CN101862330A - 二环酰胺在制备用于治疗呼吸抑制的药剂中的应用 - Google Patents
二环酰胺在制备用于治疗呼吸抑制的药剂中的应用 Download PDFInfo
- Publication number
- CN101862330A CN101862330A CN201010207140A CN201010207140A CN101862330A CN 101862330 A CN101862330 A CN 101862330A CN 201010207140 A CN201010207140 A CN 201010207140A CN 201010207140 A CN201010207140 A CN 201010207140A CN 101862330 A CN101862330 A CN 101862330A
- Authority
- CN
- China
- Prior art keywords
- unsubstituted
- substituted
- azabicyclo
- benzoxadiazol
- compound
- 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 Bicyclic amide Chemical class 0.000 title claims abstract description 42
- 239000003814 drug Substances 0.000 title claims abstract description 19
- 230000029058 respiratory gaseous exchange Effects 0.000 title abstract description 11
- 230000005764 inhibitory process Effects 0.000 title abstract description 7
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 112
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 19
- 208000004756 Respiratory Insufficiency Diseases 0.000 claims description 18
- 206010038678 Respiratory depression Diseases 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000012453 solvate Substances 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 9
- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 239000011593 sulfur Chemical group 0.000 claims description 7
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 6
- 125000004963 sulfonylalkyl group Chemical group 0.000 claims description 6
- 125000005026 carboxyaryl group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- JSXFREXUMJSKSB-UHFFFAOYSA-N 1-(2,1,3-benzoxadiazol-5-yl)octan-1-one Chemical compound C(CCCCCC)C(=O)C1=CC=2C(=NON=2)C=C1 JSXFREXUMJSKSB-UHFFFAOYSA-N 0.000 claims description 4
- XLCOYPYTNJSQFB-HTLJXXAVSA-N [(4r)-5-azabicyclo[2.2.1]hept-2-en-5-yl]-(2,1,3-benzoxadiazol-5-yl)methanone Chemical compound C1=CC2=NON=C2C=C1C(=O)N1[C@@H](C=C2)CC2C1 XLCOYPYTNJSQFB-HTLJXXAVSA-N 0.000 claims description 4
- 229940127240 opiate Drugs 0.000 claims description 4
- 239000000014 opioid analgesic Substances 0.000 claims description 4
- ICPFDEGHIWLQHT-UHFFFAOYSA-N 2,1,3-benzoxadiazol-5-yl(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methanone Chemical compound C1=CC2=NON=C2C=C1C(=O)N1C(CO2)CC2C1 ICPFDEGHIWLQHT-UHFFFAOYSA-N 0.000 claims description 3
- VLJBTMQPNFWPHP-UHFFFAOYSA-N 2,1,3-benzoxadiazol-5-yl-(2,3-dichloro-5-azabicyclo[2.2.1]heptan-5-yl)methanone Chemical compound C1=CC2=NON=C2C=C1C(=O)N(C1)C2CC1C(Cl)C2Cl VLJBTMQPNFWPHP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- QMYRVTKSHZXAMU-UHFFFAOYSA-N 2,1,3-benzoxadiazol-5-yl-(3,3-difluoro-8-azabicyclo[3.2.1]octan-8-yl)methanone Chemical compound C1=CC2=NON=C2C=C1C(=O)N1C2CCC1CC(F)(F)C2 QMYRVTKSHZXAMU-UHFFFAOYSA-N 0.000 claims description 2
- OWSSSZMWGUEXGU-UHFFFAOYSA-N 2,1,3-benzoxadiazol-5-yl-(3-fluoro-8-azabicyclo[3.2.1]oct-3-en-8-yl)methanone Chemical compound C1=CC2=NON=C2C=C1C(=O)N1C2CCC1C=C(F)C2 OWSSSZMWGUEXGU-UHFFFAOYSA-N 0.000 claims description 2
- GQXWPOIQMPNUNL-UHFFFAOYSA-N 3-azabicyclo[2.2.2]octan-3-yl(2,1,3-benzoxadiazol-5-yl)methanone Chemical compound C1=CC2=NON=C2C=C1C(=O)N1C(CC2)CCC2C1 GQXWPOIQMPNUNL-UHFFFAOYSA-N 0.000 claims description 2
- XLCOYPYTNJSQFB-UHFFFAOYSA-N 5-azabicyclo[2.2.1]hept-2-en-5-yl(2,1,3-benzoxadiazol-5-yl)methanone Chemical compound C1=CC2=NON=C2C=C1C(=O)N1C(C=C2)CC2C1 XLCOYPYTNJSQFB-UHFFFAOYSA-N 0.000 claims description 2
- JMXIVHHAHKCDSZ-UHFFFAOYSA-N 8-azabicyclo[3.2.1]octan-8-yl(2,1,3-benzoxadiazol-5-yl)methanone Chemical compound C1=CC2=NON=C2C=C1C(=O)N1C2CCC1CCC2 JMXIVHHAHKCDSZ-UHFFFAOYSA-N 0.000 claims description 2
- 229940125717 barbiturate Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000003444 anaesthetic effect Effects 0.000 claims 2
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims 1
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 claims 1
