chemical compound OC1[C@H](O)[C@@H](O)C(OP(O)(O)=O)[C@H](O)[C@@H]1O INAPMGSXUVUWAF-GCVPSNMTSA-N 0.000 description 3
- BBLDPDOSTBIXLM-UHFFFAOYSA-N [5-(3-chlorophenyl)-1,2-oxazol-3-yl]methanol Chemical compound O1N=C(CO)C=C1C1=CC=CC(Cl)=C1 BBLDPDOSTBIXLM-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 150000001413 amino acids Chemical group 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 150000001923 cyclic compounds Chemical class 0.000 description 3
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- TTWMHXOTVFSHPD-UHFFFAOYSA-N ethyl 4-(2-nitroethyl)piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(CC[N+]([O-])=O)CC1 TTWMHXOTVFSHPD-UHFFFAOYSA-N 0.000 description 3
- ISTFXVOSPPRVQD-UHFFFAOYSA-N ethyl 5-(3-chlorophenyl)-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OCC)C=C1C1=CC=CC(Cl)=C1 ISTFXVOSPPRVQD-UHFFFAOYSA-N 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000002964 excitative effect Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000002636 imidazolinyl group Chemical group 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000000842 isoxazolyl group Chemical group 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- WCRILORXQHZTCG-UHFFFAOYSA-N methyl 5-thiophen-3-yl-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OC)C=C1C1=CSC=C1 WCRILORXQHZTCG-UHFFFAOYSA-N 0.000 description 3
- KQYREKISXCBRQB-UHFFFAOYSA-N n,n-diethylethanamine;methanesulfonic acid Chemical compound CS(O)(=O)=O.CCN(CC)CC KQYREKISXCBRQB-UHFFFAOYSA-N 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical class C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 3
- 230000000269 nucleophilic effect Effects 0.000 description 3
- 125000002971 oxazolyl group Chemical group 0.000 description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
- 230000001242 postsynaptic effect Effects 0.000 description 3
- 150000003140 primary amides Chemical class 0.000 description 3
- 125000003373 pyrazinyl group Chemical group 0.000 description 3
- 125000002755 pyrazolinyl group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- RPKPFOKNXKRFTD-LURJTMIESA-N tert-butyl n-[(1s)-1-cyanoethyl]carbamate Chemical compound N#C[C@H](C)NC(=O)OC(C)(C)C RPKPFOKNXKRFTD-LURJTMIESA-N 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 230000007306 turnover Effects 0.000 description 3
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 2
- JOMNTHCQHJPVAZ-YFKPBYRVSA-N (2s)-2-methylpiperazine Chemical compound C[C@H]1CNCCN1 JOMNTHCQHJPVAZ-YFKPBYRVSA-N 0.000 description 2
- GNBKQFKYAPTXQX-GFCCVEGCSA-N (3R)-4-[[5-(2-fluoro-5-methylphenyl)-1,2-oxazol-3-yl]methyl]-3-methylpiperazine-1-carboxylic acid Chemical compound FC1=C(C=C(C=C1)C)C1=CC(=NO1)CN1[C@@H](CN(CC1)C(=O)O)C GNBKQFKYAPTXQX-GFCCVEGCSA-N 0.000 description 2
- SSEJSSNDPMMWBQ-YFKPBYRVSA-N (3s)-3-methylpiperazine-1-carboxylic acid Chemical compound C[C@H]1CN(C(O)=O)CCN1 SSEJSSNDPMMWBQ-YFKPBYRVSA-N 0.000 description 2
- UUWJBXKHMMQDED-UHFFFAOYSA-N 1-(3-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(Cl)=C1 UUWJBXKHMMQDED-UHFFFAOYSA-N 0.000 description 2
- QYKHLHSYPHBZON-UHFFFAOYSA-N 1-[5-(2-fluoro-5-methylphenyl)-1,2-oxazol-3-yl]ethanone Chemical compound O1N=C(C(=O)C)C=C1C1=CC(C)=CC=C1F QYKHLHSYPHBZON-UHFFFAOYSA-N 0.000 description 2
- HEBYWMGYEPMBPN-UHFFFAOYSA-N 1-[5-(3-chlorophenyl)-1,2,4-oxadiazol-3-yl]ethanol Chemical compound CC(O)C1=NOC(C=2C=C(Cl)C=CC=2)=N1 HEBYWMGYEPMBPN-UHFFFAOYSA-N 0.000 description 2
- UHSJRZGDQIGKGO-UHFFFAOYSA-N 1-[5-(3-chlorophenyl)-1,2-oxazol-3-yl]ethanone Chemical compound O1N=C(C(=O)C)C=C1C1=CC=CC(Cl)=C1 UHSJRZGDQIGKGO-UHFFFAOYSA-N 0.000 description 2
- AANZEVRZUBVJDZ-UHFFFAOYSA-N 1-[5-(5-chloro-2-fluorophenyl)-1,2-oxazol-3-yl]ethanol Chemical compound O1N=C(C(O)C)C=C1C1=CC(Cl)=CC=C1F AANZEVRZUBVJDZ-UHFFFAOYSA-N 0.000 description 2
- 125000006083 1-bromoethyl group Chemical group 0.000 description 2
- RSHBAGGASAJQCH-UHFFFAOYSA-N 1-iodo-3-methoxybenzene Chemical compound COC1=CC=CC(I)=C1 RSHBAGGASAJQCH-UHFFFAOYSA-N 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- LPMHVISJFZKXJM-UHFFFAOYSA-N 2-(1-bromoethyl)-5-(5-chloro-2-fluorophenyl)-1,3,4-oxadiazole Chemical compound O1C(C(Br)C)=NN=C1C1=CC(Cl)=CC=C1F LPMHVISJFZKXJM-UHFFFAOYSA-N 0.000 description 2
- MHLJGTBUYNXJKJ-UHFFFAOYSA-N 2-(5-chloro-2-fluorophenyl)-5-(chloromethyl)-1,3,4-oxadiazole Chemical compound FC1=CC=C(Cl)C=C1C1=NN=C(CCl)O1 MHLJGTBUYNXJKJ-UHFFFAOYSA-N 0.000 description 2
- RKWFWERIRVKUCB-UHFFFAOYSA-N 2-(5-chloro-2-fluorophenyl)ethynyl-trimethylsilane Chemical compound C[Si](C)(C)C#CC1=CC(Cl)=CC=C1F RKWFWERIRVKUCB-UHFFFAOYSA-N 0.000 description 2
- YFFUYGSLQXVHMB-UHFFFAOYSA-N 2-bromo-4-chloro-1-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1Br YFFUYGSLQXVHMB-UHFFFAOYSA-N 0.000 description 2
- CETPFRBYPPAFEJ-UHFFFAOYSA-N 2-fluoro-5-methylbenzohydrazide Chemical compound CC1=CC=C(F)C(C(=O)NN)=C1 CETPFRBYPPAFEJ-UHFFFAOYSA-N 0.000 description 2
- LGUHWEZQUSOAKW-UHFFFAOYSA-N 2-nitroethyl benzoate Chemical compound [O-][N+](=O)CCOC(=O)C1=CC=CC=C1 LGUHWEZQUSOAKW-UHFFFAOYSA-N 0.000 description 2
- HFOSGECIUSSYGW-UHFFFAOYSA-N 2h-oxadiazole-3-carboxylic acid Chemical compound OC(=O)N1NOC=C1 HFOSGECIUSSYGW-UHFFFAOYSA-N 0.000 description 2
- KGZAHHSPUIVWJP-UHFFFAOYSA-N 3-(chloromethyl)-5-(2,5-dichlorophenyl)-1,2,4-oxadiazole Chemical compound ClCC1=NOC(C=2C(=CC=C(Cl)C=2)Cl)=N1 KGZAHHSPUIVWJP-UHFFFAOYSA-N 0.000 description 2
- GSWMZQIUADKXLN-UHFFFAOYSA-N 3-(chloromethyl)-5-(3-methoxyphenyl)-1,2,4-oxadiazole Chemical compound COC1=CC=CC(C=2ON=C(CCl)N=2)=C1 GSWMZQIUADKXLN-UHFFFAOYSA-N 0.000 description 2
- MYZBONNONJUNGO-UHFFFAOYSA-N 3-(chloromethyl)-5-[3-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)OC1=CC=CC(C=2ON=C(CCl)N=2)=C1 MYZBONNONJUNGO-UHFFFAOYSA-N 0.000 description 2
- JKCYKISVUIVZCS-UHFFFAOYSA-N 3-bromo-4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1Br JKCYKISVUIVZCS-UHFFFAOYSA-N 0.000 description 2
- BGARPMGQRREXLN-UHFFFAOYSA-N 3-iodobenzonitrile Chemical compound IC1=CC=CC(C#N)=C1 BGARPMGQRREXLN-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- XHGWFVHYXJPVPF-UHFFFAOYSA-N 5-(2-fluoro-5-methylphenyl)-3-(1-piperazin-1-ylethyl)-1,2,4-oxadiazole Chemical compound N=1OC(C=2C(=CC=C(C)C=2)F)=NC=1C(C)N1CCNCC1 XHGWFVHYXJPVPF-UHFFFAOYSA-N 0.000 description 2
- XNUULFUAZWVWPM-UHFFFAOYSA-N 5-(3-bromophenyl)-3-(chloromethyl)-1,2,4-oxadiazole Chemical compound ClCC1=NOC(C=2C=C(Br)C=CC=2)=N1 XNUULFUAZWVWPM-UHFFFAOYSA-N 0.000 description 2
- KAAOUNHODGZJQC-UHFFFAOYSA-N 5-(3-chlorophenyl)-2-methyl-1,3-oxazole Chemical compound O1C(C)=NC=C1C1=CC=CC(Cl)=C1 KAAOUNHODGZJQC-UHFFFAOYSA-N 0.000 description 2
- DNZGJZZDZMBQBZ-UHFFFAOYSA-N 5-(3-chlorophenyl)-3-(piperazin-1-ylmethyl)-1,2,4-oxadiazole Chemical compound ClC1=CC=CC(C=2ON=C(CN3CCNCC3)N=2)=C1 DNZGJZZDZMBQBZ-UHFFFAOYSA-N 0.000 description 2
