TW202039482A - 嗎啉基、哌嗪基、氧氮雜環庚烷基及二氮雜環庚烷基o-醣蛋白-2-乙醯胺基-2-去氧-3-d-葡萄哌喃醣苷酶抑制劑 - Google Patents

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Publication number

TW202039482A

TW202039482A TW108144351A TW108144351A TW202039482A TW 202039482 A TW202039482 A TW 202039482A TW 108144351 A TW108144351 A TW 108144351A TW 108144351 A TW108144351 A TW 108144351A TW 202039482 A TW202039482 A TW 202039482A

Authority

TW

Taiwan

Prior art keywords

methyl

compound

disease

alkyl

thiazol

Prior art date

2018-12-05

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• 239000003112 inhibitor Substances 0.000 title description 3
• 125000002757 morpholinyl group Chemical group 0.000 title description 2
• 125000004193 piperazinyl group Chemical group 0.000 title description 2
• 125000005959 diazepanyl group Chemical group 0.000 title 1
• 125000005961 oxazepanyl group Chemical group 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 244
• 238000000034 method Methods 0.000 claims abstract description 93
• 150000003839 salts Chemical class 0.000 claims abstract description 83
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 54
• 201000010099 disease Diseases 0.000 claims description 46
• 125000005843 halogen group Chemical group 0.000 claims description 43
• 206010012289 Dementia Diseases 0.000 claims description 25
• 102100030122 Protein O-GlcNAcase Human genes 0.000 claims description 23
• 125000001072 heteroaryl group Chemical group 0.000 claims description 20
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• 208000010877 cognitive disease Diseases 0.000 claims description 18
• 208000032382 Ischaemic stroke Diseases 0.000 claims description 17
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 17
• 125000001424 substituent group Chemical group 0.000 claims description 16
• 208000018737 Parkinson disease Diseases 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
• 125000004970 halomethyl group Chemical group 0.000 claims description 15
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 14
• 108010045982 hexosaminidase C Proteins 0.000 claims description 14
• 208000024827 Alzheimer disease Diseases 0.000 claims description 13
• 229910052799 carbon Inorganic materials 0.000 claims description 13
• 229910052739 hydrogen Inorganic materials 0.000 claims description 13
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 12
• 125000000217 alkyl group Chemical group 0.000 claims description 12
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 12
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 10
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
• 125000003118 aryl group Chemical group 0.000 claims description 10
• 210000004556 brain Anatomy 0.000 claims description 10
• 125000004432 carbon atom Chemical group C* 0.000 claims description 10
• 125000002950 monocyclic group Chemical group 0.000 claims description 10
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 10
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 9
• 125000000623 heterocyclic group Chemical group 0.000 claims description 9
• 208000027089 Parkinsonian disease Diseases 0.000 claims description 8
• 206010034010 Parkinsonism Diseases 0.000 claims description 8
• 230000006951 hyperphosphorylation Effects 0.000 claims description 8
• 229910052757 nitrogen Inorganic materials 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 208000023105 Huntington disease Diseases 0.000 claims description 6
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 6
• 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 claims description 6
• 230000007850 degeneration Effects 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 206010015037 epilepsy Diseases 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 208000019715 inherited Creutzfeldt-Jakob disease Diseases 0.000 claims description 6
• 230000002401 inhibitory effect Effects 0.000 claims description 6
• 230000004770 neurodegeneration Effects 0.000 claims description 6
• 208000028698 Cognitive impairment Diseases 0.000 claims description 5
• 206010023497 kuru Diseases 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 claims description 4
• 206010072075 Gerstmann-Straussler-Scheinker syndrome Diseases 0.000 claims description 4
• 206010028980 Neoplasm Diseases 0.000 claims description 4
• 201000011510 cancer Diseases 0.000 claims description 4
• 210000004940 nucleus Anatomy 0.000 claims description 4
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
• 208000017227 ADan amyloidosis Diseases 0.000 claims description 3
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 3
