AU2010242910B2 - Pyrido [4,3-b] indoles and methods of use - Google Patents
Pyrido [4,3-b] indoles and methods of use Download PDFInfo
- Publication number
- AU2010242910B2 AU2010242910B2 AU2010242910A AU2010242910A AU2010242910B2 AU 2010242910 B2 AU2010242910 B2 AU 2010242910B2 AU 2010242910 A AU2010242910 A AU 2010242910A AU 2010242910 A AU2010242910 A AU 2010242910A AU 2010242910 B2 AU2010242910 B2 AU 2010242910B2
- Authority
- AU
- Australia
- Prior art keywords
- compound
- unsubstituted
- salt
- substituted
- solvate
- 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.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims abstract description 80
- RDMFHRSPDKWERA-UHFFFAOYSA-N 5H-Pyrido[4,3-b]indole Chemical class C1=NC=C2C3=CC=CC=C3NC2=C1 RDMFHRSPDKWERA-UHFFFAOYSA-N 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 551
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 120
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 58
- 102000000543 Histamine Receptors Human genes 0.000 claims abstract description 36
- 108010002059 Histamine Receptors Proteins 0.000 claims abstract description 36
- 238000011282 treatment Methods 0.000 claims abstract description 35
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims description 137
- 125000000217 alkyl group Chemical group 0.000 claims description 135
- 125000005843 halogen group Chemical group 0.000 claims description 77
- -1 aminocarbonylamino, aminocarbonyloxy, aminosulfonyl Chemical group 0.000 claims description 72
- 239000012453 solvate Substances 0.000 claims description 65
- 125000001072 heteroaryl group Chemical group 0.000 claims description 64
- 125000003118 aryl group Chemical group 0.000 claims description 56
- 208000024891 symptom Diseases 0.000 claims description 51
- 125000003545 alkoxy group Chemical group 0.000 claims description 50
- 125000000623 heterocyclic group Chemical group 0.000 claims description 47
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 125000000304 alkynyl group Chemical group 0.000 claims description 19
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 125000004442 acylamino group Chemical group 0.000 claims description 10
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 10
- 125000005102 carbonylalkoxy group Chemical group 0.000 claims description 10
- 125000005589 carbonylalkylenealkoxy group Chemical group 0.000 claims description 10
- 125000004001 thioalkyl group Chemical group 0.000 claims description 10
- 150000003573 thiols Chemical class 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 230000019771 cognition Effects 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 230000001771 impaired effect Effects 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 2
- 125000002971 oxazolyl group Chemical group 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims 2
- 125000001544 thienyl group Chemical group 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- 208000028017 Psychotic disease Diseases 0.000 abstract description 50
- 239000002858 neurotransmitter agent Substances 0.000 abstract description 37
- 230000001537 neural effect Effects 0.000 abstract description 35
- 230000001404 mediated effect Effects 0.000 abstract description 34
- 230000001225 therapeutic effect Effects 0.000 abstract description 6
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 357
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 147
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 137
- 230000000694 effects Effects 0.000 description 103
- 239000000203 mixture Substances 0.000 description 96
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 94
- 102000005962 receptors Human genes 0.000 description 92
- 108020003175 receptors Proteins 0.000 description 92
- 230000027455 binding Effects 0.000 description 90
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 81
- 239000011541 reaction mixture Substances 0.000 description 80
- 239000003446 ligand Substances 0.000 description 71
- 208000035475 disorder Diseases 0.000 description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 70
- 235000019439 ethyl acetate Nutrition 0.000 description 65
- 238000006243 chemical reaction Methods 0.000 description 63
- 238000002360 preparation method Methods 0.000 description 60
- 238000003556 assay Methods 0.000 description 57
- 239000012044 organic layer Substances 0.000 description 55
- 210000004027 cell Anatomy 0.000 description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- 229940075993 receptor modulator Drugs 0.000 description 49
- 201000000980 schizophrenia Diseases 0.000 description 49
- 229940076279 serotonin Drugs 0.000 description 49
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 47
- 239000000243 solution Substances 0.000 description 47
- 201000010099 disease Diseases 0.000 description 46
- 230000014511 neuron projection development Effects 0.000 description 46
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 45
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 45
- 239000000047 product Substances 0.000 description 45
- 108060003345 Adrenergic Receptor Proteins 0.000 description 44
- 102000017910 Adrenergic receptor Human genes 0.000 description 44
- 229910000104 sodium hydride Inorganic materials 0.000 description 40
- 102000015554 Dopamine receptor Human genes 0.000 description 38
- 108050004812 Dopamine receptor Proteins 0.000 description 38
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical class Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 37
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 36
- 239000000872 buffer Substances 0.000 description 35
- 239000005557 antagonist Substances 0.000 description 34
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 33
- 239000000556 agonist Substances 0.000 description 33
- 239000005457 ice water Substances 0.000 description 32
- 150000003891 oxalate salts Chemical class 0.000 description 32
- 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 230000005764 inhibitory process Effects 0.000 description 30
- 238000004809 thin layer chromatography Methods 0.000 description 29
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 28
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 28
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 28
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
- 239000012312 sodium hydride Substances 0.000 description 28
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 27
- 239000003981 vehicle Substances 0.000 description 27
- 229910052938 sodium sulfate Inorganic materials 0.000 description 26
- 235000011152 sodium sulphate Nutrition 0.000 description 26
- 238000011161 development Methods 0.000 description 25
- 230000018109 developmental process Effects 0.000 description 25
- 210000002569 neuron Anatomy 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 230000009870 specific binding Effects 0.000 description 24
- 208000024827 Alzheimer disease Diseases 0.000 description 23
- 102100032509 Histamine H1 receptor Human genes 0.000 description 22
- 238000010256 biochemical assay Methods 0.000 description 22
- 230000006870 function Effects 0.000 description 22
- 230000007074 memory dysfunction Effects 0.000 description 22
- 230000009871 nonspecific binding Effects 0.000 description 22
- 239000012043 crude product Substances 0.000 description 21
- 238000003653 radioligand binding assay Methods 0.000 description 21
- 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 20
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 20
- 230000015654 memory Effects 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 18
- 230000009286 beneficial effect Effects 0.000 description 18
- 230000000875 corresponding effect Effects 0.000 description 18
- 229960001340 histamine Drugs 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 17
- 101001016841 Homo sapiens Histamine H1 receptor Proteins 0.000 description 17
- 238000004440 column chromatography Methods 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 17
- 125000003107 substituted aryl group Chemical group 0.000 description 17
- MUZFLDUALLSEBH-UHFFFAOYSA-N 2,8-dimethyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=CC=C(C)C=C2C2=C1CCN(C)C2 MUZFLDUALLSEBH-UHFFFAOYSA-N 0.000 description 16
- 230000001800 adrenalinergic effect Effects 0.000 description 16
- 230000001713 cholinergic effect Effects 0.000 description 16
- 125000000753 cycloalkyl group Chemical group 0.000 description 16
- 230000004064 dysfunction Effects 0.000 description 16
- 208000027061 mild cognitive impairment Diseases 0.000 description 16
- 230000010807 negative regulation of binding Effects 0.000 description 16
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- 230000004766 neurogenesis Effects 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- KFCWIHUDWIRLEE-UHFFFAOYSA-N 8-chloro-2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=CC=C(Cl)C=C2C2=C1CCN(C)C2 KFCWIHUDWIRLEE-UHFFFAOYSA-N 0.000 description 14
- 230000003920 cognitive function Effects 0.000 description 14
- 239000012458 free base Substances 0.000 description 14
- 238000007429 general method Methods 0.000 description 14
- 230000004044 response Effects 0.000 description 14
- KUEKLFGFLZUCLQ-UHFFFAOYSA-N 4-(2-methyloxiran-2-yl)pyridine Chemical compound C=1C=NC=CC=1C1(C)CO1 KUEKLFGFLZUCLQ-UHFFFAOYSA-N 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- 241000699802 Cricetulus griseus Species 0.000 description 13
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 13
- 229960003638 dopamine Drugs 0.000 description 13
- 239000003480 eluent Substances 0.000 description 13
- 239000012535 impurity Substances 0.000 description 13
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
- 210000001672 ovary Anatomy 0.000 description 13
- 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 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 210000004556 brain Anatomy 0.000 description 12
- 208000020431 spinal cord injury Diseases 0.000 description 12
- 125000000547 substituted alkyl group Chemical group 0.000 description 12
- 102100032499 Histamine H2 receptor Human genes 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 208000018737 Parkinson disease Diseases 0.000 description 11
- 230000003247 decreasing effect Effects 0.000 description 11
- 230000006735 deficit Effects 0.000 description 11
- JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 description 11
- 206010027175 memory impairment Diseases 0.000 description 11
- 230000000508 neurotrophic effect Effects 0.000 description 11
- 208000011580 syndromic disease Diseases 0.000 description 11
