JP2003513063A - ジアリール−エニン類 - Google Patents
ジアリール−エニン類Info
- Publication number
- JP2003513063A JP2003513063A JP2001534756A JP2001534756A JP2003513063A JP 2003513063 A JP2003513063 A JP 2003513063A JP 2001534756 A JP2001534756 A JP 2001534756A JP 2001534756 A JP2001534756 A JP 2001534756A JP 2003513063 A JP2003513063 A JP 2003513063A
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- sarcosine
- penten
- alkyl
- compound according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- -1 heterocycloalkyloxy Chemical group 0.000 claims abstract description 113
- 150000001875 compounds Chemical class 0.000 claims abstract description 99
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 50
- 125000003118 aryl group Chemical group 0.000 claims abstract description 31
- 125000001424 substituent group Chemical group 0.000 claims abstract description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 10
- 125000005000 thioaryl group Chemical group 0.000 claims abstract description 9
- 125000004001 thioalkyl group Chemical group 0.000 claims abstract description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims abstract description 5
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 5
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims abstract description 5
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 4
- 150000004677 hydrates Chemical class 0.000 claims abstract description 4
- 239000012453 solvate Substances 0.000 claims abstract description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims abstract description 3
- 229940043230 sarcosine Drugs 0.000 claims description 85
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 66
- 239000004471 Glycine Substances 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 10
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- STDPMTMIUMQYKK-UHFFFAOYSA-N 2-[methyl-[3-phenyl-5-[4-(trifluoromethoxy)phenyl]pent-2-en-4-ynyl]amino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(OC(F)(F)F)C=C1 STDPMTMIUMQYKK-UHFFFAOYSA-N 0.000 claims description 4
- OGUANBSEGNLAEU-UHFFFAOYSA-N 2-[methyl-[5-(4-phenoxyphenyl)-3-phenylpent-2-en-4-ynyl]amino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC(C=C1)=CC=C1OC1=CC=CC=C1 OGUANBSEGNLAEU-UHFFFAOYSA-N 0.000 claims description 4
- 125000004864 4-thiomethylphenyl group Chemical group 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- YKKCJDHNSGEDOM-UHFFFAOYSA-N 2-[methyl-(5-naphthalen-2-yl-3-phenylpent-2-en-4-ynyl)amino]acetic acid Chemical compound C=1C=C2C=CC=CC2=CC=1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1 YKKCJDHNSGEDOM-UHFFFAOYSA-N 0.000 claims description 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 2
- QIEOXIDJWDGHRE-UHFFFAOYSA-N 2-[[5-(4-chlorophenyl)-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(Cl)C=C1 QIEOXIDJWDGHRE-UHFFFAOYSA-N 0.000 claims description 2
- VKSQEFQZQGQCCF-UHFFFAOYSA-N 2-[methyl-[5-(4-methylphenyl)-3-phenylpent-2-en-4-ynyl]amino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(C)C=C1 VKSQEFQZQGQCCF-UHFFFAOYSA-N 0.000 claims description 2
- LZFHXALVUIUALP-UHFFFAOYSA-N C(C)C1=CC=C(C=C1)C#CC(=CCN(C)CC(=O)O)C1=C(C=CC=C1)Cl.C1OC=2C=C(C=CC2O1)C#CC(=CCN(C)CC(=O)O)C1=CC(=CC=C1)F Chemical compound C(C)C1=CC=C(C=C1)C#CC(=CCN(C)CC(=O)O)C1=C(C=CC=C1)Cl.C1OC=2C=C(C=CC2O1)C#CC(=CCN(C)CC(=O)O)C1=CC(=CC=C1)F LZFHXALVUIUALP-UHFFFAOYSA-N 0.000 claims description 2
- YGTRJOGPGUOVHV-UHFFFAOYSA-N C1(=CC=CC=C1)C(=CCN(C)CC(=O)O)C#CC1=CC=CC=C1.FC(C=1C=C(C=C(C1)C(F)(F)F)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1)(F)F Chemical compound C1(=CC=CC=C1)C(=CCN(C)CC(=O)O)C#CC1=CC=CC=C1.FC(C=1C=C(C=C(C1)C(F)(F)F)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1)(F)F YGTRJOGPGUOVHV-UHFFFAOYSA-N 0.000 claims description 2
- GCLZYACTVKAVBH-UHFFFAOYSA-N N1C(=CC=C1)C1=CC=C(C=C1)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1.C1OC=2C=C(C=CC2O1)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1 Chemical compound N1C(=CC=C1)C1=CC=C(C=C1)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1.C1OC=2C=C(C=CC2O1)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1 GCLZYACTVKAVBH-UHFFFAOYSA-N 0.000 claims description 2
- CWKQXDBGYZDSOO-UHFFFAOYSA-N [N+](=O)([O-])C1=CC=C(C=C1)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1.[N+](=O)([O-])C=1C=C(C=CC1)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1 Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1.[N+](=O)([O-])C=1C=C(C=CC1)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1 CWKQXDBGYZDSOO-UHFFFAOYSA-N 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- 125000002837 carbocyclic group Chemical group 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 107