- YZVKIJZHORXKRW-UHFFFAOYSA-N 5-chloro-2-fluorobenzohydrazide Chemical compound NNC(=O)C1=CC(Cl)=CC=C1F YZVKIJZHORXKRW-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 206010003805 Autism Diseases 0.000 description 2
- 208000020706 Autistic disease Diseases 0.000 description 2
- 206010004663 Biliary colic Diseases 0.000 description 2
- 101100193519 Caenorhabditis elegans qui-1 gene Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 244000248349 Citrus limon Species 0.000 description 2
- 235000005979 Citrus limon Nutrition 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 201000005569 Gout Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 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
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 208000008930 Low Back Pain Diseases 0.000 description 2
- 208000036626 Mental retardation Diseases 0.000 description 2
- LOMVENUNSWAXEN-UHFFFAOYSA-N Methyl oxalate Chemical compound COC(=O)C(=O)OC LOMVENUNSWAXEN-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 2
- 208000004550 Postoperative Pain Diseases 0.000 description 2
- 206010038419 Renal colic Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 208000009205 Tinnitus Diseases 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 2
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000001912 cyanamides Chemical class 0.000 description 2
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- CWPSTZCYESJGPF-SSDOTTSWSA-N ethyl (2r)-2-methylpiperazine-1-carboxylate Chemical compound CCOC(=O)N1CCNC[C@H]1C CWPSTZCYESJGPF-SSDOTTSWSA-N 0.000 description 2
- CWPSTZCYESJGPF-ZETCQYMHSA-N ethyl (2s)-2-methylpiperazine-1-carboxylate Chemical compound CCOC(=O)N1CCNC[C@@H]1C CWPSTZCYESJGPF-ZETCQYMHSA-N 0.000 description 2
- UXOLDCOJRAMLTQ-UHFFFAOYSA-N ethyl 2-chloro-2-hydroxyiminoacetate Chemical compound CCOC(=O)C(Cl)=NO UXOLDCOJRAMLTQ-UHFFFAOYSA-N 0.000 description 2
- ALBHAXFFBFYARO-UHFFFAOYSA-N ethyl 4-(1,1,1-trifluoro-3-nitropropan-2-yl)piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(C(C[N+]([O-])=O)C(F)(F)F)CC1 ALBHAXFFBFYARO-UHFFFAOYSA-N 0.000 description 2
- MPOQGAGGKJCZIT-UHFFFAOYSA-N ethyl 4-(3-chlorophenyl)-2,4-dioxobutanoate Chemical compound CCOC(=O)C(=O)CC(=O)C1=CC=CC(Cl)=C1 MPOQGAGGKJCZIT-UHFFFAOYSA-N 0.000 description 2
- AJRYAYKEPOOUBW-UHFFFAOYSA-N ethyl 4-[[5-(5-cyano-2-fluorophenyl)-1,2-oxazol-3-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NOC(C=2C(=CC=C(C=2)C#N)F)=C1 AJRYAYKEPOOUBW-UHFFFAOYSA-N 0.000 description 2
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- GPSDUZXPYCFOSQ-UHFFFAOYSA-N m-toluic acid Chemical compound CC1=CC=CC(C(O)=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000005906 menstruation Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- XYXMSOYQWYKJPW-UHFFFAOYSA-N methyl 4-(2-fluoro-5-methylphenyl)-2,4-dioxobutanoate Chemical compound COC(=O)C(=O)CC(=O)C1=CC(C)=CC=C1F XYXMSOYQWYKJPW-UHFFFAOYSA-N 0.000 description 2
- NFYVEESAHPQMJI-UHFFFAOYSA-N methyl 5-chloro-2-fluorobenzoate Chemical compound COC(=O)C1=CC(Cl)=CC=C1F NFYVEESAHPQMJI-UHFFFAOYSA-N 0.000 description 2
- 125000006217 methyl sulfide group Chemical group [H]C([H])([H])S* 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 230000007472 neurodevelopment Effects 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 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
- 230000007170 pathology Effects 0.000 description 2
- 230000001991 pathophysiological effect Effects 0.000 description 2
- 150000003906 phosphoinositides Chemical class 0.000 description 2
- 125000004928 piperidonyl group Chemical group 0.000 description 2
- 125000005936 piperidyl group Chemical group 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000003518 presynaptic effect Effects 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000001422 pyrrolinyl group Chemical group 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- RPKPFOKNXKRFTD-ZCFIWIBFSA-N tert-butyl n-[(1r)-1-cyanoethyl]carbamate Chemical compound N#C[C@@H](C)NC(=O)OC(C)(C)C RPKPFOKNXKRFTD-ZCFIWIBFSA-N 0.000 description 2
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- 231100000886 tinnitus Toxicity 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- 206010044652 trigeminal neuralgia Diseases 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- XZMSNGBBJLKDHN-UHFFFAOYSA-N (1-amino-1-oxopropan-2-yl)carbamic acid Chemical compound NC(=O)C(C)NC(O)=O XZMSNGBBJLKDHN-UHFFFAOYSA-N 0.000 description 1
- QVHJQCGUWFKTSE-RXMQYKEDSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-RXMQYKEDSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-RXMQYKEDSA-N (2r)-2-methylpiperazine Chemical compound C[C@@H]1CNCCN1 JOMNTHCQHJPVAZ-RXMQYKEDSA-N 0.000 description 1
- SSEJSSNDPMMWBQ-RXMQYKEDSA-N (3r)-3-methylpiperazine-1-carboxylic acid Chemical compound C[C@@H]1CN(C(O)=O)CCN1 SSEJSSNDPMMWBQ-RXMQYKEDSA-N 0.000 description 1
- DAXJNUBSBFUTRP-RTQNCGMRSA-N (8r,9s,10r,13s,14s)-6-(hydroxymethyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(CO)C2=C1 DAXJNUBSBFUTRP-RTQNCGMRSA-N 0.000 description 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
- OKGNJIYNSOKKFT-UHFFFAOYSA-N 1,1,1-trifluoro-3-nitropropan-2-ol Chemical compound FC(F)(F)C(O)C[N+]([O-])=O OKGNJIYNSOKKFT-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- DNDPUIGGUBKRQB-UHFFFAOYSA-N 1-(2-fluoro-5-methylphenyl)ethanone Chemical compound CC(=O)C1=CC(C)=CC=C1F DNDPUIGGUBKRQB-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
- LSEHPTRPFVZENS-UHFFFAOYSA-N 1-[1-[[5-(3-chlorophenyl)-1,2,4-oxadiazol-3-yl]methyl]piperidin-4-yl]-4h-3,1-benzoxazin-2-one Chemical compound ClC1=CC=CC(C=2ON=C(CN3CCC(CC3)N3C4=CC=CC=C4COC3=O)N=2)=C1 LSEHPTRPFVZENS-UHFFFAOYSA-N 0.000 description 1
- GSRUGFKJZICJBW-UHFFFAOYSA-N 1-[5-(2-fluoro-5-methylphenyl)-1,2-oxazol-3-yl]ethanol Chemical compound O1N=C(C(O)C)C=C1C1=CC(C)=CC=C1F GSRUGFKJZICJBW-UHFFFAOYSA-N 0.000 description 1
- WMNKCUDJMXHTPN-UHFFFAOYSA-N 1-[5-(2-fluoro-5-methylphenyl)-1,2-oxazol-3-yl]ethyl methanesulfonate Chemical compound O1N=C(C(OS(C)(=O)=O)C)C=C1C1=CC(C)=CC=C1F WMNKCUDJMXHTPN-UHFFFAOYSA-N 0.000 description 1
- MVUIVJUGPUFTHI-UHFFFAOYSA-N 1-[5-(2-fluoro-5-methylphenyl)-1,2-oxazol-3-yl]propan-1-ol Chemical compound O1N=C(C(O)CC)C=C1C1=CC(C)=CC=C1F MVUIVJUGPUFTHI-UHFFFAOYSA-N 0.000 description 1
- XDGYCSUAWXOCIX-UHFFFAOYSA-N 1-[5-(2-fluoro-5-methylphenyl)-1,2-oxazol-3-yl]propan-1-one Chemical compound O1N=C(C(=O)CC)C=C1C1=CC(C)=CC=C1F XDGYCSUAWXOCIX-UHFFFAOYSA-N 0.000 description 1
- FOLGHHVVTIHOLE-UHFFFAOYSA-N 1-[5-(3-chlorophenyl)-1,2-oxazol-3-yl]ethanol Chemical compound O1N=C(C(O)C)C=C1C1=CC=CC(Cl)=C1 FOLGHHVVTIHOLE-UHFFFAOYSA-N 0.000 description 1
- SNFUOMXBPYMMFJ-UHFFFAOYSA-N 1-[5-(3-chlorophenyl)-1,2-oxazol-3-yl]ethyl methanesulfonate Chemical compound O1N=C(C(OS(C)(=O)=O)C)C=C1C1=CC=CC(Cl)=C1 SNFUOMXBPYMMFJ-UHFFFAOYSA-N 0.000 description 1
