EA007501B1 - Производные пиперазинилацилпиперидина, их получение и их терапевтическое применение - Google Patents

Info

Publication number

EA007501B1

EA007501B1 EA200401470A EA200401470A EA007501B1 EA 007501 B1 EA007501 B1 EA 007501B1 EA 200401470 A EA200401470 A EA 200401470A EA 200401470 A EA200401470 A EA 200401470A EA 007501 B1 EA007501 B1 EA 007501B1

Authority

EA

Eurasian Patent Office

Prior art keywords

compound

formula

methyl

trifluoromethyl

mixture

Prior art date

2002-06-07

Links

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• 230000001225 therapeutic effect Effects 0.000 title abstract description 4
• 238000002360 preparation method Methods 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 436
• -1 trifluoromethoxy radical Chemical class 0.000 claims abstract description 155
• 238000000034 method Methods 0.000 claims abstract description 71
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 36
• 125000005843 halogen group Chemical group 0.000 claims abstract description 26
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 24
• WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims abstract description 21
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 21
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 18
• 125000003118 aryl group Chemical group 0.000 claims abstract description 10
• 125000001424 substituent group Chemical group 0.000 claims abstract description 5
• 150000003839 salts Chemical class 0.000 claims description 29
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 25
• 239000002253 acid Substances 0.000 claims description 22
• 229910052801 chlorine Inorganic materials 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
• 239000012453 solvate Substances 0.000 claims description 18
• 125000000217 alkyl group Chemical group 0.000 claims description 15
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
• 238000011282 treatment Methods 0.000 claims description 13
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
• 229910052794 bromium Inorganic materials 0.000 claims description 10
• 239000000460 chlorine Substances 0.000 claims description 10
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
• 125000003386 piperidinyl group Chemical group 0.000 claims description 10
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
• 125000003277 amino group Chemical group 0.000 claims description 9
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 7
• DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 7
• 229910052757 nitrogen Inorganic materials 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 7
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 6
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
• 230000015572 biosynthetic process Effects 0.000 claims description 5
• 238000010511 deprotection reaction Methods 0.000 claims description 5
• 125000000524 functional group Chemical group 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 4
• 206010028980 Neoplasm Diseases 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 4
• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 4
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 3
• 206010019196 Head injury Diseases 0.000 claims description 3
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
• 229910052739 hydrogen Inorganic materials 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• 230000002093 peripheral effect Effects 0.000 claims description 3
• 201000004384 Alopecia Diseases 0.000 claims description 2
• 208000023275 Autoimmune disease Diseases 0.000 claims description 2
• 208000010392 Bone Fractures Diseases 0.000 claims description 2
• 208000020084 Bone disease Diseases 0.000 claims description 2
• 206010061218 Inflammation Diseases 0.000 claims description 2
• 206010027476 Metastases Diseases 0.000 claims description 2
• 208000002193 Pain Diseases 0.000 claims description 2
• 208000031481 Pathologic Constriction Diseases 0.000 claims description 2
• 231100000360 alopecia Toxicity 0.000 claims description 2
• 201000011510 cancer Diseases 0.000 claims description 2
• 230000001684 chronic effect Effects 0.000 claims description 2
• 230000006378 damage Effects 0.000 claims description 2
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
• 239000001257 hydrogen Substances 0.000 claims description 2
• 230000004054 inflammatory process Effects 0.000 claims description 2
• 208000032839 leukemia Diseases 0.000 claims description 2
• 208000004296 neuralgia Diseases 0.000 claims description 2
• 230000004770 neurodegeneration Effects 0.000 claims description 2
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
• 208000021722 neuropathic pain Diseases 0.000 claims description 2
• 210000001328 optic nerve Anatomy 0.000 claims description 2
• 208000027232 peripheral nervous system disease Diseases 0.000 claims description 2
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 2
• 230000002829 reductive effect Effects 0.000 claims description 2
• 210000001525 retina Anatomy 0.000 claims description 2
• 230000036573 scar formation Effects 0.000 claims description 2
• 208000020431 spinal cord injury Diseases 0.000 claims description 2
• 230000036262 stenosis Effects 0.000 claims description 2
• 208000037804 stenosis Diseases 0.000 claims description 2
• OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 claims 1
• 229940126601 medicinal product Drugs 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 261
• 239000000203 mixture Substances 0.000 description 249
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 234
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 217
• 239000000047 product Substances 0.000 description 148
• 239000002904 solvent Substances 0.000 description 111
• 239000000243 solution Substances 0.000 description 104
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 100
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
• 239000012074 organic phase Substances 0.000 description 76
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 72
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 69
• 238000003756 stirring Methods 0.000 description 51
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 44
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 42
• 239000011541 reaction mixture Substances 0.000 description 39
