CA2937430A1 - Compounds - Google Patents

Compounds Download PDF

Info

Publication number: CA2937430A1
Authority: CA; Canada
Prior art keywords: mmol; methanone; amino; compound; pharmaceutically acceptable
Prior art date: 2014-01-29
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.): Abandoned

Application number

CA2937430A

Other languages

English (en)

French (fr)

Inventor

Xiao DING

Qian Liu

Kai Long

Yingxia SANG

Luigi Piero Stasi

Zehong Wan

Qiongfeng XU

Colin Michael Edge

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

GlaxoSmithKline Intellectual Property Development Ltd

Original Assignee

GlaxoSmithKline Intellectual Property Development Ltd

Priority date (The priority date 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 date listed.)

2014-01-29

Filing date

2015-01-28

Publication date

2015-08-06

2015-01-28 Application filed by GlaxoSmithKline Intellectual Property Development Ltd filed Critical GlaxoSmithKline Intellectual Property Development Ltd

2015-08-06 Publication of CA2937430A1 publication Critical patent/CA2937430A1/en

Status Abandoned legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 300
208000018737 Parkinson disease Diseases 0.000 claims abstract description 59
238000011282 treatment Methods 0.000 claims abstract description 58
238000000034 method Methods 0.000 claims abstract description 48
150000003839 salts Chemical class 0.000 claims description 121
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
229910052757 nitrogen Inorganic materials 0.000 claims description 33
239000002253 acid Substances 0.000 claims description 32
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 29
125000001424 substituent group Chemical group 0.000 claims description 27
239000000546 pharmaceutical excipient Substances 0.000 claims description 26
125000000623 heterocyclic group Chemical group 0.000 claims description 25
229910052739 hydrogen Inorganic materials 0.000 claims description 23
239000008194 pharmaceutical composition Substances 0.000 claims description 22
239000003814 drug Substances 0.000 claims description 17
238000004519 manufacturing process Methods 0.000 claims description 12
125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
239000012458 free base Substances 0.000 claims description 5
125000004193 piperazinyl group Chemical group 0.000 claims description 4
125000002757 morpholinyl group Chemical group 0.000 claims description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 7
125000001475 halogen functional group Chemical group 0.000 claims 4
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
208000034968 autosomal dominant susceptibility to Parkinson disease 13 Diseases 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
ZLLCVOJWNDZXIO-UHFFFAOYSA-N n-propyl-4-[[4-(3,3,3-trifluoropropyl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide Chemical compound C1=CC(C(=O)NCCC)=CC=C1NC1=NC(CCC(F)(F)F)=C(C=CN2)C2=N1 ZLLCVOJWNDZXIO-UHFFFAOYSA-N 0.000 claims 1
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
125000003386 piperidinyl group Chemical group 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 152
108010020246 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Proteins 0.000 abstract description 90
102000009784 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Human genes 0.000 abstract description 86
230000000694 effects Effects 0.000 abstract description 21
206010002026 amyotrophic lateral sclerosis Diseases 0.000 abstract description 19
208000024827 Alzheimer disease Diseases 0.000 abstract description 17
238000002360 preparation method Methods 0.000 abstract description 7
230000008569 process Effects 0.000 abstract description 7
230000006806 disease prevention Effects 0.000 abstract 1
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 252
239000000243 solution Substances 0.000 description 136
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 123
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 122
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 107
239000007787 solid Substances 0.000 description 98
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 91
WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 91
-1 methylethyl Chemical group 0.000 description 88
238000005160 1H NMR spectroscopy Methods 0.000 description 77
239000012044 organic layer Substances 0.000 description 71
OFRMASLPWOMYHN-UHFFFAOYSA-N 1-[3-methoxy-4-[[6-(2-propan-2-ylsulfonylanilino)-7H-purin-2-yl]amino]phenyl]piperidin-4-ol Chemical group COc1cc(ccc1Nc1nc(Nc2ccccc2S(=O)(=O)C(C)C)c2[nH]cnc2n1)N1CCC(O)CC1 OFRMASLPWOMYHN-UHFFFAOYSA-N 0.000 description 67
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 61
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 58
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 54
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 50
201000010099 disease Diseases 0.000 description 47
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 45
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 45
229910052938 sodium sulfate Inorganic materials 0.000 description 45
235000011152 sodium sulphate Nutrition 0.000 description 45
239000007832 Na2SO4 Substances 0.000 description 44
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
239000011541 reaction mixture Substances 0.000 description 39
239000000741 silica gel Substances 0.000 description 37
229910002027 silica gel Inorganic materials 0.000 description 37
230000035772 mutation Effects 0.000 description 36
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
239000002904 solvent Substances 0.000 description 36
238000006243 chemical reaction Methods 0.000 description 35
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 34
239000000543 intermediate Substances 0.000 description 33
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 32
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 29
239000003921 oil Substances 0.000 description 28
210000004027 cell Anatomy 0.000 description 27
235000019198 oils Nutrition 0.000 description 27
238000002953 preparative HPLC Methods 0.000 description 26
238000004440 column chromatography Methods 0.000 description 25
239000012071 phase Substances 0.000 description 25
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 description 24
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 23
125000006239 protecting group Chemical group 0.000 description 21
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 19
239000002585 base Substances 0.000 description 19
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
201000011240 Frontotemporal dementia Diseases 0.000 description 18
239000012267 brine Substances 0.000 description 18
229910000027 potassium carbonate Inorganic materials 0.000 description 18
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
CROCDXCMEKSYHU-UHFFFAOYSA-N 2-chloro-4-ethoxy-7H-pyrrolo[2,3-d]pyrimidine Chemical compound ClC=1N=C(C2=C(N=1)NC=C2)OCC CROCDXCMEKSYHU-UHFFFAOYSA-N 0.000 description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
238000003556 assay Methods 0.000 description 17
JQTMGOLZSBTZMS-UHFFFAOYSA-N 4-methylpiperazine-1-carbaldehyde Chemical compound CN1CCN(C=O)CC1 JQTMGOLZSBTZMS-UHFFFAOYSA-N 0.000 description 16
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
239000003153 chemical reaction reagent Substances 0.000 description 16
238000004587 chromatography analysis Methods 0.000 description 16
239000006184 cosolvent Substances 0.000 description 16
125000005843 halogen group Chemical group 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
239000007821 HATU Substances 0.000 description 15
102200092160 rs34637584 Human genes 0.000 description 15
229910000104 sodium hydride Inorganic materials 0.000 description 15
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
238000007125 Buchwald synthesis reaction Methods 0.000 description 14
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 14
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 14
125000000217 alkyl group Chemical group 0.000 description 14
238000004296 chiral HPLC Methods 0.000 description 14
235000011181 potassium carbonates Nutrition 0.000 description 14
CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 14
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
208000031261 Acute myeloid leukaemia Diseases 0.000 description 12
206010012289 Dementia Diseases 0.000 description 12
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
208000033776 Myeloid Acute Leukemia Diseases 0.000 description 12
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
239000000872 buffer Substances 0.000 description 12
125000004432 carbon atom Chemical group C* 0.000 description 12
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 12
239000003112 inhibitor Substances 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
238000000746 purification Methods 0.000 description 12
239000012453 solvate Substances 0.000 description 12
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
239000012312 sodium hydride Substances 0.000 description 11
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