- NWRCHPFEAZVOPB-UHFFFAOYSA-N 1-[5-(5-chloro-2-fluorophenyl)-1,2-oxazol-3-yl]ethyl methanesulfonate Chemical compound O1N=C(C(OS(C)(=O)=O)C)C=C1C1=CC(Cl)=CC=C1F NWRCHPFEAZVOPB-UHFFFAOYSA-N 0.000 description 1
- RKWWASUTWAFKHA-UHFFFAOYSA-N 1-bromo-2,3-difluorobenzene Chemical compound FC1=CC=CC(Br)=C1F RKWWASUTWAFKHA-UHFFFAOYSA-N 0.000 description 1
- JZUMPNUYDJBTNO-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 JZUMPNUYDJBTNO-UHFFFAOYSA-N 0.000 description 1
- VLCPISYURGTGLP-UHFFFAOYSA-N 1-iodo-3-methylbenzene Chemical compound CC1=CC=CC(I)=C1 VLCPISYURGTGLP-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- QVTQYSFCFOGITD-UHFFFAOYSA-N 2,5-dichlorobenzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC=C1Cl QVTQYSFCFOGITD-UHFFFAOYSA-N 0.000 description 1
- SWRMUKQSYPDQRG-UHFFFAOYSA-N 2-(1-bromoethyl)-5-(5-chloro-2-fluorophenyl)-1,3,4-oxadiazole;5-chloro-2-fluorobenzohydrazide Chemical compound NNC(=O)C1=CC(Cl)=CC=C1F.O1C(C(Br)C)=NN=C1C1=CC(Cl)=CC=C1F SWRMUKQSYPDQRG-UHFFFAOYSA-N 0.000 description 1
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- NFADIXWHOHGPKA-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-(dimethylaminomethylidene)-1,3-oxazol-5-one Chemical compound O1C(=O)C(=CN(C)C)N=C1C1=CC=CC(Cl)=C1 NFADIXWHOHGPKA-UHFFFAOYSA-N 0.000 description 1
- DXEAGGDULJNNMM-UHFFFAOYSA-N 2-(bromomethyl)-5-(3-chlorophenyl)-1,3-oxazole Chemical compound ClC1=CC=CC(C=2OC(CBr)=NC=2)=C1 DXEAGGDULJNNMM-UHFFFAOYSA-N 0.000 description 1
- OZGJBRXEYZQRHC-UHFFFAOYSA-N 2-(bromomethyl)-5-(3-chlorophenyl)-1,3-oxazole 5-(3-chlorophenyl)-2-methyl-1,3-oxazole Chemical compound ClC=1C=C(C=CC1)C1=CN=C(O1)C.BrCC=1OC(=CN1)C1=CC(=CC=C1)Cl OZGJBRXEYZQRHC-UHFFFAOYSA-N 0.000 description 1
- FDYQRGBOELBIPZ-UHFFFAOYSA-N 2-(chloromethyl)-5-(2-fluoro-5-methylphenyl)-1,3,4-oxadiazole Chemical compound CC1=CC=C(F)C(C=2OC(CCl)=NN=2)=C1 FDYQRGBOELBIPZ-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- PNFVIPIQXAIUAY-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CCC(C(O)=O)NC(=O)OC(C)(C)C PNFVIPIQXAIUAY-UHFFFAOYSA-N 0.000 description 1
- FRYPWUYDPUBMRU-UHFFFAOYSA-N 2-[(4-chlorophenoxy)methyl]-5-(2,4-dichloro-5-fluorophenyl)-1,3,4-oxadiazole Chemical compound C1=C(Cl)C(F)=CC(C=2OC(COC=3C=CC(Cl)=CC=3)=NN=2)=C1Cl FRYPWUYDPUBMRU-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- UHTQHHLSGVOGQR-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-4-ium-1-yl]ethanesulfonate Chemical compound OCCN1CCN(CCS(O)(=O)=O)CC1.OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 UHTQHHLSGVOGQR-UHFFFAOYSA-N 0.000 description 1
- NPEIUNVTLXEOLT-UHFFFAOYSA-N 2-chloro-1,1,1-trimethoxyethane Chemical compound COC(CCl)(OC)OC NPEIUNVTLXEOLT-UHFFFAOYSA-N 0.000 description 1
- ZGZMEKHQIZSZOH-UHFFFAOYSA-N 2-chloro-6-methylpyridine-4-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC(Cl)=N1 ZGZMEKHQIZSZOH-UHFFFAOYSA-N 0.000 description 1
- KCLCKODCAVJSID-UHFFFAOYSA-N 2-ethylpiperazine-1-carboxylic acid Chemical compound CCC1CNCCN1C(O)=O KCLCKODCAVJSID-UHFFFAOYSA-N 0.000 description 1
- CEMYZMDITJKYDA-UHFFFAOYSA-N 2-fluoro-5-iodobenzoyl chloride Chemical compound FC1=CC=C(I)C=C1C(Cl)=O CEMYZMDITJKYDA-UHFFFAOYSA-N 0.000 description 1
- UREMNBHWTNQTMS-UHFFFAOYSA-N 2-fluoro-5-methylbenzoic acid Chemical compound CC1=CC=C(F)C(C(O)=O)=C1 UREMNBHWTNQTMS-UHFFFAOYSA-N 0.000 description 1
- WTRZAISNXMSANJ-UHFFFAOYSA-N 2-hydroxy-5-methylbenzoyl chloride Chemical compound CC1=CC=C(O)C(C(Cl)=O)=C1 WTRZAISNXMSANJ-UHFFFAOYSA-N 0.000 description 1
- APOYTRAZFJURPB-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)-n-(trifluoro-$l^{4}-sulfanyl)ethanamine Chemical compound COCCN(S(F)(F)F)CCOC APOYTRAZFJURPB-UHFFFAOYSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- PMDHIMMPXRSDML-UHFFFAOYSA-N 2-methylpyridine-4-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC=N1 PMDHIMMPXRSDML-UHFFFAOYSA-N 0.000 description 1
- BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 description 1
- GQQFUTKBTHSWPE-UHFFFAOYSA-N 2-nitro-N,N-bis[2-(trifluoromethylsulfonyl)ethyl]benzenesulfonamide Chemical compound [O-][N+](=O)C1=CC=CC=C1S(=O)(=O)N(CCS(=O)(=O)C(F)(F)F)CCS(=O)(=O)C(F)(F)F GQQFUTKBTHSWPE-UHFFFAOYSA-N 0.000 description 1
- KIPMDPDAFINLIV-UHFFFAOYSA-N 2-nitroethanol Chemical compound OCC[N+]([O-])=O KIPMDPDAFINLIV-UHFFFAOYSA-N 0.000 description 1
- PRNLNZMJMCUWNV-UHFFFAOYSA-N 2-piperidin-1-ium-2-ylacetate Chemical compound OC(=O)CC1CCCCN1 PRNLNZMJMCUWNV-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- YQUVCSBJEUQKSH-UHFFFAOYSA-M 3,4-dihydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1O YQUVCSBJEUQKSH-UHFFFAOYSA-M 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- IKMDATUFAWOLAY-UHFFFAOYSA-N 3-(chloromethyl)-5-(3-methylphenyl)-1,2,4-oxadiazole 3-methylbenzoyl chloride Chemical compound CC=1C=C(C(=O)Cl)C=CC1.ClCC1=NOC(=N1)C=1C=C(C=CC1)C IKMDATUFAWOLAY-UHFFFAOYSA-N 0.000 description 1
- INANILNLXTUPHD-UHFFFAOYSA-N 3-(chloromethyl)-5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2ON=C(CCl)N=2)=C1 INANILNLXTUPHD-UHFFFAOYSA-N 0.000 description 1
- OKPFIWIMBJNFSE-UHFFFAOYSA-N 3-(trifluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=CC(OC(F)(F)F)=C1 OKPFIWIMBJNFSE-UHFFFAOYSA-N 0.000 description 1
- RNIDWJDZNNVFDY-UHFFFAOYSA-N 3-Acetylthiophene Chemical compound CC(=O)C=1C=CSC=1 RNIDWJDZNNVFDY-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical class C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- VOIZNVUXCQLQHS-UHFFFAOYSA-N 3-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC(Br)=C1 VOIZNVUXCQLQHS-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- RPESZQVUWMFBEO-UHFFFAOYSA-N 3-cyanobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(C#N)=C1 RPESZQVUWMFBEO-UHFFFAOYSA-N 0.000 description 1
- MXNBDFWNYRNIBH-UHFFFAOYSA-N 3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1 MXNBDFWNYRNIBH-UHFFFAOYSA-N 0.000 description 1
- RZODAQZAFOBFLS-UHFFFAOYSA-N 3-iodobenzaldehyde Chemical compound IC1=CC=CC(C=O)=C1 RZODAQZAFOBFLS-UHFFFAOYSA-N 0.000 description 1
- KVBWBCRPWVKFQT-UHFFFAOYSA-N 3-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC(I)=C1 KVBWBCRPWVKFQT-UHFFFAOYSA-N 0.000 description 1
- RSFDFESMVAIVKO-UHFFFAOYSA-N 3-sulfanylbenzoic acid Chemical compound OC(=O)C1=CC=CC(S)=C1 RSFDFESMVAIVKO-UHFFFAOYSA-N 0.000 description 1
- IBOFVQJTBBUKMU-UHFFFAOYSA-N 4,4'-methylene-bis-(2-chloroaniline) Chemical compound C1=C(Cl)C(N)=CC=C1CC1=CC=C(N)C(Cl)=C1 IBOFVQJTBBUKMU-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- YIJZILBLQKPRDE-UHFFFAOYSA-N 4-[(e)-n'-hydroxycarbamimidoyl]piperazine-1-carboxylic acid Chemical compound ONC(=N)N1CCN(C(O)=O)CC1 YIJZILBLQKPRDE-UHFFFAOYSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- 229940086681 4-aminobenzoate Drugs 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- CJTIWGBQCVYTQE-UHFFFAOYSA-N 4-bromo-2-chloro-1-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1Cl CJTIWGBQCVYTQE-UHFFFAOYSA-N 0.000 description 1