- 208000030886 Traumatic Brain injury Diseases 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 239000013058 crude material Substances 0.000 description 10
- 230000006378 damage Effects 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 230000006872 improvement Effects 0.000 description 10
- 208000014674 injury Diseases 0.000 description 10
- 230000003414 procognitive effect Effects 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- 125000005017 substituted alkenyl group Chemical group 0.000 description 10
- 230000009529 traumatic brain injury Effects 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- 102100020756 D(2) dopamine receptor Human genes 0.000 description 9
- 239000012981 Hank's balanced salt solution Substances 0.000 description 9
- 101000931901 Homo sapiens D(2) dopamine receptor Proteins 0.000 description 9
- 101001016827 Homo sapiens Histamine H2 receptor Proteins 0.000 description 9
- 208000023105 Huntington disease Diseases 0.000 description 9
- 230000034994 death Effects 0.000 description 9
- 108010017146 dopamine D2L receptor Proteins 0.000 description 9
- 150000003840 hydrochlorides Chemical class 0.000 description 9
- 230000014759 maintenance of location Effects 0.000 description 9
- 210000002161 motor neuron Anatomy 0.000 description 9
- 230000004770 neurodegeneration Effects 0.000 description 9
- 208000015122 neurodegenerative disease Diseases 0.000 description 9
- 229910052701 rubidium Inorganic materials 0.000 description 9
- 125000004426 substituted alkynyl group Chemical group 0.000 description 9
- 108091005435 5-HT6 receptors Proteins 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 230000002159 abnormal effect Effects 0.000 description 8
- 125000004423 acyloxy group Chemical group 0.000 description 8
- 230000001149 cognitive effect Effects 0.000 description 8
- 238000002648 combination therapy Methods 0.000 description 8
- 208000002780 macular degeneration Diseases 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 210000000225 synapse Anatomy 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 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 7
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 7
- 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 7
- 206010003805 Autism Diseases 0.000 description 7
- 208000020706 Autistic disease Diseases 0.000 description 7
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 7
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 7
- 241000282465 Canis Species 0.000 description 7
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 7
- VAYOSLLFUXYJDT-RDTXWAMCSA-N Lysergic acid diethylamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-RDTXWAMCSA-N 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- 208000006011 Stroke Diseases 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 230000032683 aging Effects 0.000 description 7
- 208000026935 allergic disease Diseases 0.000 description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 7
- 230000006399 behavior Effects 0.000 description 7
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 230000013016 learning Effects 0.000 description 7
- 229950002454 lysergide Drugs 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 201000006417 multiple sclerosis Diseases 0.000 description 7
- 210000003205 muscle Anatomy 0.000 description 7
- 230000008447 perception Effects 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 230000000750 progressive effect Effects 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 125000005415 substituted alkoxy group Chemical group 0.000 description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
- 208000020925 Bipolar disease Diseases 0.000 description 6
- 208000001640 Fibromyalgia Diseases 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical class [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
- 230000000561 anti-psychotic effect Effects 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 238000002825 functional assay Methods 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 125000004043 oxo group Chemical group O=* 0.000 description 6
- 208000033808 peripheral neuropathy Diseases 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- VAYOSLLFUXYJDT-QZGBZKRISA-N (6ar,9r)-n,n-diethyl-7-(tritritiomethyl)-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxamide Chemical compound C1=CC(C2=C[C@H](CN([C@@H]2C2)C([3H])([3H])[3H])C(=O)N(CC)CC)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-QZGBZKRISA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 108091005436 5-HT7 receptors Proteins 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- 201000004384 Alopecia Diseases 0.000 description 5
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 5
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 5
- 208000019901 Anxiety disease Diseases 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 5
- 208000028698 Cognitive impairment Diseases 0.000 description 5
- 239000007995 HEPES buffer Substances 0.000 description 5
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 5
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 5
- 241000700157 Rattus norvegicus Species 0.000 description 5
- 239000000739 antihistaminic agent Substances 0.000 description 5
- 230000036506 anxiety Effects 0.000 description 5
- 229960005070 ascorbic acid Drugs 0.000 description 5
- 235000010323 ascorbic acid Nutrition 0.000 description 5
- 239000011668 ascorbic acid Substances 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000001086 cytosolic effect Effects 0.000 description 5
- 230000006866 deterioration Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 208000013403 hyperactivity Diseases 0.000 description 5
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 5
- 239000011630 iodine Substances 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 5
- 230000016273 neuron death Effects 0.000 description 5
- 201000001119 neuropathy Diseases 0.000 description 5
- 230000007823 neuropathy Effects 0.000 description 5
- GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000001953 sensory effect Effects 0.000 description 5
- UQIFPHOHBCBDQU-UHFFFAOYSA-N 2,3,8-trimethyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=CC=C(C)C=C2C2=C1CC(C)N(C)C2 UQIFPHOHBCBDQU-UHFFFAOYSA-N 0.000 description 4
- NSYXDDRZUMDVIW-UHFFFAOYSA-N 2-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-1-(4-fluorophenyl)ethanone Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CC(=O)C1=CC=C(F)C=C1 NSYXDDRZUMDVIW-UHFFFAOYSA-N 0.000 description 4
- WEQVCDIJDUVSID-UHFFFAOYSA-N 2-pyridin-4-ylpropan-2-ol Chemical compound CC(C)(O)C1=CC=NC=C1 WEQVCDIJDUVSID-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 4
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 108010025020 Nerve Growth Factor Proteins 0.000 description 4
- 208000028389 Nerve injury Diseases 0.000 description 4
- 208000022873 Ocular disease Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000003281 allosteric effect Effects 0.000 description 4
- 239000000538 analytical sample Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 230000002490 cerebral effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000001054 cortical effect Effects 0.000 description 4
- 210000003618 cortical neuron Anatomy 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- 230000002354 daily effect Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- 230000008764 nerve damage Effects 0.000 description 4
- 210000002241 neurite Anatomy 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 125000006574 non-aromatic ring group Chemical group 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 208000020016 psychiatric disease Diseases 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000002821 scintillation proximity assay Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- JRDUBBHIPPPSLP-NFEZXYISSA-N (2R,12bR)-3'-methyl-1'-(tritritiomethyl)spiro[1,3,4,6,7,12b-hexahydro-[1]benzofuro[2,3-a]quinolizine-2,4'-1,3-diazinane]-2'-one Chemical compound [3H]C([3H])([3H])N1CC[C@@]2(CCN3CCc4c(oc5ccccc45)[C@H]3C2)N(C)C1=O JRDUBBHIPPPSLP-NFEZXYISSA-N 0.000 description 3
- YLRRFARMTNWZKA-UHFFFAOYSA-N 1,2-dimethylpiperidin-4-one Chemical compound CC1CC(=O)CCN1C YLRRFARMTNWZKA-UHFFFAOYSA-N 0.000 description 3
- OHILVLMNCBTDJI-UHFFFAOYSA-N 2-(4-methoxyphenyl)-2-methyloxirane Chemical compound C1=CC(OC)=CC=C1C1(C)OC1 OHILVLMNCBTDJI-UHFFFAOYSA-N 0.000 description 3
- SMCXGJQYTDBFET-UHFFFAOYSA-N 2-butyl-2-(4-fluorophenyl)oxirane Chemical compound C=1C=C(F)C=CC=1C1(CCCC)CO1 SMCXGJQYTDBFET-UHFFFAOYSA-N 0.000 description 3
- 229940116892 5 Hydroxytryptamine 2B receptor antagonist Drugs 0.000 description 3
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 3
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 3
- 102100024956 5-hydroxytryptamine receptor 2B Human genes 0.000 description 3
- 101710138092 5-hydroxytryptamine receptor 2B Proteins 0.000 description 3
- WNTOAKYJMLMFNZ-UHFFFAOYSA-N 8-methyl-2-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound C1CN(CC(F)(F)F)CC2=C1NC1=CC=C(C)C=C12 WNTOAKYJMLMFNZ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108010011485 Aspartame Proteins 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 208000002177 Cataract Diseases 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 102100029503 E3 ubiquitin-protein ligase TRIM32 Human genes 0.000 description 3
- 208000004262 Food Hypersensitivity Diseases 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 229930091371 Fructose Natural products 0.000 description 3
- 239000005715 Fructose Substances 0.000 description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 3
- 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 3
- 241000238631 Hexapoda Species 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000634982 Homo sapiens E3 ubiquitin-protein ligase TRIM32 Proteins 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 239000005913 Maltodextrin Substances 0.000 description 3
- 229920002774 Maltodextrin Polymers 0.000 description 3
- 229910003827 NRaRb Inorganic materials 0.000 description 3
- 102000015336 Nerve Growth Factor Human genes 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 206010064930 age-related macular degeneration Diseases 0.000 description 3
- 125000002877 alkyl aryl group Chemical group 0.000 description 3
- 231100000360 alopecia Toxicity 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 3
- 239000000605 aspartame Substances 0.000 description 3
- 235000010357 aspartame Nutrition 0.000 description 3
- 229960003438 aspartame Drugs 0.000 description 3