229940124786 LRRK2 inhibitor Drugs 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
150000001412 amines Chemical class 0.000 description 10
238000001914 filtration Methods 0.000 description 10
230000002265 prevention Effects 0.000 description 10
239000000047 product Substances 0.000 description 10
239000000460 chlorine Substances 0.000 description 9
230000006870 function Effects 0.000 description 9
239000007858 starting material Substances 0.000 description 9
206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 8
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
238000005481 NMR spectroscopy Methods 0.000 description 8
208000027089 Parkinsonian disease Diseases 0.000 description 8
206010034010 Parkinsonism Diseases 0.000 description 8
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 8
238000003016 alphascreen Methods 0.000 description 8
125000004429 atom Chemical group 0.000 description 8
201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
208000032839 leukemia Diseases 0.000 description 8
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 8
108090000623 proteins and genes Proteins 0.000 description 8
OQHQOOLVQDEIGL-UHFFFAOYSA-N 2-methyl-2,7-diazaspiro[4.4]nonane Chemical compound C1N(C)CCC11CNCC1 OQHQOOLVQDEIGL-UHFFFAOYSA-N 0.000 description 7
208000032382 Ischaemic stroke Diseases 0.000 description 7
208000000236 Prostatic Neoplasms Diseases 0.000 description 7
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 7
208000030886 Traumatic Brain injury Diseases 0.000 description 7
229910021529 ammonia Inorganic materials 0.000 description 7
208000010877 cognitive disease Diseases 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
208000027061 mild cognitive impairment Diseases 0.000 description 7
229910000073 phosphorus hydride Inorganic materials 0.000 description 7
108090000765 processed proteins & peptides Proteins 0.000 description 7
AHRQYOSAXZQCIG-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=C=NC=N[CH]1 AHRQYOSAXZQCIG-UHFFFAOYSA-N 0.000 description 7
239000011734 sodium Substances 0.000 description 7
208000020431 spinal cord injury Diseases 0.000 description 7
239000000758 substrate Substances 0.000 description 7
238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 7
230000009529 traumatic brain injury Effects 0.000 description 7
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
208000011990 Corticobasal Degeneration Diseases 0.000 description 6
208000011231 Crohn disease Diseases 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
208000015872 Gaucher disease Diseases 0.000 description 6
208000015439 Lysosomal storage disease Diseases 0.000 description 6
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 6
208000000609 Pick Disease of the Brain Diseases 0.000 description 6
230000001594 aberrant effect Effects 0.000 description 6
210000000481 breast Anatomy 0.000 description 6
210000000349 chromosome Anatomy 0.000 description 6
238000005859 coupling reaction Methods 0.000 description 6
239000012043 crude product Substances 0.000 description 6
238000001514 detection method Methods 0.000 description 6
208000035475 disorder Diseases 0.000 description 6
239000000284 extract Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
210000004072 lung Anatomy 0.000 description 6
201000006417 multiple sclerosis Diseases 0.000 description 6
229910052763 palladium Inorganic materials 0.000 description 6
201000002212 progressive supranuclear palsy Diseases 0.000 description 6
238000006467 substitution reaction Methods 0.000 description 6
239000000725 suspension Substances 0.000 description 6
238000002636 symptomatic treatment Methods 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
238000012360 testing method Methods 0.000 description 6
229940124597 therapeutic agent Drugs 0.000 description 6
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 6
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 5
VVKKSKQZLBRBBO-UHFFFAOYSA-N 2-chloro-4-ethoxy-5-iodo-7H-pyrrolo[2,3-d]pyrimidine Chemical compound ClC=1N=C(C2=C(N=1)NC=C2I)OCC VVKKSKQZLBRBBO-UHFFFAOYSA-N 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
208000009829 Lewy Body Disease Diseases 0.000 description 5
201000002832 Lewy body dementia Diseases 0.000 description 5
108091000080 Phosphotransferase Proteins 0.000 description 5
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 5
201000004810 Vascular dementia Diseases 0.000 description 5
125000003545 alkoxy group Chemical group 0.000 description 5
239000011324 bead Substances 0.000 description 5
230000001413 cellular effect Effects 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
238000007796 conventional method Methods 0.000 description 5
230000007547 defect Effects 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
229940088598 enzyme Drugs 0.000 description 5
229910052736 halogen Inorganic materials 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
229910052742 iron Inorganic materials 0.000 description 5
239000003446 ligand Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
230000007074 memory dysfunction Effects 0.000 description 5
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 5
230000001537 neural effect Effects 0.000 description 5
208000015122 neurodegenerative disease Diseases 0.000 description 5
230000001717 pathogenic effect Effects 0.000 description 5
230000026731 phosphorylation Effects 0.000 description 5
238000006366 phosphorylation reaction Methods 0.000 description 5
102000020233 phosphotransferase Human genes 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
206010039073 rheumatoid arthritis Diseases 0.000 description 5
KNCZGHQEKWOGHY-UHFFFAOYSA-N (3-fluoro-4-nitrophenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C([N+]([O-])=O)C(F)=C1 KNCZGHQEKWOGHY-UHFFFAOYSA-N 0.000 description 4
GPRUBQPFDXFIJN-UHFFFAOYSA-N (4-amino-3-methoxyphenyl)-morpholin-4-ylmethanone Chemical compound C1=C(N)C(OC)=CC(C(=O)N2CCOCC2)=C1 GPRUBQPFDXFIJN-UHFFFAOYSA-N 0.000 description 4
GXVIPZJXBXDOHA-UHFFFAOYSA-N 2-chloro-3-methoxy-4-nitrobenzoic acid Chemical compound ClC1=C(C(=O)O)C=CC(=C1OC)[N+](=O)[O-] GXVIPZJXBXDOHA-UHFFFAOYSA-N 0.000 description 4
LSIIXEGXZZZUTM-UHFFFAOYSA-N 3-(cyclopropylmethoxy)-4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C(OCC2CC2)=C1 LSIIXEGXZZZUTM-UHFFFAOYSA-N 0.000 description 4
IRJNTPHQQOHBGU-UHFFFAOYSA-N 3-(difluoromethoxy)-4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C(OC(F)F)=C1 IRJNTPHQQOHBGU-UHFFFAOYSA-N 0.000 description 4
PWURRRRGLCVBMX-UHFFFAOYSA-N 3-methoxy-4-nitrobenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1[N+]([O-])=O PWURRRRGLCVBMX-UHFFFAOYSA-N 0.000 description 4
206010006187 Breast cancer Diseases 0.000 description 4
208000026310 Breast neoplasm Diseases 0.000 description 4
208000012661 Dyskinesia Diseases 0.000 description 4
208000004332 Evans syndrome Diseases 0.000 description 4
208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 4
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 4
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 4
206010025323 Lymphomas Diseases 0.000 description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
201000002481 Myositis Diseases 0.000 description 4
208000003670 Pure Red-Cell Aplasia Diseases 0.000 description 4
208000021386 Sjogren Syndrome Diseases 0.000 description 4
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 4
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 4
206010047115 Vasculitis Diseases 0.000 description 4
239000000556 agonist Substances 0.000 description 4
230000003281 allosteric effect Effects 0.000 description 4
201000000448 autoimmune hemolytic anemia Diseases 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000004305 biphenyl Substances 0.000 description 4
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
229910000024 caesium carbonate Inorganic materials 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
230000002068 genetic effect Effects 0.000 description 4
125000001188 haloalkyl group Chemical group 0.000 description 4
150000002367 halogens Chemical class 0.000 description 4
150000004677 hydrates Chemical class 0.000 description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
208000015181 infectious disease Diseases 0.000 description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
239000010410 layer Substances 0.000 description 4
208000020816 lung neoplasm Diseases 0.000 description 4
XJAGTAYJYBVTIH-UHFFFAOYSA-N methyl 3-(cyclopropylmethoxy)-4-nitrobenzoate Chemical compound COC(=O)C1=CC=C([N+]([O-])=O)C(OCC2CC2)=C1 XJAGTAYJYBVTIH-UHFFFAOYSA-N 0.000 description 4
IXUCYGQTKDSONM-UHFFFAOYSA-N methyl 3-(difluoromethoxy)-4-nitrobenzoate Chemical compound COC(=O)C1=CC=C([N+]([O-])=O)C(OC(F)F)=C1 IXUCYGQTKDSONM-UHFFFAOYSA-N 0.000 description 4
QSRRZKPKHJHIRB-UHFFFAOYSA-N methyl 4-[(2,5-dichloro-4-methylthiophen-3-yl)sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=C(Cl)SC(Cl)=C1C QSRRZKPKHJHIRB-UHFFFAOYSA-N 0.000 description 4
208000008795 neuromyelitis optica Diseases 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000008188 pellet Substances 0.000 description 4