- OYSKEHSKFRAUIK-UHFFFAOYSA-N 4-chloro-2-ethynyl-1-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1C#C OYSKEHSKFRAUIK-UHFFFAOYSA-N 0.000 description 1
- RZRJLVROVUWDKL-UHFFFAOYSA-N 4-iodo-2-methylpyridine Chemical compound CC1=CC(I)=CC=N1 RZRJLVROVUWDKL-UHFFFAOYSA-N 0.000 description 1
- JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
- JKWNGLFHFKJDDT-UHFFFAOYSA-N 5-(3-chlorophenyl)-3-(1-piperazin-1-ylethyl)-1,2,4-oxadiazole Chemical compound N=1OC(C=2C=C(Cl)C=CC=2)=NC=1C(C)N1CCNCC1 JKWNGLFHFKJDDT-UHFFFAOYSA-N 0.000 description 1
- UMGHRMMABKXKBC-UHFFFAOYSA-N 5-(3-chlorophenyl)-3-(1-piperazin-1-ylpropyl)-1,2,4-oxadiazole Chemical compound N=1OC(C=2C=C(Cl)C=CC=2)=NC=1C(CC)N1CCNCC1 UMGHRMMABKXKBC-UHFFFAOYSA-N 0.000 description 1
- LFXFXJCRXBYQSX-GFCCVEGCSA-N 5-(3-methylphenyl)-3-[(1r)-1-piperazin-1-ylethyl]-1,2,4-oxadiazole Chemical compound N1([C@H](C)C=2N=C(ON=2)C=2C=C(C)C=CC=2)CCNCC1 LFXFXJCRXBYQSX-GFCCVEGCSA-N 0.000 description 1
- LFXFXJCRXBYQSX-LBPRGKRZSA-N 5-(3-methylphenyl)-3-[(1s)-1-piperazin-1-ylethyl]-1,2,4-oxadiazole Chemical compound N1([C@@H](C)C=2N=C(ON=2)C=2C=C(C)C=CC=2)CCNCC1 LFXFXJCRXBYQSX-LBPRGKRZSA-N 0.000 description 1
- FPGFNPWXIJQISS-UHFFFAOYSA-N 5-(3-methylphenyl)-3-[1-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]ethyl]-1,2,4-oxadiazole Chemical compound N=1OC(C=2C=C(C)C=CC=2)=NC=1C(C)N(CC1)CCN1S(=O)(=O)C1=CC=CC=C1[N+]([O-])=O FPGFNPWXIJQISS-UHFFFAOYSA-N 0.000 description 1
- KZANPGGCZGCSFQ-UHFFFAOYSA-N 5-(5-bromo-2-fluorophenyl)-3-(chloromethyl)-1,2,4-oxadiazole Chemical compound FC1=CC=C(Br)C=C1C1=NC(CCl)=NO1 KZANPGGCZGCSFQ-UHFFFAOYSA-N 0.000 description 1
- PUWJOTOVLPHWMN-UHFFFAOYSA-N 5-(5-chloro-2-fluorophenyl)-1,2-oxazole-3-carbaldehyde Chemical compound FC1=CC=C(Cl)C=C1C1=CC(C=O)=NO1 PUWJOTOVLPHWMN-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- WGAVMKXCDMQVNF-UHFFFAOYSA-N 5-chloro-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC=C1F WGAVMKXCDMQVNF-UHFFFAOYSA-N 0.000 description 1
- VWGAATKTEAKOCO-UHFFFAOYSA-N 5-chloro-2-fluorobenzoyl chloride Chemical compound FC1=CC=C(Cl)C=C1C(Cl)=O VWGAATKTEAKOCO-UHFFFAOYSA-N 0.000 description 1
- NANJQJRZYOVMLF-UHFFFAOYSA-N 5-chloro-2-hydroxybenzoyl chloride Chemical compound OC1=CC=C(Cl)C=C1C(Cl)=O NANJQJRZYOVMLF-UHFFFAOYSA-N 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000006941 Amino Acid Transport System X-AG Human genes 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- BMIYRNLIIFBJMD-UHFFFAOYSA-N C(C)(C)(C)OC(NC(CC)C#N)=O.C(C)(C)(C)OC(NC(CC)C#N)=O Chemical compound C(C)(C)(C)OC(NC(CC)C#N)=O.C(C)(C)(C)OC(NC(CC)C#N)=O BMIYRNLIIFBJMD-UHFFFAOYSA-N 0.000 description 1
- XPOBKEHMZZGRNS-UHFFFAOYSA-N C1(CC1)[Mg]C Chemical compound C1(CC1)[Mg]C XPOBKEHMZZGRNS-UHFFFAOYSA-N 0.000 description 1
- SWWOYUZEDWCLGO-UHFFFAOYSA-N CI.COC(C1=CC(=CC=C1)SC)=O Chemical compound CI.COC(C1=CC(=CC=C1)SC)=O SWWOYUZEDWCLGO-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical class NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- YLOVWKLPCILVRA-UHFFFAOYSA-N Cc1ccc(Cl)c(c1)C(O)=O.Cc1ccc(Cl)c(c1)-c1nc(CCl)no1 Chemical compound Cc1ccc(Cl)c(c1)C(O)=O.Cc1ccc(Cl)c(c1)-c1nc(CCl)no1 YLOVWKLPCILVRA-UHFFFAOYSA-N 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
- SCGYDFGNJUVTTO-UHFFFAOYSA-N ClCC1=NOC(=N1)C1=CC(=CC=C1)Cl.ClCC1=NOC(=N1)C1=CC(=CC=C1)Cl Chemical compound ClCC1=NOC(=N1)C1=CC(=CC=C1)Cl.ClCC1=NOC(=N1)C1=CC(=CC=C1)Cl SCGYDFGNJUVTTO-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 206010012559 Developmental delay Diseases 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- MRBJHKJAZDTKHD-UHFFFAOYSA-N FC(C=C1)=CC(C2=NOC(CCl)N2)=C1F Chemical compound FC(C=C1)=CC(C2=NOC(CCl)N2)=C1F MRBJHKJAZDTKHD-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 1
- 108091006151 Glutamate transporters Proteins 0.000 description 1
- 108010078321 Guanylate Cyclase Proteins 0.000 description 1
- 102000014469 Guanylate cyclase Human genes 0.000 description 1
- 208000032041 Hearing impaired Diseases 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 102000006541 Ionotropic Glutamate Receptors Human genes 0.000 description 1
- 108010008812 Ionotropic Glutamate Receptors Proteins 0.000 description 1
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- 102100037636 Metabotropic glutamate receptor 8 Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 102000011420 Phospholipase D Human genes 0.000 description 1
- 108090000553 Phospholipase D Proteins 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101710098398 Probable alanine aminotransferase, mitochondrial Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate Chemical compound O[C@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](O)[C@H]1OP(O)(O)=O MMWCIQZXVOZEGG-HOZKJCLWSA-N 0.000 description 1
- LAWDPNGKUSMJPN-UHFFFAOYSA-N [5-(2-fluoro-5-methylphenyl)-1,2-oxazol-3-yl]methanol Chemical compound CC1=CC=C(F)C(C=2ON=C(CO)C=2)=C1 LAWDPNGKUSMJPN-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 1
- 150000004791 alkyl magnesium halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 125000005219 aminonitrile group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 150000008378 aryl ethers Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 150000001559 benzoic acids Chemical class 0.000 description 1
- 150000008359 benzonitriles Chemical class 0.000 description 1
- 125000005872 benzooxazolyl group Chemical group 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- XNNQFQFUQLJSQT-UHFFFAOYSA-N bromo(trichloro)methane Chemical compound ClC(Cl)(Cl)Br XNNQFQFUQLJSQT-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical compound CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001175 calcium sulphate Substances 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 125000004966 cyanoalkyl group Chemical group 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 238000006210 cyclodehydration reaction Methods 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- CUCGAFHQPGBKNR-UHFFFAOYSA-N cyclopropyl-[5-(2-fluoro-5-methylphenyl)-1,2-oxazol-3-yl]methanol Chemical compound CC1=CC=C(F)C(C=2ON=C(C=2)C(O)C2CC2)=C1 CUCGAFHQPGBKNR-UHFFFAOYSA-N 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000006006 difluoroethoxy group Chemical group 0.000 description 1
- 125000006001 difluoroethyl group Chemical group 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- QJRYHAKNFSAEOU-CYBMUJFWSA-N ethyl (3r)-4-[[5-(3-chlorophenyl)-1,2-oxazol-3-yl]methyl]-3-methylpiperazine-1-carboxylate Chemical compound C[C@@H]1CN(C(=O)OCC)CCN1CC1=NOC(C=2C=C(Cl)C=CC=2)=C1 QJRYHAKNFSAEOU-CYBMUJFWSA-N 0.000 description 1