- 230000003935 attention Effects 0.000 description 3
- 210000003050 axon Anatomy 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000004296 chiral HPLC Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 235000020932 food allergy Nutrition 0.000 description 3
- 230000002398 geroprotective effect Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- HPMRFMKYPGXPEP-UHFFFAOYSA-N idazoxan Chemical compound N1CCN=C1C1OC2=CC=CC=C2OC1 HPMRFMKYPGXPEP-UHFFFAOYSA-N 0.000 description 3
- 229950001476 idazoxan Drugs 0.000 description 3
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- 229940035034 maltodextrin Drugs 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 210000003470 mitochondria Anatomy 0.000 description 3
- 230000004065 mitochondrial dysfunction Effects 0.000 description 3
- 229940053128 nerve growth factor Drugs 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 230000003955 neuronal function Effects 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 239000005022 packaging material Substances 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 description 3
- 229960001999 phentolamine Drugs 0.000 description 3
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 3
- 238000007634 remodeling Methods 0.000 description 3
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 210000004885 white matter Anatomy 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- NHBJEVLRXOFTHJ-XMMPIXPASA-N (2s)-1-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(4-fluorophenyl)hexan-2-ol Chemical compound C1([C@](O)(CN2C3=CC=C(Cl)C=C3C=3CN(C)CCC=32)CCCC)=CC=C(F)C=C1 NHBJEVLRXOFTHJ-XMMPIXPASA-N 0.000 description 2
- MXLLWYGJUMMXIK-UHFFFAOYSA-N 1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(4-methoxyphenyl)propan-2-ol Chemical compound C1=CC(OC)=CC=C1C(C)(O)CN1C2=CC=C(C)C=C2C2=C1CCN(C)C2 MXLLWYGJUMMXIK-UHFFFAOYSA-N 0.000 description 2
- RAYAGSPPADIRJE-UHFFFAOYSA-N 1-(2-cyclopropyl-8-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(2-methylpyridin-4-yl)propan-2-ol Chemical compound C1=2CCN(C3CC3)CC=2C2=CC(C)=CC=C2N1CC(C)(O)C1=CC=NC(C)=C1 RAYAGSPPADIRJE-UHFFFAOYSA-N 0.000 description 2
- IEOLFLVCCZFGBO-UHFFFAOYSA-N 1-(2-cyclopropyl-8-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylpropan-2-ol Chemical compound C1=2CCN(C3CC3)CC=2C2=CC(C)=CC=C2N1CC(C)(O)C1=CC=NC=C1 IEOLFLVCCZFGBO-UHFFFAOYSA-N 0.000 description 2
- JHNYSIBNEXURAE-UHFFFAOYSA-N 1-(2-ethyl-8-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(4-fluorophenyl)propan-2-ol Chemical compound C1N(CC)CCC2=C1C1=CC(C)=CC=C1N2CC(C)(O)C1=CC=C(F)C=C1 JHNYSIBNEXURAE-UHFFFAOYSA-N 0.000 description 2
- MFDRDKNMPQTVPS-UHFFFAOYSA-N 1-(2-methyl-7-propan-2-yl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylpropan-2-ol Chemical compound C12=CC(C(C)C)=CC=C2C=2CN(C)CCC=2N1CC(C)(O)C1=CC=NC=C1 MFDRDKNMPQTVPS-UHFFFAOYSA-N 0.000 description 2
- WYCMFCPHWDZHMR-UHFFFAOYSA-N 1-(4,7-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl)-n,n-dimethylmethanesulfonamide Chemical compound C1=CC(C2CC(CN(C)C2C2)CS(=O)(=O)N(C)C)=C3C2=CN(C)C3=C1 WYCMFCPHWDZHMR-UHFFFAOYSA-N 0.000 description 2
- IEQWDIVOBHCVII-UHFFFAOYSA-N 1-(4-methylphenyl)-1-[2-(6-methylpyridin-3-yl)ethyl]hydrazine;hydrochloride Chemical compound Cl.C1=CC(C)=CC=C1N(N)CCC1=CC=C(C)N=C1 IEQWDIVOBHCVII-UHFFFAOYSA-N 0.000 description 2
- SXYZVGYORDSXET-UHFFFAOYSA-N 1-(6-methoxy-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylpropan-2-ol Chemical compound C1=2C(OC)=CC=CC=2C=2CN(C)CCC=2N1CC(C)(O)C1=CC=NC=C1 SXYZVGYORDSXET-UHFFFAOYSA-N 0.000 description 2
- NHBJEVLRXOFTHJ-UHFFFAOYSA-N 1-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(4-fluorophenyl)hexan-2-ol Chemical compound C1=2CCN(C)CC=2C2=CC(Cl)=CC=C2N1CC(O)(CCCC)C1=CC=C(F)C=C1 NHBJEVLRXOFTHJ-UHFFFAOYSA-N 0.000 description 2
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 2
- MPZYLVBVMLGMMB-UHFFFAOYSA-N 2-(2-methyloxiran-2-yl)pyrazine Chemical compound C=1N=CC=NC=1C1(C)CO1 MPZYLVBVMLGMMB-UHFFFAOYSA-N 0.000 description 2
- UMTRJXMMLKNHTA-UHFFFAOYSA-N 2-(3-fluoro-4-methoxyphenyl)-2-methyloxirane Chemical compound C1=C(F)C(OC)=CC=C1C1(C)OC1 UMTRJXMMLKNHTA-UHFFFAOYSA-N 0.000 description 2
- MKKXDTDAJBNQFR-UHFFFAOYSA-N 2-(4-chlorophenyl)-1-(8-chloro-2-propan-2-yl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)propan-2-ol Chemical compound C1N(C(C)C)CCC2=C1C1=CC(Cl)=CC=C1N2CC(C)(O)C1=CC=C(Cl)C=C1 MKKXDTDAJBNQFR-UHFFFAOYSA-N 0.000 description 2
- GUVZPBWIAWKDMV-UHFFFAOYSA-N 2-(6-methylpyridin-3-yl)-1-[8-methyl-2-(trifluoromethyl)-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl]propan-2-ol Chemical compound C1=2CCN(C(F)(F)F)CC=2C2=CC(C)=CC=C2N1CC(C)(O)C1=CC=C(C)N=C1 GUVZPBWIAWKDMV-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- CFFNISZFOSHXKX-UHFFFAOYSA-N 2-cyclopropyl-8-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound C1C=2C3=CC(C)=CC=C3NC=2CCN1C1CC1 CFFNISZFOSHXKX-UHFFFAOYSA-N 0.000 description 2
- GVLPAHGXYFQJHQ-UHFFFAOYSA-N 2-methyl-7-propan-2-yl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC=C(C(C)C)C=C1N2 GVLPAHGXYFQJHQ-UHFFFAOYSA-N 0.000 description 2
- AQCBJPZFJDPIGL-UHFFFAOYSA-N 3-(5-methyl-1h-imidazol-4-yl)-1-(1-methylindol-2-yl)propan-1-one Chemical compound N1C=NC(CCC(=O)C=2N(C3=CC=CC=C3C=2)C)=C1C AQCBJPZFJDPIGL-UHFFFAOYSA-N 0.000 description 2
- WIOBMVCWYCJKOW-UHFFFAOYSA-N 4-(2-ethyloxiran-2-yl)pyridine Chemical compound C=1C=NC=CC=1C1(CC)CO1 WIOBMVCWYCJKOW-UHFFFAOYSA-N 0.000 description 2
- VHSYIUWHNZPLTK-UHFFFAOYSA-N 4-(2-methyloxiran-2-yl)pyrimidine Chemical compound C=1C=NC=NC=1C1(C)CO1 VHSYIUWHNZPLTK-UHFFFAOYSA-N 0.000 description 2
- QPSWIRXVWVSUKU-UHFFFAOYSA-N 4-(2-propan-2-yloxiran-2-yl)pyridine Chemical compound C=1C=NC=CC=1C1(C(C)C)CO1 QPSWIRXVWVSUKU-UHFFFAOYSA-N 0.000 description 2
- QXIUMMLTJVHILT-UHFFFAOYSA-N 4-[3-(tert-butylamino)-2-hydroxypropoxy]-1H-indole-2-carbonitrile Chemical compound CC(C)(C)NCC(O)COC1=CC=CC2=C1C=C(C#N)N2 QXIUMMLTJVHILT-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 2
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 2
- AIHPVJCBRPRENO-UHFFFAOYSA-N 5-ethenyl-2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(C=C)C=N1 AIHPVJCBRPRENO-UHFFFAOYSA-N 0.000 description 2
- 102100027499 5-hydroxytryptamine receptor 1B Human genes 0.000 description 2
- 101710138639 5-hydroxytryptamine receptor 1B Proteins 0.000 description 2
- 102100040370 5-hydroxytryptamine receptor 5A Human genes 0.000 description 2
- 101710138069 5-hydroxytryptamine receptor 5A Proteins 0.000 description 2
- FVEVVXZRMUMEOX-UHFFFAOYSA-N 6-fluoro-2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=C(F)C=CC=C2C2=C1CCN(C)C2 FVEVVXZRMUMEOX-UHFFFAOYSA-N 0.000 description 2
- WCXJOWOZMZUUGW-UHFFFAOYSA-N 6-methoxy-2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C(C=CC=C1OC)=C1N2 WCXJOWOZMZUUGW-UHFFFAOYSA-N 0.000 description 2
- IOISBPMEPCGFLF-UHFFFAOYSA-N 7,8-dichloro-2-methyl-1,3,4,4a,5,9b-hexahydropyrido[4,3-b]indole Chemical compound N1C2=CC(Cl)=C(Cl)C=C2C2C1CCN(C)C2 IOISBPMEPCGFLF-UHFFFAOYSA-N 0.000 description 2
- ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- 101150051188 Adora2a gene Proteins 0.000 description 2
- 101150078577 Adora2b gene Proteins 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 208000036640 Asperger disease Diseases 0.000 description 2
- 201000006062 Asperger syndrome Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 206010012239 Delusion Diseases 0.000 description 2
- 208000003164 Diplopia Diseases 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- 229920002148 Gellan gum Polymers 0.000 description 2
- 208000004547 Hallucinations Diseases 0.000 description 2
- 108090000050 Histamine H2 Receptors Proteins 0.000 description 2
- 101001092197 Homo sapiens RNA binding protein fox-1 homolog 3 Proteins 0.000 description 2
- 102000016252 Huntingtin Human genes 0.000 description 2
- 108050004784 Huntingtin Proteins 0.000 description 2
- 102000009032 Imidazoline Receptors Human genes 0.000 description 2
- 108010049134 Imidazoline Receptors Proteins 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-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
- 208000026139 Memory disease Diseases 0.000 description 2
- UEQUQVLFIPOEMF-UHFFFAOYSA-N Mianserin Chemical compound C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 UEQUQVLFIPOEMF-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 208000010428 Muscle Weakness Diseases 0.000 description 2
- 206010028372 Muscular weakness Diseases 0.000 description 2
- 102000006386 Myelin Proteins Human genes 0.000 description 2
- 108010083674 Myelin Proteins Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010036105 Polyneuropathy Diseases 0.000 description 2
- 208000008348 Post-Concussion Syndrome Diseases 0.000 description 2
- 108010050254 Presenilins Proteins 0.000 description 2
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 2
- 102100035530 RNA binding protein fox-1 homolog 3 Human genes 0.000 description 2
- 208000006289 Rett Syndrome Diseases 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N Sec-butyl alcohol Natural products CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- MOZPSIXKYJUTKI-RLXJOQACSA-N [1-[2-(methanesulfonamido)ethyl]piperidin-4-yl]methyl 1-(tritritiomethyl)indole-3-carboxylate Chemical compound C12=CC=CC=C2N(C([3H])([3H])[3H])C=C1C(=O)OCC1CCN(CCNS(C)(=O)=O)CC1 MOZPSIXKYJUTKI-RLXJOQACSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 238000011226 adjuvant chemotherapy Methods 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- CICDSYWWNDGAGD-UHFFFAOYSA-N aminopotentidine Chemical compound C1=CC(N)=CC=C1C(=O)NCCNC(NC#N)=NCCCOC1=CC=CC(CN2CCCCC2)=C1 CICDSYWWNDGAGD-UHFFFAOYSA-N 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 229940124623 antihistamine drug Drugs 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 101150031224 app gene Proteins 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 208000029560 autism spectrum disease Diseases 0.000 description 2
- 210000004227 basal ganglia Anatomy 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 208000013404 behavioral symptom Diseases 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- YXXPNGIZHZHBTQ-UHFFFAOYSA-N butan-2-ol Chemical compound CC[C](C)O YXXPNGIZHZHBTQ-UHFFFAOYSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 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
- 210000003710 cerebral cortex Anatomy 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000007910 chewable tablet Substances 0.000 description 2
- 230000001055 chewing effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 230000006854 communication Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 231100000868 delusion Toxicity 0.000 description 2