- 229960004134 propofol Drugs 0.000 claims 1
- 201000002859 sleep apnea Diseases 0.000 abstract description 9
- 208000001797 obstructive sleep apnea Diseases 0.000 abstract description 3
- 230000002265 prevention Effects 0.000 abstract description 2
- 208000011580 syndromic disease Diseases 0.000 abstract 5
- 206010008190 Cerebrovascular accident Diseases 0.000 abstract 1
- 206010008501 Cheyne-Stokes respiration Diseases 0.000 abstract 1
- 206010010356 Congenital anomaly Diseases 0.000 abstract 1
- 208000008589 Obesity Diseases 0.000 abstract 1
- 208000006011 Stroke Diseases 0.000 abstract 1
- 208000034972 Sudden Infant Death Diseases 0.000 abstract 1
- 206010042440 Sudden infant death syndrome Diseases 0.000 abstract 1
- 208000030886 Traumatic Brain injury Diseases 0.000 abstract 1
- 235000020824 obesity Nutrition 0.000 abstract 1
- 208000020431 spinal cord injury Diseases 0.000 abstract 1
- 230000009529 traumatic brain injury Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- 238000000034 method Methods 0.000 description 49
- 239000000203 mixture Substances 0.000 description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- 102000003678 AMPA Receptors Human genes 0.000 description 33
- 108090000078 AMPA Receptors Proteins 0.000 description 33
- 239000000243 solution Substances 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 201000000980 schizophrenia Diseases 0.000 description 23
- 230000000694 effects Effects 0.000 description 22
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 21
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 239000007787 solid Substances 0.000 description 19
- 238000012360 testing method Methods 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 210000004556 brain Anatomy 0.000 description 18
- 230000006870 function Effects 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 17
- 230000006399 behavior Effects 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 238000002844 melting Methods 0.000 description 16
- 230000008018 melting Effects 0.000 description 16
- 229940079593 drug Drugs 0.000 description 14
- 230000002964 excitative effect Effects 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 210000000225 synapse Anatomy 0.000 description 13
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 229960000632 dexamfetamine Drugs 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- ZXNRTKGTQJPIJK-UHFFFAOYSA-N aniracetam Chemical compound C1=CC(OC)=CC=C1C(=O)N1C(=O)CCC1 ZXNRTKGTQJPIJK-UHFFFAOYSA-N 0.000 description 11
- 125000004093 cyano group Chemical group *C#N 0.000 description 11
- 208000035475 disorder Diseases 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- 229960000793 aniracetam Drugs 0.000 description 10
- 230000027928 long-term synaptic potentiation Effects 0.000 description 10
- 230000001404 mediated effect Effects 0.000 description 10
- 230000001242 postsynaptic effect Effects 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 230000009782 synaptic response Effects 0.000 description 10
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 229930195712 glutamate Natural products 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- ANDGGVOPIJEHOF-UHFFFAOYSA-N CX-516 Chemical class C=1C=C2N=CC=NC2=CC=1C(=O)N1CCCCC1 ANDGGVOPIJEHOF-UHFFFAOYSA-N 0.000 description 8
- 230000002708 enhancing effect Effects 0.000 description 8
- 230000000848 glutamatergic effect Effects 0.000 description 8
- 230000001771 impaired effect Effects 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- UUDAMDVQRQNNHZ-UHFFFAOYSA-N (S)-AMPA Chemical compound CC=1ONC(=O)C=1CC(N)C(O)=O UUDAMDVQRQNNHZ-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 208000026139 Memory disease Diseases 0.000 description 7
- 230000000763 evoking effect Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 230000000241 respiratory effect Effects 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 230000000946 synaptic effect Effects 0.000 description 7