- KIPKEJJKDSVXJN-AWEZNQCLSA-N ethyl (3s)-4-[[5-(2-fluoro-5-methylphenyl)-1,2-oxazol-3-yl]methyl]-3-methylpiperazine-1-carboxylate Chemical compound C[C@H]1CN(C(=O)OCC)CCN1CC1=NOC(C=2C(=CC=C(C)C=2)F)=C1 KIPKEJJKDSVXJN-AWEZNQCLSA-N 0.000 description 1
- QJRYHAKNFSAEOU-ZDUSSCGKSA-N ethyl (3s)-4-[[5-(3-chlorophenyl)-1,2-oxazol-3-yl]methyl]-3-methylpiperazine-1-carboxylate Chemical compound C[C@H]1CN(C(=O)OCC)CCN1CC1=NOC(C=2C=C(Cl)C=CC=2)=C1 QJRYHAKNFSAEOU-ZDUSSCGKSA-N 0.000 description 1
- TVSPGWOIQJZGNZ-UHFFFAOYSA-N ethyl 4-(1-nitropropan-2-yl)piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(C(C)C[N+]([O-])=O)CC1 TVSPGWOIQJZGNZ-UHFFFAOYSA-N 0.000 description 1
- QFQMLVLMUNAWJF-UHFFFAOYSA-N ethyl 4-[(5-thiophen-3-yl-1,2-oxazol-3-yl)methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NOC(C2=CSC=C2)=C1 QFQMLVLMUNAWJF-UHFFFAOYSA-N 0.000 description 1
- MTOSMBMOTXRUSV-UHFFFAOYSA-N ethyl 4-[1-(5-tributylstannyl-1,2-oxazol-3-yl)ethyl]piperazine-1-carboxylate Chemical compound O1C([Sn](CCCC)(CCCC)CCCC)=CC(C(C)N2CCN(CC2)C(=O)OCC)=N1 MTOSMBMOTXRUSV-UHFFFAOYSA-N 0.000 description 1
- CJJMZZQGSJKNJH-UHFFFAOYSA-N ethyl 4-[1-[5-(3-methylphenyl)-1,2,4-oxadiazol-3-yl]ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(C)C1=NOC(C=2C=C(C)C=CC=2)=N1 CJJMZZQGSJKNJH-UHFFFAOYSA-N 0.000 description 1
- WYSWFJQHNVTKIX-UHFFFAOYSA-N ethyl 4-[[5-(2-fluoro-5-methylphenyl)-1,2-oxazol-3-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NOC(C=2C(=CC=C(C)C=2)F)=C1 WYSWFJQHNVTKIX-UHFFFAOYSA-N 0.000 description 1
- MSZXEGISWRVEJL-UHFFFAOYSA-N ethyl 4-[[5-(3-chlorophenyl)-1,2-oxazol-3-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NOC(C=2C=C(Cl)C=CC=2)=C1 MSZXEGISWRVEJL-UHFFFAOYSA-N 0.000 description 1
- MKHBQSTYABOSJJ-UHFFFAOYSA-N ethyl 4-[[5-(3-cyanophenyl)-1,2-oxazol-3-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NOC(C=2C=C(C=CC=2)C#N)=C1 MKHBQSTYABOSJJ-UHFFFAOYSA-N 0.000 description 1
- BNVBKULRFQCICR-UHFFFAOYSA-N ethyl 4-[[5-(3-methylphenyl)-1,2,4-oxadiazol-3-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NOC(C=2C=C(C)C=CC=2)=N1 BNVBKULRFQCICR-UHFFFAOYSA-N 0.000 description 1
- FBCKIMBFWRQSPQ-UHFFFAOYSA-N ethyl 4-[[5-(3-methylphenyl)-1,2,4-oxadiazol-3-yl]methyl]piperazine-1-carboxylate;hydrochloride Chemical compound Cl.C1CN(C(=O)OCC)CCN1CC1=NOC(C=2C=C(C)C=CC=2)=N1 FBCKIMBFWRQSPQ-UHFFFAOYSA-N 0.000 description 1
- NIZQRVXFJWKOGJ-UHFFFAOYSA-N ethyl 4-[[5-(5-chloro-2-fluorophenyl)-1,2-oxazol-3-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NOC(C=2C(=CC=C(Cl)C=2)F)=C1 NIZQRVXFJWKOGJ-UHFFFAOYSA-N 0.000 description 1
- ONCZLBBDZXXFEE-UHFFFAOYSA-N ethyl 5-(3-chlorophenyl)-1,2,4-oxadiazole-3-carboxylate Chemical compound CCOC(=O)C1=NOC(C=2C=C(Cl)C=CC=2)=N1 ONCZLBBDZXXFEE-UHFFFAOYSA-N 0.000 description 1
- JVCKKVMKBIRWJV-UHFFFAOYSA-N ethyl 5-(5-chloro-2-fluorophenyl)-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OCC)C=C1C1=CC(Cl)=CC=C1F JVCKKVMKBIRWJV-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- MUQMCYOQBXGHKJ-UHFFFAOYSA-N ethyl butanoate;hydrochloride Chemical compound Cl.CCCC(=O)OCC MUQMCYOQBXGHKJ-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000003269 fluorescent indicator Substances 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- ZRZKFGDGIPLXIB-UHFFFAOYSA-N fluoroform;sulfuric acid Chemical compound FC(F)F.OS(O)(=O)=O ZRZKFGDGIPLXIB-UHFFFAOYSA-N 0.000 description 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- CYEFKCRAAGLNHW-UHFFFAOYSA-N furan-3-ylboronic acid Chemical compound OB(O)C=1C=COC=1 CYEFKCRAAGLNHW-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 239000010440 gypsum Substances 0.000 description 1
- 229910052602 gypsum Inorganic materials 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- ILVUABTVETXVMV-UHFFFAOYSA-N hydron;bromide;iodide Chemical compound Br.I ILVUABTVETXVMV-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 150000002531 isophthalic acids Chemical class 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 150000002545 isoxazoles Chemical class 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical group [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 230000020796 long term synaptic depression Effects 0.000 description 1
- 230000027928 long-term synaptic potentiation Effects 0.000 description 1
- ICYUIIJXZHPESK-UHFFFAOYSA-N m-Chloro-hippuric acid Chemical compound OC(=O)CNC(=O)C1=CC=CC(Cl)=C1 ICYUIIJXZHPESK-UHFFFAOYSA-N 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 108010038448 metabotropic glutamate receptor 8 Proteins 0.000 description 1
- 102000006239 metabotropic receptors Human genes 0.000 description 1
- 108020004083 metabotropic receptors Proteins 0.000 description 1
- BMRCCZUEIVXHEG-UHFFFAOYSA-N methanol;methyl 5-chloro-2-fluorobenzoate Chemical compound OC.COC(=O)C1=CC(Cl)=CC=C1F BMRCCZUEIVXHEG-UHFFFAOYSA-N 0.000 description 1
- OMNHXCDRKJITIR-UHFFFAOYSA-N methyl 2,4-dioxo-4-thiophen-3-ylbutanoate Chemical compound COC(=O)C(=O)CC(=O)C=1C=CSC=1 OMNHXCDRKJITIR-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- PVWUQTNZPUJCQJ-UHFFFAOYSA-N n,n-bis(2-hydroxyethyl)-2-nitrobenzenesulfonamide Chemical compound OCCN(CCO)S(=O)(=O)C1=CC=CC=C1[N+]([O-])=O PVWUQTNZPUJCQJ-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- NRQHUOPPMSBCLJ-UHFFFAOYSA-N oxadiazol-4-ylmethanamine Chemical compound NCC1=CON=N1 NRQHUOPPMSBCLJ-UHFFFAOYSA-N 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- IUPUSPIHYKKONK-UHFFFAOYSA-N piperazin-1-ium;propanoate Chemical compound CCC(O)=O.C1CNCCN1 IUPUSPIHYKKONK-UHFFFAOYSA-N 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- ZUINTLTYLSXKMV-UHFFFAOYSA-N piperidin-2-ylmethylcarbamic acid Chemical compound OC(=O)NCC1CCCCN1 ZUINTLTYLSXKMV-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000003956 synaptic plasticity Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- UXBYHJBZTWQSRO-UHFFFAOYSA-N tert-butyl n-(1-amino-1-hydroxyiminobutan-2-yl)carbamate Chemical compound ONC(=N)C(CC)NC(=O)OC(C)(C)C UXBYHJBZTWQSRO-UHFFFAOYSA-N 0.000 description 1
- RPKPFOKNXKRFTD-UHFFFAOYSA-N tert-butyl n-(1-cyanoethyl)carbamate Chemical compound N#CC(C)NC(=O)OC(C)(C)C RPKPFOKNXKRFTD-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
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- YEMJHNYABQHWHL-UHFFFAOYSA-N tributyl(ethynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#C YEMJHNYABQHWHL-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 230000004462 vestibulo-ocular reflex Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000031836 visual learning Effects 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/14—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