- 210000001787 dendrite Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 150000002118 epoxides Chemical class 0.000 description 2
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
- GWQVMPWSEVRGPY-UHFFFAOYSA-N europium cryptate Chemical compound [Eu+3].N=1C2=CC=CC=1CN(CC=1N=C(C=CC=1)C=1N=C(C3)C=CC=1)CC(N=1)=CC(C(=O)NCCN)=CC=1C(N=1)=CC(C(=O)NCCN)=CC=1CN3CC1=CC=CC2=N1 GWQVMPWSEVRGPY-UHFFFAOYSA-N 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 235000010492 gellan gum Nutrition 0.000 description 2
- 239000000216 gellan gum Substances 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 208000024963 hair loss Diseases 0.000 description 2
- 230000003676 hair loss 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
- 230000002008 hemorrhagic effect Effects 0.000 description 2
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 2
- 229960005417 ketanserin Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 201000010901 lateral sclerosis Diseases 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 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
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229960000582 mepyramine Drugs 0.000 description 2
- 229960003955 mianserin Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000004898 mitochondrial function Effects 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 201000005518 mononeuropathy Diseases 0.000 description 2
- 206010028417 myasthenia gravis Diseases 0.000 description 2
- 210000005012 myelin Anatomy 0.000 description 2
- 238000003522 neurite outgrowth assay Methods 0.000 description 2
- 210000000715 neuromuscular junction Anatomy 0.000 description 2
- 230000005015 neuronal process Effects 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- 210000004248 oligodendroglia Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229960001779 pargyline Drugs 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 2
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 2
- 230000007824 polyneuropathy Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 2
- 229960003081 probenecid Drugs 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 201000008752 progressive muscular atrophy Diseases 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- 201000003004 ptosis Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- BLGXFZZNTVWLAY-DIRVCLHFSA-N rauwolscine Chemical compound C1=CC=C2C(CCN3C[C@H]4CC[C@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-DIRVCLHFSA-N 0.000 description 2
- 229940044601 receptor agonist Drugs 0.000 description 2
- 239000000018 receptor agonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 208000013406 repetitive behavior Diseases 0.000 description 2
- 230000003989 repetitive behavior Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000006403 short-term memory Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 230000008454 sleep-wake cycle Effects 0.000 description 2
- 230000003997 social interaction Effects 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- 230000008448 thought Effects 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- ZLQFJQMVLGXRSE-UHFFFAOYSA-N (1-pyridin-4-ylcyclopropyl)methyl methanesulfonate Chemical compound C=1C=NC=CC=1C1(COS(=O)(=O)C)CC1 ZLQFJQMVLGXRSE-UHFFFAOYSA-N 0.000 description 1
- TZXUSMWPXPKCEV-UHFFFAOYSA-N (2-methyl-2-pyridin-4-ylpropyl) methanesulfonate Chemical compound CS(=O)(=O)OCC(C)(C)C1=CC=NC=C1 TZXUSMWPXPKCEV-UHFFFAOYSA-N 0.000 description 1
- WMQWGFBKVULIPU-QHCPKHFHSA-N (2r)-1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(4-fluorophenyl)butan-2-ol Chemical compound C1([C@@](O)(CN2C3=CC=C(C)C=C3C=3CN(C)CCC=32)CC)=CC=C(F)C=C1 WMQWGFBKVULIPU-QHCPKHFHSA-N 0.000 description 1
- MXLLWYGJUMMXIK-QHCPKHFHSA-N (2r)-1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(4-methoxyphenyl)propan-2-ol Chemical compound C1=CC(OC)=CC=C1[C@@](C)(O)CN1C2=CC=C(C)C=C2C2=C1CCN(C)C2 MXLLWYGJUMMXIK-QHCPKHFHSA-N 0.000 description 1
- IPFQISBRAHCMTC-QFIPXVFZSA-N (2r)-1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylbutan-2-ol Chemical compound C1([C@@](O)(CN2C3=CC=C(C)C=C3C=3CN(C)CCC=32)CC)=CC=NC=C1 IPFQISBRAHCMTC-QFIPXVFZSA-N 0.000 description 1
- NHBJEVLRXOFTHJ-DEOSSOPVSA-N (2r)-1-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(4-fluorophenyl)hexan-2-ol Chemical compound C1([C@@](O)(CN2C3=CC=C(Cl)C=C3C=3CN(C)CCC=32)CCCC)=CC=C(F)C=C1 NHBJEVLRXOFTHJ-DEOSSOPVSA-N 0.000 description 1
- WMQWGFBKVULIPU-HSZRJFAPSA-N (2s)-1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(4-fluorophenyl)butan-2-ol Chemical compound C1([C@](O)(CN2C3=CC=C(C)C=C3C=3CN(C)CCC=32)CC)=CC=C(F)C=C1 WMQWGFBKVULIPU-HSZRJFAPSA-N 0.000 description 1
- MXLLWYGJUMMXIK-HSZRJFAPSA-N (2s)-1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(4-methoxyphenyl)propan-2-ol Chemical compound C1=CC(OC)=CC=C1[C@](C)(O)CN1C2=CC=C(C)C=C2C2=C1CCN(C)C2 MXLLWYGJUMMXIK-HSZRJFAPSA-N 0.000 description 1
- IPFQISBRAHCMTC-JOCHJYFZSA-N (2s)-1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylbutan-2-ol Chemical compound C1([C@](O)(CN2C3=CC=C(C)C=C3C=3CN(C)CCC=32)CC)=CC=NC=C1 IPFQISBRAHCMTC-JOCHJYFZSA-N 0.000 description 1
- BYJCRUCIXAVEBY-UHFFFAOYSA-N (3-propan-2-ylphenyl)hydrazine;hydrochloride Chemical compound [Cl-].CC(C)C1=CC=CC(N[NH3+])=C1 BYJCRUCIXAVEBY-UHFFFAOYSA-N 0.000 description 1
- HMHWNJGOHUYVMD-UHFFFAOYSA-N (4-methylanilino)azanium;chloride Chemical compound Cl.CC1=CC=C(NN)C=C1 HMHWNJGOHUYVMD-UHFFFAOYSA-N 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- ZUISDUGWFJNEPA-UHFFFAOYSA-N 1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(3-fluoro-4-methoxyphenyl)propan-2-ol Chemical compound C1=C(F)C(OC)=CC=C1C(C)(O)CN1C2=CC=C(C)C=C2C2=C1CCN(C)C2 ZUISDUGWFJNEPA-UHFFFAOYSA-N 0.000 description 1
- WMQWGFBKVULIPU-UHFFFAOYSA-N 1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(4-fluorophenyl)butan-2-ol Chemical compound C1=2CCN(C)CC=2C2=CC(C)=CC=C2N1CC(O)(CC)C1=CC=C(F)C=C1 WMQWGFBKVULIPU-UHFFFAOYSA-N 0.000 description 1
- IRLRNWRMIBNDMJ-UHFFFAOYSA-N 1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyrazin-2-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CC(C)(O)C1=CN=CC=N1 IRLRNWRMIBNDMJ-UHFFFAOYSA-N 0.000 description 1
- FHGOXDWNWJQYGK-UHFFFAOYSA-N 1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyrimidin-4-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CC(C)(O)C1=CC=NC=N1 FHGOXDWNWJQYGK-UHFFFAOYSA-N 0.000 description 1
- IABZWPDEAGALDE-UHFFFAOYSA-N 1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-3-methyl-2-pyridin-4-ylbutan-2-ol Chemical compound C1=2CCN(C)CC=2C2=CC(C)=CC=C2N1CC(O)(C(C)C)C1=CC=NC=C1 IABZWPDEAGALDE-UHFFFAOYSA-N 0.000 description 1
- HRQIDUFZNZJPDC-UHFFFAOYSA-N 1-(3-hydroxypropyl)piperidin-4-one Chemical compound OCCCN1CCC(=O)CC1 HRQIDUFZNZJPDC-UHFFFAOYSA-N 0.000 description 1
- YLCSXUFYAITZNI-UHFFFAOYSA-N 1-(4-chlorophenyl)-1-[2-(6-methylpyridin-3-yl)ethyl]hydrazine Chemical compound C1=NC(C)=CC=C1CCN(N)C1=CC=C(Cl)C=C1 YLCSXUFYAITZNI-UHFFFAOYSA-N 0.000 description 1
- BUZYGTVTZYSBCU-UHFFFAOYSA-N 1-(4-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1 BUZYGTVTZYSBCU-UHFFFAOYSA-N 0.000 description 1
- ZDPAWHACYDRYIW-UHFFFAOYSA-N 1-(4-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(F)C=C1 ZDPAWHACYDRYIW-UHFFFAOYSA-N 0.000 description 1
- WZQNXRRWXFORAM-UHFFFAOYSA-N 1-(4-hydroxybutyl)piperidin-4-one Chemical compound OCCCCN1CCC(=O)CC1 WZQNXRRWXFORAM-UHFFFAOYSA-N 0.000 description 1
- MSWINDLFZDBCLY-UHFFFAOYSA-N 1-(4-methylphenyl)-1-[2-(6-methylpyridin-3-yl)ethyl]hydrazine Chemical compound C1=CC(C)=CC=C1N(N)CCC1=CC=C(C)N=C1 MSWINDLFZDBCLY-UHFFFAOYSA-N 0.000 description 1
- YWDBIOKQVQJPBO-UHFFFAOYSA-N 1-(4-methylphenyl)-1-[2-[6-(trifluoromethyl)pyridin-3-yl]ethyl]hydrazine Chemical compound C1=CC(C)=CC=C1N(N)CCC1=CC=C(C(F)(F)F)N=C1 YWDBIOKQVQJPBO-UHFFFAOYSA-N 0.000 description 1
- TYEZKOVIACRRGE-UHFFFAOYSA-N 1-(6-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC=CC(Cl)=C1N2CC(C)(O)C1=CC=NC=C1 TYEZKOVIACRRGE-UHFFFAOYSA-N 0.000 description 1
- QRUAKLHDJDQXFR-UHFFFAOYSA-N 1-(6-fluoro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC=CC(F)=C1N2CC(C)(O)C1=CC=NC=C1 QRUAKLHDJDQXFR-UHFFFAOYSA-N 0.000 description 1
- UYCVKKGODKBIIQ-UHFFFAOYSA-N 1-(7,8-dichloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC(Cl)=C(Cl)C=C1N2CC(C)(O)C1=CC=NC=C1 UYCVKKGODKBIIQ-UHFFFAOYSA-N 0.000 description 1
- YAQSIBDLQYMABD-UHFFFAOYSA-N 1-(7-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC=C(Cl)C=C1N2CC(C)(O)C1=CC=NC=C1 YAQSIBDLQYMABD-UHFFFAOYSA-N 0.000 description 1
- GPDOQWMVEXTBOT-UHFFFAOYSA-N 1-(8,9-dichloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=C(Cl)C(Cl)=CC=C1N2CC(C)(O)C1=CC=NC=C1 GPDOQWMVEXTBOT-UHFFFAOYSA-N 0.000 description 1
- PTUZCMGIQGFPDX-UHFFFAOYSA-N 1-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-(3-fluoro-4-methoxyphenyl)propan-2-ol Chemical compound C1=C(F)C(OC)=CC=C1C(C)(O)CN1C2=CC=C(Cl)C=C2C2=C1CCN(C)C2 PTUZCMGIQGFPDX-UHFFFAOYSA-N 0.000 description 1
- MEOIDNYSEVQDDW-UHFFFAOYSA-N 1-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyrazin-2-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC(Cl)=CC=C1N2CC(C)(O)C1=CN=CC=N1 MEOIDNYSEVQDDW-UHFFFAOYSA-N 0.000 description 1
- CJQZLXSKBWKKTD-UHFFFAOYSA-N 1-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-3-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC(Cl)=CC=C1N2CC(C)(O)C1=CC=CN=C1 CJQZLXSKBWKKTD-UHFFFAOYSA-N 0.000 description 1
- NTSHFUQMJOVRJZ-UHFFFAOYSA-N 1-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylbutan-2-ol Chemical compound C1=2CCN(C)CC=2C2=CC(Cl)=CC=C2N1CC(O)(CC)C1=CC=NC=C1 NTSHFUQMJOVRJZ-UHFFFAOYSA-N 0.000 description 1
- VPCFFEJIVPIEPA-UHFFFAOYSA-N 1-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyrimidin-4-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC(Cl)=CC=C1N2CC(C)(O)C1=CC=NC=N1 VPCFFEJIVPIEPA-UHFFFAOYSA-N 0.000 description 1
- YJRGOONEJAQERR-UHFFFAOYSA-N 1-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-3-methyl-2-pyridin-4-ylbutan-2-ol Chemical compound C1=2CCN(C)CC=2C2=CC(Cl)=CC=C2N1CC(O)(C(C)C)C1=CC=NC=C1 YJRGOONEJAQERR-UHFFFAOYSA-N 0.000 description 1
- VBCVLENMDUHZEA-UHFFFAOYSA-N 1-(8-fluoro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylpropan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC(F)=CC=C1N2CC(C)(O)C1=CC=NC=C1 VBCVLENMDUHZEA-UHFFFAOYSA-N 0.000 description 1
- RUYNZISVBRTPPB-UHFFFAOYSA-N 1-(8-methoxy-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-pyridin-4-ylpropan-2-ol Chemical compound C1=2CCN(C)CC=2C2=CC(OC)=CC=C2N1CC(C)(O)C1=CC=NC=C1 RUYNZISVBRTPPB-UHFFFAOYSA-N 0.000 description 1