- 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 6
- 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
- 208000019022 Mood disease Diseases 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 230000032683 aging Effects 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 6
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- QUTYKIXIUDQOLK-PRJMDXOYSA-N 5-O-(1-carboxyvinyl)-3-phosphoshikimic acid Chemical compound O[C@H]1[C@H](OC(=C)C(O)=O)CC(C(O)=O)=C[C@H]1OP(O)(O)=O QUTYKIXIUDQOLK-PRJMDXOYSA-N 0.000 description 5
- 108010025020 Nerve Growth Factor Proteins 0.000 description 5
- 102000007072 Nerve Growth Factors Human genes 0.000 description 5
- 125000003368 amide group Chemical group 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 230000003935 attention Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000019771 cognition Effects 0.000 description 5
- 230000003920 cognitive function Effects 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 210000001320 hippocampus Anatomy 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000033001 locomotion Effects 0.000 description 5
- 230000004770 neurodegeneration Effects 0.000 description 5
- 208000015122 neurodegenerative disease Diseases 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 239000003900 neurotrophic factor Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- KEOXCGCFKGIMNP-UHFFFAOYSA-N 1,2,3-benzoxadiazole-5-carbonyl chloride Chemical compound ClC(=O)C1=CC=C2ON=NC2=C1 KEOXCGCFKGIMNP-UHFFFAOYSA-N 0.000 description 4
- WZUFYJFTOVGJJT-UHFFFAOYSA-N 2,1,3-benzoxadiazole-5-carboxylic acid Chemical class C1=C(C(=O)O)C=CC2=NON=C21 WZUFYJFTOVGJJT-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical class CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 4
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000036982 action potential Effects 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000001054 cortical effect Effects 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000036749 excitatory postsynaptic potential Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000002858 neurotransmitter agent Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 208000020016 psychiatric disease Diseases 0.000 description 4
- 208000019116 sleep disease Diseases 0.000 description 4
- 208000020685 sleep-wake disease Diseases 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- ZZNAYFWAXZJITH-UHFFFAOYSA-N 4-amino-3-nitrobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1[N+]([O-])=O ZZNAYFWAXZJITH-UHFFFAOYSA-N 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 208000000044 Amnesia Diseases 0.000 description 3
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 3
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 3
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- 102000018899 Glutamate Receptors Human genes 0.000 description 3
- 108010027915 Glutamate Receptors Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 208000020358 Learning disease Diseases 0.000 description 3
- 208000016285 Movement disease Diseases 0.000 description 3
- IDBPHNDTYPBSNI-UHFFFAOYSA-N N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide Chemical compound C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 IDBPHNDTYPBSNI-UHFFFAOYSA-N 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- 208000028017 Psychotic disease Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 208000024791 Schizotypal Personality disease Diseases 0.000 description 3
- 201000001880 Sexual dysfunction Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 229960001391 alfentanil Drugs 0.000 description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 125000004104 aryloxy group Chemical group 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 229960002428 fentanyl Drugs 0.000 description 3
- IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 201000003723 learning disability Diseases 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 230000006984 memory degeneration Effects 0.000 description 3
- 208000023060 memory loss Diseases 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000001953 sensory effect Effects 0.000 description 3
- 231100000872 sexual dysfunction Toxicity 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 208000023516 stroke disease Diseases 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 150000003568 thioethers Chemical class 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 230000002747 voluntary effect Effects 0.000 description 3
- FNQJDLTXOVEEFB-UHFFFAOYSA-N 1,2,3-benzothiadiazole Chemical compound C1=CC=C2SN=NC2=C1 FNQJDLTXOVEEFB-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- NGPYWZBQSYAKKK-UHFFFAOYSA-N 2,1,3-benzoxadiazole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=NON=C12 NGPYWZBQSYAKKK-UHFFFAOYSA-N 0.000 description 2
- ODCMBRSQNVPDOK-UHFFFAOYSA-N 2,1,3-benzoxadiazole-5-carbonyl chloride Chemical compound C1=C(C(=O)Cl)C=CC2=NON=C21 ODCMBRSQNVPDOK-UHFFFAOYSA-N 0.000 description 2
- OZJPLYNZGCXSJM-UHFFFAOYSA-N 5-valerolactone Chemical compound O=C1CCCCO1 OZJPLYNZGCXSJM-UHFFFAOYSA-N 0.000 description 2
- 239000005964 Acibenzolar-S-methyl Substances 0.000 description 2
- 208000017194 Affective disease Diseases 0.000 description 2
- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 description 2
- 208000009810 Catatonic Schizophrenia Diseases 0.000 description 2
- 208000003417 Central Sleep Apnea 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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000006289 Rett Syndrome Diseases 0.000 description 2
- 208000036754 Schizophrenia, catatonic type Diseases 0.000 description 2
- 208000036753 Schizophrenia, disorganised type Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 2
- 150000003936 benzamides Chemical class 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000007844 bleaching agent Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000005518 carboxamido group Chemical group 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940114081 cinnamate Drugs 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 230000007831 electrophysiology Effects 0.000 description 2
- 238000002001 electrophysiology Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000003528 hypoglutamatergic effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000036734 inhibitory postsynaptic potential Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 2
- 229950006874 kainic acid Drugs 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
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 210000002161 motor neuron Anatomy 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 239000002664 nootropic agent Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- NMRPBPVERJPACX-UHFFFAOYSA-N octan-3-ol Chemical compound CCCCCC(O)CC NMRPBPVERJPACX-UHFFFAOYSA-N 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 210000000578 peripheral nerve Anatomy 0.000 description 2
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 2
- 229960002695 phenobarbital Drugs 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- UTEQROVYZDJSOO-UHFFFAOYSA-N quinoxaline-6-carbonyl chloride Chemical compound N1=CC=NC2=CC(C(=O)Cl)=CC=C21 UTEQROVYZDJSOO-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 2
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 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
- QQXLDOJGLXJCSE-KNVOCYPGSA-N tropinone Chemical compound C1C(=O)C[C@H]2CC[C@@H]1N2C QQXLDOJGLXJCSE-KNVOCYPGSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- DDUFYKNOXPZZIW-AKGZTFGVSA-N (4r)-3-azabicyclo[2.2.1]hept-5-en-2-one Chemical compound C1C2C=C[C@]1([H])NC2=O DDUFYKNOXPZZIW-AKGZTFGVSA-N 0.000 description 1