- 239000003921 oil Substances 0.000 description 73
- 235000019198 oils Nutrition 0.000 description 73
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 47
- 239000007787 solid Substances 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 239000012230 colorless oil Substances 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 18
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 16
- 101710083171 Sodium- and chloride-dependent glycine transporter 1 Proteins 0.000 description 15
- 102100023145 Sodium- and chloride-dependent glycine transporter 1 Human genes 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- 239000006260 foam Substances 0.000 description 12
- 239000003446 ligand Substances 0.000 description 11
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- PQJOSEVTIKYWLH-UHFFFAOYSA-N 1-iodo-4-propan-2-ylbenzene Chemical compound CC(C)C1=CC=C(I)C=C1 PQJOSEVTIKYWLH-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 7
- 239000004327 boric acid Substances 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 239000002858 neurotransmitter agent Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- 108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 description 6
- 102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 description 6
- 102000011714 Glycine Receptors Human genes 0.000 description 6
- 108010076533 Glycine Receptors Proteins 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 6
- 108010077895 Sarcosine Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000001503 aryl iodides Chemical class 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 5
- 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 5
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 5
- 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 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- WQVIVQDHNKQWTM-UHFFFAOYSA-N 1-tert-butyl-4-iodobenzene Chemical compound CC(C)(C)C1=CC=C(I)C=C1 WQVIVQDHNKQWTM-UHFFFAOYSA-N 0.000 description 4
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 4
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 108010078791 Carrier Proteins Proteins 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 235000011089 carbon dioxide Nutrition 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000003107 substituted aryl group Chemical group 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 210000000225 synapse Anatomy 0.000 description 4
- 229930192474 thiophene Natural products 0.000 description 4
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 101710083167 Sodium- and chloride-dependent glycine transporter 2 Proteins 0.000 description 3
- 102100028886 Sodium- and chloride-dependent glycine transporter 2 Human genes 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940000406 drug candidate Drugs 0.000 description 3
- 230000002964 excitative effect Effects 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000010304 firing Methods 0.000 description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- 230000027928 long-term synaptic potentiation Effects 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 210000004129 prosencephalon Anatomy 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 230000005062 synaptic transmission Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- CMLWFCUAXGSMBB-UHFFFAOYSA-N tris(2,6-dimethoxyphenyl)phosphane Chemical compound COC1=CC=CC(OC)=C1P(C=1C(=CC=CC=1OC)OC)C1=C(OC)C=CC=C1OC CMLWFCUAXGSMBB-UHFFFAOYSA-N 0.000 description 3
- SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 2
- GWQSENYKCGJTRI-UHFFFAOYSA-N 1-chloro-4-iodobenzene Chemical compound ClC1=CC=C(I)C=C1 GWQSENYKCGJTRI-UHFFFAOYSA-N 0.000 description 2
- OOLSRHZMXAYDFB-UHFFFAOYSA-N 1-ethyl-4-iodobenzene Chemical compound CCC1=CC=C(I)C=C1 OOLSRHZMXAYDFB-UHFFFAOYSA-N 0.000 description 2
- TYHUGKGZNOULKD-UHFFFAOYSA-N 1-fluoro-2-iodobenzene Chemical compound FC1=CC=CC=C1I TYHUGKGZNOULKD-UHFFFAOYSA-N 0.000 description 2
- KGNQDBQYEBMPFZ-UHFFFAOYSA-N 1-fluoro-4-iodobenzene Chemical compound FC1=CC=C(I)C=C1 KGNQDBQYEBMPFZ-UHFFFAOYSA-N 0.000 description 2
- SORQIYFSJAWBNQ-UHFFFAOYSA-N 1-iodo-2-propan-2-ylbenzene Chemical compound CC(C)C1=CC=CC=C1I SORQIYFSJAWBNQ-UHFFFAOYSA-N 0.000 description 2
- SKGRFPGOGCHDPC-UHFFFAOYSA-N 1-iodo-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(I)C=C1 SKGRFPGOGCHDPC-UHFFFAOYSA-N 0.000 description 2