- YDDXVAXDYKBWDX-UHFFFAOYSA-N 1-cyano-3-[2-[[2-(diaminomethylideneamino)-4-thiazolyl]methylthio]ethyl]-2-methylguanidine Chemical compound N#CNC(=NC)NCCSCC1=CSC(N=C(N)N)=N1 YDDXVAXDYKBWDX-UHFFFAOYSA-N 0.000 description 1
- BFQFMADLJDMRLG-UHFFFAOYSA-N 1-cyclobutyl-1-(4-fluorophenyl)ethanol Chemical compound C=1C=C(F)C=CC=1C(O)(C)C1CCC1 BFQFMADLJDMRLG-UHFFFAOYSA-N 0.000 description 1
- RWJZQZVBGBCVFN-UHFFFAOYSA-N 1-cyclohexyl-2-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-1-(4-fluorophenyl)ethanol Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CC(O)(C=1C=CC(F)=CC=1)C1CCCCC1 RWJZQZVBGBCVFN-UHFFFAOYSA-N 0.000 description 1
- DTUJRJIWGWTNFQ-UHFFFAOYSA-N 1-cyclopropylpiperidin-4-one Chemical compound C1CC(=O)CCN1C1CC1 DTUJRJIWGWTNFQ-UHFFFAOYSA-N 0.000 description 1
- HVOAMIOKNARIMR-UHFFFAOYSA-N 1-pyridin-4-ylethanol Chemical compound CC(O)C1=CC=NC=C1 HVOAMIOKNARIMR-UHFFFAOYSA-N 0.000 description 1
- KJZCUPMXUFTZLV-UHFFFAOYSA-N 2,3,8-trimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)C(C)CC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 KJZCUPMXUFTZLV-UHFFFAOYSA-N 0.000 description 1
- HMYDVYGSXLBJKK-UHFFFAOYSA-N 2,3,8-trimethyl-5-[2-(6-methylpyridin-3-yl)propyl]-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1=2CC(C)N(C)CC=2C2=CC(C)=CC=C2N1CC(C)C1=CC=C(C)N=C1 HMYDVYGSXLBJKK-UHFFFAOYSA-N 0.000 description 1
- GWBNMWZVMVGQEY-UHFFFAOYSA-N 2,4,8-trimethyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=CC=C(C)C=C2C2=C1C(C)CN(C)C2 GWBNMWZVMVGQEY-UHFFFAOYSA-N 0.000 description 1
- CYJQCYXRNNCURD-UHFFFAOYSA-N 2,8-dimethyl-1,3,4,4a,5,9b-hexahydropyrido[4,3-b]indole Chemical compound N1C2=CC=C(C)C=C2C2C1CCN(C)C2 CYJQCYXRNNCURD-UHFFFAOYSA-N 0.000 description 1
- VDNUKKJGOKIGOK-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)propan-2-ol Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CC(C)(O)C1=CC=C(F)C=C1F VDNUKKJGOKIGOK-UHFFFAOYSA-N 0.000 description 1
- LOLFYIWPYGTMJO-UHFFFAOYSA-N 2-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-1-(4-fluorophenyl)ethanol Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CC(O)C1=CC=C(F)C=C1 LOLFYIWPYGTMJO-UHFFFAOYSA-N 0.000 description 1
- FWIKWZGVKPJVNJ-UHFFFAOYSA-N 2-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-1-phenylethanone Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CC(=O)C1=CC=CC=C1 FWIKWZGVKPJVNJ-UHFFFAOYSA-N 0.000 description 1
- SUVSPFLMQVVURA-UHFFFAOYSA-N 2-(4-fluorophenyl)hexan-2-ol Chemical compound CCCCC(C)(O)C1=CC=C(F)C=C1 SUVSPFLMQVVURA-UHFFFAOYSA-N 0.000 description 1
- LMNPAYKJOZJLRU-UHFFFAOYSA-N 2-(6-methylpyridin-3-yl)ethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCC1=CC=C(C)N=C1 LMNPAYKJOZJLRU-UHFFFAOYSA-N 0.000 description 1
- VPYSJGVLDQLIDR-UHFFFAOYSA-N 2-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-1-(4-chlorophenyl)ethanone Chemical compound C1N(C)CCC2=C1C1=CC(Cl)=CC=C1N2CC(=O)C1=CC=C(Cl)C=C1 VPYSJGVLDQLIDR-UHFFFAOYSA-N 0.000 description 1
- OVFFBWXBLFAZQI-UHFFFAOYSA-N 2-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-1-(4-fluorophenyl)ethanone Chemical compound C1N(C)CCC2=C1C1=CC(Cl)=CC=C1N2CC(=O)C1=CC=C(F)C=C1 OVFFBWXBLFAZQI-UHFFFAOYSA-N 0.000 description 1
- KZSRTBKZNFOLNX-UHFFFAOYSA-N 2-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-1-cyclobutyl-1-(4-fluorophenyl)ethanol Chemical compound C1N(C)CCC2=C1C1=CC(Cl)=CC=C1N2CC(O)(C=1C=CC(F)=CC=1)C1CCC1 KZSRTBKZNFOLNX-UHFFFAOYSA-N 0.000 description 1
- ZPVALAHVRBXBDR-UHFFFAOYSA-N 2-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-1-phenylethanone Chemical compound C1N(C)CCC2=C1C1=CC(Cl)=CC=C1N2CC(=O)C1=CC=CC=C1 ZPVALAHVRBXBDR-UHFFFAOYSA-N 0.000 description 1
- FFPDVUKDLHXYPS-UHFFFAOYSA-N 2-(8-chloro-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-ylethanol Chemical compound C1N(C)CCC2=C1C1=CC(Cl)=CC=C1N2CC(O)C1=CC=NC=C1 FFPDVUKDLHXYPS-UHFFFAOYSA-N 0.000 description 1
- UYJHHQDSLWOEIO-UHFFFAOYSA-N 2-[3-(5-ethenylpyridin-2-yl)propyl]isoindole-1,3-dione Chemical compound N1=CC(C=C)=CC=C1CCCN1C(=O)C2=CC=CC=C2C1=O UYJHHQDSLWOEIO-UHFFFAOYSA-N 0.000 description 1
- FLAYZKKEOIAALB-UHFFFAOYSA-N 2-bromo-1-(4-chlorophenyl)ethanone Chemical compound ClC1=CC=C(C(=O)CBr)C=C1 FLAYZKKEOIAALB-UHFFFAOYSA-N 0.000 description 1
- ZJFWCELATJMDNO-UHFFFAOYSA-N 2-bromo-1-(4-fluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CBr)C=C1 ZJFWCELATJMDNO-UHFFFAOYSA-N 0.000 description 1
- AGLOIYDVKKGLGM-UHFFFAOYSA-N 2-cyclobutyl-2-(4-fluorophenyl)oxirane Chemical compound C1=CC(F)=CC=C1C1(C2CCC2)OC1 AGLOIYDVKKGLGM-UHFFFAOYSA-N 0.000 description 1
- BNBBMQNFYSHKDQ-UHFFFAOYSA-N 2-ethenyl-4-prop-1-en-2-ylpyridine Chemical compound CC(=C)C1=CC=NC(C=C)=C1 BNBBMQNFYSHKDQ-UHFFFAOYSA-N 0.000 description 1
- FYHWPFXPFFPQRT-UHFFFAOYSA-N 2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1CCN(C)C2 FYHWPFXPFFPQRT-UHFFFAOYSA-N 0.000 description 1
- MRXPNWXSFCODDY-UHFFFAOYSA-N 2-methyl-2-phenyloxirane Chemical compound C=1C=CC=CC=1C1(C)CO1 MRXPNWXSFCODDY-UHFFFAOYSA-N 0.000 description 1
- GJFICMVGNQQCEE-UHFFFAOYSA-N 2-methyl-5-prop-1-en-2-ylpyridine Chemical compound CC(=C)C1=CC=C(C)N=C1 GJFICMVGNQQCEE-UHFFFAOYSA-N 0.000 description 1
- XTKGYFYMBQPUDH-UHFFFAOYSA-N 2-pyrazin-2-ylpropan-2-ol Chemical compound CC(C)(O)C1=CN=CC=N1 XTKGYFYMBQPUDH-UHFFFAOYSA-N 0.000 description 1
- PNTLCFXUOFMATF-UHFFFAOYSA-N 2-pyridin-4-yl-1-(2,3,8-trimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)propan-2-ol Chemical compound C1N(C)C(C)CC2=C1C1=CC(C)=CC=C1N2CC(C)(O)C1=CC=NC=C1 PNTLCFXUOFMATF-UHFFFAOYSA-N 0.000 description 1
- CKZPTOHBDNSETM-UHFFFAOYSA-N 2-pyridin-4-ylbutan-2-ol Chemical compound CCC(C)(O)C1=CC=NC=C1 CKZPTOHBDNSETM-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- PLSUQXJQIFLVLI-UHFFFAOYSA-N 2-pyrimidin-4-ylpropan-2-ol Chemical compound CC(C)(O)C1=CC=NC=N1 PLSUQXJQIFLVLI-UHFFFAOYSA-N 0.000 description 1
- UQCWLNFMSBBTOS-UHFFFAOYSA-N 3-(2-methyloxiran-2-yl)pyridine Chemical compound C=1C=CN=CC=1C1(C)CO1 UQCWLNFMSBBTOS-UHFFFAOYSA-N 0.000 description 1
- HLBOAQSKBNNHMW-UHFFFAOYSA-N 3-(3-methoxyphenyl)pyridine Chemical compound COC1=CC=CC(C=2C=NC=CC=2)=C1 HLBOAQSKBNNHMW-UHFFFAOYSA-N 0.000 description 1
- XUSNPFGLKGCWGN-UHFFFAOYSA-N 3-[4-(3-aminopropyl)piperazin-1-yl]propan-1-amine Chemical compound NCCCN1CCN(CCCN)CC1 XUSNPFGLKGCWGN-UHFFFAOYSA-N 0.000 description 1
- RWZMVPSBSUJAPW-UHFFFAOYSA-N 3-[5-[2-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)ethyl]pyridin-2-yl]propan-1-amine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(CCCN)N=C1 RWZMVPSBSUJAPW-UHFFFAOYSA-N 0.000 description 1
- MZWRHCBZOUSXRZ-UHFFFAOYSA-N 3-[8-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-3,4-dihydro-1h-pyrido[4,3-b]indol-2-yl]propanenitrile Chemical compound C1=2CCN(CCC#N)CC=2C2=CC(C)=CC=C2N1CCC1=CC=C(C)N=C1 MZWRHCBZOUSXRZ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MFRSKZVSVMETKA-UHFFFAOYSA-N 3-methyl-2-pyridin-4-ylbutan-2-ol Chemical compound CC(C)C(C)(O)C1=CC=NC=C1 MFRSKZVSVMETKA-UHFFFAOYSA-N 0.000 description 1
- PUDAFGXRSMFBKZ-UHFFFAOYSA-N 3-pyridin-4-ylpentan-3-ol Chemical compound CCC(O)(CC)C1=CC=NC=C1 PUDAFGXRSMFBKZ-UHFFFAOYSA-N 0.000 description 1
- KRROYLIDJBSPDW-UHFFFAOYSA-N 4-(oxiran-2-yl)pyridine Chemical compound C1OC1C1=CC=NC=C1 KRROYLIDJBSPDW-UHFFFAOYSA-N 0.000 description 1
- FKAGVDSAIOJBEG-UHFFFAOYSA-N 4-[1-(2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indol-5-yl)-2-hydroxypropan-2-yl]phenol Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CC(C)(O)C1=CC=C(O)C=C1 FKAGVDSAIOJBEG-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 102000006969 5-HT2B Serotonin Receptor Human genes 0.000 description 1
- 108010072584 5-HT2B Serotonin Receptor Proteins 0.000 description 1
- 108091005477 5-HT3 receptors Proteins 0.000 description 1
- 102000035037 5-HT3 receptors Human genes 0.000 description 1
- 108091005482 5-HT4 receptors Proteins 0.000 description 1
- 229940124801 5-HT6 antagonist Drugs 0.000 description 1
- 102100040368 5-hydroxytryptamine receptor 6 Human genes 0.000 description 1
- 101710150235 5-hydroxytryptamine receptor 6 Proteins 0.000 description 1
- GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
- OIGCTBWIZDTJJY-UHFFFAOYSA-N 6-chloro-2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=C(Cl)C=CC=C2C2=C1CCN(C)C2 OIGCTBWIZDTJJY-UHFFFAOYSA-N 0.000 description 1
- QYGUNKGNTGPWAX-UHFFFAOYSA-N 7-chloro-2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=CC(Cl)=CC=C2C2=C1CCN(C)C2 QYGUNKGNTGPWAX-UHFFFAOYSA-N 0.000 description 1
- FJLRAIYQDBDRLE-UHFFFAOYSA-N 8-chloro-2,3-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)C(C)CC2=C1C1=CC(Cl)=CC=C1N2CCC1=CC=C(C)N=C1 FJLRAIYQDBDRLE-UHFFFAOYSA-N 0.000 description 1
- DFBGAQRXYSMOMN-UHFFFAOYSA-N 8-methoxy-2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound C1CN(C)CC2=C1NC1=CC=C(OC)C=C12 DFBGAQRXYSMOMN-UHFFFAOYSA-N 0.000 description 1
- JCPPGNFHTRTYGX-UHFFFAOYSA-N 8-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-1,2,3,4-tetrahydropyrido[4,3-b]indole Chemical compound C1=2CCNCC=2C2=CC(C)=CC=C2N1CCC1=CC=C(C)N=C1 JCPPGNFHTRTYGX-UHFFFAOYSA-N 0.000 description 1
- YQTFPJLMJDAXTM-UHFFFAOYSA-N 8-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2-(2,2,2-trifluoroethyl)-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1=2CCN(CC(F)(F)F)CC=2C2=CC(C)=CC=C2N1CCC1=CC=C(C)N=C1 YQTFPJLMJDAXTM-UHFFFAOYSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- 208000006888 Agnosia Diseases 0.000 description 1
- 239000012109 Alexa Fluor 568 Substances 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 206010002027 Amyotrophy Diseases 0.000 description 1
- 206010002942 Apathy Diseases 0.000 description 1
- 108010060159 Apolipoprotein E4 Proteins 0.000 description 1
- 206010003062 Apraxia Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000025978 Athletic injury Diseases 0.000 description 1
- 206010061666 Autonomic neuropathy Diseases 0.000 description 1
- 208000037663 Best vitelliform macular dystrophy Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006100 Bradykinesia Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 208000027104 Chemotherapy-Related Cognitive Impairment Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- 206010009696 Clumsiness Diseases 0.000 description 1
- 206010009848 Cogwheel rigidity Diseases 0.000 description 1
- 208000006992 Color Vision Defects Diseases 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 102000012437 Copper-Transporting ATPases Human genes 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012559 Developmental delay Diseases 0.000 description 1
- 208000012239 Developmental disease 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