- DDUFYKNOXPZZIW-BRJRFNKRSA-N (4s)-3-azabicyclo[2.2.1]hept-5-en-2-one Chemical compound C1C2C=C[C@@]1([H])NC2=O DDUFYKNOXPZZIW-BRJRFNKRSA-N 0.000 description 1
- IHLRGGLJGGTPCY-HWKANZROSA-N (e)-hept-5-en-3-one Chemical compound CCC(=O)C\C=C\C IHLRGGLJGGTPCY-HWKANZROSA-N 0.000 description 1
- SLLFVLKNXABYGI-UHFFFAOYSA-N 1,2,3-benzoxadiazole Chemical class C1=CC=C2ON=NC2=C1 SLLFVLKNXABYGI-UHFFFAOYSA-N 0.000 description 1
- UTUCCQKGZLURPM-UHFFFAOYSA-N 1-(2,1,3-benzoxadiazol-5-yl)-2-methylhept-5-en-1-one Chemical class CC(CCC=CC)C(=O)C1=CC=2C(=NON=2)C=C1 UTUCCQKGZLURPM-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- 125000005939 1-azabicyclo[2.2.1]heptyl group Chemical group 0.000 description 1
- AXRCJZJVVZUOHN-UHFFFAOYSA-N 1-oxido-2,1,3-benzoxadiazol-1-ium-5-carboxylic acid Chemical compound C1=C(C(=O)O)C=CC2=[N+]([O-])ON=C21 AXRCJZJVVZUOHN-UHFFFAOYSA-N 0.000 description 1
- AWBOSXFRPFZLOP-UHFFFAOYSA-N 2,1,3-benzoxadiazole Chemical class C1=CC=CC2=NON=C21 AWBOSXFRPFZLOP-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- DIQOUXNTSMWQSA-UHFFFAOYSA-N 2-oxa-5-azabicyclo[2.2.1]heptane Chemical compound C1OC2CNC1C2 DIQOUXNTSMWQSA-UHFFFAOYSA-N 0.000 description 1
- CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 description 1
- HEMGYNNCNNODNX-UHFFFAOYSA-N 3,4-diaminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1N HEMGYNNCNNODNX-UHFFFAOYSA-N 0.000 description 1
- DDUFYKNOXPZZIW-UHFFFAOYSA-N 3-azabicyclo[2.2.1]hept-5-en-2-one Chemical compound C1C2C(=O)NC1C=C2 DDUFYKNOXPZZIW-UHFFFAOYSA-N 0.000 description 1
- YNNURKHFFDDBMP-UHFFFAOYSA-N 3-azabicyclo[2.2.1]heptan-3-yl(2,1,3-benzoxadiazol-5-yl)methanone Chemical class C1=CC2=NON=C2C=C1C(=O)N1C(C2)CCC2C1 YNNURKHFFDDBMP-UHFFFAOYSA-N 0.000 description 1
- XQJMXPAEFMWDOZ-UHFFFAOYSA-N 3exo-benzoyloxy-tropane Natural products CN1C(C2)CCC1CC2OC(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-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
- DRNGLYHKYPNTEA-UHFFFAOYSA-N 4-azaniumylcyclohexane-1-carboxylate Chemical compound NC1CCC(C(O)=O)CC1 DRNGLYHKYPNTEA-UHFFFAOYSA-N 0.000 description 1
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 101150035467 BDNF gene Proteins 0.000 description 1
- 208000021500 Breathing-related sleep disease Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 208000001495 Disorganized Schizophrenia Diseases 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000001914 Fragile X syndrome Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 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 1
- 102000006541 Ionotropic Glutamate Receptors Human genes 0.000 description 1
- 108010008812 Ionotropic Glutamate Receptors Proteins 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- HOKKHZGPKSLGJE-UHFFFAOYSA-N N-methyl-D-aspartic acid Natural products CNC(C(O)=O)CC(O)=O HOKKHZGPKSLGJE-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 241001274216 Naso Species 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- 208000020114 Schizophrenia and other psychotic disease Diseases 0.000 description 1
- 208000036755 Schizophrenia simple Diseases 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 241000269370 Xenopus <genus> Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 150000001449 anionic compounds Chemical class 0.000 description 1
- 208000008784 apnea Diseases 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-M barbiturate Chemical compound O=C1CC(=O)[N-]C(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-M 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 1
- 150000005130 benzoxazines Chemical class 0.000 description 1
- 150000001602 bicycloalkyls Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- ARQRPTNYUOLOGH-RWQOXAPSSA-N chloroform trichloro(deuterio)methane Chemical class [2H]C(Cl)(Cl)Cl.C(Cl)(Cl)Cl ARQRPTNYUOLOGH-RWQOXAPSSA-N 0.000 description 1
- 239000002475 cognitive enhancer Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