- UDHAWRUAECEBHC-UHFFFAOYSA-N 1-iodo-4-methylbenzene Chemical compound CC1=CC=C(I)C=C1 UDHAWRUAECEBHC-UHFFFAOYSA-N 0.000 description 2
- KIGCTKNPXSPYMQ-XKZIYDEJSA-N 2-[[(e)-5-[4-(furan-3-yl)phenyl]-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=CC=CC=1C(=C/CN(C)CC(O)=O)\C#CC(C=C1)=CC=C1C=1C=COC=1 KIGCTKNPXSPYMQ-XKZIYDEJSA-N 0.000 description 2
- UJACLHZGYAYKTK-UHFFFAOYSA-N 2-[[3-(2-chlorophenyl)-5-(4-propylphenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C1=CC(CCC)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1Cl UJACLHZGYAYKTK-UHFFFAOYSA-N 0.000 description 2
- PCPOUEJDMUWZGR-UHFFFAOYSA-N 2-[[5-(1,3-benzodioxol-5-yl)-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=C2OCOC2=CC=1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1 PCPOUEJDMUWZGR-UHFFFAOYSA-N 0.000 description 2
- GEEMWPAZWCICOD-UHFFFAOYSA-N 2-[[5-(4-benzylphenyl)-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC(C=C1)=CC=C1CC1=CC=CC=C1 GEEMWPAZWCICOD-UHFFFAOYSA-N 0.000 description 2
- DIAWDCJXECNMKZ-UHFFFAOYSA-N 2-[methyl-(5-naphthalen-1-yl-3-phenylpent-2-en-4-ynyl)amino]acetic acid Chemical compound C=1C=CC2=CC=CC=C2C=1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1 DIAWDCJXECNMKZ-UHFFFAOYSA-N 0.000 description 2
- CTFYGRJMAPAQAN-UHFFFAOYSA-N 2-[methyl-[3-phenyl-5-(2-propan-2-ylphenyl)pent-2-en-4-ynyl]amino]acetic acid Chemical compound CC(C)C1=CC=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1 CTFYGRJMAPAQAN-UHFFFAOYSA-N 0.000 description 2
- IPOFUKZEMHWTJF-UHFFFAOYSA-N 2-[methyl-[3-phenyl-5-(4-propan-2-ylphenyl)pent-2-en-4-ynyl]amino]acetic acid Chemical compound C1=CC(C(C)C)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1 IPOFUKZEMHWTJF-UHFFFAOYSA-N 0.000 description 2
- VRGSXCNISZGPAZ-UHFFFAOYSA-N 2-[methyl-[3-phenyl-5-[4-(trifluoromethyl)phenyl]pent-2-en-4-ynyl]amino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(C(F)(F)F)C=C1 VRGSXCNISZGPAZ-UHFFFAOYSA-N 0.000 description 2
- DSYKPPXELIYFJG-UHFFFAOYSA-N 2-[methyl-[5-[4-(4-methylfuran-3-yl)phenyl]-3-phenylpent-2-en-4-ynyl]amino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC(C=C1)=CC=C1C1=COC=C1C DSYKPPXELIYFJG-UHFFFAOYSA-N 0.000 description 2
- WBSZZKMQWAVIIV-UHFFFAOYSA-N 2-[tert-butyl(methyl)amino]acetic acid;hydrochloride Chemical compound Cl.CC(C)(C)N(C)CC(O)=O WBSZZKMQWAVIIV-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 2
- 101000631937 Homo sapiens Sodium- and chloride-dependent glycine transporter 2 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical group CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
- BSOVPFVRRYEZHC-UHFFFAOYSA-N N1C(=CC=C1)C1=CC=C(C=C1)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1 Chemical compound N1C(=CC=C1)C1=CC=C(C=C1)C#CC(=CCN(C)CC(=O)O)C1=CC=CC=C1 BSOVPFVRRYEZHC-UHFFFAOYSA-N 0.000 description 2
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 2
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000036982 action potential Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 230000000971 hippocampal effect Effects 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical class CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical class C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002032 methanolic fraction Substances 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 150000002790 naphthalenes Chemical class 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 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 2
- 239000008188 pellet Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 230000000946 synaptic effect Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- ASTZHAOQWJACEX-UHFFFAOYSA-N (5-bromo-3-phenylpent-3-en-1-ynyl)-trimethylsilane Chemical compound C[Si](C)(C)C#CC(=CCBr)C1=CC=CC=C1 ASTZHAOQWJACEX-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- FCUNNMLRHRWXAM-UHFFFAOYSA-N 1-benzyl-4-iodobenzene Chemical compound C1=CC(I)=CC=C1CC1=CC=CC=C1 FCUNNMLRHRWXAM-UHFFFAOYSA-N 0.000 description 1
- OIRHKGBNGGSCGS-UHFFFAOYSA-N 1-bromo-2-iodobenzene Chemical compound BrC1=CC=CC=C1I OIRHKGBNGGSCGS-UHFFFAOYSA-N 0.000 description 1
- UCCUXODGPMAHRL-UHFFFAOYSA-N 1-bromo-4-iodobenzene Chemical compound BrC1=CC=C(I)C=C1 UCCUXODGPMAHRL-UHFFFAOYSA-N 0.000 description 1
- XILRUONFYBUYIE-UHFFFAOYSA-N 1-butyl-4-iodobenzene Chemical compound CCCCC1=CC=C(I)C=C1 XILRUONFYBUYIE-UHFFFAOYSA-N 0.000 description 1