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 3
• 208000009093 Diffuse Neurofibrillary Tangles with Calcification Diseases 0.000 claims description 3
• 201000010374 Down Syndrome Diseases 0.000 claims description 3
• 208000032612 Glial tumor Diseases 0.000 claims description 3
• 206010018338 Glioma Diseases 0.000 claims description 3
• 201000000194 ITM2B-related cerebral amyloid angiopathy 2 Diseases 0.000 claims description 3
• 208000001089 Multiple system atrophy Diseases 0.000 claims description 3
• 206010068871 Myotonic dystrophy Diseases 0.000 claims description 3
• 208000014060 Niemann-Pick disease Diseases 0.000 claims description 3
• 102000029797 Prion Human genes 0.000 claims description 3
• 108091000054 Prion Proteins 0.000 claims description 3
• 208000024777 Prion disease Diseases 0.000 claims description 3
• 208000013200 Stress disease Diseases 0.000 claims description 3
• 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 claims description 3
• 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 claims description 3
• 238000009825 accumulation Methods 0.000 claims description 3
• 210000000349 chromosome Anatomy 0.000 claims description 3
• 230000001054 cortical effect Effects 0.000 claims description 3
• 206010012601 diabetes mellitus Diseases 0.000 claims description 3
• 206010014599 encephalitis Diseases 0.000 claims description 3
• 201000006061 fatal familial insomnia Diseases 0.000 claims description 3
• 125000005347 halocycloalkyl group Chemical group 0.000 claims description 3
• 229910052742 iron Inorganic materials 0.000 claims description 3
• 201000010901 lateral sclerosis Diseases 0.000 claims description 3
• 208000005264 motor neuron disease Diseases 0.000 claims description 3
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
• 230000000750 progressive effect Effects 0.000 claims description 3
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
• 208000023697 ABri amyloidosis Diseases 0.000 claims description 2
• 206010002027 Amyotrophy Diseases 0.000 claims description 2
• 201000000162 ITM2B-related cerebral amyloid angiopathy 1 Diseases 0.000 claims description 2
• 206010044688 Trisomy 21 Diseases 0.000 claims description 2
• 125000004429 atom Chemical group 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 238000006467 substitution reaction Methods 0.000 claims description 2
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical class [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 1
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 276
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 137
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 130
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 104
• -1 morpholine-yl Chemical group 0.000 description 103
• 239000000203 mixture Substances 0.000 description 89
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 67
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 62
• 239000000543 intermediate Substances 0.000 description 62
• 238000005481 NMR spectroscopy Methods 0.000 description 60
• 239000002904 solvent Substances 0.000 description 45
• LAPWQPYYMGKHNZ-UHFFFAOYSA-N n-[5-(chloromethyl)-1,3-thiazol-2-yl]acetamide Chemical group CC(=O)NC1=NC=C(CCl)S1 LAPWQPYYMGKHNZ-UHFFFAOYSA-N 0.000 description 44
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 37
• 238000006243 chemical reaction Methods 0.000 description 36
• 239000000243 solution Substances 0.000 description 35
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
• 235000019439 ethyl acetate Nutrition 0.000 description 32
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 28
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
• 238000004090 dissolution Methods 0.000 description 24
• 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 23
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 22
• 102000013498 tau Proteins Human genes 0.000 description 21
• 108010026424 tau Proteins Proteins 0.000 description 21
• RLXCSEPIBOWMOJ-MRVPVSSYSA-N tert-butyl (2s)-2-(bromomethyl)morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCO[C@H](CBr)C1 RLXCSEPIBOWMOJ-MRVPVSSYSA-N 0.000 description 21
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
• 150000002148 esters Chemical class 0.000 description 20
• 238000010898 silica gel chromatography Methods 0.000 description 20
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• 239000011734 sodium Substances 0.000 description 18
• 229910052805 deuterium Inorganic materials 0.000 description 16
• 239000011541 reaction mixture Substances 0.000 description 16