- 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
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 210000001947 dentate gyrus Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 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
- 235000001727 glucose Nutrition 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000010365 information processing Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229910001412 inorganic anion Inorganic materials 0.000 description 1
- 230000003434 inspiratory effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000004370 n-butenyl group Chemical group [H]\C([H])=C(/[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000000478 neocortex Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 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
- 210000000287 oocyte Anatomy 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000002891 organic anions Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 210000001769 parahippocampal gyrus Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000001871 perforant pathway Anatomy 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000002974 pharmacogenomic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- MUKCXROGIQHFNN-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1.O=C1CNCCN1 MUKCXROGIQHFNN-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000005495 pyridazyl group Chemical group 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 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
- 230000011514 reflex Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000010332 selective attention Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical compound C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 description 1
- 229930004006 tropane Natural products 0.000 description 1
- CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical compound C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 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
- 230000002618 waking effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/06—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing isoquinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96436207P | 2007-08-10 | 2007-08-10 | |
| US60/964,362 | 2007-08-10 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008801025333A Division CN101896183B (zh) | 2007-08-10 | 2008-08-08 | 用于增强谷氨酸能突触反应的二环酰胺 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101862330A true CN101862330A (zh) | 2010-10-20 |
Family
ID=40351347
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010207140A Pending CN101862330A (zh) | 2007-08-10 | 2008-08-08 | 二环酰胺在制备用于治疗呼吸抑制的药剂中的应用 |
| CN2008801025333A Expired - Fee Related CN101896183B (zh) | 2007-08-10 | 2008-08-08 | 用于增强谷氨酸能突触反应的二环酰胺 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008801025333A Expired - Fee Related CN101896183B (zh) | 2007-08-10 | 2008-08-08 | 用于增强谷氨酸能突触反应的二环酰胺 |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US8263591B2 (enExample) |
| EP (1) | EP2187888B1 (enExample) |
| JP (2) | JP5576277B2 (enExample) |
| KR (2) | KR20100045507A (enExample) |
| CN (2) | CN101862330A (enExample) |
| AU (2) | AU2008287445A1 (enExample) |
| BR (2) | BRPI0814149A2 (enExample) |
| CA (2) | CA2702292A1 (enExample) |
| ES (1) | ES2560095T3 (enExample) |
| MX (2) | MX2010001630A (enExample) |
| NZ (1) | NZ583823A (enExample) |
| RU (2) | RU2010106975A (enExample) |
| SG (1) | SG163526A1 (enExample) |
| WO (1) | WO2009023126A2 (enExample) |
| ZA (1) | ZA201001691B (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008085506A1 (en) | 2007-01-03 | 2008-07-17 | Cortex Pharmaceuticals, Inc. | 3-substituted-[1,2,3]-benzotriazinone compound for enhancing glutamatergic synaptic responses |
| CA2685858C (en) | 2007-05-17 | 2015-11-24 | Cortex Pharmaceuticals, Inc. | Di-substituted amides for enhancing glutamatergic synaptic responses |