- MPEOPBCQHNWNFB-UHFFFAOYSA-N 1-chloro-2-iodobenzene Chemical compound ClC1=CC=CC=C1I MPEOPBCQHNWNFB-UHFFFAOYSA-N 0.000 description 1
- IGZGUYVVBABKOY-UHFFFAOYSA-N 1-iodo-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1I IGZGUYVVBABKOY-UHFFFAOYSA-N 0.000 description 1
- CBYAZOKPJYBCHE-UHFFFAOYSA-N 1-iodo-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(I)=C1 CBYAZOKPJYBCHE-UHFFFAOYSA-N 0.000 description 1
- ABEHQMOOXFPCPF-UHFFFAOYSA-N 1-iodo-3-propan-2-ylbenzene Chemical compound CC(C)C1=CC=CC(I)=C1 ABEHQMOOXFPCPF-UHFFFAOYSA-N 0.000 description 1
- RTUDBROGOZBBIC-UHFFFAOYSA-N 1-iodo-4-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=C(I)C=C1 RTUDBROGOZBBIC-UHFFFAOYSA-N 0.000 description 1
- SCCCFNJTCDSLCY-UHFFFAOYSA-N 1-iodo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(I)C=C1 SCCCFNJTCDSLCY-UHFFFAOYSA-N 0.000 description 1
- MTRMOYSZRPLAOL-UHFFFAOYSA-N 1-iodo-4-pentylbenzene Chemical compound CCCCCC1=CC=C(I)C=C1 MTRMOYSZRPLAOL-UHFFFAOYSA-N 0.000 description 1
- BDKOUDYNKRCDEC-UHFFFAOYSA-N 1-iodo-4-phenoxybenzene Chemical compound C1=CC(I)=CC=C1OC1=CC=CC=C1 BDKOUDYNKRCDEC-UHFFFAOYSA-N 0.000 description 1
- ZRWCHMFGMKNWEC-UHFFFAOYSA-N 1-iodo-4-propylbenzene Chemical compound CCCC1=CC=C(I)C=C1 ZRWCHMFGMKNWEC-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YKLDMAPEGQYZRT-UHFFFAOYSA-N 2,4-difluoro-1-iodobenzene Chemical compound FC1=CC=C(I)C(F)=C1 YKLDMAPEGQYZRT-UHFFFAOYSA-N 0.000 description 1
- UKNKDSVYWIYHPP-UHFFFAOYSA-N 2-(4-iodophenyl)-1h-pyrrole Chemical compound C1=CC(I)=CC=C1C1=CC=CN1 UKNKDSVYWIYHPP-UHFFFAOYSA-N 0.000 description 1
- WZTGMIUAQRQHMA-UHFFFAOYSA-N 2-[3,5-diphenylpent-2-en-4-ynyl(methyl)amino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC=CC=C1 WZTGMIUAQRQHMA-UHFFFAOYSA-N 0.000 description 1
- BZEOXRWTYSTRQC-UHFFFAOYSA-N 2-[3-(2-fluorophenyl)pent-2-en-4-ynyl-methylamino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C)C1=CC=CC=C1F BZEOXRWTYSTRQC-UHFFFAOYSA-N 0.000 description 1
- NHFPWOSGUDHORM-UHFFFAOYSA-N 2-[3-(3-fluorophenyl)pent-2-en-4-ynyl-methylamino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C)C1=CC=CC(F)=C1 NHFPWOSGUDHORM-UHFFFAOYSA-N 0.000 description 1
- GURGCHIVWCOQLI-UHFFFAOYSA-N 2-[3-(4-fluorophenyl)pent-2-en-4-ynyl-methylamino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C)C1=CC=C(F)C=C1 GURGCHIVWCOQLI-UHFFFAOYSA-N 0.000 description 1
- QECFPJZNXUZYEI-UHFFFAOYSA-N 2-[3-(4-methoxyphenyl)pent-2-en-4-ynyl-methylamino]acetic acid Chemical compound COC1=CC=C(C(=CCN(C)CC(O)=O)C#C)C=C1 QECFPJZNXUZYEI-UHFFFAOYSA-N 0.000 description 1
- SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 1
- WWSJZGAPAVMETJ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-ethoxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCC WWSJZGAPAVMETJ-UHFFFAOYSA-N 0.000 description 1
- FYELSNVLZVIGTI-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-5-ethylpyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1CC)CC(=O)N1CC2=C(CC1)NN=N2 FYELSNVLZVIGTI-UHFFFAOYSA-N 0.000 description 1
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- VMUNXBUEOYOOAR-UHFFFAOYSA-N 2-[[3-(2-chlorophenyl)-5-(4-ethylphenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C1=CC(CC)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1Cl VMUNXBUEOYOOAR-UHFFFAOYSA-N 0.000 description 1
- GJTIERIFRWCIAK-UHFFFAOYSA-N 2-[[3-(2-chlorophenyl)-5-(4-propan-2-ylphenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C1=CC(C(C)C)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1Cl GJTIERIFRWCIAK-UHFFFAOYSA-N 0.000 description 1
- MKNIKYXIPZPRGS-UHFFFAOYSA-N 2-[[3-(2-chlorophenyl)-5-trimethylsilylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C[Si](C)(C)C)C1=CC=CC=C1Cl MKNIKYXIPZPRGS-UHFFFAOYSA-N 0.000 description 1
- VTPTWAQYSIXMRJ-UHFFFAOYSA-N 2-[[3-(2-fluorophenyl)-5-(4-propan-2-ylphenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C1=CC(C(C)C)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1F VTPTWAQYSIXMRJ-UHFFFAOYSA-N 0.000 description 1
- CHCIFCRVWRVRRT-UHFFFAOYSA-N 2-[[3-(2-fluorophenyl)-5-trimethylsilylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C[Si](C)(C)C)C1=CC=CC=C1F CHCIFCRVWRVRRT-UHFFFAOYSA-N 0.000 description 1
- AUDHXIZUJLUWPV-UHFFFAOYSA-N 2-[[3-(3-fluorophenyl)-5-(4-propan-2-ylphenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C1=CC(C(C)C)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=CC(F)=C1 AUDHXIZUJLUWPV-UHFFFAOYSA-N 0.000 description 1
- LWNJQLWSTZAAMU-UHFFFAOYSA-N 2-[[3-(3-fluorophenyl)-5-trimethylsilylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C[Si](C)(C)C)C1=CC=CC(F)=C1 LWNJQLWSTZAAMU-UHFFFAOYSA-N 0.000 description 1