• ANSMRNCOBLTNBO-UHFFFAOYSA-N 2-bromo-5-fluoropyrimidine Chemical compound FC1=CN=C(Br)N=C1 ANSMRNCOBLTNBO-UHFFFAOYSA-N 0.000 description 15
• YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 15
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 15
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
• 239000012267 brine Substances 0.000 description 13
• 239000000460 chlorine Substances 0.000 description 13
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
• 108010031186 Glycoside Hydrolases Proteins 0.000 description 12
• 102000005744 Glycoside Hydrolases Human genes 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 11
• 239000003208 petroleum Substances 0.000 description 10
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
• YFTGMMXMLPTTAY-UHFFFAOYSA-N 4-bromo-2-methoxypyridine Chemical compound COC1=CC(Br)=CC=N1 YFTGMMXMLPTTAY-UHFFFAOYSA-N 0.000 description 9
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 9
• JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 8
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
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• 102000004169 proteins and genes Human genes 0.000 description 8
• 108090000623 proteins and genes Proteins 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
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• 101001120790 Caenorhabditis elegans UDP-N-acetylglucosamine-peptide N-acetylglucosaminyltransferase Proteins 0.000 description 7
• 101710081801 Protein O-GlcNAcase Proteins 0.000 description 7
• FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 7
• 238000004128 high performance liquid chromatography Methods 0.000 description 7
• 229960005141 piperazine Drugs 0.000 description 7
• 230000008569 process Effects 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 6
• 108090000790 Enzymes Proteins 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• 208000012902 Nervous system disease Diseases 0.000 description 6
• AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
• 239000003643 water by type Substances 0.000 description 6
• TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 description 5
• OFKWIQJLYCKDNY-UHFFFAOYSA-N 5-bromo-2-methylpyridine Chemical compound CC1=CC=C(Br)C=N1 OFKWIQJLYCKDNY-UHFFFAOYSA-N 0.000 description 5
• OBJOQVLWWLTNLQ-DTWKUNHWSA-N BrC[C@@H]1CN([C@H](CO1)C)C(=O)OC(C)(C)C Chemical compound BrC[C@@H]1CN([C@H](CO1)C)C(=O)OC(C)(C)C OBJOQVLWWLTNLQ-DTWKUNHWSA-N 0.000 description 5
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
• 125000002619 bicyclic group Chemical group 0.000 description 5
• 238000001514 detection method Methods 0.000 description 5
• VAAPKQNASNXGQY-UHFFFAOYSA-N n-(5-methyl-1,3-thiazol-2-yl)acetamide Chemical compound CC(=O)NC1=NC=C(C)S1 VAAPKQNASNXGQY-UHFFFAOYSA-N 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 239000000741 silica gel Substances 0.000 description 5
• 229910002027 silica gel Inorganic materials 0.000 description 5
• WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 4
• VTRFAYHJKSKHGY-UHFFFAOYSA-N 4-bromo-2,6-dimethylpyridine Chemical compound CC1=CC(Br)=CC(C)=N1 VTRFAYHJKSKHGY-UHFFFAOYSA-N 0.000 description 4
• JFBMFWHEXBLFCR-UHFFFAOYSA-N 4-bromo-2-methylpyridine Chemical compound CC1=CC(Br)=CC=N1 JFBMFWHEXBLFCR-UHFFFAOYSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 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
• 241001465754 Metazoa Species 0.000 description 4
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• 230000002378 acidificating effect Effects 0.000 description 4
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 4
• 125000005997 bromomethyl group Chemical group 0.000 description 4
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• 239000012279 sodium borohydride Substances 0.000 description 4
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• 208000024891 symptom Diseases 0.000 description 4
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
• PJXWCRXOPLGFLX-VIFPVBQESA-N (2s)-2-(benzylamino)propan-1-ol Chemical compound OC[C@H](C)NCC1=CC=CC=C1 PJXWCRXOPLGFLX-VIFPVBQESA-N 0.000 description 3
• OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 3
• MCRCVCVGQNSZST-UHFFFAOYSA-N 1-o-benzyl 4-o-tert-butyl piperazine-1,4-dicarboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(=O)OCC1=CC=CC=C1 MCRCVCVGQNSZST-UHFFFAOYSA-N 0.000 description 3
• IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical compound COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 description 3
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 3
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
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