235000015320 potassium carbonate Nutrition 0.000 description 4
239000000843 powder Substances 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
102200092223 rs33939927 Human genes 0.000 description 4
208000017520 skin disease Diseases 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
201000000596 systemic lupus erythematosus Diseases 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
UFVKIYCXXSGEHM-UHFFFAOYSA-N (3-ethoxy-4-nitrophenyl)-morpholin-4-ylmethanone Chemical compound C(C)OC=1C=C(C=CC=1[N+](=O)[O-])C(=O)N1CCOCC1 UFVKIYCXXSGEHM-UHFFFAOYSA-N 0.000 description 3
DVWPBDJBUIJVSI-UHFFFAOYSA-N (3-fluoro-4-nitrophenyl)-morpholin-4-ylmethanone Chemical compound C1=C(F)C([N+](=O)[O-])=CC=C1C(=O)N1CCOCC1 DVWPBDJBUIJVSI-UHFFFAOYSA-N 0.000 description 3
VJRGJYUEJPBPEN-UHFFFAOYSA-N (4-amino-3-methoxyphenyl)-(4-fluoropiperidin-1-yl)methanone Chemical compound C1=C(N)C(OC)=CC(C(=O)N2CCC(F)CC2)=C1 VJRGJYUEJPBPEN-UHFFFAOYSA-N 0.000 description 3
MMGJIPZQQGLXAF-SECBINFHSA-N (4-amino-3-methoxyphenyl)-[(3r)-3-methylmorpholin-4-yl]methanone Chemical compound C1=C(N)C(OC)=CC(C(=O)N2[C@@H](COCC2)C)=C1 MMGJIPZQQGLXAF-SECBINFHSA-N 0.000 description 3
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
SILRXJAFPBVTIU-UHFFFAOYSA-N ClC=1N=C(C2=C(N=1)NC=C2)OCC1CC1 Chemical compound ClC=1N=C(C2=C(N=1)NC=C2)OCC1CC1 SILRXJAFPBVTIU-UHFFFAOYSA-N 0.000 description 3
229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
206010024229 Leprosy Diseases 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 3
208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 3
SJTGNEQZIRYEFF-UHFFFAOYSA-N [3-(dimethylamino)-4-nitrophenyl]-morpholin-4-ylmethanone Chemical compound CN(C=1C=C(C=CC=1[N+](=O)[O-])C(=O)N1CCOCC1)C SJTGNEQZIRYEFF-UHFFFAOYSA-N 0.000 description 3
XCQZSMPJFKRMEC-UHFFFAOYSA-N [3-ethoxy-4-[(4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino]phenyl]-morpholin-4-ylmethanone Chemical compound C(C)OC=1C=C(C=CC=1NC=1N=C(C2=C(N=1)NC=C2)OCC)C(=O)N1CCOCC1 XCQZSMPJFKRMEC-UHFFFAOYSA-N 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
150000001413 amino acids Chemical class 0.000 description 3
239000012131 assay buffer Substances 0.000 description 3
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
210000004556 brain Anatomy 0.000 description 3
239000002775 capsule Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
239000007884 disintegrant Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
206010013663 drug dependence Diseases 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
238000005516 engineering process Methods 0.000 description 3
230000005284 excitation Effects 0.000 description 3
239000000945 filler Substances 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
238000011534 incubation Methods 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
238000002955 isolation Methods 0.000 description 3
239000000314 lubricant Substances 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
239000002609 medium Substances 0.000 description 3
SBPSDEQYWNQMHM-UHFFFAOYSA-N methyl 2-chloro-3-methoxy-4-nitrobenzoate Chemical compound ClC1=C(C(=O)OC)C=CC(=C1OC)[N+](=O)[O-] SBPSDEQYWNQMHM-UHFFFAOYSA-N 0.000 description 3
CBTDHGHNLNIBQS-UHFFFAOYSA-N morpholin-4-yl-(4-nitro-3-propan-2-yloxyphenyl)methanone Chemical compound C(C)(C)OC=1C=C(C=CC=1[N+](=O)[O-])C(=O)N1CCOCC1 CBTDHGHNLNIBQS-UHFFFAOYSA-N 0.000 description 3
230000004770 neurodegeneration Effects 0.000 description 3
239000008184 oral solid dosage form Substances 0.000 description 3
210000000056 organ Anatomy 0.000 description 3
230000002018 overexpression Effects 0.000 description 3
YYROPELSRYBVMQ-UHFFFAOYSA-N p-toluenesulfonyl chloride Substances CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
238000002600 positron emission tomography Methods 0.000 description 3
239000011347 resin Substances 0.000 description 3
229920005989 resin Polymers 0.000 description 3
229910052701 rubidium Inorganic materials 0.000 description 3
150000003384 small molecules Chemical class 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
239000003381 stabilizer Substances 0.000 description 3
210000000130 stem cell Anatomy 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
208000011117 substance-related disease Diseases 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
239000003826 tablet Substances 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
210000001685 thyroid gland Anatomy 0.000 description 3
238000011830 transgenic mouse model Methods 0.000 description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
241000701447 unidentified baculovirus Species 0.000 description 3
239000003643 water by type Substances 0.000 description 3
DISHZSZNLADMLH-SECBINFHSA-N (3-methoxy-4-nitrophenyl)-[(3R)-3-methylmorpholin-4-yl]methanone Chemical compound COC=1C=C(C=CC=1[N+](=O)[O-])C(=O)N1[C@@H](COCC1)C DISHZSZNLADMLH-SECBINFHSA-N 0.000 description 2
ZBVAADHKVJYWHF-UHFFFAOYSA-N (4-amino-3-methoxyphenyl)-[1-(methoxymethyl)-3-azabicyclo[3.1.0]hexan-3-yl]methanone Chemical compound NC1=C(C=C(C=C1)C(=O)N1CC2(CC2C1)COC)OC ZBVAADHKVJYWHF-UHFFFAOYSA-N 0.000 description 2
FQIPRWUQUGZEON-UHFFFAOYSA-N (4-amino-3-methoxyphenyl)-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]methanone Chemical compound C1=C(N)C(OC)=CC(C(=O)N2CCC(CC2)N2CCN(C)CC2)=C1 FQIPRWUQUGZEON-UHFFFAOYSA-N 0.000 description 2
PIILVZKNRZVYSH-UHFFFAOYSA-N (4-amino-3-propan-2-yloxyphenyl)-morpholin-4-ylmethanone Chemical compound C1=C(N)C(OC(C)C)=CC(C(=O)N2CCOCC2)=C1 PIILVZKNRZVYSH-UHFFFAOYSA-N 0.000 description 2
KMWMHGDGKNFOMV-UHFFFAOYSA-N 2-chloro-3-hydroxy-4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C(O)=C1Cl KMWMHGDGKNFOMV-UHFFFAOYSA-N 0.000 description 2
CSXHYQCXIKBLLX-UHFFFAOYSA-N 2-chloro-4-ethoxy-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile Chemical compound ClC=1N=C(C2=C(N=1)NC=C2C#N)OCC CSXHYQCXIKBLLX-UHFFFAOYSA-N 0.000 description 2
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical compound CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 description 2
PHOQTUXRQPJPJY-UHFFFAOYSA-O 6-carboxy-2-hydroxy-3-nitrobenzenediazonium Chemical compound C(=O)(O)C1=CC=C(C(=C1[N+]#N)O)[N+](=O)[O-] PHOQTUXRQPJPJY-UHFFFAOYSA-O 0.000 description 2
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 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
206010061818 Disease progression Diseases 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
102000013446 GTP Phosphohydrolases Human genes 0.000 description 2
108091006109 GTPases Proteins 0.000 description 2
101100021877 Homo sapiens LRRK2 gene Proteins 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
101150081013 LRRK2 gene Proteins 0.000 description 2
102220596654 Leucine-rich repeat serine/threonine-protein kinase 2_R1441C_mutation Human genes 0.000 description 2
102220577884 Leucine-rich repeat serine/threonine-protein kinase 2_Y1699C_mutation Human genes 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
108091062154 Mir-205 Proteins 0.000 description 2
229920000881 Modified starch Polymers 0.000 description 2
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
208000012902 Nervous system disease Diseases 0.000 description 2
208000025966 Neurological disease Diseases 0.000 description 2
239000012124 Opti-MEM Substances 0.000 description 2
WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
229910021120 PdC12 Inorganic materials 0.000 description 2
241001494479 Pecora Species 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
240000006394 Sorghum bicolor Species 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
208000006011 Stroke Diseases 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
208000034799 Tauopathies Diseases 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
229920004890 Triton X-100 Polymers 0.000 description 2
239000013504 Triton X-100 Substances 0.000 description 2
241000700605 Viruses Species 0.000 description 2
208000027418 Wounds and injury Diseases 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
235000010443 alginic acid Nutrition 0.000 description 2
239000000783 alginic acid Substances 0.000 description 2
229920000615 alginic acid Polymers 0.000 description 2
229960001126 alginic acid Drugs 0.000 description 2
150000004781 alginic acids Chemical class 0.000 description 2
102000003802 alpha-Synuclein Human genes 0.000 description 2
108090000185 alpha-Synuclein Proteins 0.000 description 2
229910052782 aluminium Inorganic materials 0.000 description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
229940077388 benzenesulfonate Drugs 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
230000030833 cell death Effects 0.000 description 2
230000012292 cell migration Effects 0.000 description 2
230000004663 cell proliferation Effects 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
208000015114 central nervous system disease Diseases 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
238000001816 cooling Methods 0.000 description 2
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
238000012937 correction Methods 0.000 description 2