- FDTCGWZINAWCJF-UHFFFAOYSA-N 2-[[3-(4-chlorophenyl)-5-(4-propan-2-ylphenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C1=CC(C(C)C)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=C(Cl)C=C1 FDTCGWZINAWCJF-UHFFFAOYSA-N 0.000 description 1
- HJSLAVRTHLUTDO-UHFFFAOYSA-N 2-[[3-(4-chlorophenyl)-5-trimethylsilylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C[Si](C)(C)C)C1=CC=C(Cl)C=C1 HJSLAVRTHLUTDO-UHFFFAOYSA-N 0.000 description 1
- FULFEKMGCLHKBC-UHFFFAOYSA-N 2-[[3-(4-fluorophenyl)-5-(4-propan-2-ylphenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C1=CC(C(C)C)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=C(F)C=C1 FULFEKMGCLHKBC-UHFFFAOYSA-N 0.000 description 1
- ADBAPBBKVYNJFS-UHFFFAOYSA-N 2-[[3-(4-fluorophenyl)-5-trimethylsilylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C[Si](C)(C)C)C1=CC=C(F)C=C1 ADBAPBBKVYNJFS-UHFFFAOYSA-N 0.000 description 1
- PCGXQSGWFYETLI-UHFFFAOYSA-N 2-[[3-(4-methoxyphenyl)-5-(4-propan-2-ylphenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C1=CC(OC)=CC=C1C(=CCN(C)CC(O)=O)C#CC1=CC=C(C(C)C)C=C1 PCGXQSGWFYETLI-UHFFFAOYSA-N 0.000 description 1
- XKPIZEFDDPAHCV-UHFFFAOYSA-N 2-[[3-(4-methoxyphenyl)-5-trimethylsilylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound COC1=CC=C(C(=CCN(C)CC(O)=O)C#C[Si](C)(C)C)C=C1 XKPIZEFDDPAHCV-UHFFFAOYSA-N 0.000 description 1
- WOPPFSTYGZWJOH-UHFFFAOYSA-N 2-[[5-(1,3-benzodioxol-5-yl)-3-(3-fluorophenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=C2OCOC2=CC=1C#CC(=CCN(C)CC(O)=O)C1=CC=CC(F)=C1 WOPPFSTYGZWJOH-UHFFFAOYSA-N 0.000 description 1
- FBINHDCDQAUGQG-UHFFFAOYSA-N 2-[[5-(2,4-difluorophenyl)-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(F)C=C1F FBINHDCDQAUGQG-UHFFFAOYSA-N 0.000 description 1
- SNMMXXKDYGWCFX-UHFFFAOYSA-N 2-[[5-(3,4-dimethoxyphenyl)-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C1=C(OC)C(OC)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1 SNMMXXKDYGWCFX-UHFFFAOYSA-N 0.000 description 1
- IQCRTPFYIXADQR-UHFFFAOYSA-N 2-[[5-(3,4-dimethylphenyl)-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(C)C(C)=C1 IQCRTPFYIXADQR-UHFFFAOYSA-N 0.000 description 1
- GONHAQYEOLUJQG-UHFFFAOYSA-N 2-[[5-(4-bromophenyl)-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(Br)C=C1 GONHAQYEOLUJQG-UHFFFAOYSA-N 0.000 description 1
- KFPFPSCLMYYJAY-UHFFFAOYSA-N 2-[[5-(4-fluorophenyl)-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(F)C=C1 KFPFPSCLMYYJAY-UHFFFAOYSA-N 0.000 description 1
- LSJKVTYGISSIJH-UHFFFAOYSA-N 2-[[5-(4-methoxyphenyl)-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C1=CC(OC)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1 LSJKVTYGISSIJH-UHFFFAOYSA-N 0.000 description 1
- BTBMWMIONZNCKH-UHFFFAOYSA-N 2-[[5-(4-tert-butylphenyl)-3-(2-chlorophenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=CC=C(Cl)C=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(C(C)(C)C)C=C1 BTBMWMIONZNCKH-UHFFFAOYSA-N 0.000 description 1
- DHCFJRYMDHOIPV-UHFFFAOYSA-N 2-[[5-(4-tert-butylphenyl)-3-(2-fluorophenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=CC=C(F)C=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(C(C)(C)C)C=C1 DHCFJRYMDHOIPV-UHFFFAOYSA-N 0.000 description 1
- YRNQWIKYKJPFAX-UHFFFAOYSA-N 2-[[5-(4-tert-butylphenyl)-3-(4-chlorophenyl)pent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=C(Cl)C=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC=C(C(C)(C)C)C=C1 YRNQWIKYKJPFAX-UHFFFAOYSA-N 0.000 description 1
- VLDMLEQMEVTNRX-UHFFFAOYSA-N 2-[[5-[3,5-bis(trifluoromethyl)phenyl]-3-phenylpent-2-en-4-ynyl]-methylamino]acetic acid Chemical compound C=1C=CC=CC=1C(=CCN(C)CC(O)=O)C#CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VLDMLEQMEVTNRX-UHFFFAOYSA-N 0.000 description 1
- KKKBEBLTMLHLFV-UHFFFAOYSA-N 2-[methyl(3-thiophen-3-ylpent-2-en-4-ynyl)amino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C)C=1C=CSC=1 KKKBEBLTMLHLFV-UHFFFAOYSA-N 0.000 description 1
- CGGVOPOBEUIJIV-UHFFFAOYSA-N 2-[methyl-(3-thiophen-3-yl-5-trimethylsilylpent-2-en-4-ynyl)amino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C[Si](C)(C)C)C=1C=CSC=1 CGGVOPOBEUIJIV-UHFFFAOYSA-N 0.000 description 1
- QWAIEMMSLHUSJF-UHFFFAOYSA-N 2-[methyl-[3-[4-(trifluoromethyl)phenyl]-5-trimethylsilylpent-2-en-4-ynyl]amino]acetic acid Chemical compound OC(=O)CN(C)CC=C(C#C[Si](C)(C)C)C1=CC=C(C(F)(F)F)C=C1 QWAIEMMSLHUSJF-UHFFFAOYSA-N 0.000 description 1
