CN102724875B - 吡啶并[3,4-b]吲哚化合物及其使用方法 - Google Patents
吡啶并[3,4-b]吲哚化合物及其使用方法 Download PDFInfo
- Publication number
- CN102724875B CN102724875B CN201080047262.3A CN201080047262A CN102724875B CN 102724875 B CN102724875 B CN 102724875B CN 201080047262 A CN201080047262 A CN 201080047262A CN 102724875 B CN102724875 B CN 102724875B
- Authority
- CN
- China
- Prior art keywords
- unsubstituted
- replacement
- alkyl
- compound
- formula
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title abstract description 133
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical class N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 title abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 563
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 122
- 238000011282 treatment Methods 0.000 claims abstract description 63
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 55
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 52
- 239000002858 neurotransmitter agent Substances 0.000 claims abstract description 40
- 230000001537 neural effect Effects 0.000 claims abstract description 39
- 229910052736 halogen Inorganic materials 0.000 claims description 203
- 150000002367 halogens Chemical class 0.000 claims description 189
- 125000003118 aryl group Chemical group 0.000 claims description 178
- 125000001072 heteroaryl group Chemical group 0.000 claims description 161
- 125000000217 alkyl group Chemical group 0.000 claims description 117
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 117
- 201000010099 disease Diseases 0.000 claims description 114
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 109
- 229910052799 carbon Inorganic materials 0.000 claims description 95
- 150000003839 salts Chemical class 0.000 claims description 92
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 82
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 78
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 70
- 239000000203 mixture Substances 0.000 claims description 57
- 125000004076 pyridyl group Chemical group 0.000 claims description 48
- 125000000623 heterocyclic group Chemical group 0.000 claims description 41
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 239000005864 Sulphur Substances 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims 6
- 102000000543 Histamine Receptors Human genes 0.000 abstract description 50
- 108010002059 Histamine Receptors Proteins 0.000 abstract description 50
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 8
- 230000001225 therapeutic effect Effects 0.000 abstract description 8
- 230000001404 mediated effect Effects 0.000 abstract description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 423
- 125000003545 alkoxy group Chemical group 0.000 description 288
- -1 Pyrido [3,4-b] benzazolyl compounds Chemical class 0.000 description 270
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 252
- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical group [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 description 110
- 230000000694 effects Effects 0.000 description 100
- 125000004442 acylamino group Chemical group 0.000 description 85
- 230000027455 binding Effects 0.000 description 82
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 78
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 75
- 239000000370 acceptor Substances 0.000 description 73
- 125000001188 haloalkyl group Chemical group 0.000 description 71
- 125000004093 cyano group Chemical group *C#N 0.000 description 67
- ZPFKRQXYKULZKP-UHFFFAOYSA-N butylidene Chemical group [CH2+]CC[CH-] ZPFKRQXYKULZKP-UHFFFAOYSA-N 0.000 description 64
- 239000003446 ligand Substances 0.000 description 63
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 57
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 57
- 238000012360 testing method Methods 0.000 description 57
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 56
- 125000000753 cycloalkyl group Chemical group 0.000 description 54
- 208000024891 symptom Diseases 0.000 description 54
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 51
- 125000004423 acyloxy group Chemical group 0.000 description 50
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 49
- 239000003795 chemical substances by application Substances 0.000 description 49
- 125000002252 acyl group Chemical group 0.000 description 44
- 102000015554 Dopamine receptor Human genes 0.000 description 43
- 108050004812 Dopamine receptor Proteins 0.000 description 43
- 230000014511 neuron projection development Effects 0.000 description 42
- 125000000304 alkynyl group Chemical group 0.000 description 39
- 239000002585 base Substances 0.000 description 39
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 39
- 150000001721 carbon Chemical group 0.000 description 38
- 108060003345 Adrenergic Receptor Proteins 0.000 description 37
- 102000017910 Adrenergic receptor Human genes 0.000 description 37
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 36
- 125000003710 aryl alkyl group Chemical group 0.000 description 35
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 31
- 125000004104 aryloxy group Chemical group 0.000 description 31
- 125000003396 thiol group Chemical group [H]S* 0.000 description 31
- 239000000460 chlorine Substances 0.000 description 30
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 28
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 28
- 229910052801 chlorine Inorganic materials 0.000 description 28
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 28
- 210000005036 nerve Anatomy 0.000 description 28
- 125000002769 thiazolinyl group Chemical group 0.000 description 28
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 26
- 150000001412 amines Chemical class 0.000 description 26
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 26
- 208000024827 Alzheimer disease Diseases 0.000 description 25
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 25