238000006880 cross-coupling reaction Methods 0.000 description 2
125000000753 cycloalkyl group Chemical group 0.000 description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
SNRCKKQHDUIRIY-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron(2+) Chemical compound [Fe+2].ClCCl.Cl[Pd]Cl.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 SNRCKKQHDUIRIY-UHFFFAOYSA-L 0.000 description 2
GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 2
230000006378 damage Effects 0.000 description 2
238000011161 development Methods 0.000 description 2
IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
230000005750 disease progression Effects 0.000 description 2
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
230000004064 dysfunction Effects 0.000 description 2
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
239000012091 fetal bovine serum Substances 0.000 description 2
210000002950 fibroblast Anatomy 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
239000006260 foam Substances 0.000 description 2
230000014509 gene expression Effects 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
230000006951 hyperphosphorylation Effects 0.000 description 2
210000000987 immune system Anatomy 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
210000004263 induced pluripotent stem cell Anatomy 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
208000014674 injury Diseases 0.000 description 2
230000003993 interaction Effects 0.000 description 2
229940043355 kinase inhibitor Drugs 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
229910001629 magnesium chloride Inorganic materials 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000000463 material Substances 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
108020004999 messenger RNA Proteins 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-UHFFFAOYSA-N 0.000 description 2
UEGCRFNWTGYVKX-UHFFFAOYSA-N methyl 3-hydroxy-4-nitrobenzoate Chemical compound COC(=O)C1=CC=C([N+]([O-])=O)C(O)=C1 UEGCRFNWTGYVKX-UHFFFAOYSA-N 0.000 description 2
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
238000013508 migration Methods 0.000 description 2
230000002314 neuroinflammatory effect Effects 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
230000008506 pathogenesis Effects 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
239000003757 phosphotransferase inhibitor Substances 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229920001592 potato starch Polymers 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000000018 receptor agonist Substances 0.000 description 2
229940044601 receptor agonist Drugs 0.000 description 2
229940044551 receptor antagonist Drugs 0.000 description 2
239000002464 receptor antagonist Substances 0.000 description 2
238000004366 reverse phase liquid chromatography Methods 0.000 description 2
238000012552 review Methods 0.000 description 2
239000011435 rock Substances 0.000 description 2
102220010566 rs74163686 Human genes 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
238000000926 separation method Methods 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
229940032147 starch Drugs 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
238000010189 synthetic method Methods 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
MRYZPLULYNZMJD-VGMNWLOBSA-N tert-butyl (1s,3s,5s)-3-cyano-2-azabicyclo[3.1.0]hexane-2-carboxylate Chemical compound C1[C@@H](C#N)N(C(=O)OC(C)(C)C)[C@H]2C[C@H]21 MRYZPLULYNZMJD-VGMNWLOBSA-N 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
238000001851 vibrational circular dichroism spectroscopy Methods 0.000 description 2
ZQSMZFIOPBRRKZ-SRQIZXRXSA-N (1s,3s,5s)-2-azabicyclo[3.1.0]hexane-3-carbonitrile Chemical compound N1[C@H](C#N)C[C@@H]2C[C@@H]21 ZQSMZFIOPBRRKZ-SRQIZXRXSA-N 0.000 description 1
VASDEEBNVDJQRB-GAJRHLONSA-N (1s,3s,5s)-2-azabicyclo[3.1.0]hexane-3-carbonitrile;hydrochloride Chemical compound Cl.N1[C@H](C#N)C[C@@H]2C[C@@H]21 VASDEEBNVDJQRB-GAJRHLONSA-N 0.000 description 1
YDIKCZBMBPOGFT-DIONPBRTSA-N (2s,3r,4s,5s,6r)-2-[5,7-dihydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)chromenylium-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol;chloride Chemical compound [Cl-].COC1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1 YDIKCZBMBPOGFT-DIONPBRTSA-N 0.000 description 1
AKDDPJJPMJXXEF-UHFFFAOYSA-N (3-methoxy-4-nitrophenyl)-(2-oxa-7-azaspiro[3.4]octan-7-yl)methanone Chemical compound COC1=CC(=CC=C1[N+]([O-])=O)C(=O)N1CCC2(COC2)C1 AKDDPJJPMJXXEF-UHFFFAOYSA-N 0.000 description 1
DISHZSZNLADMLH-VIFPVBQESA-N (3-methoxy-4-nitrophenyl)-[(3S)-3-methylmorpholin-4-yl]methanone Chemical compound COC1=C(C=CC(=C1)C(=O)N1CCOC[C@@H]1C)[N+]([O-])=O DISHZSZNLADMLH-VIFPVBQESA-N 0.000 description 1
SLTNMZFIUOVGMI-UHFFFAOYSA-N (3-methoxy-4-nitrophenyl)-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]methanone Chemical compound COC1=C(C=CC(=C1)C(=O)N1CCC(CC1)N1CCN(C)CC1)[N+]([O-])=O SLTNMZFIUOVGMI-UHFFFAOYSA-N 0.000 description 1
MLMBJSUQMNEIFJ-UHFFFAOYSA-N (4-amino-2-fluoro-5-methoxyphenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound NC1=CC(=C(C=C1OC)C(=O)N1CCN(CC1)C)F MLMBJSUQMNEIFJ-UHFFFAOYSA-N 0.000 description 1
ZGEFJQYUWKKSKT-UHFFFAOYSA-N (4-amino-2-fluoro-5-methoxyphenyl)-morpholin-4-ylmethanone Chemical compound C1=C(N)C(OC)=CC(C(=O)N2CCOCC2)=C1F ZGEFJQYUWKKSKT-UHFFFAOYSA-N 0.000 description 1
NRMHMZCGQFWWFL-UHFFFAOYSA-N (4-amino-3-fluorophenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(N)C(F)=C1 NRMHMZCGQFWWFL-UHFFFAOYSA-N 0.000 description 1
SXIBDSYYUVQGGX-UHFFFAOYSA-N (4-amino-3-methoxyphenyl)-(1,3-oxazolidin-3-yl)methanone Chemical compound COC1=C(N)C=CC(=C1)C(=O)N1CCOC1 SXIBDSYYUVQGGX-UHFFFAOYSA-N 0.000 description 1
ZWSCQQVYRLNBOU-UHFFFAOYSA-N (4-amino-3-methoxyphenyl)-(2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone Chemical compound C1=C(N)C(OC)=CC(C(=O)N2CC3(COC3)C2)=C1 ZWSCQQVYRLNBOU-UHFFFAOYSA-N 0.000 description 1
PWEMXKRWQYCDSH-UHFFFAOYSA-N (4-amino-3-methoxyphenyl)-(2-oxa-7-azaspiro[3.4]octan-7-yl)methanone Chemical compound NC1=C(C=C(C=C1)C(=O)N1CC2(COC2)CC1)OC PWEMXKRWQYCDSH-UHFFFAOYSA-N 0.000 description 1
ONSLAZXAMOMVKL-UHFFFAOYSA-N (4-amino-3-methoxyphenyl)-(6-azaspiro[2.5]octan-6-yl)methanone Chemical compound COC1=C(N)C=CC(=C1)C(=O)N1CCC2(CC2)CC1 ONSLAZXAMOMVKL-UHFFFAOYSA-N 0.000 description 1
XYNUWQYJZBUQCR-SNVBAGLBSA-N (4-amino-3-methoxyphenyl)-[(2R)-2,4-dimethylpiperazin-1-yl]methanone Chemical compound COC1=C(N)C=CC(=C1)C(=O)N1CCN(C)C[C@H]1C XYNUWQYJZBUQCR-SNVBAGLBSA-N 0.000 description 1
XKTUTAITYNMIMS-AOOOYVTPSA-N (4-amino-3-methoxyphenyl)-[(2R,6S)-2,6-dimethylmorpholin-4-yl]methanone Chemical compound NC1=C(C=C(C=C1)C(=O)N1C[C@H](O[C@H](C1)C)C)OC XKTUTAITYNMIMS-AOOOYVTPSA-N 0.000 description 1
XYNUWQYJZBUQCR-JTQLQIEISA-N (4-amino-3-methoxyphenyl)-[(2S)-2,4-dimethylpiperazin-1-yl]methanone Chemical compound COC1=C(N)C=CC(=C1)C(=O)N1CCN(C)C[C@@H]1C XYNUWQYJZBUQCR-JTQLQIEISA-N 0.000 description 1
MMGJIPZQQGLXAF-VIFPVBQESA-N (4-amino-3-methoxyphenyl)-[(3s)-3-methylmorpholin-4-yl]methanone Chemical compound C1=C(N)C(OC)=CC(C(=O)N2[C@H](COCC2)C)=C1 MMGJIPZQQGLXAF-VIFPVBQESA-N 0.000 description 1
DNUUIHCAKALIEA-UHFFFAOYSA-N (4-amino-3-propan-2-yloxyphenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound NC1=C(C=C(C=C1)C(=O)N1CCN(CC1)C)OC(C)C DNUUIHCAKALIEA-UHFFFAOYSA-N 0.000 description 1
WEHVQIQNGXWTME-UHFFFAOYSA-N (4-aminophenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(N)=CC=C1C(=O)N1CCOCC1 WEHVQIQNGXWTME-UHFFFAOYSA-N 0.000 description 1
NDYMQOUYJJXCKJ-UHFFFAOYSA-N (4-fluorophenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CCOCC1 NDYMQOUYJJXCKJ-UHFFFAOYSA-N 0.000 description 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
ARHYWWAJZDAYDJ-UHFFFAOYSA-N 1,2-dimethylpiperazine Chemical compound CC1CNCCN1C ARHYWWAJZDAYDJ-UHFFFAOYSA-N 0.000 description 1
LBYYDCLPMZOATJ-UHFFFAOYSA-N 1-methoxy-4-methylpiperazine Chemical compound CON1CCN(C)CC1 LBYYDCLPMZOATJ-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
GHXBPCSSQOKKGB-UHFFFAOYSA-N 2,4-dichloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC(Cl)=C2C=CNC2=N1 GHXBPCSSQOKKGB-UHFFFAOYSA-N 0.000 description 1
KYFXPHPBTUJULU-UHFFFAOYSA-N 2-(2-methoxyanilino)-2-(2-phenylmethoxyphenyl)acetonitrile Chemical compound COC1=CC=CC=C1NC(C#N)C1=CC=CC=C1OCC1=CC=CC=C1 KYFXPHPBTUJULU-UHFFFAOYSA-N 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 1
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
AWGBKZRMLNVLAF-UHFFFAOYSA-N 3,5-dibromo-n,2-dihydroxybenzamide Chemical compound ONC(=O)C1=CC(Br)=CC(Br)=C1O AWGBKZRMLNVLAF-UHFFFAOYSA-N 0.000 description 1
WAVYWHRLGFPXMJ-UHFFFAOYSA-N 4,6-dichloro-3-methyl-2h-pyrazolo[3,4-d]pyrimidine Chemical compound ClC1=NC(Cl)=C2C(C)=NNC2=N1 WAVYWHRLGFPXMJ-UHFFFAOYSA-N 0.000 description 1
SGCJDQPUPGNUIZ-UHFFFAOYSA-N 4-[(4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino]-3-methoxybenzoic acid Chemical compound C(C)OC=1C2=C(N=C(N=1)NC1=C(C=C(C(=O)O)C=C1)OC)NC=C2 SGCJDQPUPGNUIZ-UHFFFAOYSA-N 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
YIYBPEDZAUFQLO-UHFFFAOYSA-N 4-amino-3-chlorobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1Cl YIYBPEDZAUFQLO-UHFFFAOYSA-N 0.000 description 1
JNFGLYJROFAOQP-UHFFFAOYSA-N 4-amino-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1N JNFGLYJROFAOQP-UHFFFAOYSA-N 0.000 description 1
HVBSAKJJOYLTQU-UHFFFAOYSA-M 4-aminobenzenesulfonate Chemical compound NC1=CC=C(S([O-])(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-M 0.000 description 1
WFVOJAADOCCDAK-FQEVSTJZSA-N 4-ethoxy-N-[2-methoxy-4-[[(3S)-3-methylmorpholin-4-yl]methyl]phenyl]-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidin-2-amine Chemical compound C(C)OC=1C2=C(N=C(N=1)NC1=C(C=C(C=C1)CN1[C@H](COCC1)C)OC)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1 WFVOJAADOCCDAK-FQEVSTJZSA-N 0.000 description 1
UEALKTCRMBVTFN-UHFFFAOYSA-N 4-nitroanthranilic acid Chemical compound NC1=CC([N+]([O-])=O)=CC=C1C(O)=O UEALKTCRMBVTFN-UHFFFAOYSA-N 0.000 description 1
WCIGMFCFPXZRMQ-UHFFFAOYSA-N 5-(2-fluoropyridin-4-yl)-2-phenylmethoxy-n-pyridin-3-ylbenzamide Chemical compound C1=NC(F)=CC(C=2C=C(C(OCC=3C=CC=CC=3)=CC=2)C(=O)NC=2C=NC=CC=2)=C1 WCIGMFCFPXZRMQ-UHFFFAOYSA-N 0.000 description 1
108091005482 5-HT4 receptors Proteins 0.000 description 1
108091005435 5-HT6 receptors Proteins 0.000 description 1
102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
MYCCSWIILBRZKV-UHFFFAOYSA-N 6-azaspiro[2.5]octan-6-yl-(3-methoxy-4-nitrophenyl)methanone Chemical compound COC1=C(C=CC(=C1)C(=O)N1CCC2(CC2)CC1)[N+]([O-])=O MYCCSWIILBRZKV-UHFFFAOYSA-N 0.000 description 1
LERWQWRKAGZJMX-UHFFFAOYSA-N 6-azaspiro[2.5]octan-7-ylmethanol Chemical compound C1CC11CC(NCC1)CO LERWQWRKAGZJMX-UHFFFAOYSA-N 0.000 description 1
NVZWMJWMTWOVNJ-UHFFFAOYSA-N 6-azaspiro[3.4]octane Chemical compound C1CCC21CNCC2 NVZWMJWMTWOVNJ-UHFFFAOYSA-N 0.000 description 1
DNLMWWLLGMTQII-UHFFFAOYSA-N 6-chloro-4-ethoxy-1h-pyrazolo[3,4-d]pyrimidine Chemical compound CCOC1=NC(Cl)=NC2=C1C=NN2 DNLMWWLLGMTQII-UHFFFAOYSA-N 0.000 description 1
DUMZNUKZTTUQQA-UHFFFAOYSA-N 6-chloro-4-ethoxy-3-methyl-2h-pyrazolo[3,4-d]pyrimidine Chemical compound CCOC1=NC(Cl)=NC2=NNC(C)=C12 DUMZNUKZTTUQQA-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
AFQMLHYSJLGTSO-OAQYLSRUSA-N C(C)OC=1C2=C(N=C(N=1)NC1=C(C=C(C=C1)C(=O)N1[C@H](CCC1)COC)OC)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1 Chemical compound C(C)OC=1C2=C(N=C(N=1)NC1=C(C=C(C=C1)C(=O)N1[C@H](CCC1)COC)OC)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1 AFQMLHYSJLGTSO-OAQYLSRUSA-N 0.000 description 1
SXDPQGRNHSLZPC-ZJNRKIDTSA-N CNC(=O)C[C@@H]1C[C@H]([C@@H](CN1)NC(=O)c1cc(c(Cl)o1)-c1c(Cl)cnn1C)c1ccc(F)c(F)c1 Chemical compound CNC(=O)C[C@@H]1C[C@H]([C@@H](CN1)NC(=O)c1cc(c(Cl)o1)-c1c(Cl)cnn1C)c1ccc(F)c(F)c1 SXDPQGRNHSLZPC-ZJNRKIDTSA-N 0.000 description 1
DVYOPEZFDVRESE-SNVBAGLBSA-N COC1=C(N)C=CC(=C1)C(=O)N1CCN(C)[C@H](C)C1 Chemical compound COC1=C(N)C=CC(=C1)C(=O)N1CCN(C)[C@H](C)C1 DVYOPEZFDVRESE-SNVBAGLBSA-N 0.000 description 1
BNVRYZZCYNOIKT-UHFFFAOYSA-N COCC1CC11CCN(CC1)C(=O)C1=CC(OC)=C(N)C=C1 Chemical compound COCC1CC11CCN(CC1)C(=O)C1=CC(OC)=C(N)C=C1 BNVRYZZCYNOIKT-UHFFFAOYSA-N 0.000 description 1
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
241000283707 Capra Species 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
206010010774 Constipation Diseases 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-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
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
229920002307 Dextran Polymers 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
208000000655 Distemper Diseases 0.000 description 1
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
239000001692 EU approved anti-caking agent Substances 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
229910052693 Europium Inorganic materials 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
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 1
AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
229920002907 Guar gum Polymers 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
241000282412 Homo Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
239000004233 Indanthrene blue RS Substances 0.000 description 1
208000008839 Kidney Neoplasms Diseases 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 description 1
102220578200 Leucine-rich repeat serine/threonine-protein kinase 2_G2385R_mutation Human genes 0.000 description 1
102220596659 Leucine-rich repeat serine/threonine-protein kinase 2_R1441H_mutation Human genes 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
108091022875 Microtubule Proteins 0.000 description 1
102000029749 Microtubule Human genes 0.000 description 1
102100027869 Moesin Human genes 0.000 description 1
208000016285 Movement disease Diseases 0.000 description 1
102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
108010021466 Mutant Proteins Proteins 0.000 description 1
102000008300 Mutant Proteins Human genes 0.000 description 1
KEOHLOIPFXSCQW-LBPRGKRZSA-N NC1=C(C=C(C=C1)C(=O)N1C[C@H]2N(CC1)CCC2)OC Chemical compound NC1=C(C=C(C=C1)C(=O)N1C[C@H]2N(CC1)CCC2)OC KEOHLOIPFXSCQW-LBPRGKRZSA-N 0.000 description 1
229940127523 NMDA Receptor Antagonists Drugs 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
206010029260 Neuroblastoma Diseases 0.000 description 1
102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 1
108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
208000002192 Parkinson disease 3 Diseases 0.000 description 1
102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
241000009328 Perro Species 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
102100022127 Radixin Human genes 0.000 description 1
206010038389 Renal cancer Diseases 0.000 description 1
XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
108091006629 SLC13A2 Proteins 0.000 description 1
208000034189 Sclerosis Diseases 0.000 description 1
108010034546 Serratia marcescens nuclease Proteins 0.000 description 1
208000000453 Skin Neoplasms Diseases 0.000 description 1
241000256251 Spodoptera frugiperda Species 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
108010090804 Streptavidin Proteins 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
239000012505 Superdex™ Substances 0.000 description 1
238000006069 Suzuki reaction reaction Methods 0.000 description 1
208000032859 Synucleinopathies Diseases 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
229920002253 Tannate Polymers 0.000 description 1
229940122777 Tau aggregation inhibitor Drugs 0.000 description 1
208000024770 Thyroid neoplasm Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102000004243 Tubulin Human genes 0.000 description 1
108090000704 Tubulin Proteins 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
RACBJESQSVIGMZ-UHFFFAOYSA-N [2-(methoxymethyl)pyrrolidin-1-yl]methanone Chemical compound COCC1CCCN1[C]=O RACBJESQSVIGMZ-UHFFFAOYSA-N 0.000 description 1
AFQMLHYSJLGTSO-NRFANRHFSA-N [4-[[4-ethoxy-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxyphenyl]-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methanone Chemical compound C(C)OC=1C2=C(N=C(N=1)NC1=C(C=C(C=C1)C(=O)N1[C@@H](CCC1)COC)OC)N(C=C2)S(=O)(=O)C1=CC=C(C)C=C1 AFQMLHYSJLGTSO-NRFANRHFSA-N 0.000 description 1
YGTVTCXPKCEENE-UHFFFAOYSA-N [4-amino-3-(dimethylamino)phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound CN(C)C1=CC(=CC=C1N)C(=O)N1CCN(C)CC1 YGTVTCXPKCEENE-UHFFFAOYSA-N 0.000 description 1
XQAXGZLFSSPBMK-UHFFFAOYSA-M [7-(dimethylamino)phenothiazin-3-ylidene]-dimethylazanium;chloride;trihydrate Chemical compound O.O.O.[Cl-].C1=CC(=[N+](C)C)C=C2SC3=CC(N(C)C)=CC=C3N=C21 XQAXGZLFSSPBMK-UHFFFAOYSA-M 0.000 description 1
IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 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
229940048053 acrylate Drugs 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
238000013019 agitation Methods 0.000 description 1
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
230000004075 alteration Effects 0.000 description 1
230000001668 ameliorated effect Effects 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
235000012538 ammonium bicarbonate Nutrition 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
230000003321 amplification Effects 0.000 description 1
201000002783 amyotrophic lateral sclerosis type 12 Diseases 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
229940072107 ascorbate Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000004642 autophagic pathway Effects 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
230000008901 benefit Effects 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
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 1
230000033228 biological regulation Effects 0.000 description 1
239000000090 biomarker Substances 0.000 description 1
229960000074 biopharmaceutical Drugs 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
125000005998 bromoethyl group Chemical group 0.000 description 1
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000007894 caplet Substances 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000008004 cell lysis buffer Substances 0.000 description 1
230000007248 cellular mechanism Effects 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
230000004915 chaperone-mediated autophagy Effects 0.000 description 1
239000013522 chelant Substances 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
239000000544 cholinesterase inhibitor Substances 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
230000001149 cognitive effect Effects 0.000 description 1
239000003086 colorant Substances 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
229960000913 crospovidone Drugs 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000034994 death Effects 0.000 description 1
230000007423 decrease Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000006735 deficit Effects 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
150000001975 deuterium Chemical group 0.000 description 1
229910052805 deuterium Inorganic materials 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
235000019700 dicalcium phosphate Nutrition 0.000 description 1
229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
230000003292 diminished effect Effects 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
230000009429 distress Effects 0.000 description 1
POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 description 1
229960003135 donepezil hydrochloride Drugs 0.000 description 1
229960003638 dopamine Drugs 0.000 description 1
229940052760 dopamine agonists Drugs 0.000 description 1
239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
210000005064 dopaminergic neuron Anatomy 0.000 description 1
208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
238000001952 enzyme assay Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
229950000206 estolate Drugs 0.000 description 1
AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
MSYHIJNSNXQIQS-UHFFFAOYSA-N ethyl 6-azaspiro[2.5]octane-2-carboxylate Chemical compound CCOC(=O)C1CC11CCNCC1 MSYHIJNSNXQIQS-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
208000015756 familial Alzheimer disease Diseases 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000012634 fragment Substances 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
230000005021 gait Effects 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000007429 general method Methods 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
230000005484 gravity Effects 0.000 description 1
239000000665 guar gum Substances 0.000 description 1
235000010417 guar gum Nutrition 0.000 description 1
229960002154 guar gum Drugs 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
201000005787 hematologic cancer Diseases 0.000 description 1
208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
125000000592 heterocycloalkyl group Chemical group 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
230000001900 immune effect Effects 0.000 description 1
238000003018 immunoassay Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
239000003999 initiator Substances 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
208000037906 ischaemic injury Diseases 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 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
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000000366 juvenile effect Effects 0.000 description 1
201000010982 kidney cancer Diseases 0.000 description 1
229940116871 l-lactate Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229940070765 laurate Drugs 0.000 description 1
210000004901 leucine-rich repeat Anatomy 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000006210 lotion Substances 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
239000006166 lysate Substances 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
230000006655 lysosomal degradation pathway Effects 0.000 description 1
230000004142 macroautophagy Effects 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
206010025482 malaise Diseases 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
241001515942 marmosets Species 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000010197 meta-analysis Methods 0.000 description 1
229960001797 methadone Drugs 0.000 description 1
AWUPLMYXZJKHEG-UHFFFAOYSA-N methyl 2-chloro-2,2-difluoroacetate Chemical compound COC(=O)C(F)(F)Cl AWUPLMYXZJKHEG-UHFFFAOYSA-N 0.000 description 1
IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
229940095102 methyl benzoate Drugs 0.000 description 1
LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
229960000907 methylthioninium chloride Drugs 0.000 description 1
230000002025 microglial effect Effects 0.000 description 1
210000004688 microtubule Anatomy 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000006676 mitochondrial damage Effects 0.000 description 1
230000002438 mitochondrial effect Effects 0.000 description 1
239000012046 mixed solvent Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
108010071525 moesin Proteins 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
239000003149 muscarinic antagonist Substances 0.000 description 1
238000001964 muscle biopsy Methods 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
125000000740 n-pentyl group Chemical group [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
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000002241 neurite Anatomy 0.000 description 1
238000002610 neuroimaging Methods 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
208000018360 neuromuscular disease Diseases 0.000 description 1
230000014511 neuron projection development Effects 0.000 description 1
230000007135 neurotoxicity Effects 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
229920002113 octoxynol Polymers 0.000 description 1
239000002674 ointment Substances 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
238000012856 packing Methods 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000004031 partial agonist Substances 0.000 description 1
239000006072 paste Substances 0.000 description 1
231100000255 pathogenic effect Toxicity 0.000 description 1
230000003950 pathogenic mechanism Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
208000024335 physical disease Diseases 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000013612 plasmid Substances 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
102000054765 polymorphisms of proteins Human genes 0.000 description 1
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
229940069328 povidone Drugs 0.000 description 1
238000000634 powder X-ray diffraction Methods 0.000 description 1
FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
229960003089 pramipexole Drugs 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
230000007112 pro inflammatory response Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000007111 proteostasis Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
108010048484 radixin Proteins 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
229960004136 rivastigmine Drugs 0.000 description 1
238000011808 rodent model Methods 0.000 description 1
UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
229960001879 ropinirole Drugs 0.000 description 1
229940080817 rotenone Drugs 0.000 description 1
JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
239000000523 sample Substances 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000008786 sensory perception of smell Effects 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
125000003003 spiro group Chemical group 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
208000037100 susceptibility to 1 spondyloarthropathy Diseases 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
229960001685 tacrine Drugs 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
DATRVIMZZZVHMP-QMMMGPOBSA-N tert-butyl (2s)-2-methylpiperazine-1-carboxylate Chemical compound C[C@H]1CNCCN1C(=O)OC(C)(C)C DATRVIMZZZVHMP-QMMMGPOBSA-N 0.000 description 1
BTWDGFQQIGGAPU-UHFFFAOYSA-N tert-butyl 1-(hydroxymethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2CC21CO BTWDGFQQIGGAPU-UHFFFAOYSA-N 0.000 description 1
IGNPZIKVBPDVMR-UHFFFAOYSA-N tert-butyl 7-(hydroxymethyl)-6-azaspiro[2.5]octane-6-carboxylate Chemical compound C1C(CO)N(C(=O)OC(C)(C)C)CCC11CC1 IGNPZIKVBPDVMR-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
238000003354 tissue distribution assay Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
238000001890 transfection Methods 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
230000007704 transition Effects 0.000 description 1
ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
230000004565 tumor cell growth Effects 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- 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
- A61K31/435—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
- A61K31/4375—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 six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CA2937430A 2014-01-29 2015-01-28 Compounds Abandoned CA2937430A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
CN2014000140		2014-01-29
CNPCT/CN2014/000140		2014-01-29
PCT/CN2015/000054 WO2015113451A1 (en)	2014-01-29	2015-01-28	Compounds

Publications (1)

Publication Number	Publication Date
CA2937430A1 true CA2937430A1 (en)	2015-08-06

Family

ID=53756223

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2937430A Abandoned CA2937430A1 (en)	2014-01-29	2015-01-28	Compounds

Country Status (9)

Country	Link
US (1)	US9815841B2 (2)
EP (1)	EP3099694B1 (2)
JP (1)	JP6474826B2 (2)
CN (1)	CN105980388B (2)
AU (2)	AU2015210554A1 (2)
CA (1)	CA2937430A1 (2)
ES (1)	ES2717757T3 (2)
RU (1)	RU2016134751A (2)
WO (1)	WO2015113451A1 (2)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US11208412B2 (en) *	2017-02-22	2021-12-28	Daegu-Gyeongbuk Medical Innovation Foundation	Pyrrolo-pyrimidine derivative compound, preparation method therefor, and pharmaceutical composition comprising same compound as effective ingredient for preventing or treating protein kinase-related disease

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR20160106622A (ko)	2014-01-29	2016-09-12	글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드	화합물
AU2016219102B2 (en) *	2015-02-13	2020-10-15	Dana-Farber Cancer Institute, Inc.	LRRK2 inhibitors and methods of making and using the same
JP2018537502A (ja)	2015-12-16	2018-12-20	サウザーンリサーチインスチチュート	ピロロピリミジン化合物、キナーゼｌｒｒｋ２阻害剤としての使用、及びその調製方法
JP2020505459A (ja) *	2017-01-25	2020-02-20	グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅＩｎｔｅｌｌｅｃｔｕａｌＰｒｏｐｅｒｔｙＤｅｖｅｌｏｐｍｅｎｔＬｉｍｉｔｅｄ	化合物
BR112019015314A2 (pt)	2017-01-25	2020-05-19	Glaxosmithkline Ip Dev Ltd	compostos para inibir a atividade da quinase lrrk2
KR101896568B1 (ko) *	2017-03-23	2018-09-10	재단법인 대구경북첨단의료산업진흥재단	피롤로-피리딘 유도체 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물
CN113614086A (zh) *	2019-01-18	2021-11-05	沃若诺伊公司	吡咯并嘧啶衍生物以及包含其作为活性成分的用于预防或治疗蛋白激酶相关的疾病的药物组合物
US12240844B2 (en)	2019-01-18	2025-03-04	Voronoi, Inc.	Pyrrolopyridine derivative and use thereof in prevention and treatment of protein kinase-related disease
CZ308800B6 (cs)	2019-02-12	2021-05-26	Univerzita Palackého v Olomouci	Heterocyklické dusíkaté deriváty purinu, farmaceutické přípravky obsahující tyto deriváty a jejich použití při neuroprotekci
US12479847B2 (en)	2019-05-16	2025-11-25	Dana-Farber Cancer Institute, Inc.	Pyrrolopyrimidine inhibitors of wild-type and mutant forms of LRRK2
CN111205216B (zh) *	2020-03-11	2022-03-29	连云港恒运药业有限公司	一种制备沙格列汀的方法
CN114426542B (zh) *	2020-10-29	2023-06-30	苏州亚宝药物研发有限公司	取代的二芳基胺化合物及其药物组合物、制备方法和用途
KR20220081631A (ko)	2020-12-09	2022-06-16	보로노이 주식회사	염증성 질환의 예방 및/또는 치료를 위한 피롤로-피리딘 유도체 화합물의 신규 용도
WO2022155419A1 (en) *	2021-01-15	2022-07-21	ESCAPE Bio, Inc.	Indazoles and azaindazoles as lrrk2 inhibitors
CA3214360A1 (en)	2021-03-23	2022-09-29	Halia Therapeutics, Inc.	Pyrimidine derivatives useful as lrrk2 kinase inhibitors
JP2024541934A (ja)	2021-10-27	2024-11-13	ハー・ルンドベック・アクチエゼルスカベット	Ｌｒｒｋ２阻害剤
CN115108991B (zh) *	2022-06-30	2023-05-05	南京理工大学	一种硝仿基吡唑起爆药及其制备方法
AR130483A1 (es)	2022-09-15	2024-12-11	H Lundbeck As	Inhibidores de la cinasa con repeticiones ricas en leucina 2 (lrrk2)