- CQARXQOLYOGXOC-UHFFFAOYSA-N 2-[methyl-[3-phenyl-5-(3-propan-2-ylphenyl)pent-2-en-4-ynyl]amino]acetic acid Chemical compound CC(C)C1=CC=CC(C#CC(=CCN(C)CC(O)=O)C=2C=CC=CC=2)=C1 CQARXQOLYOGXOC-UHFFFAOYSA-N 0.000 description 1
- VBIMGGZGBMWFBU-UHFFFAOYSA-N 2-[methyl-[5-(4-pentylphenyl)-3-phenylpent-2-en-4-ynyl]amino]acetic acid Chemical compound C1=CC(CCCCC)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=CC=C1 VBIMGGZGBMWFBU-UHFFFAOYSA-N 0.000 description 1
- HSQDNPFDVVYEFY-UHFFFAOYSA-N 2-[methyl-[5-(4-propan-2-ylphenyl)-3-[4-(trifluoromethyl)phenyl]pent-2-en-4-ynyl]amino]acetic acid Chemical compound C1=CC(C(C)C)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CC=C(C(F)(F)F)C=C1 HSQDNPFDVVYEFY-UHFFFAOYSA-N 0.000 description 1
- FZMACHLWDGBOBW-UHFFFAOYSA-N 2-[methyl-[5-(4-propan-2-ylphenyl)-3-thiophen-3-ylpent-2-en-4-ynyl]amino]acetic acid Chemical compound C1=CC(C(C)C)=CC=C1C#CC(=CCN(C)CC(O)=O)C1=CSC=C1 FZMACHLWDGBOBW-UHFFFAOYSA-N 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- FRWYFWZENXDZMU-UHFFFAOYSA-N 2-iodoquinoline Chemical compound C1=CC=CC2=NC(I)=CC=C21 FRWYFWZENXDZMU-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- AVPXJFDBXHAGQM-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-trimethylsilylpent-2-en-4-yn-1-ol Chemical compound C[Si](C)(C)C#CC(=CCO)C1=CC=CC=C1Cl AVPXJFDBXHAGQM-UHFFFAOYSA-N 0.000 description 1
- UADNKEXOHPGJFK-UHFFFAOYSA-N 3-(2-fluorophenyl)-5-trimethylsilylpent-2-en-4-yn-1-ol Chemical compound C[Si](C)(C)C#CC(=CCO)C1=CC=CC=C1F UADNKEXOHPGJFK-UHFFFAOYSA-N 0.000 description 1
- IVDSIQHLCKGRCR-UHFFFAOYSA-N 3-(2-iodophenyl)thiophene Chemical compound IC1=CC=CC=C1C1=CSC=C1 IVDSIQHLCKGRCR-UHFFFAOYSA-N 0.000 description 1
- DPZLVUDJCWTRBJ-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-trimethylsilylpent-2-en-4-yn-1-ol Chemical compound C[Si](C)(C)C#CC(=CCO)C1=CC=CC(F)=C1 DPZLVUDJCWTRBJ-UHFFFAOYSA-N 0.000 description 1
- LZJMJCPSZGCOGB-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-trimethylsilylpent-2-en-4-yn-1-ol Chemical compound C[Si](C)(C)C#CC(=CCO)C1=CC=C(Cl)C=C1 LZJMJCPSZGCOGB-UHFFFAOYSA-N 0.000 description 1
- NEMKGNWLNMNHMA-UHFFFAOYSA-N 3-(4-fluorophenyl)-5-trimethylsilylpent-2-en-4-yn-1-ol Chemical compound C[Si](C)(C)C#CC(=CCO)C1=CC=C(F)C=C1 NEMKGNWLNMNHMA-UHFFFAOYSA-N 0.000 description 1
- KAJILLRHTVHBOT-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-trimethylsilylpent-2-en-4-yn-1-ol Chemical compound COC1=CC=C(C(=CCO)C#C[Si](C)(C)C)C=C1 KAJILLRHTVHBOT-UHFFFAOYSA-N 0.000 description 1
- BKTOQULLAWBTDS-UHFFFAOYSA-N 3-[4-(trifluoromethyl)phenyl]-5-trimethylsilylpent-2-en-4-yn-1-ol Chemical compound C[Si](C)(C)C#CC(=CCO)C1=CC=C(C(F)(F)F)C=C1 BKTOQULLAWBTDS-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical class NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- WGKRMQIQXMJVFZ-UHFFFAOYSA-N 3-iodothiophene Chemical compound IC=1C=CSC=1 WGKRMQIQXMJVFZ-UHFFFAOYSA-N 0.000 description 1
- PUCISUQLWLKKJH-UHFFFAOYSA-N 4-iodo-1,2-dimethoxybenzene Chemical compound COC1=CC=C(I)C=C1OC PUCISUQLWLKKJH-UHFFFAOYSA-N 0.000 description 1
- CSFRCLYFVINMBZ-UHFFFAOYSA-N 4-iodo-1,2-dimethylbenzene Chemical compound CC1=CC=C(I)C=C1C CSFRCLYFVINMBZ-UHFFFAOYSA-N 0.000 description 1
- NMMCBIXYIYQHCP-UHFFFAOYSA-N 5-iodo-1,3-benzodioxole Chemical compound IC1=CC=C2OCOC2=C1 NMMCBIXYIYQHCP-UHFFFAOYSA-N 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010062745 Chloride Channels Proteins 0.000 description 1
- 102000011045 Chloride Channels Human genes 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000790917 Dioxys <bee> Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- DLGBCDPSBFWZIO-UHFFFAOYSA-N FC1=C(C=CC(=C1)F)CCC(=CC)C1=CC=CC=C1 Chemical compound FC1=C(C=CC(=C1)F)CCC(=CC)C1=CC=CC=C1 DLGBCDPSBFWZIO-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 101000684936 Homo sapiens Sodium- and chloride-dependent glycine transporter 1 Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 241000270322 Lepidosauria Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 101000934342 Mus musculus T-cell surface glycoprotein CD5 Proteins 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- 101800000135 N-terminal protein Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 102000005665 Neurotransmitter Transport Proteins Human genes 0.000 description 1
- 108010084810 Neurotransmitter Transport Proteins Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 101800001452 P1 proteinase Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 101000872823 Xenopus laevis Probable histone deacetylase 1-A Proteins 0.000 description 1