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010013486 Distractibility Diseases 0.000 description 1
- 229940098778 Dopamine receptor agonist Drugs 0.000 description 1
- 229940121891 Dopamine receptor antagonist Drugs 0.000 description 1
- 201000001353 Doyne honeycomb retinal dystrophy Diseases 0.000 description 1
- 206010052805 Drug tolerance decreased Diseases 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 206010013976 Dyspraxia Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- 208000013171 Fahr disease Diseases 0.000 description 1
- 208000037312 Familial drusen Diseases 0.000 description 1
- 208000001308 Fasciculation Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000016988 Hemorrhagic Stroke Diseases 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 102000004384 Histamine H3 receptors Human genes 0.000 description 1
- 108090000981 Histamine H3 receptors Proteins 0.000 description 1
- 229940123322 Histamine receptor agonist Drugs 0.000 description 1
- 229940122236 Histamine receptor antagonist Drugs 0.000 description 1
- 101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 0.000 description 1
- 101000979001 Homo sapiens Methionine aminopeptidase 2 Proteins 0.000 description 1
- 101000969087 Homo sapiens Microtubule-associated protein 2 Proteins 0.000 description 1
- 241000257303 Hymenoptera Species 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000032578 Inherited retinal disease Diseases 0.000 description 1
- 208000015592 Involuntary movements Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 201000003533 Leber congenital amaurosis Diseases 0.000 description 1
- 201000000639 Leber hereditary optic neuropathy Diseases 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000008948 Menkes Kinky Hair Syndrome Diseases 0.000 description 1
- 208000012583 Menkes disease Diseases 0.000 description 1
- RLJFTICUTYVZDG-UHFFFAOYSA-N Methiothepine Chemical group C12=CC(SC)=CC=C2SC2=CC=CC=C2CC1N1CCN(C)CC1 RLJFTICUTYVZDG-UHFFFAOYSA-N 0.000 description 1
- 102100021118 Microtubule-associated protein 2 Human genes 0.000 description 1
- 206010027918 Mononeuropathy multiplex Diseases 0.000 description 1
- 208000002740 Muscle Rigidity Diseases 0.000 description 1
- 206010028347 Muscle twitching Diseases 0.000 description 1
- FHQDWPCFSJMNCT-UHFFFAOYSA-N N(tele)-methylhistamine Chemical compound CN1C=NC(CCN)=C1 FHQDWPCFSJMNCT-UHFFFAOYSA-N 0.000 description 1
- KAHMEWANVDFFCQ-UHFFFAOYSA-N N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-2-(2,6-dimethoxyphenoxy)ethanamine hydrochloride Chemical compound Cl.COC1=CC=CC(OC)=C1OCCNCC1OC2=CC=CC=C2OC1 KAHMEWANVDFFCQ-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 1
- 102000008763 Neurofilament Proteins Human genes 0.000 description 1
- 108010088373 Neurofilament Proteins Proteins 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 208000016113 North Carolina macular dystrophy Diseases 0.000 description 1
- 208000013661 Oguchi disease Diseases 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000034247 Pattern dystrophy Diseases 0.000 description 1
- 208000028361 Penetrating Head injury Diseases 0.000 description 1
- 206010034719 Personality change Diseases 0.000 description 1
- 206010067206 Postural reflex impairment Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 206010037779 Radiculopathy Diseases 0.000 description 1
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 208000032430 Retinal dystrophy Diseases 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 206010040030 Sensory loss Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 208000022758 Sorsby fundus dystrophy Diseases 0.000 description 1
- 208000014604 Specific Language disease Diseases 0.000 description 1
- 201000010829 Spina bifida Diseases 0.000 description 1
- 208000006097 Spinal Dysraphism Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000027073 Stargardt disease Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 102000019355 Synuclein Human genes 0.000 description 1
- 108050006783 Synuclein Proteins 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
- 206010043431 Thinking abnormal Diseases 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 208000028552 Treatment-Resistant Depressive disease Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 208000014769 Usher Syndromes Diseases 0.000 description 1
- 241000256856 Vespidae Species 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- SAHIZENKTPRYSN-UHFFFAOYSA-N [2-[3-(phenoxymethyl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound O(C1=CC=CC=C1)CC=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 SAHIZENKTPRYSN-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 208000037919 acquired disease Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- 239000013566 allergen 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
- 230000004075 alteration Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000005121 aminocarbonylalkoxy group Chemical group 0.000 description 1
- CAMXVZOXBADHNJ-UHFFFAOYSA-N ammonium nitrite Chemical compound [NH4+].[O-]N=O CAMXVZOXBADHNJ-UHFFFAOYSA-N 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 210000002453 autonomic neuron Anatomy 0.000 description 1
- 201000002922 basal ganglia calcification Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 231100000871 behavioral problem Toxicity 0.000 description 1
- MNJNPLVXBISNSX-WDNDVIMCSA-N bemesetron Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C1=CC(Cl)=CC(Cl)=C1 MNJNPLVXBISNSX-WDNDVIMCSA-N 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 208000016791 bilateral striopallidodentate calcinosis Diseases 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000000035 biogenic effect Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 230000004641 brain development Effects 0.000 description 1
- 208000029028 brain injury Diseases 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
- AQNQQHJNRPDOQV-UHFFFAOYSA-N bromocyclohexane Chemical compound BrC1CCCCC1 AQNQQHJNRPDOQV-UHFFFAOYSA-N 0.000 description 1
- BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
- 210000001775 bruch membrane Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000003491 cAMP production Effects 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 206010007776 catatonia Diseases 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010267 cellular communication Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 208000012601 choreatic disease Diseases 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000014107 chromosome localization Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 230000037411 cognitive enhancing Effects 0.000 description 1
- 230000036992 cognitive tasks Effects 0.000 description 1
- 201000007254 color blindness Diseases 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 231100000867 compulsive behavior Toxicity 0.000 description 1
- 208000006623 congenital stationary night blindness Diseases 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 125000005508 decahydronaphthalenyl group Chemical group 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003796 diagnosis of exclusion Methods 0.000 description 1
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000004982 dihaloalkyl group Chemical group 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 208000029444 double vision Diseases 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 210000003372 endocrine gland Anatomy 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003256 environmental substance Substances 0.000 description 1
- 230000001073 episodic memory Effects 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000008921 facial expression Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000003269 fluorescent indicator Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 201000006321 fundus dystrophy Diseases 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 229940125384 geroprotector Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 210000004884 grey matter Anatomy 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 239000003386 histamine H2 receptor agonist Substances 0.000 description 1
- 239000003453 histamine agonist Substances 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- HECSHXUNOVTAIJ-UHFFFAOYSA-N hydron;(2-methoxyphenyl)hydrazine;chloride Chemical compound Cl.COC1=CC=CC=C1NN HECSHXUNOVTAIJ-UHFFFAOYSA-N 0.000 description 1
- SXWRTZOXMUOJER-UHFFFAOYSA-N hydron;piperidin-4-one;chloride;hydrate Chemical compound O.Cl.O=C1CCNCC1 SXWRTZOXMUOJER-UHFFFAOYSA-N 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000010365 information processing Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 208000017532 inherited retinal dystrophy Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 1
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 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
- 238000002955 isolation Methods 0.000 description 1
- 229960001317 isoprenaline Drugs 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000008449 language Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000003715 limbic system Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- GFTXWCQFWLOXAT-UHFFFAOYSA-M magnesium;cyclohexane;bromide Chemical compound [Mg+2].[Br-].C1CC[CH-]CC1 GFTXWCQFWLOXAT-UHFFFAOYSA-M 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 208000024714 major depressive disease Diseases 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
- 239000003550 marker Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000003924 mental process Effects 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- WZHJKEUHNJHDLS-QTGUNEKASA-N metergoline Chemical compound C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4N(C)C=C(C=34)C2)C1)C)NC(=O)OCC1=CC=CC=C1 WZHJKEUHNJHDLS-QTGUNEKASA-N 0.000 description 1
- 229960004650 metergoline Drugs 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000007625 mitochondrial abnormality Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 201000002003 mononeuritis multiplex Diseases 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 description 1
- 210000003007 myelin sheath Anatomy 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000005157 neural retina Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 238000002610 neuroimaging Methods 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 230000003557 neuropsychological effect Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000001909 oculomotor nerve paralysis Diseases 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 208000035824 paresthesia Diseases 0.000 description 1