- C07D271/07—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/107—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with two aryl or substituted aryl radicals attached in positions 2 and 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/113—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Psychology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40203902P | 2002-08-09 | 2002-08-09 | |
| PCT/US2003/024912 WO2004014370A2 (en) | 2002-08-09 | 2003-08-08 | Oxadiazoles as modulators of metabotropic glutamate receptor-5 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA05001592A true MXPA05001592A (es) | 2005-05-05 |
Family
ID=31715776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA05001592A MXPA05001592A (es) | 2002-08-09 | 2003-08-08 | Oxadiazoles como moduladores de receptor-5 de glutamato metabotropico. |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US20040132726A1 (enExample) |
| EP (1) | EP1536790A2 (enExample) |
| JP (1) | JP2006506340A (enExample) |
| KR (1) | KR20050039846A (enExample) |
| CN (1) | CN1691944A (enExample) |
| AR (1) | AR041508A1 (enExample) |
| AU (1) | AU2003268064A1 (enExample) |
| BR (1) | BR0313266A (enExample) |
| CA (1) | CA2495120A1 (enExample) |
| IL (1) | IL166650A0 (enExample) |
| MX (1) | MXPA05001592A (enExample) |
| NO (1) | NO20051223L (enExample) |
| NZ (1) | NZ538339A (enExample) |
| TW (2) | TW200424183A (enExample) |
| WO (1) | WO2004014370A2 (enExample) |
| ZA (1) | ZA200501101B (enExample) |
Families Citing this family (104)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2770035T3 (es) | 2003-04-11 | 2020-06-30 | Ptc Therapeutics Inc | Compuesto de ácido 1,2,4-oxadiazol benzoico y su uso para la supresión sin sentido y el tratamiento de enfermedades |
| EP1669348A4 (en) | 2003-09-30 | 2009-03-11 | Eisai R&D Man Co Ltd | NEW ANTIPILIC AGENT CONTAINING A HETEROCYCLIC COMPOUND |
| WO2005077373A2 (en) * | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Treatment of gastro-esophageal reflux disease (gerd) |
| EP1716130A1 (en) * | 2004-02-18 | 2006-11-02 | AstraZeneca AB | Acetylinic piperazine compounds and their use as metabotropic glutamate receptor antagonists |
| US7585881B2 (en) * | 2004-02-18 | 2009-09-08 | Astrazeneca Ab | Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| TW200538108A (en) | 2004-02-19 | 2005-12-01 | Astrazeneca Ab | Fused heterocyclic compounds and their use as metabotropic glutamate receptor antagonists |
| JP2007533743A (ja) * | 2004-04-20 | 2007-11-22 | メルク エンド カムパニー インコーポレーテッド | アルツハイマー病治療のためのβ−セクレターゼ阻害薬として有用な1,3,5−置換フェニル誘導体化合物 |
| WO2006004142A1 (ja) * | 2004-06-30 | 2006-01-12 | Banyu Pharmaceutical Co., Ltd. | ビアリール誘導体 |
| JP4557685B2 (ja) | 2004-11-15 | 2010-10-06 | 独立行政法人理化学研究所 | 蛍光蛋白質 |
| WO2006089076A2 (en) | 2005-02-18 | 2006-08-24 | Neurogen Corporation | Thiazole amides, imidazole amides and related analogues |
| US8101618B2 (en) * | 2005-04-06 | 2012-01-24 | Msd K.K. | 1,4-substituted piperazine derivatives |
| US8716321B2 (en) | 2005-04-08 | 2014-05-06 | Ptc Therapeutics, Inc. | Methods for dosing an orally active 1,2,4-oxadiazole |
| JP3789465B1 (ja) | 2005-04-28 | 2006-06-21 | 学校法人立教学院 | イソオキサゾール誘導体又はジヒドロイソオキサゾール誘導体の製造方法 |
| GB0510140D0 (en) | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds B2 |
| JP2008540635A (ja) * | 2005-05-18 | 2008-11-20 | アデックス ファーマ ソシエテ アノニム | 代謝型グルタミン酸受容体の正のアロステリック調節因子としての置換されたオキシジアゾール誘導体 |
| GB0510139D0 (en) * | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds B1 |
| TW200800946A (en) * | 2005-08-15 | 2008-01-01 | Astrazeneca Ab | Substituted piperazines as metabotropic glutamate receptor antagonists |
| TW200800204A (en) * | 2005-08-15 | 2008-01-01 | Astrazeneca Ab | Bicyclic piperazines as metabotropic glutatmate receptor antagonists |
| AR058807A1 (es) | 2005-09-29 | 2008-02-27 | Astrazeneca Ab | 5-(fenilisoxazoletoxi)-triazol-3-il piridinas sustituidas, para el tratamiento de trastornos mediados por el receptor mglur5 |
| TWI385169B (zh) | 2005-10-31 | 2013-02-11 | Eisai R&D Man Co Ltd | 經雜環取代之吡啶衍生物及含有彼之抗真菌劑 |
| EP2387995A1 (en) | 2006-03-30 | 2011-11-23 | PTC Therapeutics, Inc. | Methods for the production of functional protein from DNA having a nonsense mutation and the treatment of disorders associated therewith |
| TW200811157A (en) | 2006-05-05 | 2008-03-01 | Astrazeneca Ab | mGluR5 modulators I |
| TW200811179A (en) * | 2006-05-05 | 2008-03-01 | Astrazeneca Ab | mGluR5 modulators VI |
| TW200808800A (en) * | 2006-05-05 | 2008-02-16 | Astrazeneca Ab | MGluR5 modulators V |
| US7943622B2 (en) | 2006-06-06 | 2011-05-17 | Cornerstone Therapeutics, Inc. | Piperazines, pharmaceutical compositions and methods of use thereof |
| EP2081905B1 (en) | 2006-07-28 | 2012-09-12 | Boehringer Ingelheim International GmbH | Sulfonyl compounds which modulate the cb2 receptor |
| DK2059513T3 (da) * | 2006-09-08 | 2013-05-06 | Ptc Therapeutics Inc | Fremgangsmåde til fremstillingen af 1,2,4-oxadiazolbenzoesyrer |
| EP2065377B1 (en) | 2006-09-21 | 2011-11-23 | Eisai R&D Management Co., Ltd. | Pyridine derivative substituted by heteroaryl ring, and antifungal agent comprising the same |
| SG185979A1 (en) * | 2006-09-25 | 2012-12-28 | Ptc Therapeutics Inc | Crystalline forms of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]-benzoic acid |
| WO2008130370A1 (en) | 2006-09-25 | 2008-10-30 | Ptc Therapeutics, Inc. | Hydroxylated 1,2,4-oxadiazole benzoic acid compounds, compositions thereof and the use for nonsense suppression |
| SI2073805T1 (sl) * | 2006-10-12 | 2015-10-30 | Ptc Therapeutics, Inc. | Postopki za odmerjanje peroralno aktivnega 1,2,4-oksadiazola za zdravljenje supresije nesmiselnih mutacij |
| WO2008050200A1 (en) * | 2006-10-24 | 2008-05-02 | Pfizer Products Inc. | Oxadiazole compounds as calcium channel antagonists |
| UY30892A1 (es) * | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
| WO2008117148A1 (en) * | 2007-03-23 | 2008-10-02 | Pfizer Products Inc. | Substituted oxadiazole analogs as calcium channel antagonists |
| TW200841879A (en) | 2007-04-27 | 2008-11-01 | Eisai R&D Man Co Ltd | Pyridine derivatives substituted by heterocyclic ring and phosphonoamino group, and anti-fungal agent containing same |
| PT2164825E (pt) | 2007-06-05 | 2014-06-24 | Sanofi Sa | Derivados de di(hetero)arilciclo-hexano, sua preparação, sua utilização e composições farmacêuticas compreendendo os mesmos |
| SI2209778T1 (sl) | 2007-09-21 | 2012-12-31 | Array Biopharma, Inc. | Piridin-2-il-amino-I, 2,4-tiadiazol derivati kot aktivatorji glukokinaze za zdravljenje sladkorne bolezni |
| WO2009061652A1 (en) | 2007-11-07 | 2009-05-14 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
| US8513287B2 (en) | 2007-12-27 | 2013-08-20 | Eisai R&D Management Co., Ltd. | Heterocyclic ring and phosphonoxymethyl group substituted pyridine derivatives and antifungal agent containing same |
| ATE552255T1 (de) | 2008-06-05 | 2012-04-15 | Glaxo Group Ltd | 4-aminoindazole |