- QOKMIHKIMQNRES-UHFFFAOYSA-L [Cl-].[Cl-].[Cr++]Cc1ccccc1 Chemical compound [Cl-].[Cl-].[Cr++]Cc1ccccc1 QOKMIHKIMQNRES-UHFFFAOYSA-L 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000004419 alkynylene group Chemical group 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- WZRXFPOWHQQSRJ-UHFFFAOYSA-N cyclohexyloxyboronic acid Chemical compound OB(O)OC1CCCCC1 WZRXFPOWHQQSRJ-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- YXXQTQYRRHHWFL-UHFFFAOYSA-N diiodophosphanyl(diiodo)phosphane Chemical compound IP(I)P(I)I YXXQTQYRRHHWFL-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- LBOJYSIDWZQNJS-CVEARBPZSA-N dizocilpine Chemical compound C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 LBOJYSIDWZQNJS-CVEARBPZSA-N 0.000 description 1
- 229950004794 dizocilpine Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 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
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 150000002332 glycine derivatives Chemical class 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000009539 inhibitory neurotransmission Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000011707 mineral Chemical class 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960005453 strychnine Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000003956 synaptic plasticity Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 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
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
- 125000004035 thiopropyl group Chemical group [H]SC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
-
- 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
- A61P25/18—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
- A61P25/28—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/40—Y being a hydrogen or a carbon atom
- C07C323/41—Y being a hydrogen or an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Confectionery (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Quinoline Compounds (AREA)
- Furan Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43102299A | 1999-11-01 | 1999-11-01 | |
| US09/431,022 | 1999-11-01 | ||
| PCT/US2000/030074 WO2001032602A1 (en) | 1999-11-01 | 2000-11-01 | Diaryl-enynes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2003513063A true JP2003513063A (ja) | 2003-04-08 |
Family
ID=23710104
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001534756A Pending JP2003513063A (ja) | 1999-11-01 | 2000-11-01 | ジアリール−エニン類 |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP1226108A4 (no) |
| JP (1) | JP2003513063A (no) |
| KR (1) | KR100702717B1 (no) |
| CN (1) | CN100357274C (no) |
| AU (1) | AU780922C (no) |
| BG (1) | BG65275B1 (no) |
| BR (1) | BR0015199A (no) |
| CA (1) | CA2387660A1 (no) |
| CZ (1) | CZ20021545A3 (no) |
| EA (1) | EA004602B1 (no) |
| EE (1) | EE05031B1 (no) |
| HR (1) | HRP20020376A2 (no) |
| HU (1) | HUP0203182A3 (no) |
| IL (1) | IL149347A0 (no) |
| MX (1) | MXPA02004354A (no) |
| NO (1) | NO20021936L (no) |
| NZ (1) | NZ529245A (no) |
| PL (1) | PL355425A1 (no) |
| SK (1) | SK6202002A3 (no) |
| UA (1) | UA73749C2 (no) |
| WO (1) | WO2001032602A1 (no) |
| ZA (1) | ZA200203458B (no) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000501707A (ja) * | 1995-12-07 | 2000-02-15 | ジャビット，ダニエル・シー | グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 |
| JP2002505277A (ja) * | 1998-03-06 | 2002-02-19 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | グリシン輸送阻害剤 |
| JP2002505332A (ja) * | 1998-03-06 | 2002-02-19 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | グリシン輸送阻害剤 |
| JP2002519322A (ja) * | 1998-06-26 | 2002-07-02 | ワーナー−ランバート・カンパニー | ４−ベンジルピペリジンアルキルスルホキシド複素環化合物およびそれらのサブタイプ−選択的ｎｍｄａ受容体アンタゴニストとしての使用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04225953A (ja) * | 1990-05-07 | 1992-08-14 | Shionogi & Co Ltd | スピロ ジベンゾスベラン誘導体 |
| ATE136461T1 (de) * | 1990-08-13 | 1996-04-15 | Searle & Co | Verwendung von heterozyklischen aminoalkoholverbindungen zur herstellung eines medikaments für die behandlung von erkrankungen des zns |
| UA52698C2 (uk) * | 1996-10-04 | 2003-01-15 | Х. Луннбек А/С | Похідні (3-алкоксіізоксазол-4-іл)заміщеної 2-амінокарбонової кислоти та їх сірковмісні аналоги, фармацевтична композиція на їх основі |
| US6103743A (en) * | 1999-08-06 | 2000-08-15 | Allelix Neuroscience, Inc. | Unsaturated amino acid derivatives |
-
2000
- 2000-01-11 UA UA2002043703A patent/UA73749C2/uk unknown