- 102000045222 parkin Human genes 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000002243 primary neuron Anatomy 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 201000002241 progressive bulbar palsy Diseases 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- VQGISNOMGHCEPX-UHFFFAOYSA-N propanenitrile Chemical compound C[CH]C#N VQGISNOMGHCEPX-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 108010006590 serotonin 5 receptor Proteins 0.000 description 1
- 239000003751 serotonin 6 antagonist Substances 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 229940121356 serotonin receptor antagonist Drugs 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 208000026473 slurred speech Diseases 0.000 description 1
- 230000011273 social behavior Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000002320 spinal muscular atrophy Diseases 0.000 description 1
- 210000000273 spinal nerve root Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000001913 submandibular gland Anatomy 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000007470 synaptic degeneration Effects 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229950011533 tiotidine Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 125000004950 trifluoroalkyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 201000007790 vitelliform macular dystrophy Diseases 0.000 description 1
- 208000020938 vitelliform macular dystrophy 2 Diseases 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 230000003936 working memory Effects 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- 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
- C07D471/04—Ortho-condensed systems
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2013203575A AU2013203575A1 (en) | 2009-04-29 | 2013-04-10 | Pyrido [4,3-b] indoles and methods of use |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1136/MUM/2009 | 2009-04-29 | ||
| IN1136MU2009 | 2009-04-29 | ||
| US18126209P | 2009-05-26 | 2009-05-26 | |
| US61/181,262 | 2009-05-26 | ||
| PCT/US2010/033053 WO2010127177A1 (en) | 2009-04-29 | 2010-04-29 | Pyrido [4,3-b] indoles and methods of use |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013203575A Division AU2013203575A1 (en) | 2009-04-29 | 2013-04-10 | Pyrido [4,3-b] indoles and methods of use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2010242910A1 AU2010242910A1 (en) | 2011-11-17 |
| AU2010242910B2 true AU2010242910B2 (en) | 2015-11-12 |
Family
ID=43032567
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2010242910A Ceased AU2010242910B2 (en) | 2009-04-29 | 2010-04-29 | Pyrido [4,3-b] indoles and methods of use |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9255094B2 (enExample) |
| EP (1) | EP2424364A4 (enExample) |
| JP (1) | JP5711725B2 (enExample) |
| CN (1) | CN102480955B (enExample) |
| AU (1) | AU2010242910B2 (enExample) |
| BR (1) | BRPI1006602A2 (enExample) |
| CA (1) | CA2760541A1 (enExample) |
| WO (1) | WO2010127177A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2007139634A (ru) | 2007-10-25 | 2009-04-27 | Сергей Олегович Бачурин (RU) | Новые тиазол-, триазол- или оксадиазол-содержащие тетрациклические соединения |
| RU2544856C2 (ru) * | 2008-01-25 | 2015-03-20 | Сергей Олегович Бачурин | НОВЫЕ ПРОИЗВОДНЫЕ 2,3,4,5-ТЕТРАГИДРО-1-ПИРИДО[4,3-b]ИНДОЛА И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| BRPI0906245A2 (pt) * | 2008-03-24 | 2015-06-30 | Medivation Technologies Inc | Composto, método para tratar um distúrbio cognitivo, psicótico, mediado por neurotransmissor ou um distúrbio neuronal em indivíduo, uso de um composto, composição farmacêutica e kit |
| WO2009120717A2 (en) * | 2008-03-24 | 2009-10-01 | Medivation Technologies, Inc. | Pyrido [3, 4-b] indoles and methods of use |
| CN102271508B (zh) | 2008-10-31 | 2015-04-29 | 梅迪维新技术公司 | 含有刚性部分的吡啶并[4,3-b]吲哚类化合物 |
| EP2348847A4 (en) | 2008-10-31 | 2012-05-23 | Medivation Technologies Inc | AZEPINO [4, 5-B] INDOLE AND USE PROCESS |
| SG173639A1 (en) | 2009-02-11 | 2011-09-29 | Sunovion Pharmaceuticals Inc | Histamine h3 inverse agonists and antagonists and methods of use thereof |
| CN102480956B (zh) * | 2009-04-29 | 2015-04-08 | 梅迪维新技术公司 | 吡啶并[4,3-b]吲哚类和使用方法 |
| WO2010127177A1 (en) | 2009-04-29 | 2010-11-04 | Medivation Technologies, Inc. | Pyrido [4,3-b] indoles and methods of use |
| BR112012006646A2 (pt) * | 2009-09-23 | 2019-09-24 | Medivation Technologies Inc | composto, composição farmacêutica, método de tratamento de um distùrbio cognitivo, distúrbio psicótico, distúrbio mediado por neurotransmissor ou um distúrbio neuronal e kit |
| CN102711466A (zh) | 2009-09-23 | 2012-10-03 | 梅迪维新技术公司 | 桥连杂环化合物及其使用方法 |
| CA2775328A1 (en) | 2009-09-23 | 2011-03-31 | Medivation Technologies, Inc. | Pyrido[4,3-b]indoles and methods of use |
| US9193728B2 (en) | 2010-02-18 | 2015-11-24 | Medivation Technologies, Inc. | Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| US9034865B2 (en) | 2010-02-18 | 2015-05-19 | Medivation Technologies, Inc. | Pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| WO2011103485A1 (en) | 2010-02-18 | 2011-08-25 | Medivation Technologies, Inc. | Fused tetracyclic pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| US9187471B2 (en) | 2010-02-19 | 2015-11-17 | Medivation Technologies, Inc. | Pyrido [4,3-b] indole and pyrido [3,4-b] indole derivatives and methods of use |
| AU2011320565A1 (en) * | 2010-10-28 | 2013-05-23 | Innocrin Pharmaceuticals, Inc. | Metalloenzyme inhibitor compounds |
| WO2012112964A2 (en) | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | PYRIDO[4,3-b]INDOLE AND PYRIDO[3,4-b]INDOLE DERIVATIVES AND METHODS OF USE |
| CN103476416B (zh) * | 2011-02-18 | 2016-09-21 | 梅迪维新技术公司 | 治疗高血压的化合物和方法 |
| WO2012112963A1 (en) | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | Compounds and methods for treatment of hypertension |
| US20140303144A1 (en) | 2011-02-18 | 2014-10-09 | Medivation Technologies, Inc. | Compounds and methods of treating hypertension |
| RU2490268C2 (ru) * | 2011-11-10 | 2013-08-20 | Федеральное Государственное Бюджетное Учреждение Науки Институт Физиологически Активных Веществ Российской Академии Наук (Ифав Ран) | ХЛОРГИДРАТЫ ФТОРСОДЕРЖАЩИХ ЗАМЕЩЕННЫХ 5-[2-(ПИРИД-3-ИЛ)-ЭТИЛ]-2,3,4,5-ТЕТРАГИДРО-1Н-ПИРИДО[4,3-b]ИНДОЛОВ, В КАЧЕСТВЕ СРЕДСТВ СНИЖЕНИЯ НЕКОНТРОЛИРУЕМОЙ АГРЕГАЦИИ БЕЛКОВ В НЕРВНОЙ СИСТЕМЕ, ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ИХ ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| CN103974956B (zh) * | 2011-11-29 | 2016-07-06 | 南京奥昭生物科技有限公司 | 作为hdac6抑制剂和用作抗肿瘤剂的杂环酰胺化合物 |
| WO2014031170A1 (en) * | 2012-08-22 | 2014-02-27 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| EP2887805A4 (en) * | 2012-08-22 | 2016-08-17 | Medivation Technologies Inc | COMPOUNDS AND METHOD FOR TREATING BLOOD HIGH PRESSURE |
| US9907786B2 (en) | 2014-10-21 | 2018-03-06 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing harmine and isovanillin components, and methods of use thereof |
| US10092550B2 (en) | 2014-10-21 | 2018-10-09 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing curcumin, harmine, and isovanillin components, and methods of use thereof |
| US12129265B2 (en) | 2020-07-21 | 2024-10-29 | Ankh Life Sciences Limited | Therapeutic agents and uses thereof |
| KR20230171634A (ko) * | 2022-06-14 | 2023-12-21 | 주식회사 레고켐 바이오사이언스 | 엑토뉴클레오티드 피로포스파타아제 포스포디에스터라아제-1 저해 화합물 및 이를 함유하는 약제학적 조성물 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007087425A1 (en) * | 2006-01-25 | 2007-08-02 | Medivation Neurology,Inc. | Methods and compositions for treating schizophrenia |
| WO2008123796A2 (ru) * | 2007-04-05 | 2008-10-16 | Alla Chem, Llc | Замещенные 2,3,4,5-tetpaгидpo-1h-пиpидo[4,3-b]иhдoлы, способ их получения и применения |
| WO2009017836A1 (en) * | 2007-08-01 | 2009-02-05 | Medivation Neurology, Inc. | Methods and compositions for treating schizophrenia using antipsychotic combination therapy |
| WO2009038764A1 (en) * | 2007-09-20 | 2009-03-26 | D2E, Llc | Fluoro-containing derivatives of hydrogented pyrido[4,3-b]indoles with neuroprotective and cognition enhancing properties, process for preparing, and use |
| RU2007139634A (ru) * | 2007-10-25 | 2009-04-27 | Сергей Олегович Бачурин (RU) | Новые тиазол-, триазол- или оксадиазол-содержащие тетрациклические соединения |
| WO2010051501A1 (en) * | 2008-10-31 | 2010-05-06 | Medivation Technologies, Inc. | Pyrido (4,3-b) indoles containing rigid moieties |
Family Cites Families (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3484449A (en) | 1966-05-12 | 1969-12-16 | Hoffmann La Roche | Certain substituted phenyl amino-ethylpyridine intermediates |
| US3409628A (en) | 1966-05-12 | 1968-11-05 | Hoffmann La Roche | 5-(3-pyridylethyl)pyridoindole derivatives |
| US3502688A (en) | 1968-09-10 | 1970-03-24 | Hoffmann La Roche | 5-(4-pyridylethyl)-pyridoindole derivatives |
| US3646045A (en) | 1968-09-10 | 1972-02-29 | Hoffmann La Roche | Intermediates for 5-(4-pyridylethyl)-pyridoindole derivatives |
| JPS5143863B2 (enExample) | 1973-06-18 | 1976-11-25 | ||
| US4754038A (en) | 1987-02-26 | 1988-06-28 | American Home Products Corporation | Carboline histamine H1 antagonists |
| NO169714C (no) | 1988-08-02 | 1992-07-29 | Glaxo Group Ltd | Analogifremgangsmaate for fremstilling av terapeutisk aktive laktamderivater |
| RU2140417C1 (ru) | 1995-10-17 | 1999-10-27 | Институт физиологически активных веществ РАН | Производные гидрированных пиридо(4,3-b)индолов, способы их получения, фармацевтическая композиция и способ лечения |
| RU2106864C1 (ru) | 1995-10-23 | 1998-03-20 | Николай Серафимович Зефиров | Средство для лечения болезни альцгеймера |
| DE10030375A1 (de) | 2000-06-21 | 2002-01-03 | Bayer Ag | Verwendung von MTP-Inhibitoren zur Senkung von ppTRL |
| BR0211608A (pt) * | 2001-08-08 | 2006-04-04 | Upjohn Co | 1h-pirido[4,3-b]indóis terapêuticos |
| RU2283108C2 (ru) | 2003-12-08 | 2006-09-10 | Сергей Олегович Бачурин | ГЕРОПРОТЕКТОР НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b) ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| EA014956B1 (ru) | 2004-12-17 | 2011-04-29 | ГЛЕНМАРК ФАРМАСЬЮТИКАЛС Эс.Эй. | Гетероциклические соединения, применяемые для лечения воспалительных и аллергических нарушений |
| WO2007016353A2 (en) | 2005-07-28 | 2007-02-08 | Bristol-Myers Squibb Company | Substituted tetrahydro-1h-pyrido[4,3,b]indoles as serotonin receptor agonists and antagonists |
| WO2007041697A2 (en) | 2005-10-04 | 2007-04-12 | Medivation, Inc. | Hydrogenated pyrido-indole compounds for the treatment of huntington ' s disease |