| ES2445199T3 (es) | 2008-06-05 | 2014-02-28 | Glaxo Group Limited | Derivados de benzpirazol como inhibidores de PI3-quinasas |
| ES2526966T3 (es) | 2008-06-05 | 2015-01-19 | Glaxo Group Limited | Compuestos novedosos |
| EP2326629B1 (en) | 2008-07-10 | 2013-10-02 | Boehringer Ingelheim International GmbH | Sulfone compounds which modulate the cb2 receptor |
| NZ591111A (en) | 2008-09-25 | 2013-08-30 | Boehringer Ingelheim Int | Sulfonyl compounds which selectively modulate the cb2 receptor |
| US8188119B2 (en) | 2008-10-24 | 2012-05-29 | Eisai R&D Management Co., Ltd | Pyridine derivatives substituted with heterocyclic ring and γ-glutamylamino group, and antifungal agents containing same |
| DE102009041242A1 (de) | 2009-09-11 | 2011-12-15 | Bayer Schering Pharma Aktiengesellschaft | Heterocyclisch substituierte Aryl-Verbindungen und ihre Verwendung |
| DE102009041241A1 (de) | 2009-09-11 | 2011-08-04 | Bayer Schering Pharma Aktiengesellschaft, 13353 | Substituierte Aryl-Verbindungen und ihre Verwendung |
| DE102008057343A1 (de) | 2008-11-14 | 2010-05-20 | Bayer Schering Pharma Aktiengesellschaft | Heterocyclisch substituierte Aryl-Verbindungen und ihre Verwendung |
| DE102008057364A1 (de) | 2008-11-14 | 2010-05-20 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Aryl-Verbindungen und ihre Verwendung |
| DE102008057344A1 (de) | 2008-11-14 | 2010-05-20 | Bayer Schering Pharma Aktiengesellschaft | Aminoalkyl-substituierte Aryl-Verbindungen und ihre Verwendung |
| HRP20150355T1 (hr) | 2009-01-12 | 2015-06-19 | Pfizer Limited | Sulfonamidni derivati |
| PE20120003A1 (es) * | 2009-01-30 | 2012-02-12 | Glaxosmithkline Llc | Hidrocloruro de n-{(1s)-2-amino-1-[(3-fluorofenil)metil)etil}-5-cloro-4-(4-cloro-1-metil-1h-pirazol-5-il)-2-tiofenocarboxamida cristalino |
| WO2010096371A2 (en) | 2009-02-18 | 2010-08-26 | Boehringer Ingelheim International Gmbh | Heterocyclic compounds which modulate the cb2 receptor |
| WO2010102958A1 (en) | 2009-03-09 | 2010-09-16 | Glaxo Group Limited | 4-oxadiazol-2 -yl- indazoles as inhibitors of p13 kinases |
| CA2759476C (en) | 2009-04-30 | 2018-10-09 | Julie Nicole Hamblin | Novel compounds |
| MX2011013016A (es) | 2009-06-05 | 2012-04-20 | Link Medicine Corp | Derivados de aminopirrolidinona y usos de los mismos. |
| US8299103B2 (en) | 2009-06-15 | 2012-10-30 | Boehringer Ingelheim International Gmbh | Compounds which selectively modulate the CB2 receptor |
| US8383615B2 (en) | 2009-06-16 | 2013-02-26 | Boehringer Ingelheim International Gmbh | Azetidine 2-carboxamide derivatives which modulate the CB2 receptor |
| EP2480544A1 (en) | 2009-09-22 | 2012-08-01 | Boehringer Ingelheim International GmbH | Compounds which selectively modulate the cb2 receptor |
| EP2523936A1 (en) | 2010-01-15 | 2012-11-21 | Boehringer Ingelheim International GmbH | Compounds which modulate the cb2 receptor |
| WO2011109324A1 (en) | 2010-03-05 | 2011-09-09 | Boehringer Ingelheim International Gmbh | Tetrazole compounds which selectively modulate the cb2 receptor |
| CA2829790C (en) | 2010-03-30 | 2018-06-05 | Verseon Corporation | Multisubstituted aromatic compounds as inhibitors of thrombin |
| EP2590972B1 (en) | 2010-07-09 | 2015-01-21 | Pfizer Limited | N-sulfonylbenzamides as inhibitors of voltage-gated sodium channels |
| JP5746764B2 (ja) | 2010-07-22 | 2015-07-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Cb2受容体を調節する化合物 |
| GB201018124D0 (en) | 2010-10-27 | 2010-12-08 | Glaxo Group Ltd | Polymorphs and salts |
| AR086113A1 (es) | 2011-04-30 | 2013-11-20 | Abbott Lab | Isoxazolinas como agentes terapeuticos |
| EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| JP2013028559A (ja) * | 2011-07-28 | 2013-02-07 | Nippon Light Metal Co Ltd | 3−クロロ−4−メチル安息香酸イソプロピル及びその製造方法 |
| US8729263B2 (en) | 2012-08-13 | 2014-05-20 | Novartis Ag | 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions |
| US9040712B2 (en) | 2013-01-23 | 2015-05-26 | Novartis Ag | Thiadiazole analogs thereof and methods for treating SMN-deficiency-related-conditions |
| CN112521369A (zh) | 2013-03-13 | 2021-03-19 | 福马治疗股份有限公司 | 用于抑制fasn的化合物及组合物 |
| CA2902431A1 (en) | 2013-03-15 | 2014-09-25 | Kevin Michael Short | Halogenopyrazoles as inhibitors of thrombin |
| PE20161035A1 (es) | 2013-03-15 | 2016-11-13 | Global Blood Therapeutics Inc | Compuestos y usos de estos para la modulacion de la hemoglobina |
| EP3421036B8 (en) | 2013-03-15 | 2020-12-30 | Verseon International Corporation | Multisubstituted aromatic compounds as serine protease inhibitors |
| EP2803668A1 (en) | 2013-05-17 | 2014-11-19 | Boehringer Ingelheim International Gmbh | Novel (cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles |
| CN105492444B (zh) | 2013-07-02 | 2018-09-07 | 百时美施贵宝公司 | 作为rock抑制剂的三环吡啶-甲酰胺衍生物 |
| EP3016950B1 (en) | 2013-07-02 | 2017-06-07 | Bristol-Myers Squibb Company | Tricyclic pyrido-carboxamide derivatives as rock inhibitors |
| MX2020011652A (es) | 2013-07-31 | 2022-09-27 | Novartis Ag | Derivados de piridazina 1,4-disustituida, y su uso para el tratamiento de afecciones relacionadas con la deficiencia de smn. |
| EA201992707A1 (ru) | 2013-11-18 | 2020-06-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| GB201402277D0 (en) | 2014-02-10 | 2014-03-26 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| EP2907806A1 (en) * | 2014-02-14 | 2015-08-19 | Universita Degli Studi Di Genova | New compounds as selective PDE4D inhibitors |
| KR102497273B1 (ko) | 2014-03-06 | 2023-02-07 | 피티씨 테라퓨틱스, 인크. | 1,2,4-옥사디아졸 벤조산의 약학 조성물 및 염 |
| ES2905280T3 (es) * | 2014-07-03 | 2022-04-07 | Celgene Quanticel Res Inc | Inhibidores de la desmetilasa 1 específica de lisina |
| RU2017112739A (ru) * | 2014-09-17 | 2018-10-17 | Версеон Корпорейшн | Пиразолил-замещенные пиридоновые соединения как ингибиторы сериновых протеаз |
| BR112017018119B1 (pt) | 2015-02-24 | 2021-11-03 | Bayer Cropscience Aktiengesellschaft | Processo para a preparação de triazóis |
| SG11201706411YA (en) | 2015-02-27 | 2017-09-28 | Verseon Corp | Substituted pyrazole compounds as serine protease inhibitors |
| JP2018531924A (ja) | 2015-09-24 | 2018-11-01 | ファイザー・インク | テトラヒドロピラノ[3,4−d][1,3]オキサジン誘導体、およびbace阻害剤としてのその使用 |
| US10517853B2 (en) | 2015-10-30 | 2019-12-31 | Ptc Therapeutics, Inc. | Methods for treating epilepsy |
| CA2968836C (en) | 2016-06-13 | 2025-09-02 | Gilead Sciences Inc | Fxr (nr1h4) modulating compounds |
| CA3026512A1 (en) | 2016-06-13 | 2017-12-21 | Gilead Sciences, Inc. | Fxr (nr1h4) modulating compounds |
| WO2018089967A1 (en) | 2016-11-14 | 2018-05-17 | Virginia Commonwealth University | Inhibitors of cancer invasion, attachment, and/or metastasis |
| EP4122464B1 (en) | 2017-03-28 | 2024-05-15 | Gilead Sciences, Inc. | Therapeutic combinations for treating liver diseases |