- 2000-11-01 JP JP2001534756A patent/JP2003513063A/ja active Pending
- 2000-11-01 NZ NZ529245A patent/NZ529245A/en active Application Filing
- 2000-11-01 KR KR1020027005593A patent/KR100702717B1/ko not_active IP Right Cessation
- 2000-11-01 CN CNB008151970A patent/CN100357274C/zh not_active Expired - Fee Related
- 2000-11-01 EA EA200200521A patent/EA004602B1/ru not_active IP Right Cessation
- 2000-11-01 PL PL00355425A patent/PL355425A1/xx not_active IP Right Cessation
- 2000-11-01 WO PCT/US2000/030074 patent/WO2001032602A1/en active IP Right Grant
- 2000-11-01 CZ CZ20021545A patent/CZ20021545A3/cs unknown
- 2000-11-01 MX MXPA02004354A patent/MXPA02004354A/es active IP Right Grant
- 2000-11-01 HU HU0203182A patent/HUP0203182A3/hu unknown
- 2000-11-01 BR BR0015199-8A patent/BR0015199A/pt not_active Application Discontinuation
- 2000-11-01 CA CA002387660A patent/CA2387660A1/en not_active Abandoned
- 2000-11-01 EP EP00976775A patent/EP1226108A4/en not_active Withdrawn
- 2000-11-01 IL IL14934700A patent/IL149347A0/xx unknown
- 2000-11-01 AU AU14507/01A patent/AU780922C/en not_active Ceased
- 2000-11-01 EE EEP200200229A patent/EE05031B1/xx not_active IP Right Cessation
- 2000-11-01 SK SK620-2002A patent/SK6202002A3/sk unknown
-
2002
- 2002-04-24 NO NO20021936A patent/NO20021936L/no not_active Application Discontinuation
- 2002-04-29 HR HR20020376A patent/HRP20020376A2/hr not_active Application Discontinuation
- 2002-04-30 BG BG106671A patent/BG65275B1/bg unknown
- 2002-04-30 ZA ZA200203458A patent/ZA200203458B/xx unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000501707A (ja) * | 1995-12-07 | 2000-02-15 | ジャビット，ダニエル・シー | グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 |
| JP2002505277A (ja) * | 1998-03-06 | 2002-02-19 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | グリシン輸送阻害剤 |
| JP2002505332A (ja) * | 1998-03-06 | 2002-02-19 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | グリシン輸送阻害剤 |
| JP2002519322A (ja) * | 1998-06-26 | 2002-07-02 | ワーナー−ランバート・カンパニー | ４−ベンジルピペリジンアルキルスルホキシド複素環化合物およびそれらのサブタイプ−選択的ｎｍｄａ受容体アンタゴニストとしての使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| HRP20020376A2 (en) | 2004-02-29 |
| EA200200521A1 (ru) | 2002-10-31 |
| EP1226108A1 (en) | 2002-07-31 |
| NO20021936D0 (no) | 2002-04-24 |
| HUP0203182A2 (hu) | 2003-01-28 |
| CZ20021545A3 (cs) | 2002-10-16 |
| EA004602B1 (ru) | 2004-06-24 |
| BR0015199A (pt) | 2002-07-09 |
| AU780922B2 (en) | 2005-04-28 |
| CN100357274C (zh) | 2007-12-26 |
| MXPA02004354A (es) | 2003-10-06 |
| PL355425A1 (en) | 2004-04-19 |
| EE200200229A (et) | 2003-06-16 |
| AU780922C (en) | 2005-10-20 |
| CN1387507A (zh) | 2002-12-25 |
| EP1226108A4 (en) | 2004-06-16 |
| KR20020060961A (ko) | 2002-07-19 |
| CA2387660A1 (en) | 2001-05-10 |
| NZ529245A (en) | 2005-09-30 |
| BG106671A (en) | 2003-02-28 |
| UA73749C2 (en) | 2005-09-15 |
| ZA200203458B (en) | 2003-10-29 |
| EE05031B1 (et) | 2008-06-16 |
| WO2001032602A1 (en) | 2001-05-10 |
| HUP0203182A3 (en) | 2003-04-28 |
| AU1450701A (en) | 2001-05-14 |
| NO20021936L (no) | 2002-07-01 |
| SK6202002A3 (en) | 2002-10-08 |
| KR100702717B1 (ko) | 2007-04-03 |
| IL149347A0 (en) | 2002-11-10 |
| BG65275B1 (bg) | 2007-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6525085B2 (en) | Diaryl-enynes | |
| EP1296950A2 (en) | Aminopiperidines for use as glyt-1 inhibitors | |
| JP2003510319A (ja) | 医薬として活性なスルホンアミド誘導体 | |
| US5739164A (en) | Pharmaceutical compounds for the treatment of CNS diseases | |
| US5863947A (en) | Phenylglycine derivatives useful for treating disorders of the central nervous system | |
| JP2002521443A (ja) | スルホンアミド誘導体 | |
| US6417183B1 (en) | 1,4-diazacycloheptane derivatives | |
| US5847125A (en) | Amino acid derivatives with anticholecystokinin activity | |
| JP2003513063A (ja) | ジアリール−エニン類 | |
| EP1368336B1 (en) | Thiophene substituted amine derivatives as glyt-1 inhibitors | |
| Shinozaki et al. | Synthesis and thromboxane A2 antagonistic activity of indane derivatives | |
| AU2002235682A1 (en) | Thiophene substituted amine derivatives as GLYT-1 inhibitors | |
| JP3094450B2 (ja) | 神経保護特性を有するピペリジン誘導体 | |
| JPH08208595A (ja) | スルホンアミド化合物、その製造法および剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20071011 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20080812 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20080812 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20080812 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20101019 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20110426 |