| AU2008287445A1 (en) | 2007-08-10 | 2009-02-19 | Cortex Pharmaceuticals, Inc. | Bicyclic amides for enhancing glutamatergic synaptic responses |
| US8168632B2 (en) | 2007-08-10 | 2012-05-01 | Cortex Pharmaceuticals, Inc. | Bicyclic amide derivatives for the treatment of respiratory disorders |
| AU2010208646A1 (en) * | 2009-02-02 | 2011-09-01 | Cortex Pharmaceuticals, Inc. | Bicyclic amide derivatives for enhancing glutamatergic synaptic responses |
| EP2811997B1 (en) * | 2012-02-07 | 2018-04-11 | Eolas Therapeutics Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| AR101558A1 (es) | 2014-08-13 | 2016-12-28 | Eolas Therapeutics Inc | Difluoropirrolidinas como moduladores del receptor de orexina |
| US9739787B2 (en) | 2015-09-01 | 2017-08-22 | Abdulmohsen Ebrahim Alterki | Method for diagnosing sleep apnea by measuring adipsin and betatrophin levels |
| HUE059280T2 (hu) | 2016-02-12 | 2022-11-28 | Astrazeneca Ab | Halogén-szubsztituált piperidinek mint orexin receptor modulátorok |
| EP3436021A4 (en) * | 2016-03-29 | 2019-11-06 | RespireRx Pharmaceuticals Inc. | COMPOSITIONS AND METHODS FOR TREATING ATTENTION DEFICIT DISORDER |
| AU2020286381C1 (en) | 2019-06-04 | 2025-07-10 | Hager Biosciences, Llc | Imidazolo derivatives, compositions and methods as orexin antagonists |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3723436A (en) * | 1971-02-25 | 1973-03-27 | Sun Oil Co | Process for aromatic lactams |
| FR2597103B1 (fr) * | 1986-04-15 | 1988-12-16 | Provesan Sa | Procede de preparation de derives d'oxazinobenzothiazine 6,6-dioxyde |
| PT651746E (pt) | 1992-07-24 | 2002-09-30 | Univ California | Drogas que intensificam as respostas sinapticas mediadas por receptores de ampa |
| US20020099050A1 (en) | 1993-07-23 | 2002-07-25 | Lynch Gary S. | Drugs that enhance synaptic responses mediated by AMPA receptors |
| US5650409A (en) * | 1995-06-02 | 1997-07-22 | Cortex Pharmaceuticals, Inc. | Benzoyl piperidines/pyrrolidines for enhancing synaptic response |
| US5736543A (en) * | 1996-04-03 | 1998-04-07 | The Regents Of The University Of California | Benzoxazines for enhancing synaptic response |
| US6030968A (en) * | 1996-09-17 | 2000-02-29 | The Regents Of The University Of California | Positive AMPA receptor modulation to enhance brain neurotrophic factor expression |
| US6110935A (en) | 1997-02-13 | 2000-08-29 | The Regents Of The University Of California | Benzofurazan compounds for enhancing glutamatergic synaptic responses |
| WO1999021422A1 (en) * | 1997-10-27 | 1999-05-06 | Cortex Pharmaceuticals, Inc. | Treatment of schizophrenia with ampakines and neuroleptics |
| US5985871A (en) | 1997-12-24 | 1999-11-16 | Cortex Pharmaceuticals, Inc. | Benzoxazine compounds for enhancing synaptic response |
| ZA991301B (en) | 1998-02-18 | 1999-09-13 | Neurosearch As | Glutamate receptor modulators. |
| US6713474B2 (en) * | 1998-09-18 | 2004-03-30 | Abbott Gmbh & Co. Kg | Pyrrolopyrimidines as therapeutic agents |
| US6303542B1 (en) * | 2000-08-18 | 2001-10-16 | Rohm And Haas Company | Herbicidal 3-substituted-phenyl-1,2,3-benzotriazin-4-ones |
| PA8535601A1 (es) * | 2000-12-21 | 2002-11-28 | Pfizer | Derivados benzimidazol y piridilimidazol como ligandos para gabaa |
| AUPS255202A0 (en) | 2002-05-27 | 2002-06-13 | Monash University | Agents and methods for the treatment of disorders associated with motor neuron degeneration |
| JP2006522750A (ja) | 2003-04-11 | 2006-10-05 | ノボ ノルディスク アクティーゼルスカブ | 代謝性症候群ならびに関連の疾患および障害を治療するために、11β−ヒドロキシステロイドデヒドロゲナーゼ1型阻害剤および抗高血圧剤を使用する併用療法 |
| US20050085446A1 (en) | 2003-04-14 | 2005-04-21 | Babu M.K. M. | Fluoroquinolone formulations and methods of making and using the same |
| GB0317482D0 (en) * | 2003-07-25 | 2003-08-27 | Pfizer Ltd | Nicotinamide derivatives useful as pde4 inhibitors |
| CN1897950A (zh) * | 2003-10-14 | 2007-01-17 | 惠氏公司 | 稠合芳基和杂芳基衍生物及其使用方法 |