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 25
- FHDKOPWCFICHAZ-UHFFFAOYSA-N NC(=O)N(OC(=O)O)N Chemical compound NC(=O)N(OC(=O)O)N FHDKOPWCFICHAZ-UHFFFAOYSA-N 0.000 description 25
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 25
- 230000004064 dysfunction Effects 0.000 description 23
- 230000003750 conditioning effect Effects 0.000 description 22
- 230000007074 memory dysfunction Effects 0.000 description 22
- 230000008859 change Effects 0.000 description 21
- 230000008569 process Effects 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 20
- 230000000875 corresponding effect Effects 0.000 description 20
- 125000005843 halogen group Chemical group 0.000 description 20
- 238000011161 development Methods 0.000 description 19
- 230000018109 developmental process Effects 0.000 description 19
- 239000012453 solvate Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 238000010828 elution Methods 0.000 description 18
- 230000015654 memory Effects 0.000 description 18
- 230000006378 damage Effects 0.000 description 17
- 208000027061 mild cognitive impairment Diseases 0.000 description 17
- 102000005962 receptors Human genes 0.000 description 17
- 108020003175 receptors Proteins 0.000 description 17
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 16
- 239000000556 agonist Substances 0.000 description 16
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 16
- 208000011580 syndromic disease Diseases 0.000 description 16
- 208000012902 Nervous system disease Diseases 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 125000005243 carbonyl alkyl group Chemical group 0.000 description 15
- 230000019771 cognition Effects 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 230000009467 reduction Effects 0.000 description 15
- 201000000980 schizophrenia Diseases 0.000 description 15
- 230000003920 cognitive function Effects 0.000 description 14
- 230000001934 delay Effects 0.000 description 14
- 229960003638 dopamine Drugs 0.000 description 14
- 239000012071 phase Substances 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 13
- 230000001713 cholinergic effect Effects 0.000 description 13
- 239000012535 impurity Substances 0.000 description 13
- 208000021075 Creatine deficiency syndrome Diseases 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 208000020339 Spinal injury Diseases 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 230000006399 behavior Effects 0.000 description 12
- 210000004556 brain Anatomy 0.000 description 12
- 201000008609 cerebral creatine deficiency syndrome Diseases 0.000 description 12
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 12
- 229940075993 receptor modulator Drugs 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- 238000006243 chemical reaction Methods 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
- 239000002243 precursor Substances 0.000 description 11
- 230000001105 regulatory effect Effects 0.000 description 11
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 208000030886 Traumatic Brain injury Diseases 0.000 description 10
- 125000006598 aminocarbonylamino group Chemical group 0.000 description 10
- 230000003042 antagnostic effect Effects 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 206010027175 memory impairment Diseases 0.000 description 10
- 230000000508 neurotrophic effect Effects 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 230000009529 traumatic brain injury Effects 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 206010003805 Autism Diseases 0.000 description 9
- 208000020706 Autistic disease Diseases 0.000 description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 9
- 208000023105 Huntington disease Diseases 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 208000018737 Parkinson disease Diseases 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 208000027418 Wounds and injury Diseases 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 239000011737 fluorine Substances 0.000 description 9
- 229910052731 fluorine Inorganic materials 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 208000014674 injury Diseases 0.000 description 9
- 208000002780 macular degeneration Diseases 0.000 description 9
- 230000004770 neurodegeneration Effects 0.000 description 9
- 208000015122 neurodegenerative disease Diseases 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 9
- 230000008447 perception Effects 0.000 description 9
- 125000004193 piperazinyl group Chemical group 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 238000002648 combination therapy Methods 0.000 description 8
- 239000013058 crude material Substances 0.000 description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
- 230000002708 enhancing effect Effects 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 229960001340 histamine Drugs 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 210000002161 motor neuron Anatomy 0.000 description 8
- 125000006574 non-aromatic ring group Chemical group 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000004088 simulation Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 7
- 206010008190 Cerebrovascular accident Diseases 0.000 description 7
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 7
- 208000006011 Stroke Diseases 0.000 description 7
- 230000032683 aging Effects 0.000 description 7
- 125000004414 alkyl thio group Chemical group 0.000 description 7
- 230000001149 cognitive effect Effects 0.000 description 7
- 230000034994 death Effects 0.000 description 7
- 125000002757 morpholinyl group Chemical group 0.000 description 7
- 201000006417 multiple sclerosis Diseases 0.000 description 7
- 210000003205 muscle Anatomy 0.000 description 7
- 208000033808 peripheral neuropathy Diseases 0.000 description 7
- 230000035807 sensation Effects 0.000 description 7
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 6