| CN107382990B (zh) * | 2017-08-09 | 2020-08-04 | 济南大学 | 一种具有1,2,4-恶二唑结构片段的化合物及其制备方法和应用 |
| CA3072362A1 (en) | 2017-10-06 | 2019-04-11 | Forma Therapeutics, Inc. | Inhibiting ubiquitin specific peptidase 30 |
| SG11202011299PA (en) | 2018-05-17 | 2020-12-30 | Forma Therapeutics Inc | Fused bicyclic compounds useful as ubiquitin-specific peptidase 30 inhibitors |
| MY209034A (en) | 2018-10-05 | 2025-06-17 | Forma Therapeutics Inc | Fused pyrrolines which act as ubiquitin-specific protease 30 (usp30) inhibitors |
| TWI767148B (zh) | 2018-10-10 | 2022-06-11 | 美商弗瑪治療公司 | 抑制脂肪酸合成酶(fasn) |
| WO2020092395A1 (en) | 2018-10-29 | 2020-05-07 | Forma Therapeutics, Inc. | SOLID FORMS OF (4-(2-FLUORO-4-(1-METHYL-1 H-BENZO[d]IMIDAZOL-5-YL)BENZOYL) PIPERAZIN-1-YL)(1-HYDROXYCYCLOPROPYL)METHANONE |
| LT3911647T (lt) | 2019-01-15 | 2024-03-25 | Gilead Sciences, Inc. | Izoksazolo junginys kaip fxr agonistas ir jį apimančios farmacinės kompozicijos |
| KR102732207B1 (ko) | 2019-01-31 | 2024-11-22 | 화이자 인코포레이티드 | Cdk2에 대한 억제 활성을 갖는 3-카본일아미노-5-사이클로펜틸-1h-피라졸 화합물 |
| CA3129949C (en) | 2019-02-19 | 2024-04-30 | Gilead Sciences, Inc. | Solid forms of fxr agonists |
| US11932630B2 (en) | 2021-04-16 | 2024-03-19 | Novartis Ag | Heteroaryl aminopropanol derivatives |
| CN113248455A (zh) * | 2021-05-25 | 2021-08-13 | 湖北科技学院 | 一种3,5-二取代异噁唑类衍生物及其合成方法 |
| CN119173506A (zh) | 2022-05-19 | 2024-12-20 | 阿斯利康(瑞典)有限公司 | 用于治疗肝病的酰胺杂芳香族化合物 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3740434A (en) * | 1966-12-23 | 1973-06-19 | American Cyanamid Co | Substituted nitroimidazolylthiadiazoles and oxadiazoles as antiprotozoal agents |
| US3816426A (en) * | 1970-10-27 | 1974-06-11 | Abbott Lab | 1-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazines |
| JPS56127364A (en) * | 1980-03-01 | 1981-10-06 | Mitsui Toatsu Chem Inc | Novel piperazine compound, its preparation and utilization |
| JP3003148B2 (ja) * | 1989-01-05 | 2000-01-24 | 藤沢薬品工業株式会社 | チアゾール化合物、その製造法およびそれを含有する医薬組成物 |
| IL96891A0 (en) * | 1990-01-17 | 1992-03-29 | Merck Sharp & Dohme | Indole-substituted five-membered heteroaromatic compounds,their preparation and pharmaceutical compositions containing them |
| ATE182139T1 (de) * | 1992-10-23 | 1999-07-15 | Merck Sharp & Dohme | Dopamin rezeptor subtyp liganden |
| DE19858191A1 (de) * | 1998-12-17 | 2000-06-21 | Aventis Cropscience Gmbh | 4-Haloalkyl-3-heterocyclylpyridine und 4-Haloalkyl-5-heterocyclyl-pyrimidine und ihre Verwendung als Repellentien |
| CO5170501A1 (es) * | 1999-04-14 | 2002-06-27 | Novartis Ag | AZOLES SUSTITUIDOS UTILES PARA EL TRATAMIENTO DE ENFERMEDADES MEDIADAS POR TNFa eIL-1 Y ENFERMEDADES DEL METABOLISMO OSEO |
| PL353825A1 (en) * | 1999-08-19 | 2003-12-01 | Nps Pharmaceuticals, Inc.Nps Pharmaceuticals, Inc. | Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| TWI283577B (en) * | 1999-10-11 | 2007-07-11 | Sod Conseils Rech Applic | Pharmaceutical composition of imidazole derivatives acting as modulators of sodium channels and the use thereof |
| US7199137B2 (en) * | 2000-09-21 | 2007-04-03 | Smithkline Beecham Plc | Imidazole derivatives as Raf kinase inhibitors |
| ATE288898T1 (de) * | 2000-12-04 | 2005-02-15 | Hoffmann La Roche | Phenylethenyl- oder phenylethinylderivate als glutamatrezeptorantagonisten |
| DK1406898T3 (da) * | 2001-07-19 | 2005-05-30 | Cv Therapeutics Inc | Substituerede piperazinforbindelser og anvendelse af disse som fedtsyreoxidationsinhibitorer |
-
2003
- 2003-08-08 TW TW092121861A patent/TW200424183A/zh unknown
- 2003-08-08 US US10/636,965 patent/US20040132726A1/en not_active Abandoned
- 2003-08-08 NZ NZ538339A patent/NZ538339A/en unknown
- 2003-08-08 BR BR0313266-8A patent/BR0313266A/pt not_active IP Right Cessation
- 2003-08-08 TW TW096135411A patent/TW200812986A/zh unknown
- 2003-08-08 MX MXPA05001592A patent/MXPA05001592A/es unknown
- 2003-08-08 JP JP2004527912A patent/JP2006506340A/ja active Pending
- 2003-08-08 EP EP03749015A patent/EP1536790A2/en not_active Withdrawn
- 2003-08-08 AU AU2003268064A patent/AU2003268064A1/en not_active Abandoned
- 2003-08-08 CN CNA038238594A patent/CN1691944A/zh active Pending
- 2003-08-08 WO PCT/US2003/024912 patent/WO2004014370A2/en not_active Ceased
- 2003-08-08 CA CA002495120A patent/CA2495120A1/en not_active Abandoned
- 2003-08-08 AR ARP030102892A patent/AR041508A1/es unknown
- 2003-08-08 KR KR1020057002200A patent/KR20050039846A/ko not_active Withdrawn
-
2005
- 2005-02-02 IL IL16665005A patent/IL166650A0/xx unknown
- 2005-02-07 ZA ZA200501101A patent/ZA200501101B/xx unknown
- 2005-03-09 NO NO20051223A patent/NO20051223L/no not_active Application Discontinuation
- 2005-11-10 US US11/270,617 patent/US20060063772A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004014370A2 (en) | 2004-02-19 |
| CN1691944A (zh) | 2005-11-02 |
| NZ538339A (en) | 2007-01-26 |
| US20060063772A1 (en) | 2006-03-23 |
| TW200424183A (en) | 2004-11-16 |
| AR041508A1 (es) | 2005-05-18 |
| US20040132726A1 (en) | 2004-07-08 |
| EP1536790A2 (en) | 2005-06-08 |
| KR20050039846A (ko) | 2005-04-29 |
| WO2004014370A3 (en) | 2004-10-21 |
| TW200812986A (en) | 2008-03-16 |
| NO20051223L (no) | 2005-05-03 |
| AU2003268064A1 (en) | 2004-02-25 |
| JP2006506340A (ja) | 2006-02-23 |
| CA2495120A1 (en) | 2004-02-19 |
| ZA200501101B (en) | 2006-02-22 |
| IL166650A0 (en) | 2006-01-15 |
| BR0313266A (pt) | 2005-06-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MXPA05001592A (es) | Oxadiazoles como moduladores de receptor-5 de glutamato metabotropico. | |
| US7074809B2 (en) | Compounds | |
| AU717699B2 (en) | Chemical compounds | |
| JP4637578B2 (ja) | 代謝調節型グルタミン酸受容体−5の調節因子としての1,2,4−オキサジアゾール類 | |
| JP4912157B2 (ja) | 追加の複素多環式化合物及びそれらの代謝調節型グルタミン酸受容体アンタゴニストとしての使用 | |
| JP4958560B2 (ja) | Gpcr受容体作動薬としてのヘテロ環誘導体 | |
| MXPA06009023A (es) | Compuestos poliheterociclicos y su uso como antagonistas del receptor de glutamato metabotropico. | |
| JP2008545007A (ja) | Gpcrアゴニスト | |
| JP2007523183A (ja) | 縮合複素環式化合物及び代謝調節型グルタミン酸受容体アンタゴニストとしてのその使用 | |
| MX2012012857A (es) | Heteroaril-ciclohexil-tetraazabenzo[e]azulenos. | |
| WO2004072050A1 (en) | Heterocyclic compounds useful as nurr-1 activators | |
| US20070037820A1 (en) | Substituted piperazines as metabotropic glutamate receptor antagonists | |
| EP1723126A2 (en) | Novel mch receptor antagonists | |
| US20070293497A1 (en) | 2,3,4,6-Substituted Pyridyl Derivative Compounds Useful As Beta-Secretase Inhibitors For The Treatment Of Alzheimer's Disease | |
| DE102004016845A1 (de) | Phenylthioessigsäure-Derivate und ihre Verwendung | |
| WO2012099200A1 (ja) | ピラゾール誘導体 | |
| RU2376302C2 (ru) | Производные (индол-3-ил)гетероциклических соединений в качестве агонистов каннабиноидных рецепторов св1 | |
| HK1116491A (en) | New heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| GB | Transfer or rights |