| JP2010501597A (ja) | 2006-08-31 | 2010-01-21 | ザ ガバナーズ オブ ザ ユニバーシティー オブ アルバータ | 正のアロステリックampa受容体モジュレーターを用いて呼吸抑制を阻害する方法 |
| WO2008085506A1 (en) | 2007-01-03 | 2008-07-17 | Cortex Pharmaceuticals, Inc. | 3-substituted-[1,2,3]-benzotriazinone compound for enhancing glutamatergic synaptic responses |
| US20100041647A1 (en) * | 2007-01-03 | 2010-02-18 | Cortex Pharmaceuticals, Inc. | 3-Substituted-[1,2,3]-Benzotriazinone compounds for enhancing glutamatergic synaptic responses |
| CA2685858C (en) * | 2007-05-17 | 2015-11-24 | Cortex Pharmaceuticals, Inc. | Di-substituted amides for enhancing glutamatergic synaptic responses |
| AU2008287445A1 (en) | 2007-08-10 | 2009-02-19 | Cortex Pharmaceuticals, Inc. | Bicyclic amides for enhancing glutamatergic synaptic responses |
| JP2010540436A (ja) | 2007-09-20 | 2010-12-24 | コーテックス ファーマシューティカルズ, インコーポレイテッド | グルタミン酸作動性シナプス反応を増大するための3−置換1,2,3−トリアジン−4−オン及び3−置換1,3−ピリミジン−オン |
-
2008
- 2008-08-08 AU AU2008287445A patent/AU2008287445A1/en not_active Abandoned
- 2008-08-08 CN CN201010207140A patent/CN101862330A/zh active Pending
- 2008-08-08 BR BRPI0814149-5A patent/BRPI0814149A2/pt not_active IP Right Cessation
- 2008-08-08 WO PCT/US2008/009508 patent/WO2009023126A2/en not_active Ceased
- 2008-08-08 NZ NZ583823A patent/NZ583823A/en not_active IP Right Cessation
- 2008-08-08 KR KR1020107005366A patent/KR20100045507A/ko not_active Withdrawn
- 2008-08-08 MX MX2010001630A patent/MX2010001630A/es unknown
- 2008-08-08 CA CA2702292A patent/CA2702292A1/en not_active Abandoned
- 2008-08-08 RU RU2010106975/04A patent/RU2010106975A/ru not_active Application Discontinuation
- 2008-08-08 JP JP2010520992A patent/JP5576277B2/ja not_active Expired - Fee Related
- 2008-08-08 MX MX2010001631A patent/MX2010001631A/es active IP Right Grant
- 2008-08-08 CA CA2695742A patent/CA2695742C/en not_active Expired - Fee Related
- 2008-08-08 BR BRPI0823262-8A2A patent/BRPI0823262A2/pt not_active Application Discontinuation
- 2008-08-08 EP EP08795126.5A patent/EP2187888B1/en active Active
- 2008-08-08 US US12/733,073 patent/US8263591B2/en not_active Expired - Fee Related
- 2008-08-08 ES ES08795126.5T patent/ES2560095T3/es active Active
- 2008-08-08 CN CN2008801025333A patent/CN101896183B/zh not_active Expired - Fee Related
- 2008-08-08 SG SG201004604-3A patent/SG163526A1/en unknown
- 2008-08-08 KR KR1020107004015A patent/KR20100051678A/ko not_active Ceased
-
2010
- 2010-02-17 AU AU2010200563A patent/AU2010200563A1/en not_active Abandoned
- 2010-03-04 RU RU2010107795/15A patent/RU2010107795A/ru not_active Application Discontinuation
- 2010-03-09 ZA ZA2010/01691A patent/ZA201001691B/en unknown
- 2010-04-21 JP JP2010098175A patent/JP2010215630A/ja active Pending
- 2010-09-03 US US12/807,379 patent/US8110584B2/en not_active Expired - Fee Related
-
2012
- 2012-07-25 US US13/557,681 patent/US9492440B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101896183B (zh) | 用于增强谷氨酸能突触反应的二环酰胺 | |
| JP5694765B2 (ja) | グルタミン酸作動性シナプス反応を増強するための二置換アミド | |
| EP2233140A1 (en) | Bicyclic amides for enhancing glutamatergic synaptic responses | |
| US8507482B2 (en) | Bicyclic amide derivatives for enhancing glutamatergic synaptic responses | |
| HK1149711A (en) | Use of bicyclic amide in preparing pharmaceuticals for treatment of respiratory | |
| HK1147677B (en) | Bicyclic amides for enhancing glutamatergic synaptic responses | |
| AU2013205446A1 (en) | Bicyclic amides for enhancing glutamatergic synaptic responses | |
| KR20110115139A (ko) | 글루타메이트성 시냅틱 반응을 향상시키기 위한 비시클릭 아미드 유도체 | |
| HK1163693A (en) | Bicyclic amide derivatives for enhancing glutamatergic synaptic responses |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1149711 Country of ref document: HK |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20101020 |
|
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1149711 Country of ref document: HK |