- 241000282465 Canis Species 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 208000001640 Fibromyalgia Diseases 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 230000002052 anaphylactic effect Effects 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 230000002596 correlated effect Effects 0.000 description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 6
- 230000008030 elimination Effects 0.000 description 6
- 238000003379 elimination reaction Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 125000004043 oxo group Chemical group O=* 0.000 description 6
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 230000010349 pulsation Effects 0.000 description 6
- 230000001629 suppression Effects 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- WYKHSBAVLOPISI-UHFFFAOYSA-N 2-phenyl-1,3-thiazole Chemical class C1=CSC(C=2C=CC=CC=2)=N1 WYKHSBAVLOPISI-UHFFFAOYSA-N 0.000 description 5
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 5
- 201000004384 Alopecia Diseases 0.000 description 5
- 208000019901 Anxiety disease Diseases 0.000 description 5
- 208000020925 Bipolar disease Diseases 0.000 description 5
- 208000028698 Cognitive impairment Diseases 0.000 description 5
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 5
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 5
- PMZXXNPJQYDFJX-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid Chemical compound CC#N.OC(=O)C(F)(F)F PMZXXNPJQYDFJX-UHFFFAOYSA-N 0.000 description 5
- 125000002877 alkyl aryl group Chemical group 0.000 description 5
- 230000000561 anti-psychotic effect Effects 0.000 description 5
- 239000000739 antihistaminic agent Substances 0.000 description 5
- 230000036506 anxiety Effects 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 description 5
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 5
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 5
- 210000003470 mitochondria Anatomy 0.000 description 5
- 230000016273 neuron death Effects 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 125000005936 piperidyl group Chemical group 0.000 description 5
- 208000020016 psychiatric disease Diseases 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-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
- 206010057315 Daydreaming Diseases 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 206010020651 Hyperkinesia Diseases 0.000 description 4
- 208000000269 Hyperkinesis Diseases 0.000 description 4
- 102000006386 Myelin Proteins Human genes 0.000 description 4
- 108010083674 Myelin Proteins Proteins 0.000 description 4
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 4
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 150000001350 alkyl halides Chemical class 0.000 description 4
- 230000001387 anti-histamine Effects 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 208000030533 eye disease Diseases 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 201000009277 hairy cell leukemia Diseases 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 208000013403 hyperactivity Diseases 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000013016 learning Effects 0.000 description 4
- 210000005012 myelin Anatomy 0.000 description 4
- 230000003955 neuronal function Effects 0.000 description 4
- 201000001119 neuropathy Diseases 0.000 description 4
- 230000007823 neuropathy Effects 0.000 description 4
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 4
- 229940067157 phenylhydrazine Drugs 0.000 description 4
- 125000003373 pyrazinyl group Chemical group 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010002198 Anaphylactic reaction Diseases 0.000 description 3
- 108010011485 Aspartame Proteins 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 208000002177 Cataract Diseases 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
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- 208000028389 Nerve injury Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 101100228853 Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2) gds gene Proteins 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 231100000360 alopecia Toxicity 0.000 description 3
- 230000036783 anaphylactic response Effects 0.000 description 3
- 208000003455 anaphylaxis Diseases 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
- 235000010357 aspartame Nutrition 0.000 description 3
- 239000000605 aspartame Substances 0.000 description 3
- 229960003438 aspartame Drugs 0.000 description 3
- 230000003935 attention Effects 0.000 description 3
- 230000008901 benefit Effects 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
- 230000037396 body weight Effects 0.000 description 3
- 230000000739 chaotic effect Effects 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 230000006866 deterioration Effects 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000009545 invasion Effects 0.000 description 3
- 230000008449 language Effects 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 230000008764 nerve damage 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
- 150000007524 organic acids Chemical class 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000010572 single replacement reaction Methods 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000007738 vacuum evaporation Methods 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
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- QEHMBCDTVQBATA-UHFFFAOYSA-N 3-pyrrolidin-3-yl-1h-indole Chemical class C1NCCC1C1=CNC2=CC=CC=C12 QEHMBCDTVQBATA-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 241000824799 Canis lupus dingo Species 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- 206010015995 Eyelid ptosis Diseases 0.000 description 2
- 208000013171 Fahr disease Diseases 0.000 description 2
- 241000282324 Felis Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 102000009032 Imidazoline Receptors Human genes 0.000 description 2
- 108010049134 Imidazoline Receptors Proteins 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
- 208000009829 Lewy Body Disease Diseases 0.000 description 2
- 201000002832 Lewy body dementia Diseases 0.000 description 2
- 208000035719 Maculopathy Diseases 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- 208000002720 Malnutrition Diseases 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 206010028372 Muscular weakness Diseases 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 206010034719 Personality change Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010050254 Presenilins Proteins 0.000 description 2
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 2
- 229920003110 Primojel Polymers 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 208000006289 Rett Syndrome Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 206010044565 Tremor Diseases 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 230000009471 action Effects 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
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- 125000001118 alkylidene group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 101150031224 app gene Proteins 0.000 description 2
- 239000012752 auxiliary agent Substances 0.000 description 2
- 210000004227 basal ganglia Anatomy 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 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
- 230000002490 cerebral effect Effects 0.000 description 2
- 239000007910 chewable tablet Substances 0.000 description 2
- 229940068682 chewable tablet Drugs 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 230000003930 cognitive ability Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 210000005064 dopaminergic neuron Anatomy 0.000 description 2
- 208000024732 dysthymic disease Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 208000024963 hair loss Diseases 0.000 description 2
- 230000003676 hair loss Effects 0.000 description 2
- 150000002429 hydrazines Chemical class 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 201000010901 lateral sclerosis Diseases 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000001071 malnutrition Effects 0.000 description 2
- 235000000824 malnutrition Nutrition 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 229910021645 metal ion Inorganic materials 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
- 230000002438 mitochondrial effect Effects 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
- 230000036473 myasthenia Effects 0.000 description 2
- 206010028417 myasthenia gravis Diseases 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 210000002241 neurite Anatomy 0.000 description 2
- 229960002748 norepinephrine Drugs 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
- 208000015380 nutritional deficiency disease Diseases 0.000 description 2
- 210000004248 oligodendroglia Anatomy 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 201000003004 ptosis Diseases 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- ZFRKQXVRDFCRJG-UHFFFAOYSA-N skatole Chemical compound C1=CC=C2C(C)=CNC2=C1 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 description 2
- 229940074386 skatole Drugs 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 230000003997 social interaction Effects 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 238000009834 vaporization Methods 0.000 description 2
- 230000008016 vaporization Effects 0.000 description 2
- 208000029257 vision disease Diseases 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
- MEIRRNXMZYDVDW-MQQKCMAXSA-N (2E,4E)-2,4-hexadien-1-ol Chemical compound C\C=C\C=C\CO MEIRRNXMZYDVDW-MQQKCMAXSA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical class C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
- 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 1
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 208000017194 Affective disease Diseases 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 1
- 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 1
- 206010002942 Apathy Diseases 0.000 description 1
- 241000256844 Apis mellifera Species 0.000 description 1
- 108010060159 Apolipoprotein E4 Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010061666 Autonomic neuropathy Diseases 0.000 description 1
- 208000004130 Blepharoptosis Diseases 0.000 description 1
- 206010005176 Blindness congenital Diseases 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
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010056467 Cerebral dysgenesis Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- 206010009848 Cogwheel rigidity Diseases 0.000 description 1
- 208000036693 Color-vision disease Diseases 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
- 101710112752 Cytotoxin Proteins 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 201000004624 Dermatitis 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
- 208000003164 Diplopia Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010013486 Distractibility Diseases 0.000 description 1
- 229940121891 Dopamine receptor antagonist Drugs 0.000 description 1
- 201000001353 Doyne honeycomb retinal dystrophy Diseases 0.000 description 1
- 206010049712 Dysacusis Diseases 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- KGWDUNBJIMUFAP-KVVVOXFISA-N Ethanolamine Oleate Chemical compound NCCO.CCCCCCCC\C=C/CCCCCCCC(O)=O KGWDUNBJIMUFAP-KVVVOXFISA-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
- 208000037312 Familial drusen Diseases 0.000 description 1
- 208000003492 Fundus albipunctatus Diseases 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
- 240000004859 Gamochaeta purpurea Species 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000016621 Hearing disease 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
- 241000238631 Hexapoda Species 0.000 description 1
- 241000167880 Hirundinidae Species 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
- 101001109698 Homo sapiens Nuclear receptor subfamily 4 group A member 2 Proteins 0.000 description 1
- 101001092197 Homo sapiens RNA binding protein fox-1 homolog 3 Proteins 0.000 description 1
- 102000016252 Huntingtin Human genes 0.000 description 1
- 108050004784 Huntingtin Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 206010021283 IIIrd nerve paralysis Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 201000000639 Leber hereditary optic neuropathy Diseases 0.000 description 1
- 241001289721 Lethe Species 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 206010025412 Macular dystrophy congenital 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
- 102100021118 Microtubule-associated protein 2 Human genes 0.000 description 1
- 206010027918 Mononeuropathy multiplex Diseases 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 208000002740 Muscle Rigidity Diseases 0.000 description 1
- 206010056720 Muscle mass Diseases 0.000 description 1
- 206010028347 Muscle twitching Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 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
- 208000008457 Neurologic Manifestations Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 208000001140 Night Blindness Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102100022676 Nuclear receptor subfamily 4 group A member 2 Human genes 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 102000015094 Paraproteins Human genes 0.000 description 1
- 108010064255 Paraproteins Proteins 0.000 description 1
- 208000034247 Pattern dystrophy Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000028361 Penetrating Head injury Diseases 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 102100035530 RNA binding protein fox-1 homolog 3 Human genes 0.000 description 1
- 206010037779 Radiculopathy Diseases 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 206010039203 Road traffic accident Diseases 0.000 description 1
- CWHJIJJSDGEHNS-MYLFLSLOSA-N Senegenin Chemical compound C1[C@H](O)[C@H](O)[C@@](C)(C(O)=O)[C@@H]2CC[C@@]3(C)C(CC[C@]4(CCC(C[C@H]44)(C)C)C(O)=O)=C4[C@@H](CCl)C[C@@H]3[C@]21C CWHJIJJSDGEHNS-MYLFLSLOSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 208000005392 Spasm 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
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 206010043431 Thinking abnormal Diseases 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 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
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- VFIJBTVGUHVPPW-UHFFFAOYSA-N [Br].C=C Chemical compound [Br].C=C VFIJBTVGUHVPPW-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 208000037919 acquired disease Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 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
- 230000001270 agonistic effect Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 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
- 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
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 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
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000002453 autonomic neuron Anatomy 0.000 description 1
- 201000002922 basal ganglia calcification Diseases 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 231100000871 behavioral problem Toxicity 0.000 description 1
- 230000003542 behavioural effect Effects 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
- 239000003150 biochemical marker Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 230000003925 brain function 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
- 210000001775 bruch membrane Anatomy 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 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
- 230000036952 cancer formation Effects 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 206010007776 catatonia Diseases 0.000 description 1
- 230000023402 cell communication Effects 0.000 description 1
- 229950010118 cellacefate Drugs 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000015111 chews Nutrition 0.000 description 1
- 230000006949 cholinergic function Effects 0.000 description 1
- 210000002932 cholinergic neuron Anatomy 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
- 230000001684 chronic effect Effects 0.000 description 1
- 230000037410 cognitive enhancement Effects 0.000 description 1
- 230000036992 cognitive tasks Effects 0.000 description 1
- 201000007254 color blindness Diseases 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 231100000867 compulsive behavior Toxicity 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 208000006623 congenital stationary night blindness Diseases 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- CFBGXYDUODCMNS-UHFFFAOYSA-N cyclobutene Chemical compound C1CC=C1 CFBGXYDUODCMNS-UHFFFAOYSA-N 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
- UKPXULFIISGBHG-UHFFFAOYSA-N cyclopropene Chemical compound [CH]1C=C1 UKPXULFIISGBHG-UHFFFAOYSA-N 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 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
- 230000008034 disappearance Effects 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 238000002001 electrophysiology Methods 0.000 description 1
- 230000007831 electrophysiology Effects 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-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
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000008921 facial expression Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 201000006321 fundus dystrophy Diseases 0.000 description 1
- 230000002398 geroprotective effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 210000004884 grey matter Anatomy 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000004295 hippocampal neuron Anatomy 0.000 description 1
- 230000000742 histaminergic effect Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 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
- 230000002045 lasting effect Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000003715 limbic system Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 206010026820 marasmus Diseases 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003924 mental process Effects 0.000 description 1
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 1
- 229960000582 mepyramine Drugs 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004065 mitochondrial dysfunction Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 201000002003 mononeuritis multiplex Diseases 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007383 nerve stimulation Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000005155 neural progenitor cell Anatomy 0.000 description 1
- 210000005157 neural retina Anatomy 0.000 description 1
- 230000036403 neuro physiology Effects 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
- 230000002232 neuromuscular Effects 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 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
- 210000004273 ophthalmic nerve Anatomy 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 102000045222 parkin Human genes 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 230000007824 polyneuropathy Effects 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
- 239000000843 powder Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000003414 procognitive effect Effects 0.000 description 1
- 201000002241 progressive bulbar palsy Diseases 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 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 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
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 229940121356 serotonin receptor antagonist Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 208000026473 slurred speech Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 230000011273 social behavior Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 208000027765 speech disease Diseases 0.000 description 1
- 210000000273 spinal nerve root Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000007470 synaptic degeneration Effects 0.000 description 1
- 230000003107 synaptogenic effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000009871 tenuigenin Substances 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins 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
- 229960004418 trolamine Drugs 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 201000007790 vitelliform macular dystrophy Diseases 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000003936 working memory Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—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 three hetero rings
- C07D471/18—Bridged systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24514709P | 2009-09-23 | 2009-09-23 | |
| US24526009P | 2009-09-23 | 2009-09-23 | |
| US61/245,260 | 2009-09-23 | ||
| US61/245,147 | 2009-09-23 | ||
| PCT/US2010/050080 WO2011038163A1 (en) | 2009-09-23 | 2010-09-23 | Pyrido[3,4-b]indoles and methods of use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102724875A CN102724875A (zh) | 2012-10-10 |
| CN102724875B true CN102724875B (zh) | 2015-05-27 |
Family
ID=43796211
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080047262.3A Expired - Fee Related CN102724875B (zh) | 2009-09-23 | 2010-09-23 | 吡啶并[3,4-b]吲哚化合物及其使用方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US9079904B2 (enExample) |
| EP (1) | EP2480080A4 (enExample) |
| JP (1) | JP5791612B2 (enExample) |
| CN (1) | CN102724875B (enExample) |
| AU (1) | AU2010298168B2 (enExample) |
| BR (1) | BR112012006646A2 (enExample) |
| CA (1) | CA2775133A1 (enExample) |
| WO (1) | WO2011038163A1 (enExample) |
Families Citing this family (38)
| 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 |
| EP2280968A2 (en) | 2008-03-24 | 2011-02-09 | Medivation Technologies, Inc. | Pyrido [3, 4-b]indoles and methods of use |
| WO2009120720A1 (en) | 2008-03-24 | 2009-10-01 | Medivation Technologies,Inc. | Bridged heterocyclic compounds and methods of use |
| CA2742320A1 (en) | 2008-10-31 | 2010-05-06 | Medivation Technologies, Inc. | Pyrido[4,3-b]indoles containing rigid moieties |
| AU2009308708B2 (en) * | 2008-10-31 | 2015-11-19 | Medivation Technologies, Inc. | Azepino [4, 5-b] indoles and methods of use |
| EP2424364A4 (en) | 2009-04-29 | 2012-12-19 | Medivation Technologies Inc | PYRIDO [4.3-B] INDOLES AND METHODS OF USE |
| AU2010282990B2 (en) | 2009-04-29 | 2015-11-05 | Medivation Technologies, Inc. | Pyrido [4, 3-b] indoles and methods of use |
| AU2010298169B2 (en) | 2009-09-23 | 2015-10-29 | Medivation Technologies, Inc. | Bridged heterocyclic compounds and methods of use |
| AU2010298168B2 (en) | 2009-09-23 | 2015-11-19 | Medivation Technologies, Inc. | Pyrido(3,4-b)indoles and methods of use |
| JP5779183B2 (ja) | 2009-09-23 | 2015-09-16 | メディベイション テクノロジーズ, インコーポレイテッド | ピリド[4,3−b]インドールおよび使用方法 |
| WO2011103433A1 (en) | 2010-02-18 | 2011-08-25 | 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 |
| 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 |
| US9035056B2 (en) | 2011-02-18 | 2015-05-19 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| WO2012112962A1 (en) | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| IN2013MN01699A (enExample) | 2011-02-18 | 2015-06-12 | Medivation Technologies Inc | |
| US20140303144A1 (en) | 2011-02-18 | 2014-10-09 | Medivation Technologies, Inc. | Compounds and methods of treating hypertension |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| EP2887805A4 (en) * | 2012-08-22 | 2016-08-17 | Medivation Technologies Inc | COMPOUNDS AND METHOD FOR TREATING BLOOD HIGH PRESSURE |
| WO2014207241A1 (en) * | 2013-06-28 | 2014-12-31 | Alzprotect | NEW Na-SUBSTITUTED CARBOLINE COMPOUNDS USABLE FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES |
| PE20160685A1 (es) | 2013-10-04 | 2016-07-23 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos |
| WO2015051241A1 (en) | 2013-10-04 | 2015-04-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| JP2017505346A (ja) | 2014-02-12 | 2017-02-16 | アイティーオス セラペウティクス | 新規な3−(インドール−3−イル)−ピリジン誘導体、医薬組成物、および使用方法 |
| CN113620958A (zh) | 2014-03-19 | 2021-11-09 | 无限药品股份有限公司 | 用于治疗PI3K-γ介导的障碍的杂环化合物 |
| SG11201608708WA (en) * | 2014-05-15 | 2016-11-29 | Iteos Therapeutics | Pyrrolidine-2,5-dione derivatives, pharmaceutical compositions and methods for use as ido1 inhibitors |
| US9708348B2 (en) | 2014-10-03 | 2017-07-18 | Infinity Pharmaceuticals, Inc. | Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof |
| WO2016147144A1 (en) | 2015-03-17 | 2016-09-22 | Pfizer Inc. | Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
| TW201710258A (zh) | 2015-06-23 | 2017-03-16 | 碩騰服務公司 | 咔啉抗寄生蟲藥 |
| CA2994917A1 (en) | 2015-08-10 | 2017-02-16 | Pfizer Inc. | 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
| PH12018500554B1 (en) | 2015-09-14 | 2024-01-24 | Infinity Pharmaceuticals Inc | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| CN110372631B (zh) * | 2019-07-24 | 2021-03-02 | 东南大学成贤学院 | 一种氨噻肟酰胺乙醛的制备方法 |
| US10947253B2 (en) | 2019-08-05 | 2021-03-16 | Ankh Life Sciences Limited | Fused polycyclic dimers |
| EP4165042A4 (en) * | 2020-06-10 | 2024-05-29 | Delix Therapeutics, Inc. | TRICYCLIC PSYCHOPLASTOGENS AND USES THEREOF |
| US12129265B2 (en) | 2020-07-21 | 2024-10-29 | Ankh Life Sciences Limited | Therapeutic agents and uses thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996034865A1 (en) * | 1995-05-05 | 1996-11-07 | Novo Nordisk A/S | Novel heterocyclic chemistry |
| CN1282743A (zh) * | 1999-07-23 | 2001-02-07 | 阿迪尔公司 | 新颖的β-咔啉化合物、它们的制备方法和含有它们的药物组合物 |
| US20050101623A1 (en) * | 2003-07-23 | 2005-05-12 | Pharmacia Corporation | Beta-carboline compounds and analogues thereof as mitogen-activated protein kinase-activated protein kinase-2 inhibitors |
Family Cites Families (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2642438A (en) | 1949-07-15 | 1953-06-16 | Hoffmann La Roche | Pyridindoles and method of manufacture |
| GB721171A (en) * | 1951-04-30 | 1954-12-29 | Bayer Ag | Derivatives of ª‰- and ª†- carbolines |
| IL34822A0 (en) * | 1969-07-07 | 1970-08-19 | American Home Prod | Indole derivatives,their preparation and pharmaceutical compositions containing them |
| AR205790A1 (es) | 1972-05-01 | 1976-06-07 | American Home Prod | Proceso para la preparacion de 2,3,5,6,11,11b-hexahidro-1h-pirido (3', 2': 4,5) pirrolo (3,2-g) indolicina-4-oxidos |
| US3911130A (en) * | 1973-04-18 | 1975-10-07 | American Home Prod | Novel 7-azaindole fused heterocyclic compounds for producing analgesia |
| HUT75522A (en) * | 1994-03-11 | 1997-05-28 | Lilly Co Eli | Indole-, pyrido-indole-, indolo-quinoline- and benzo-pyrido-indole-derivatives, method for treating 5ht2b receptor related conditions, pharmaceutical compositions containing them |
| RU2106864C1 (ru) | 1995-10-23 | 1998-03-20 | Николай Серафимович Зефиров | Средство для лечения болезни альцгеймера |
| HRP20041026A2 (en) * | 2002-04-03 | 2005-06-30 | Orion Corporation | Polycyclic compounds as potent alpha2-adrenoceptor antagonists |
| US7736889B2 (en) | 2003-06-10 | 2010-06-15 | The United States Of America As Represented By The Secretary Of The Navy | Fluidic force discrimination |
| US20060235012A1 (en) * | 2003-06-16 | 2006-10-19 | Chroma Therapeutics Limited | Carboline and betacarboline derivatives for use as hdac enzyme inhibitors |
| US20070179174A1 (en) * | 2003-12-08 | 2007-08-02 | Bachurin Sergei O | Methods and compositions for slowing aging |
| 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 |
| CA2624731A1 (en) * | 2005-10-04 | 2007-04-12 | Medivation, Inc. | Hydrogenated pyrido-indole compounds for the treatment of huntington's disease |
| RU2338537C2 (ru) * | 2006-01-25 | 2008-11-20 | Сергей Олегович Бачурин | СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ШИЗОФРЕНИИ НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b)ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| US20100099700A1 (en) * | 2006-09-20 | 2010-04-22 | David Hung | Hydrogenated pyrido (4,3-b) indoles for treating amyotrophic lateral sclerosis (als) |
| JP2010504337A (ja) * | 2006-09-20 | 2010-02-12 | メディベイション ニューロロジー, インコーポレイテッド | イヌの認知機能障害症候群の治療のためのディメボン(dimebon)などの水素化ピリド[4,3−b]インドール |
| ATE549021T1 (de) * | 2006-10-27 | 2012-03-15 | Medivation Neurology Inc | Kombinationstherapien zur behandlung von morbus alzheimer mit dimebon und donepezil |
| 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 |
| KR20090130105A (ko) | 2007-04-05 | 2009-12-17 | 알라 캠, 엘엘씨 | 치환된 2,3,4,5-테트라히드로-1h-피리도[4,3-b] 인돌, 그 제조방법 및 용도 |
| CA2688327A1 (en) | 2007-05-25 | 2008-12-04 | Medivation Neurology, Inc. | Methods and compositions for stimulating cells |
| JP2008297278A (ja) | 2007-06-01 | 2008-12-11 | Astellas Pharma Inc | Lpa受容体アゴニスト |
| 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 |
| WO2009017836A1 (en) | 2007-08-01 | 2009-02-05 | Medivation Neurology, Inc. | Methods and compositions for treating schizophrenia using antipsychotic combination therapy |
| WO2009039420A1 (en) | 2007-09-21 | 2009-03-26 | Medivation Neurology, Inc. | Methods and compositions for treating neuronal death mediated ocular diseases |
| RU2007139634A (ru) * | 2007-10-25 | 2009-04-27 | Сергей Олегович Бачурин (RU) | Новые тиазол-, триазол- или оксадиазол-содержащие тетрациклические соединения |
| EP2236511A4 (en) | 2007-12-21 | 2011-04-13 | Alla Chem Llc | LIGANDS OF ALPHA ADRENOCEPTORS AND OF DOPAMINE, HISTAMIN, IMIDAZOLIN AND SEROTONIN RECEPTORS AND THEIR APPLICATION THEREOF |
| 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 |
| WO2009120720A1 (en) * | 2008-03-24 | 2009-10-01 | Medivation Technologies,Inc. | Bridged heterocyclic compounds and methods of use |