| EP2066322A2 (en) | 2006-09-20 | 2009-06-10 | Medivation Neurology, Inc. | Hydrogenated pyrido [4,3-b] indoles such as dimebon for treating canine cognitive dysfunction syndrome |
| CA2664099A1 (en) | 2006-09-20 | 2008-03-27 | Medivation Neurology, Inc. | Methods and compositions for treating amyotrophic lateral sclerosis (als) |
| CA2667553A1 (en) | 2006-10-27 | 2008-05-02 | Medivation Neurology, Inc. | Methods and combination therapies for treating alzheimer's disease |
| RU2329044C1 (ru) | 2006-11-16 | 2008-07-20 | Андрей Александрович Иващенко | Лиганды 5-ht6 рецепторов, фармацевтическая композиция, способ ее получения и лекарственное средство |
| RU2334514C1 (ru) | 2006-12-01 | 2008-09-27 | Институт физиологически активных веществ Российской Академии наук | СРЕДСТВО ДЛЯ УЛУЧШЕНИЯ КОГНИТИВНЫХ ФУНКЦИЙ И ПАМЯТИ НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО (4,3-b) ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| RU2340342C2 (ru) | 2006-12-07 | 2008-12-10 | Сергей Олегович Бачурин | СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ОСТРЫХ И ХРОНИЧЕСКИХ НАРУШЕНИЙ МОЗГОВОГО КРОВООБРАЩЕНИЯ, В ТОМ ЧИСЛЕ ИНСУЛЬТА, НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО[4,3-b]ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| RU2338745C1 (ru) | 2007-03-21 | 2008-11-20 | Андрей Александрович Иващенко | ЗАМЕЩЕННЫЕ 2,3,4,5-ТЕТРАГИДРО-1Н-ПИРИДО[4,3-b]ИНДОЛЫ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ |
| RU2339637C1 (ru) * | 2007-04-05 | 2008-11-27 | Андрей Александрович Иващенко | Блокаторы гистаминного рецептора для фармацевтических композиций, обладающих противоаллергическим и аутоиммунным действием |
| JP2010528016A (ja) | 2007-05-25 | 2010-08-19 | メディベーション ニューロロジー, インコーポレイテッド | 細胞を刺激するための方法および組成物 |
| RU2338533C1 (ru) | 2007-06-28 | 2008-11-20 | Сергей Олегович Бачурин | СРЕДСТВО, ОБЛАДАЮЩЕЕ АНКСИОЛИТИЧЕСКИМ ДЕЙСТВИЕМ, НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b)ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| WO2009039420A1 (en) | 2007-09-21 | 2009-03-26 | Medivation Neurology, Inc. | Methods and compositions for treating neuronal death mediated ocular diseases |
| WO2009082268A2 (ru) | 2007-12-21 | 2009-07-02 | Alla Chem, Llc | ЛИГАНДЫ α-АДРЕНОЦЕПТОРОВ, ДОПАМИНОВЫХ, ГИСТАМИНОВЫХ, ИМИДАЗОЛИНОВЫХ И СЕРОТОНИНОВЫХ РЕЦЕПТОРОВ И ИХ ПРИМЕНЕНИЕ |
| RU2544856C2 (ru) | 2008-01-25 | 2015-03-20 | Сергей Олегович Бачурин | НОВЫЕ ПРОИЗВОДНЫЕ 2,3,4,5-ТЕТРАГИДРО-1-ПИРИДО[4,3-b]ИНДОЛА И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| WO2009111540A1 (en) | 2008-03-04 | 2009-09-11 | Medivation Neurology, Inc. | Methods for preparing pyridylethyl-substituted carbolines |
| WO2009120717A2 (en) | 2008-03-24 | 2009-10-01 | Medivation Technologies, Inc. | Pyrido [3, 4-b] indoles and methods of use |
| BRPI0906245A2 (pt) | 2008-03-24 | 2015-06-30 | Medivation Technologies Inc | Composto, método para tratar um distúrbio cognitivo, psicótico, mediado por neurotransmissor ou um distúrbio neuronal em indivíduo, uso de um composto, composição farmacêutica e kit |
| WO2009135091A1 (en) | 2008-04-30 | 2009-11-05 | Medivation Technologies, Inc. | Use of asenapine and related compounds for the treatment of neuronal or non-neuronal diseases or conditions |
| US20100029706A1 (en) | 2008-07-30 | 2010-02-04 | Edison Parmaceuticals, Inc. a Delaware Corporation | HYDROGENATED PYRIDO[4,3-b]INDOLES FOR THE TREATMENT OF OXIDATIVE STRESS |
| US9625475B2 (en) | 2008-09-29 | 2017-04-18 | Abbvie Inc. | Indole and indoline derivatives and methods of use thereof |
| AR073701A1 (es) | 2008-09-29 | 2010-11-24 | Abbott Lab | Derivados de indol y de indolicina, metodos para su preparacion, una composicion farmaceutica que los comprende y su uso en el tratamiento de enfermedades neurodegenerativas. |
| EP2348847A4 (en) | 2008-10-31 | 2012-05-23 | Medivation Technologies Inc | AZEPINO [4, 5-B] INDOLE AND USE PROCESS |
| US9962368B2 (en) | 2009-01-09 | 2018-05-08 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| US8362277B2 (en) | 2009-01-09 | 2013-01-29 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| WO2010081115A1 (en) | 2009-01-09 | 2010-07-15 | University Of Texas Southwestern Medical Center | Pro-neurogenic compounds |
| WO2010127177A1 (en) | 2009-04-29 | 2010-11-04 | Medivation Technologies, Inc. | Pyrido [4,3-b] indoles and methods of use |
| CN102480956B (zh) | 2009-04-29 | 2015-04-08 | 梅迪维新技术公司 | 吡啶并[4,3-b]吲哚类和使用方法 |
| WO2011008312A2 (en) | 2009-07-14 | 2011-01-20 | Abbott Laboratories | Indole and indoline derivatives and methods of use thereof |
| WO2011014695A1 (en) | 2009-07-29 | 2011-02-03 | Medivation Technologies, Inc. | New 2,3,4,5-tetrahydro-1h-pyrido[4,3-b] indoles and methods of use |
| BR112012006644A2 (pt) | 2009-09-23 | 2019-09-24 | Medivation Neurology Inc | composto,método de tratamento de um distúrbio cognitivo, distúrbio psicótico, distúrbio mediado por neurotransmissor ou um distúrbio neuronal, composição farmacêutica, uso de um composto e kit |
| BR112012006646A2 (pt) | 2009-09-23 | 2019-09-24 | Medivation Technologies Inc | composto, composição farmacêutica, método de tratamento de um distùrbio cognitivo, distúrbio psicótico, distúrbio mediado por neurotransmissor ou um distúrbio neuronal e kit |
| CN102711466A (zh) | 2009-09-23 | 2012-10-03 | 梅迪维新技术公司 | 桥连杂环化合物及其使用方法 |
| CA2775328A1 (en) | 2009-09-23 | 2011-03-31 | Medivation Technologies, Inc. | Pyrido[4,3-b]indoles and methods of use |
| US9034865B2 (en) | 2010-02-18 | 2015-05-19 | Medivation Technologies, Inc. | Pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| US9193728B2 (en) | 2010-02-18 | 2015-11-24 | Medivation Technologies, Inc. | Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| WO2011103485A1 (en) | 2010-02-18 | 2011-08-25 | Medivation Technologies, Inc. | Fused tetracyclic pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| US20130172320A1 (en) | 2010-02-18 | 2013-07-04 | Sarvajit Chakravarty | Pyrido [4,3-b] indole and pyrido [3,4-b] indole derivatives and methods of use |
| US9187471B2 (en) | 2010-02-19 | 2015-11-17 | Medivation Technologies, Inc. | Pyrido [4,3-b] indole and pyrido [3,4-b] indole derivatives and methods of use |
| WO2011103448A1 (en) | 2010-02-19 | 2011-08-25 | Medivation Technologies, Inc. | Methods and compositions for treating psychotic disorders using antipsychotic combination therapy |
| CN103415289B (zh) | 2010-07-07 | 2017-04-12 | 得克萨斯州大学系统董事会 | 前神经原性化合物 |
| WO2012112963A1 (en) | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | Compounds and methods for treatment of hypertension |
| US20140303144A1 (en) | 2011-02-18 | 2014-10-09 | Medivation Technologies, Inc. | Compounds and methods of treating hypertension |
| CN103476416B (zh) | 2011-02-18 | 2016-09-21 | 梅迪维新技术公司 | 治疗高血压的化合物和方法 |
| WO2012112964A2 (en) | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | PYRIDO[4,3-b]INDOLE AND PYRIDO[3,4-b]INDOLE DERIVATIVES AND METHODS OF USE |
| WO2014031170A1 (en) | 2012-08-22 | 2014-02-27 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| EP2887805A4 (en) | 2012-08-22 | 2016-08-17 | Medivation Technologies Inc | COMPOUNDS AND METHOD FOR TREATING BLOOD HIGH PRESSURE |
| WO2014031125A1 (en) | 2012-08-24 | 2014-02-27 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
-
2010
- 2010-04-29 WO PCT/US2010/033053 patent/WO2010127177A1/en not_active Ceased
- 2010-04-29 US US13/318,123 patent/US9255094B2/en not_active Expired - Fee Related
- 2010-04-29 BR BRPI1006602A patent/BRPI1006602A2/pt not_active IP Right Cessation
- 2010-04-29 JP JP2012508751A patent/JP5711725B2/ja not_active Expired - Fee Related
- 2010-04-29 CN CN201080028795.7A patent/CN102480955B/zh not_active Expired - Fee Related
- 2010-04-29 CA CA2760541A patent/CA2760541A1/en not_active Abandoned
- 2010-04-29 AU AU2010242910A patent/AU2010242910B2/en not_active Ceased
- 2010-04-29 EP EP10770380A patent/EP2424364A4/en not_active Withdrawn
-
2013
- 2013-03-08 US US13/791,796 patent/US20130190328A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007087425A1 (en) * | 2006-01-25 | 2007-08-02 | Medivation Neurology,Inc. | Methods and compositions for treating schizophrenia |
| WO2008123796A2 (ru) * | 2007-04-05 | 2008-10-16 | Alla Chem, Llc | Замещенные 2,3,4,5-tetpaгидpo-1h-пиpидo[4,3-b]иhдoлы, способ их получения и применения |
| WO2009017836A1 (en) * | 2007-08-01 | 2009-02-05 | Medivation Neurology, Inc. | Methods and compositions for treating schizophrenia using antipsychotic combination therapy |
| WO2009038764A1 (en) * | 2007-09-20 | 2009-03-26 | D2E, Llc | Fluoro-containing derivatives of hydrogented pyrido[4,3-b]indoles with neuroprotective and cognition enhancing properties, process for preparing, and use |
| RU2007139634A (ru) * | 2007-10-25 | 2009-04-27 | Сергей Олегович Бачурин (RU) | Новые тиазол-, триазол- или оксадиазол-содержащие тетрациклические соединения |
| WO2010051501A1 (en) * | 2008-10-31 | 2010-05-06 | Medivation Technologies, Inc. | Pyrido (4,3-b) indoles containing rigid moieties |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2010242910A1 (en) | 2011-11-17 |
| CN102480955A (zh) | 2012-05-30 |
| JP2012525430A (ja) | 2012-10-22 |
| HK1170380A1 (en) | 2013-03-01 |
| BRPI1006602A2 (pt) | 2019-01-15 |
| EP2424364A4 (en) | 2012-12-19 |
| CN102480955B (zh) | 2015-08-05 |
| US20130190328A1 (en) | 2013-07-25 |
| WO2010127177A8 (en) | 2011-12-15 |
| US9255094B2 (en) | 2016-02-09 |
| WO2010127177A1 (en) | 2010-11-04 |
| EP2424364A1 (en) | 2012-03-07 |
| CA2760541A1 (en) | 2010-11-04 |
| US20120136008A1 (en) | 2012-05-31 |
| JP5711725B2 (ja) | 2015-05-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2010242910B2 (en) | Pyrido [4,3-b] indoles and methods of use | |
| AU2010282990B2 (en) | Pyrido [4, 3-b] indoles and methods of use | |
| AU2010298167B2 (en) | Pyrido(3,4-b)indoles and methods of use | |
| AU2009228401B2 (en) | Bridged heterocyclic compounds and methods of use | |
| AU2010298168B2 (en) | Pyrido(3,4-b)indoles and methods of use | |
| AU2010298166B2 (en) | Pyrido[4,3-b]indoles and methods of use | |
| WO2011038164A1 (en) | Bridged heterocyclic compounds and methods of use | |
| WO2011103487A1 (en) | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use | |
| AU2013203575A1 (en) | Pyrido [4,3-b] indoles and methods of use | |
| AU2013203580A1 (en) | Bridged heterocyclic compounds and methods of use | |
| AU2013203574A1 (en) | Pyrido [4,3-b] indoles and methods of use | |
| AU2013203573A1 (en) | Pyrido(3,4-b)indoles and methods of use | |
| HK1170380B (en) | Pyrido [4,3-b] indoles and methods of use | |
| HK1176814A (en) | Pyrido[3,4-b]indoles and methods of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |