MX2008016083A - Metodo para modular la excrecion de neuritas por el uso de un antagonista del receptor de galanina-3. - Google Patents
Metodo para modular la excrecion de neuritas por el uso de un antagonista del receptor de galanina-3.Info
- Publication number
- MX2008016083A MX2008016083A MX2008016083A MX2008016083A MX2008016083A MX 2008016083 A MX2008016083 A MX 2008016083A MX 2008016083 A MX2008016083 A MX 2008016083A MX 2008016083 A MX2008016083 A MX 2008016083A MX 2008016083 A MX2008016083 A MX 2008016083A
- Authority
- MX
- Mexico
- Prior art keywords
- aryl
- straight
- alkyl
- branched chain
- galanin
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 144
- 102000001972 Galanin receptor 3 Human genes 0.000 title claims abstract description 63
- 108050009372 Galanin receptor 3 Proteins 0.000 title claims abstract description 63
- 230000014511 neuron projection development Effects 0.000 title claims abstract description 55
- 239000002464 receptor antagonist Substances 0.000 title claims abstract description 54
- 229940044551 receptor antagonist Drugs 0.000 title claims abstract description 54
- 241001465754 Metazoa Species 0.000 claims abstract description 17
- 210000004027 cell Anatomy 0.000 claims description 109
- 150000001875 compounds Chemical class 0.000 claims description 89
- TXCGMRVPXUBHAL-UHFFFAOYSA-N 1-phenyl-3-[3-(trifluoromethyl)phenyl]iminoindol-2-one Chemical group FC(F)(F)C1=CC=CC(N=C2C(N(C=3C=CC=CC=3)C3=CC=CC=C32)=O)=C1 TXCGMRVPXUBHAL-UHFFFAOYSA-N 0.000 claims description 69
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 239000000203 mixture Substances 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 238000011282 treatment Methods 0.000 claims description 40
- 210000002569 neuron Anatomy 0.000 claims description 38
- -1 methylenedioxy group Chemical group 0.000 claims description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 208000014674 injury Diseases 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
- 230000008733 trauma Effects 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 20
- 125000000304 alkynyl group Chemical group 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 20
- 210000000130 stem cell Anatomy 0.000 claims description 19
- 201000010099 disease Diseases 0.000 claims description 18
- 150000002466 imines Chemical class 0.000 claims description 15
- 230000001537 neural effect Effects 0.000 claims description 15
- 210000003169 central nervous system Anatomy 0.000 claims description 13
- 230000006378 damage Effects 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 10
- 230000005779 cell damage Effects 0.000 claims description 9
- 208000037887 cell injury Diseases 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000005557 antagonist Substances 0.000 claims description 8
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 230000004770 neurodegeneration Effects 0.000 claims description 7
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 230000003902 lesion Effects 0.000 claims description 5
- 201000001119 neuropathy Diseases 0.000 claims description 5
- 230000007823 neuropathy Effects 0.000 claims description 5
- 230000002093 peripheral effect Effects 0.000 claims description 5
- 238000001356 surgical procedure Methods 0.000 claims description 5
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 4
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 4
- 201000011452 Adrenoleukodystrophy Diseases 0.000 claims description 3
- 208000018126 Adrenomyeloneuropathy Diseases 0.000 claims description 3
- 208000003808 Amyloid Neuropathies Diseases 0.000 claims description 3
- 206010003591 Ataxia Diseases 0.000 claims description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
- 208000009119 Giant Axonal Neuropathy Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 208000016988 Hemorrhagic Stroke Diseases 0.000 claims description 3
- 208000032382 Ischaemic stroke Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 claims description 3
- 241000097929 Porphyria Species 0.000 claims description 3
- 208000010642 Porphyrias Diseases 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 230000001977 ataxic effect Effects 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 238000002513 implantation Methods 0.000 claims description 3
- 208000020658 intracerebral hemorrhage Diseases 0.000 claims description 3
- 210000000653 nervous system Anatomy 0.000 claims description 3
- 230000000149 penetrating effect Effects 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 201000005572 sensory peripheral neuropathy Diseases 0.000 claims description 3
- 210000000278 spinal cord Anatomy 0.000 claims description 3
- 239000003053 toxin Substances 0.000 claims description 3
- 231100000765 toxin Toxicity 0.000 claims description 3
- 108700012359 toxins Proteins 0.000 claims description 3
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 206010067633 Peripheral nerve lesion Diseases 0.000 claims description 2
- 208000029028 brain injury Diseases 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 206010019196 Head injury Diseases 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 208000037920 primary disease Diseases 0.000 claims 1
- 238000002271 resection Methods 0.000 claims 1
- 210000002241 neurite Anatomy 0.000 description 74
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 230000000694 effects Effects 0.000 description 48
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- 101150029234 Hes5 gene Proteins 0.000 description 33
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- 210000004295 hippocampal neuron Anatomy 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 230000014509 gene expression Effects 0.000 description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 23
- 239000003981 vehicle Substances 0.000 description 22
- 108020004459 Small interfering RNA Proteins 0.000 description 20
- 125000001841 imino group Chemical group [H]N=* 0.000 description 20
- 239000000243 solution Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 16
- 108010025020 Nerve Growth Factor Proteins 0.000 description 15
- 101150041968 CDC13 gene Proteins 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 102000015336 Nerve Growth Factor Human genes 0.000 description 13
- 108020004999 messenger RNA Proteins 0.000 description 13
- 239000007787 solid Substances 0.000 description 12
- 238000003753 real-time PCR Methods 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 208000027418 Wounds and injury Diseases 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 238000011002 quantification Methods 0.000 description 10
- 230000010076 replication Effects 0.000 description 10
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 9
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 9
- 230000029142 excretion Effects 0.000 description 9
- 230000004766 neurogenesis Effects 0.000 description 9
- 125000003710 aryl alkyl group Chemical group 0.000 description 8
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 108010001517 Galectin 3 Proteins 0.000 description 7
- 102100039558 Galectin-3 Human genes 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 6
- 230000004031 neuronal differentiation Effects 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 239000013058 crude material Substances 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 238000003522 neurite outgrowth assay Methods 0.000 description 5
- UWCPWBIMRYXUOU-UHFFFAOYSA-N 1-phenylindole-2,3-dione Chemical compound C12=CC=CC=C2C(=O)C(=O)N1C1=CC=CC=C1 UWCPWBIMRYXUOU-UHFFFAOYSA-N 0.000 description 4
- LVOWFWVRAPVYDX-UHFFFAOYSA-N 1-thiophen-3-ylindole-2,3-dione Chemical compound C12=CC=CC=C2C(=O)C(=O)N1C=1C=CSC=1 LVOWFWVRAPVYDX-UHFFFAOYSA-N 0.000 description 4
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 4
- 102000012422 Collagen Type I Human genes 0.000 description 4
- 108010022452 Collagen Type I Proteins 0.000 description 4
- 102000019432 Galanin Human genes 0.000 description 4
- 101800002068 Galanin Proteins 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 4
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- YAFMLULIFQLJRJ-UHFFFAOYSA-N 1-[(5-chloro-1-benzothiophen-3-yl)methyl]indole-2,3-dione Chemical compound O=C1C(=O)C2=CC=CC=C2N1CC1=CSC2=CC=C(Cl)C=C21 YAFMLULIFQLJRJ-UHFFFAOYSA-N 0.000 description 3
- BNSKFCOAYKYHCS-UHFFFAOYSA-N 3-[3-(trifluoromethyl)anilino]indol-2-one Chemical compound FC(F)(F)C1=CC=CC(NC=2C(N=C3C=CC=CC3=2)=O)=C1 BNSKFCOAYKYHCS-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 208000018652 Closed Head injury Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 102100025169 Max-binding protein MNT Human genes 0.000 description 3
- 101150064037 NGF gene Proteins 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 150000002475 indoles Chemical class 0.000 description 3
- 150000005624 indolones Chemical class 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- SLZIZIJTGAYEKK-CIJSCKBQSA-N molport-023-220-247 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CNC=N1 SLZIZIJTGAYEKK-CIJSCKBQSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000000946 synaptic effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 3
- 108091006107 transcriptional repressors Proteins 0.000 description 3
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
- DPUCWQUWEJBKPK-UHFFFAOYSA-N 3-aminoindol-2-one Chemical class C1=CC=C2C(=N)C(=O)NC2=C1 DPUCWQUWEJBKPK-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BBJPQDMHSQEXNS-UZYVYHOESA-N C1=C(Cl)C(C)=CC(\N=C/2C3=CC=CC=C3N(C3=CSC=C3)C\2=O)=C1 Chemical compound C1=C(Cl)C(C)=CC(\N=C/2C3=CC=CC=C3N(C3=CSC=C3)C\2=O)=C1 BBJPQDMHSQEXNS-UZYVYHOESA-N 0.000 description 2
- RZSSWZGDKWLFMF-JZJYNLBNSA-N C1=CC(Cl)=CC=C1\N=C/1C2=CC=CC=C2N(C2=CSC=C2)C\1=O Chemical compound C1=CC(Cl)=CC=C1\N=C/1C2=CC=CC=C2N(C2=CSC=C2)C\1=O RZSSWZGDKWLFMF-JZJYNLBNSA-N 0.000 description 2
- 241000289695 Eutheria Species 0.000 description 2
- 208000023329 Gun shot wound Diseases 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 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
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 2
- 102000007072 Nerve Growth Factors Human genes 0.000 description 2
- 208000001738 Nervous System Trauma Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 102000006467 TATA-Box Binding Protein Human genes 0.000 description 2
- 108010044281 TATA-Box Binding Protein Proteins 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 125000005619 boric acid group Chemical group 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 208000025997 central nervous system neoplasm Diseases 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000020595 eating behavior Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 230000003169 placental effect Effects 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
- MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 description 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- AAYZREZLTCRJHR-UHFFFAOYSA-N 1-[(5-chlorothiophen-2-yl)methyl]indole-2,3-dione Chemical compound S1C(Cl)=CC=C1CN1C2=CC=CC=C2C(=O)C1=O AAYZREZLTCRJHR-UHFFFAOYSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ZCBIFHNDZBSCEP-UHFFFAOYSA-N 1H-indol-5-amine Chemical compound NC1=CC=C2NC=CC2=C1 ZCBIFHNDZBSCEP-UHFFFAOYSA-N 0.000 description 1
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 1
- RXWOHFUULDINMC-UHFFFAOYSA-N 2-(3-nitrothiophen-2-yl)acetic acid Chemical compound OC(=O)CC=1SC=CC=1[N+]([O-])=O RXWOHFUULDINMC-UHFFFAOYSA-N 0.000 description 1
- NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical class ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- MQTKXCOGYOYAMW-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)thiophene Chemical compound ClCC1=CC=C(Cl)S1 MQTKXCOGYOYAMW-UHFFFAOYSA-N 0.000 description 1
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 1
- GPWQHYMVUZYWIK-UHFFFAOYSA-N 2-methyl-1,3-benzothiazol-5-amine Chemical compound NC1=CC=C2SC(C)=NC2=C1 GPWQHYMVUZYWIK-UHFFFAOYSA-N 0.000 description 1
- VJTGACQFXSATHA-UHFFFAOYSA-N 3-(2-methoxyphenyl)imino-1-phenylindol-2-one Chemical compound COC1=CC=CC=C1N=C1C2=CC=CC=C2N(C=2C=CC=CC=2)C1=O VJTGACQFXSATHA-UHFFFAOYSA-N 0.000 description 1
- YHFSSVLGIARFQM-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)imino-1-prop-2-enylindol-2-one Chemical compound C1=C(Cl)C(Cl)=CC=C1N=C1C2=CC=CC=C2N(CC=C)C1=O YHFSSVLGIARFQM-UHFFFAOYSA-N 0.000 description 1
- GUOCQDADKJJVBQ-UHFFFAOYSA-N 3-(3,5-dichlorophenyl)imino-1-phenylindol-2-one Chemical compound ClC1=CC(Cl)=CC(N=C2C3=CC=CC=C3N(C2=O)C=2C=CC=CC=2)=C1 GUOCQDADKJJVBQ-UHFFFAOYSA-N 0.000 description 1
- BFPPOJSNKOGZKR-UHFFFAOYSA-N 3-(3,5-dimethylphenyl)imino-1-phenylindol-2-one Chemical compound CC1=CC(C)=CC(N=C2C3=CC=CC=C3N(C2=O)C=2C=CC=CC=2)=C1 BFPPOJSNKOGZKR-UHFFFAOYSA-N 0.000 description 1
- USPOXDNSVVNQGP-UHFFFAOYSA-N 3-(3-chlorophenyl)imino-1-phenylindol-2-one Chemical compound ClC1=CC=CC(N=C2C3=CC=CC=C3N(C2=O)C=2C=CC=CC=2)=C1 USPOXDNSVVNQGP-UHFFFAOYSA-N 0.000 description 1
- DHZXAAPQTLKMSF-UHFFFAOYSA-N 3-(4-fluorophenyl)imino-1-phenylindol-2-one Chemical compound C1=CC(F)=CC=C1N=C1C2=CC=CC=C2N(C=2C=CC=CC=2)C1=O DHZXAAPQTLKMSF-UHFFFAOYSA-N 0.000 description 1
- KLIDPMQVSPVTRZ-UHFFFAOYSA-N 3-(4-methoxyphenyl)imino-1-phenylindol-2-one Chemical compound C1=CC(OC)=CC=C1N=C1C2=CC=CC=C2N(C=2C=CC=CC=2)C1=O KLIDPMQVSPVTRZ-UHFFFAOYSA-N 0.000 description 1
- DAPJCWNYEGPGIY-UHFFFAOYSA-N 3-(4-methylphenyl)imino-1-thiophen-3-ylindol-2-one Chemical compound C1=CC(C)=CC=C1N=C1C2=CC=CC=C2N(C2=CSC=C2)C1=O DAPJCWNYEGPGIY-UHFFFAOYSA-N 0.000 description 1
- VGDRXUZZWBBWQM-UHFFFAOYSA-N 3-(4-phenoxyphenyl)imino-1-phenylindol-2-one Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC=CC=C2C1=NC(C=C1)=CC=C1OC1=CC=CC=C1 VGDRXUZZWBBWQM-UHFFFAOYSA-N 0.000 description 1
- LUWLJWVSTCVJCZ-UHFFFAOYSA-N 3-(6-chloropyridin-3-yl)imino-1-phenylindol-2-one Chemical compound C1=NC(Cl)=CC=C1N=C1C2=CC=CC=C2N(C=2C=CC=CC=2)C1=O LUWLJWVSTCVJCZ-UHFFFAOYSA-N 0.000 description 1
- FKQSFVITUNJLCY-UHFFFAOYSA-N 3-(bromomethyl)-5-chloro-1-benzothiophene Chemical compound ClC1=CC=C2SC=C(CBr)C2=C1 FKQSFVITUNJLCY-UHFFFAOYSA-N 0.000 description 1
- CNQCWYFDIQSALX-UHFFFAOYSA-N 3-(chloromethyl)pyridine Chemical class ClCC1=CC=CN=C1 CNQCWYFDIQSALX-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- PIHGLGYAADMJEP-UHFFFAOYSA-N 3-[2-methyl-5-(trifluoromethyl)phenyl]imino-1-phenylindol-2-one Chemical compound CC1=CC=C(C(F)(F)F)C=C1N=C1C2=CC=CC=C2N(C=2C=CC=CC=2)C1=O PIHGLGYAADMJEP-UHFFFAOYSA-N 0.000 description 1
- MKASXAGBWHIGCF-UHFFFAOYSA-N 3-methoxy-n-phenylaniline Chemical compound COC1=CC=CC(NC=2C=CC=CC=2)=C1 MKASXAGBWHIGCF-UHFFFAOYSA-N 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- NIFAUKBQIAURIM-UHFFFAOYSA-N 4-(chloromethyl)-3,5-dimethyl-1,2-oxazole Chemical class CC1=NOC(C)=C1CCl NIFAUKBQIAURIM-UHFFFAOYSA-N 0.000 description 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
- 102000035038 5-HT1 receptors Human genes 0.000 description 1
- 108091005478 5-HT1 receptors Proteins 0.000 description 1
- KMEBUNSLFRQSEM-UHFFFAOYSA-N 5-amino-2-methylisoindole-1,3-dione Chemical compound C1=C(N)C=C2C(=O)N(C)C(=O)C2=C1 KMEBUNSLFRQSEM-UHFFFAOYSA-N 0.000 description 1
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
- QAJYCQZQLVENRZ-UHFFFAOYSA-N 6-chloropyridin-3-amine Chemical compound NC1=CC=C(Cl)N=C1 QAJYCQZQLVENRZ-UHFFFAOYSA-N 0.000 description 1
- HDZQQDLKJDRSBY-UHFFFAOYSA-N 6-methoxy-1-phenylindole-2,3-dione Chemical compound C12=CC(OC)=CC=C2C(=O)C(=O)N1C1=CC=CC=C1 HDZQQDLKJDRSBY-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000237967 Aplysia Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 102000018720 Basic Helix-Loop-Helix Transcription Factors Human genes 0.000 description 1
- 108010027344 Basic Helix-Loop-Helix Transcription Factors Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- FHDYAIXKXWDQAN-QOCHGBHMSA-N BrC1=CC=CC(\N=C/2C3=CC=CC=C3N(C\2=O)C=2C=CC=CC=2)=C1 Chemical compound BrC1=CC=CC(\N=C/2C3=CC=CC=C3N(C\2=O)C=2C=CC=CC=2)=C1 FHDYAIXKXWDQAN-QOCHGBHMSA-N 0.000 description 1
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
- ICVGVTUEJFJFEQ-LVWGJNHUSA-N C12=CC=CC=C2\C(=N\C=2C3=CC=CN=C3C=CC=2)C(=O)N1C1=CC=CC=C1 Chemical compound C12=CC=CC=C2\C(=N\C=2C3=CC=CN=C3C=CC=2)C(=O)N1C1=CC=CC=C1 ICVGVTUEJFJFEQ-LVWGJNHUSA-N 0.000 description 1
- WMYQFCIAGWFBPA-LNVKXUELSA-N C12=CC=CC=C2\C(=N\C=2C=C3C=CC=CC3=CC=2)C(=O)N1C=1C=CSC=1 Chemical compound C12=CC=CC=C2\C(=N\C=2C=C3C=CC=CC3=CC=2)C(=O)N1C=1C=CSC=1 WMYQFCIAGWFBPA-LNVKXUELSA-N 0.000 description 1
- HPLOOVYJCZOECL-ATJXCDBQSA-N C12=CC=CC=C2\C(=N\C=2C=C3C=CC=NC3=CC=2)C(=O)N1C=1C=CSC=1 Chemical compound C12=CC=CC=C2\C(=N\C=2C=C3C=CC=NC3=CC=2)C(=O)N1C=1C=CSC=1 HPLOOVYJCZOECL-ATJXCDBQSA-N 0.000 description 1
- PZRZVIPXQYSSRL-BZZOAKBMSA-N C12=CC=CC=C2\C(=N\C=2C=CC(=CC=2)C2CCCCC2)C(=O)N1C=1C=CSC=1 Chemical compound C12=CC=CC=C2\C(=N\C=2C=CC(=CC=2)C2CCCCC2)C(=O)N1C=1C=CSC=1 PZRZVIPXQYSSRL-BZZOAKBMSA-N 0.000 description 1
- UASCMOBTKRDZNB-BZZOAKBMSA-N C12=CC=CC=C2\C(=N\C=2C=CC(OC=3C=CC=CC=3)=CC=2)C(=O)N1C=1C=CSC=1 Chemical compound C12=CC=CC=C2\C(=N\C=2C=CC(OC=3C=CC=CC=3)=CC=2)C(=O)N1C=1C=CSC=1 UASCMOBTKRDZNB-BZZOAKBMSA-N 0.000 description 1
- XNKUGWVSYWFWNX-FXBPSFAMSA-N C1=C(Cl)C(Cl)=CC=C1\N=C/1C2=CC=CC=C2N(C2=CSC=C2)C\1=O Chemical compound C1=C(Cl)C(Cl)=CC=C1\N=C/1C2=CC=CC=C2N(C2=CSC=C2)C\1=O XNKUGWVSYWFWNX-FXBPSFAMSA-N 0.000 description 1
- CPMIIJIZBQPBMD-NMWGTECJSA-N C1=C(F)C(F)=CC=C1\N=C/1C2=CC=CC=C2N(C=2C=CC=CC=2)C\1=O Chemical compound C1=C(F)C(F)=CC=C1\N=C/1C2=CC=CC=C2N(C=2C=CC=CC=2)C\1=O CPMIIJIZBQPBMD-NMWGTECJSA-N 0.000 description 1
- RJVFFAGKTZQUFB-CLCOLTQESA-N C1=C(F)C(F)=CC=C1\N=C/1C2=CC=CC=C2N(CC=2C=NC=CC=2)C\1=O Chemical compound C1=C(F)C(F)=CC=C1\N=C/1C2=CC=CC=C2N(CC=2C=NC=CC=2)C\1=O RJVFFAGKTZQUFB-CLCOLTQESA-N 0.000 description 1
- FVIVOMHWEKZSFA-CLCOLTQESA-N C1=C(F)C(F)=CC=C1\N=C/1C2=CC=CC=C2N(CC=2N=CC=CC=2)C\1=O Chemical compound C1=C(F)C(F)=CC=C1\N=C/1C2=CC=CC=C2N(CC=2N=CC=CC=2)C\1=O FVIVOMHWEKZSFA-CLCOLTQESA-N 0.000 description 1
- HUNDXLQFLHGWDU-JZJYNLBNSA-N C1=CC(Br)=CC=C1\N=C/1C2=CC=CC=C2N(C2=CSC=C2)C\1=O Chemical compound C1=CC(Br)=CC=C1\N=C/1C2=CC=CC=C2N(C2=CSC=C2)C\1=O HUNDXLQFLHGWDU-JZJYNLBNSA-N 0.000 description 1
- DAPJCWNYEGPGIY-ZZEZOPTASA-N C1=CC(C)=CC=C1\N=C/1C2=CC=CC=C2N(C2=CSC=C2)C\1=O Chemical compound C1=CC(C)=CC=C1\N=C/1C2=CC=CC=C2N(C2=CSC=C2)C\1=O DAPJCWNYEGPGIY-ZZEZOPTASA-N 0.000 description 1
- GMBYWRHRQZUZEC-QOCHGBHMSA-N C1=CC(I)=CC=C1\N=C/1C2=CC=CC=C2N(C=2C=CC=CC=2)C\1=O Chemical compound C1=CC(I)=CC=C1\N=C/1C2=CC=CC=C2N(C=2C=CC=CC=2)C\1=O GMBYWRHRQZUZEC-QOCHGBHMSA-N 0.000 description 1
- FXSHECHTDWCXRM-SILNSSARSA-N C1=NC(Cl)=CC=C1\N=C/1C2=CC=CC=C2N(C2=CSC=C2)C\1=O Chemical compound C1=NC(Cl)=CC=C1\N=C/1C2=CC=CC=C2N(C2=CSC=C2)C\1=O FXSHECHTDWCXRM-SILNSSARSA-N 0.000 description 1
- HEKYOIUPWBJWOT-XDOYNYLZSA-N CC(C)C1=CC=CC(\N=C/2C3=CC=CC=C3N(C3=CSC=C3)C\2=O)=C1 Chemical compound CC(C)C1=CC=CC(\N=C/2C3=CC=CC=C3N(C3=CSC=C3)C\2=O)=C1 HEKYOIUPWBJWOT-XDOYNYLZSA-N 0.000 description 1
- OYPXVJGOVRKFPH-ZZEZOPTASA-N CC1=CC=CC(\N=C/2C3=CC=CC=C3N(C3=CSC=C3)C\2=O)=C1 Chemical compound CC1=CC=CC(\N=C/2C3=CC=CC=C3N(C3=CSC=C3)C\2=O)=C1 OYPXVJGOVRKFPH-ZZEZOPTASA-N 0.000 description 1
- AZRIFFGEZHTWRL-NMWGTECJSA-N CC1=NOC(C)=C1CN(C\1=O)C2=CC=CC=C2C/1=N/C1=CC(Cl)=CC(Cl)=C1 Chemical compound CC1=NOC(C)=C1CN(C\1=O)C2=CC=CC=C2C/1=N/C1=CC(Cl)=CC(Cl)=C1 AZRIFFGEZHTWRL-NMWGTECJSA-N 0.000 description 1
- PQABNDLOIWKIHV-NMWGTECJSA-N CC1=NOC(C)=C1CN(C\1=O)C2=CC=CC=C2C/1=N/C1=CC=C(Cl)C(Cl)=C1 Chemical compound CC1=NOC(C)=C1CN(C\1=O)C2=CC=CC=C2C/1=N/C1=CC=C(Cl)C(Cl)=C1 PQABNDLOIWKIHV-NMWGTECJSA-N 0.000 description 1
- RCCWXKUWRPYVAL-LNVKXUELSA-N COC1=CC(OC)=CC=C1\N=C/1C2=CC=CC=C2N(C=2C=CC=CC=2)C\1=O Chemical compound COC1=CC(OC)=CC=C1\N=C/1C2=CC=CC=C2N(C=2C=CC=CC=2)C\1=O RCCWXKUWRPYVAL-LNVKXUELSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108091005944 Cerulean Proteins 0.000 description 1
- HVTODYGJSWUKNV-ATJXCDBQSA-N ClC1=CC(C)=CC=C1\N=C/1C2=CC=CC=C2N(C=2C=CC=CC=2)C\1=O Chemical compound ClC1=CC(C)=CC=C1\N=C/1C2=CC=CC=C2N(C=2C=CC=CC=2)C\1=O HVTODYGJSWUKNV-ATJXCDBQSA-N 0.000 description 1
- FDAGMLIGZTYIRI-PLRJNAJWSA-N ClC1=CC(Cl)=CC(N2C3=CC=CC=C3C(=N/C=3C=C(Cl)C(Cl)=CC=3)/C2=O)=C1 Chemical compound ClC1=CC(Cl)=CC(N2C3=CC=CC=C3C(=N/C=3C=C(Cl)C(Cl)=CC=3)/C2=O)=C1 FDAGMLIGZTYIRI-PLRJNAJWSA-N 0.000 description 1
- BFLIFTQDBMZNMQ-CLCOLTQESA-N ClC1=CC(Cl)=CC(\N=C/2C3=CC=CC=C3N(CC=3C=NC=CC=3)C\2=O)=C1 Chemical compound ClC1=CC(Cl)=CC(\N=C/2C3=CC=CC=C3N(CC=3C=NC=CC=3)C\2=O)=C1 BFLIFTQDBMZNMQ-CLCOLTQESA-N 0.000 description 1
- NNOLAUGDZNMKKW-CLCOLTQESA-N ClC1=CC(Cl)=CC(\N=C/2C3=CC=CC=C3N(CC=3N=CC=CC=3)C\2=O)=C1 Chemical compound ClC1=CC(Cl)=CC(\N=C/2C3=CC=CC=C3N(CC=3N=CC=CC=3)C\2=O)=C1 NNOLAUGDZNMKKW-CLCOLTQESA-N 0.000 description 1
- SVIDQPMUCGFWIV-JZJYNLBNSA-N ClC1=CC=CC(\N=C/2C3=CC=CC=C3N(C3=CSC=C3)C\2=O)=C1 Chemical compound ClC1=CC=CC(\N=C/2C3=CC=CC=C3N(C3=CSC=C3)C\2=O)=C1 SVIDQPMUCGFWIV-JZJYNLBNSA-N 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229940127007 Compound 39 Drugs 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- TWXGCIVERWGICD-FXBPSFAMSA-N FC1=CC(F)=CC(\N=C/2C3=CC=CC=C3N(C3=CSC=C3)C\2=O)=C1 Chemical compound FC1=CC(F)=CC(\N=C/2C3=CC=CC=C3N(C3=CSC=C3)C\2=O)=C1 TWXGCIVERWGICD-FXBPSFAMSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000289419 Metatheria Species 0.000 description 1
- 241000237852 Mollusca Species 0.000 description 1
- 241000289390 Monotremata Species 0.000 description 1
- 101100480774 Mus musculus Tbp gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methyl-N-phenylamine Natural products CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- NFLSUPGPZVXMIA-GFMRDNFCSA-N O=C1N(C=2C=CC=CC=2)C2=CC(OC)=CC=C2\C1=N\C1=CC=C(Cl)C(Cl)=C1 Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC(OC)=CC=C2\C1=N\C1=CC=C(Cl)C(Cl)=C1 NFLSUPGPZVXMIA-GFMRDNFCSA-N 0.000 description 1
- ZVYLAKSOBOCQCY-ATJXCDBQSA-N O=C1N(C=2C=CC=CC=2)C2=CC(OC)=CC=C2\C1=N\C1=CC=CC(Cl)=C1 Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC(OC)=CC=C2\C1=N\C1=CC=CC(Cl)=C1 ZVYLAKSOBOCQCY-ATJXCDBQSA-N 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 208000010886 Peripheral nerve injury Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009500 colour coating Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 229940125878 compound 36 Drugs 0.000 description 1
- 229940125807 compound 37 Drugs 0.000 description 1
- 229940127573 compound 38 Drugs 0.000 description 1
- 229940126540 compound 41 Drugs 0.000 description 1
- 229940125936 compound 42 Drugs 0.000 description 1
- 229940125844 compound 46 Drugs 0.000 description 1
- 229940127271 compound 49 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 229940126545 compound 53 Drugs 0.000 description 1
- 229940125900 compound 59 Drugs 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000003633 gene expression assay Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036433 growing body Effects 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000009808 hippocampal neurogenesis Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- UVNXNSUKKOLFBM-UHFFFAOYSA-N imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=CSC2=NC=CN21 UVNXNSUKKOLFBM-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical group C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 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
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 230000013016 learning Effects 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- YCJZWBZJSYLMPB-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-2,5-dimethyl-1-phenylimidazole-4-carboxamide Chemical compound CC=1N(C=2C=CC=CC=2)C(C)=NC=1C(=O)NC1=CC=NC(Cl)=N1 YCJZWBZJSYLMPB-UHFFFAOYSA-N 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 208000028412 nervous system injury Diseases 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000008180 pharmaceutical surfactant Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 125000005545 phthalimidyl group Chemical group 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- SWGJCIMEBVHMTA-UHFFFAOYSA-K trisodium;6-oxido-4-sulfo-5-[(4-sulfonatonaphthalen-1-yl)diazenyl]naphthalene-2-sulfonate Chemical compound [Na+].[Na+].[Na+].C1=CC=C2C(N=NC3=C4C(=CC(=CC4=CC=C3O)S([O-])(=O)=O)S([O-])(=O)=O)=CC=C(S([O-])(=O)=O)C2=C1 SWGJCIMEBVHMTA-UHFFFAOYSA-K 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81668206P | 2006-06-26 | 2006-06-26 | |
| PCT/US2007/072166 WO2008002946A2 (en) | 2006-06-26 | 2007-06-26 | Method of modulating neurite outgrowth by the use of a galanin-3 receptor antagonist |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2008016083A true MX2008016083A (es) | 2009-03-20 |
Family
ID=38738789
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2008016083A MX2008016083A (es) | 2006-06-26 | 2007-06-26 | Metodo para modular la excrecion de neuritas por el uso de un antagonista del receptor de galanina-3. |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20080039496A1 (enExample) |
| EP (1) | EP2032135A2 (enExample) |
| JP (2) | JP2009541493A (enExample) |
| CN (1) | CN101484159A (enExample) |
| AU (1) | AU2007265088B2 (enExample) |
| BR (1) | BRPI0712938A2 (enExample) |
| CA (1) | CA2655829A1 (enExample) |
| IL (1) | IL195903A0 (enExample) |
| MX (1) | MX2008016083A (enExample) |
| SG (1) | SG172735A1 (enExample) |
| WO (1) | WO2008002946A2 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7642281B2 (en) * | 2002-08-07 | 2010-01-05 | Helicon Therapeutics, Inc. | Indolone compounds useful to treat cognitive impairment |
| US20100028839A1 (en) * | 2008-07-18 | 2010-02-04 | Tully Timothy P | Methods and systems for evaluating memory agents |
| EP2313098A4 (en) * | 2008-07-18 | 2011-12-21 | Dart Neuroscience Llc | METHOD AND SYSTEMS FOR THE ASSESSMENT OF MEMORY-PROMOTING ACTIVE SUBSTANCES |
| AU2012222869B2 (en) * | 2011-03-02 | 2015-08-13 | Bionomics Limited | Methods of treating a disease or condition of the central nervous system |
| US8277842B1 (en) | 2012-01-20 | 2012-10-02 | Dart Neuroscience (Cayman) Ltd. | Enteric-coated HT-2157 compositions and methods of their use |
| CR20160578A (es) * | 2014-06-26 | 2017-02-21 | Hoffmann La Roche | Derivados de indolin-2-ona o pirrolo-piridin-2-ona |
| CN108349942B (zh) | 2015-11-06 | 2021-03-30 | 豪夫迈·罗氏有限公司 | 用于治疗cns和相关疾病的二氢吲哚-2-酮衍生物 |
| CA3002489C (en) | 2015-11-06 | 2023-11-07 | F.Hoffmann-La Roche Ag | Indolin-2-one derivatives |
| JP6857651B2 (ja) | 2015-11-06 | 2021-04-14 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｃｎｓ疾患の処置に有用なインドリン−２−オン誘導体 |
| WO2017076842A1 (en) | 2015-11-06 | 2017-05-11 | F. Hoffmann-La Roche Ag | Indolin-2-one derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7081470B2 (en) * | 2001-01-31 | 2006-07-25 | H. Lundbeck A/S | Use of GALR3 receptor antagonists for the treatment of depression and/or anxiety and compounds useful in such methods |
| US7220775B2 (en) * | 2002-08-07 | 2007-05-22 | H. Lundbeck A/S | Compound useful for the treatment of neuropathic pain |
-
2007
- 2007-06-26 MX MX2008016083A patent/MX2008016083A/es not_active Application Discontinuation
- 2007-06-26 SG SG2011047032A patent/SG172735A1/en unknown
- 2007-06-26 CN CNA2007800241434A patent/CN101484159A/zh active Pending
- 2007-06-26 AU AU2007265088A patent/AU2007265088B2/en not_active Ceased
- 2007-06-26 JP JP2009518522A patent/JP2009541493A/ja active Pending
- 2007-06-26 WO PCT/US2007/072166 patent/WO2008002946A2/en not_active Ceased
- 2007-06-26 US US11/768,889 patent/US20080039496A1/en not_active Abandoned
- 2007-06-26 CA CA002655829A patent/CA2655829A1/en not_active Abandoned
- 2007-06-26 BR BRPI0712938-6A patent/BRPI0712938A2/pt not_active IP Right Cessation
- 2007-06-26 EP EP07799059A patent/EP2032135A2/en not_active Withdrawn
-
2008
- 2008-12-11 IL IL195903A patent/IL195903A0/en unknown
-
2013
- 2013-08-15 JP JP2013168863A patent/JP2013227357A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| SG172735A1 (en) | 2011-07-28 |
| JP2013227357A (ja) | 2013-11-07 |
| AU2007265088A1 (en) | 2008-01-03 |
| JP2009541493A (ja) | 2009-11-26 |
| EP2032135A2 (en) | 2009-03-11 |
| BRPI0712938A2 (pt) | 2013-03-26 |
| US20080039496A1 (en) | 2008-02-14 |
| WO2008002946A3 (en) | 2008-05-02 |
| CA2655829A1 (en) | 2008-01-03 |
| IL195903A0 (en) | 2009-09-01 |
| CN101484159A (zh) | 2009-07-15 |
| AU2007265088B2 (en) | 2013-05-23 |
| WO2008002946A2 (en) | 2008-01-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MX2008016083A (es) | Metodo para modular la excrecion de neuritas por el uso de un antagonista del receptor de galanina-3. | |
| US10183011B2 (en) | Anti-depression compounds | |
| US20130224151A1 (en) | Use of FAAH Inhibitors for Treating Abdominal, Visceral and Pelvic Pain | |
| CN106715417A (zh) | 药物中使用的吲哚衍生物 | |
| CN102271763A (zh) | 抑制hdac2以促进记忆 | |
| KR20010079616A (ko) | 과도한 물질 ｐ에 의해 야기된 문제점을 치료하기 위한약물 제조에 사용되는 아릴(또는헤테로아릴)아졸일카르비놀 유도체의 용도 | |
| WO2018214796A1 (zh) | 一类异吲哚酮-酰亚胺环-1,3-二酮-2-烯化合物、其组合物和用途 | |
| CA3006764A1 (en) | Use of sgc stimulators for the treatment of gastrointestinal sphincter dysfunction | |
| KR20200036920A (ko) | 행동 변경 치료 방법 | |
| JP6563998B2 (ja) | 治療計画 | |
| US6562858B2 (en) | Method for treating depression | |
| KR102891465B1 (ko) | 뇌졸중으로부터의 회복을 위한 방법 및 조성물 | |
| MX2008011015A (es) | Inhibidores de pai-1 para tratamiento de afecciones musculares. | |
| US9427439B1 (en) | Methods and compositions for recovery from stroke | |
| CN109563054B (zh) | 新型芳基乙烯衍生物以及以该新型芳基乙烯为有效成分的药物组合物 | |
| JPH10511931A (ja) | 非インシュリン依存性糖尿病の患者において胃空腹を抑制する１，５−ベンゾジアゼピン誘導体の使用 | |
| TWI403509B (zh) | 一種用以治療癌症之藥學組合物 | |
| WO2025164698A1 (ja) | ハンチントン病治療剤及び治療用組成物 | |
| JP2007063278A (ja) | うつ病、不安症および認知障害用の５−ｈｔ１ｂアンタゴニスト組成物 | |
| CN101378750B (zh) | 用于治疗认知损害的吲哚酮化合物 | |
| RU2799049C2 (ru) | Способы лечения изменений поведения | |
| JP2012528881A (ja) | 精神障害およびその症状の治療のためのｋｃｎｑカリウムチャネル活性の調節方法 | |
| EA046894B1 (ru) | Ингибиторы rho-ассоциированной, содержащей суперспираль протеинкиназы | |
| HK1111915A (en) | Jnk inhibitors for treatment of cns injury |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HH | Correction or change in general | ||
| FA | Abandonment or withdrawal |