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2005028480A2 (en)	2003-09-03	2005-03-31	Neurogen Corporation	5-aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds
GB0420719D0 (en)	2004-09-17	2004-10-20	Addex Pharmaceuticals Sa	Novel allosteric modulators
US7855205B2 (en)	2004-10-29	2010-12-21	Janssen Pharmaceutica Nv	Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders
WO2007042298A1 (en) *	2005-10-13	2007-04-19	Glaxo Group Limited	Pyrrolopyrimidine derivatives as syk inhibitors
CA2651072A1 (en)	2006-05-01	2007-11-08	Pfizer Products Inc.	Substituted 2-amino-fused heterocyclic compounds
WO2009036066A1 (en)	2007-09-10	2009-03-19	Curis, Inc.	Vegfr inhibitors containing a zinc binding moiety
US9315449B2 (en)	2008-05-15	2016-04-19	Duke University	Substituted pyrazoles as heat shock transcription factor activators
WO2009143018A2 (en)	2008-05-19	2009-11-26	Plexxikon, Inc.	Compounds and methods for kinase modulation, and indications therefor
WO2009143404A1 (en)	2008-05-23	2009-11-26	Wyeth	Piperazine metabotropic glutamate receptor 5 (mglur5) negative allosteric modulators for anxiety/depression
KR101705158B1 (ko)	2009-05-05	2017-02-09	다나-파버 캔서 인스티튜트 인크.	Ｅｇｆｒ 억제제 및 질환 치료방법
MX2012003778A (es)	2009-09-29	2012-06-01	Glaxo Group Ltd	Compuestos novedosos.
WO2011153553A2 (en)	2010-06-04	2011-12-08	The Regents Of The University Of California	Methods and compositions for kinase inhibition
PT2576541T (pt) *	2010-06-04	2016-07-08	Hoffmann La Roche	Derivados de aminopirimidina como moduladores de lrrk2
WO2012009258A2 (en)	2010-07-13	2012-01-19	Edward Roberts	Peptidomimetic galanin receptor modulators
WO2012045195A1 (en) *	2010-10-09	2012-04-12	Abbott Laboratories	Pyrrolopyrimidines as fak and alk inhibiters for treatment of cancers and other diseases
JP2013545749A (ja)	2010-11-10	2013-12-26	インフィニティーファーマシューティカルズ，インコーポレイテッド	複素環化合物及びその使用
HRP20172006T1 (hr)	2010-11-10	2018-02-09	Genentech, Inc.	Derivati pirazol-aminopiridina kao lrrk2-modulatori
EP2651405A2 (en)	2010-12-14	2013-10-23	Electrophoretics Limited	Casein kinase 1 (ck1 ) inhibitors
MX363696B (es) *	2011-04-21	2019-03-28	Origenis Gmbh	Pirazolo[4,3-d]pirimidinas utiles como inhibidores de cinasas.
KR20140059246A (ko)	2011-09-22	2014-05-15	화이자 인코포레이티드	피롤로피리미딘 및 퓨린 유도체
EP2785381B1 (en)	2011-11-30	2016-05-18	F.Hoffmann-La Roche Ag	Fluorine-18 and carbon-11 labeled radioligands for positron emission tomography (pet) imaging for lrrk2
GB201204985D0 (en)	2012-03-21	2012-05-02	Genentech Inc	Compounds
RU2637947C2 (ru)	2012-05-03	2017-12-08	Дженентек, Инк.	Производные пиразоламинопиримидина в качестве модуляторов обогащенной лейциновыми повторами киназы 2
CN106279202A (zh)	2012-05-03	2017-01-04	霍夫曼-拉罗奇有限公司	作为lrrk2调节剂用于治疗帕金森病的吡唑氨基嘧啶衍生物
WO2014001973A1 (en)	2012-06-29	2014-01-03	Pfizer Inc.	NOVEL 4-(SUBSTITUTED-AMINO)-7H-PYRROLO[2,3-d]PYRIMIDINES AS LRRK2 INHIBITORS
KR20160106622A (ko)	2014-01-29	2016-09-12	글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드	화합물

2015
- 2015-01-28 ES ES15743645T patent/ES2717757T3/es active Active
- 2015-01-28 JP JP2016549113A patent/JP6474826B2/ja not_active Expired - Fee Related
- 2015-01-28 CA CA2937430A patent/CA2937430A1/en not_active Abandoned
- 2015-01-28 CN CN201580006294.1A patent/CN105980388B/zh not_active Expired - Fee Related
- 2015-01-28 EP EP15743645.2A patent/EP3099694B1/en active Active
- 2015-01-28 RU RU2016134751A patent/RU2016134751A/ru not_active Application Discontinuation
- 2015-01-28 AU AU2015210554A patent/AU2015210554A1/en not_active Abandoned
- 2015-01-28 WO PCT/CN2015/000054 patent/WO2015113451A1/en not_active Ceased
- 2015-01-28 US US15/114,857 patent/US9815841B2/en not_active Expired - Fee Related
2018
- 2018-01-12 AU AU2018200271A patent/AU2018200271A1/en not_active Abandoned

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US11208412B2 (en) *	2017-02-22	2021-12-28	Daegu-Gyeongbuk Medical Innovation Foundation	Pyrrolo-pyrimidine derivative compound, preparation method therefor, and pharmaceutical composition comprising same compound as effective ingredient for preventing or treating protein kinase-related disease

Also Published As

Publication number	Publication date
US9815841B2 (en)	2017-11-14
EP3099694A4 (en)	2017-06-14
WO2015113451A1 (en)	2015-08-06
EP3099694B1 (en)	2019-01-16
EP3099694A1 (en)	2016-12-07
CN105980388A (zh)	2016-09-28
AU2018200271A1 (en)	2018-02-01
ES2717757T3 (es)	2019-06-25
JP6474826B2 (ja)	2019-02-27
AU2015210554A1 (en)	2016-07-07
CN105980388B (zh)	2018-01-16
JP2017504635A (ja)	2017-02-09
US20170022204A1 (en)	2017-01-26
RU2016134751A (ru)	2018-03-02

Legal Events

Date	Code	Title	Description
2020-03-24	FZDE	Dead	Effective date: 20200128

Publication	Publication Date	Title
US9815841B2 (en)	2017-11-14	Compounds
KR101792837B1 (ko)	2017-11-02	키나아제 억제제로서 사용을 위한 이미다조피라진
DK3183247T3 (en)	2018-01-15	Aminopyrimidinyl compounds as JAK inhibitors
JP6545106B2 (ja)	2019-07-17	ＰＩ３Ｋδ関連障害治療のためのピラゾロピリミジン誘導体の使用
JP2020526543A (ja)	2020-08-31	ロイシンリッチリピートキナーゼ２の阻害剤
US8877742B2 (en)	2014-11-04	Compounds
TW200835481A (en)	2008-09-01	Imidazotriazines and imidazopyrimidines as kinase inhibitors
US11034696B2 (en)	2021-06-15	Compounds for inhibiting LRRK2 kinase activity
CA2937431A1 (en)	2015-08-06	Compounds
WO2018137607A1 (en)	2018-08-02	Compounds
US20210130339A1 (en)	2021-05-06	Compounds
KR20160106623A (ko)	2016-09-12	화합물
US20220041597A1 (en)	2022-02-10	Inhibiting ubiquitin specific peptidase 9x
CN1842529A (zh)	2006-10-04	用作蛋白激酶抑制剂的化合物和组合物
US20130029967A1 (en)	2013-01-31	Fused Imidazo [3,2 - D] Pyrazines as P13 Kinase Inhibitors
CN111587250A (zh)	2020-08-25	作为jak抑制剂的吡唑并嘧啶化合物
US20190389850A1 (en)	2019-12-26	Compounds
HK40019825A (en)	2020-10-16	Therapeutic compounds and compositions, and methods of use thereof
HK1167142B (en)	2014-12-12	Imidazopyrazines as inhibitors of protein kinases

CA2937430A1 - Compounds - Google Patents

Info

Links

Classifications

Landscapes

Applications Claiming Priority (3)

Publications (1)

Family

ID=53756223

Family Applications (1)

Country Status (9)

Cited By (1)

Families Citing this family (18)

Family Cites Families (26)

Cited By (1)

Also Published As

Similar Documents

Legal Events