| EP2280968A2 (en) * | 2008-03-24 | 2011-02-09 | Medivation Technologies, Inc. | Pyrido [3, 4-b]indoles and methods of use |
| 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 |
| TW201018694A (en) * | 2008-09-29 | 2010-05-16 | Abbott Lab | Indole and indoline derivatives and methods of use thereof |
| AU2009308708B2 (en) * | 2008-10-31 | 2015-11-19 | Medivation Technologies, Inc. | Azepino [4, 5-b] indoles and methods of use |
| CA2742320A1 (en) | 2008-10-31 | 2010-05-06 | Medivation Technologies, Inc. | Pyrido[4,3-b]indoles containing rigid moieties |
| EP2385829B1 (en) | 2009-01-09 | 2018-08-01 | Board of Regents of the University of Texas System | Pro-neurogenic compounds |
| 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 |
| AU2010282990B2 (en) | 2009-04-29 | 2015-11-05 | Medivation Technologies, Inc. | Pyrido [4, 3-b] indoles and methods of use |
| EP2424364A4 (en) | 2009-04-29 | 2012-12-19 | Medivation Technologies Inc | PYRIDO [4.3-B] INDOLES AND METHODS OF USE |
| 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 |
| AU2010298169B2 (en) | 2009-09-23 | 2015-10-29 | Medivation Technologies, Inc. | Bridged heterocyclic compounds and methods of use |
| AU2010298168B2 (en) * | 2009-09-23 | 2015-11-19 | Medivation Technologies, Inc. | Pyrido(3,4-b)indoles and methods of use |
| US20130137705A1 (en) * | 2009-09-23 | 2013-05-30 | Sarvajit Chakravarty | Pyrido[3,4-b]indoles and methods of use |
| JP5779183B2 (ja) * | 2009-09-23 | 2015-09-16 | メディベイション テクノロジーズ, インコーポレイテッド | ピリド[4,3−b]インドールおよび使用方法 |
| WO2011103433A1 (en) | 2010-02-18 | 2011-08-25 | 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 |
| 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 |
| 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 |
| WO2011103448A1 (en) | 2010-02-19 | 2011-08-25 | Medivation Technologies, Inc. | Methods and compositions for treating psychotic disorders using antipsychotic combination therapy |
| 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 |
| 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 |
| US9035056B2 (en) * | 2011-02-18 | 2015-05-19 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| US20140303144A1 (en) | 2011-02-18 | 2014-10-09 | Medivation Technologies, Inc. | Compounds and methods of treating hypertension |
| IN2013MN01699A (enExample) | 2011-02-18 | 2015-06-12 | Medivation Technologies Inc | |
| WO2012112962A1 (en) | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| EP2887805A4 (en) | 2012-08-22 | 2016-08-17 | Medivation Technologies Inc | COMPOUNDS AND METHOD FOR TREATING BLOOD HIGH PRESSURE |
| 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 |
| EP2925129A4 (en) | 2012-08-24 | 2016-06-08 | Univ Texas | PRO-NEUROGENIC COMPOUNDS |
-
2010
- 2010-09-23 AU AU2010298168A patent/AU2010298168B2/en not_active Ceased
- 2010-09-23 EP EP10819492.9A patent/EP2480080A4/en not_active Withdrawn
- 2010-09-23 WO PCT/US2010/050080 patent/WO2011038163A1/en not_active Ceased
- 2010-09-23 BR BR112012006646A patent/BR112012006646A2/pt not_active IP Right Cessation
- 2010-09-23 CN CN201080047262.3A patent/CN102724875B/zh not_active Expired - Fee Related
- 2010-09-23 CA CA2775133A patent/CA2775133A1/en not_active Abandoned
- 2010-09-23 JP JP2012531044A patent/JP5791612B2/ja not_active Expired - Fee Related
- 2010-09-23 US US12/889,323 patent/US9079904B2/en not_active Expired - Fee Related
-
2013
- 2013-03-08 US US13/791,559 patent/US9085580B2/en not_active Expired - Fee Related
-
2015
- 2015-06-12 US US14/738,465 patent/US9271971B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996034865A1 (en) * | 1995-05-05 | 1996-11-07 | Novo Nordisk A/S | Novel heterocyclic chemistry |
| CN1282743A (zh) * | 1999-07-23 | 2001-02-07 | 阿迪尔公司 | 新颖的β-咔啉化合物、它们的制备方法和含有它们的药物组合物 |
| US20050101623A1 (en) * | 2003-07-23 | 2005-05-12 | Pharmacia Corporation | Beta-carboline compounds and analogues thereof as mitogen-activated protein kinase-activated protein kinase-2 inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013505947A (ja) | 2013-02-21 |
| EP2480080A4 (en) | 2014-01-08 |
| US20110237582A1 (en) | 2011-09-29 |
| CA2775133A1 (en) | 2011-03-31 |
| AU2010298168A1 (en) | 2012-04-12 |
| US9085580B2 (en) | 2015-07-21 |
| US20130190308A1 (en) | 2013-07-25 |
| WO2011038163A1 (en) | 2011-03-31 |
| BR112012006646A2 (pt) | 2019-09-24 |
| HK1176813A1 (en) | 2013-08-09 |
| EP2480080A1 (en) | 2012-08-01 |
| CN102724875A (zh) | 2012-10-10 |
| US9079904B2 (en) | 2015-07-14 |
| JP5791612B2 (ja) | 2015-10-07 |
| AU2010298168B2 (en) | 2015-11-19 |
| US20150352087A1 (en) | 2015-12-10 |
| US9271971B2 (en) | 2016-03-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102724875B (zh) | 吡啶并[3,4-b]吲哚化合物及其使用方法 | |
| CN102083830B (zh) | 吡啶并[3,4-b]吲哚和应用方法 | |
| AU2010242910B2 (en) | Pyrido [4,3-b] indoles and methods of use | |
| US8927571B2 (en) | Pyrido[4,3-B]indoles and methods of use | |
| CN102046625B (zh) | 桥连杂环化合物及其使用方法 | |
| AU2010298169B2 (en) | Bridged heterocyclic compounds and methods of use | |
| AU2010298166B2 (en) | Pyrido[4,3-b]indoles and methods of use | |
| CN102711467A (zh) | 吡啶并[3,4-b]吲哚类及使用方法 | |
| HK1176813B (en) | Pyrido[3,4-b]indoles and methods of use | |
| AU2013203574A1 (en) | Pyrido [4,3-b] indoles and methods of use | |
| AU2013203575A1 (en) | Pyrido [4,3-b] indoles and methods of use | |
| HK1171167B (en) | Pyrido [4, 3-b] indoles and methods of use | |
| HK1176814A (en) | Pyrido[3,4-b]indoles and methods of use | |
| HK1176811B (en) | Pyrido[4,3-b]indoles and methods of use | |
| AU2013203691A1 (en) | Pyrido[3,4-b]indoles and methods of use | |
| AU2013203572A1 (en) | Pyrido[4,3-b]indoles and methods of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1176813 Country of ref document: HK |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1176813 Country of ref document: HK |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150527 Termination date: 20160923 |