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 29
• 239000000706 filtrate Substances 0.000 description 29
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
• 238000010898 silica gel chromatography Methods 0.000 description 28
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 239000003054 catalyst Substances 0.000 description 27
• 239000002244 precipitate Substances 0.000 description 26
• 238000010992 reflux Methods 0.000 description 24
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 22
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 21
• 102000005962 receptors Human genes 0.000 description 21
• 108020003175 receptors Proteins 0.000 description 21
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
• 239000002585 base Substances 0.000 description 19
• 238000001953 recrystallisation Methods 0.000 description 18
• 239000012047 saturated solution Substances 0.000 description 18
• 210000004027 cell Anatomy 0.000 description 16
• 238000001819 mass spectrum Methods 0.000 description 16
• 239000011734 sodium Substances 0.000 description 16
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• 230000006907 apoptotic process Effects 0.000 description 15
• HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 13
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
• 239000000543 intermediate Substances 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• 239000000741 silica gel Substances 0.000 description 12
• 229910002027 silica gel Inorganic materials 0.000 description 12
• 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 12
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
• 239000002609 medium Substances 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 229910000027 potassium carbonate Inorganic materials 0.000 description 10
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 9
• 239000008346 aqueous phase Substances 0.000 description 9
• 238000006243 chemical reaction Methods 0.000 description 9
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• 230000027455 binding Effects 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• 229910000104 sodium hydride Inorganic materials 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 7
• 108010025020 Nerve Growth Factor Proteins 0.000 description 7
• 102000007072 Nerve Growth Factors Human genes 0.000 description 7
• 239000007868 Raney catalyst Substances 0.000 description 7
• 229910000564 Raney nickel Inorganic materials 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• 238000007796 conventional method Methods 0.000 description 7
• 239000012312 sodium hydride Substances 0.000 description 7
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 230000002378 acidificating effect Effects 0.000 description 6
• 239000011777 magnesium Substances 0.000 description 6
• 229910052749 magnesium Inorganic materials 0.000 description 6
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• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 235000011114 ammonium hydroxide Nutrition 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• GTCAXTIRRLKXRU-UHFFFAOYSA-N carbamic acid methyl ester Natural products COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 208000028867 ischemia Diseases 0.000 description 5
• 235000015320 potassium carbonate Nutrition 0.000 description 5
• 235000011181 potassium carbonates Nutrition 0.000 description 5
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 5
• QZQUHNFXIXYHGA-UHFFFAOYSA-N 1-[4-(aminomethyl)-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]-2-(4-pyrazin-2-ylpiperazin-1-yl)ethanone Chemical compound C1CC(CN)(C=2C=C(C=CC=2)C(F)(F)F)CCN1C(=O)CN(CC1)CCN1C1=CN=CC=N1 QZQUHNFXIXYHGA-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
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• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
• 102100029946 Sialic acid-binding Ig-like lectin 7 Human genes 0.000 description 4
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• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• JDNTVTDBYZXFEU-UHFFFAOYSA-N 1-[4-(methylaminomethyl)-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]-2-(4-pyrazin-2-ylpiperazin-1-yl)ethanone Chemical compound C1CC(CNC)(C=2C=C(C=CC=2)C(F)(F)F)CCN1C(=O)CN(CC1)CCN1C1=CN=CC=N1 JDNTVTDBYZXFEU-UHFFFAOYSA-N 0.000 description 3
• JOIYKSLWXLFGGR-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]acetonitrile Chemical compound FC(F)(F)C1=CC=CC(CC#N)=C1 JOIYKSLWXLFGGR-UHFFFAOYSA-N 0.000 description 3
• TWXSQWIBFLBSNW-UHFFFAOYSA-N 4-(4-benzylpiperazin-1-yl)-5-chloro-1h-pyridazin-6-one Chemical compound C1=NNC(=O)C(Cl)=C1N1CCN(CC=2C=CC=CC=2)CC1 TWXSQWIBFLBSNW-UHFFFAOYSA-N 0.000 description 3
• FJKNODHPDAZWON-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]piperidine-4-carbonitrile;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC(C2(CCNCC2)C#N)=C1 FJKNODHPDAZWON-UHFFFAOYSA-N 0.000 description 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
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• 241000282412 Homo Species 0.000 description 3
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• DDSZWBCJXDRQDU-UHFFFAOYSA-N [N].C1CCNCC1 Chemical group [N].C1CCNCC1 DDSZWBCJXDRQDU-UHFFFAOYSA-N 0.000 description 3
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
• 229910001516 alkali metal iodide Inorganic materials 0.000 description 3
• 230000003376 axonal effect Effects 0.000 description 3
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 150000004677 hydrates Chemical class 0.000 description 3
• 239000011261 inert gas Substances 0.000 description 3
• 239000012280 lithium aluminium hydride Substances 0.000 description 3
• 230000016273 neuron death Effects 0.000 description 3
• 210000004248 oligodendroglia Anatomy 0.000 description 3
• 230000007170 pathology Effects 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
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• 229920006395 saturated elastomer Polymers 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• GZYDEJABHMSOIM-UHFFFAOYSA-N tert-butyl 4-(2-chloropyrimidin-4-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=NC(Cl)=N1 GZYDEJABHMSOIM-UHFFFAOYSA-N 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• FQZLNQAUUMSUHT-UHFFFAOYSA-N tert-butyl n,n-bis(2-chloroethyl)carbamate Chemical compound CC(C)(C)OC(=O)N(CCCl)CCCl FQZLNQAUUMSUHT-UHFFFAOYSA-N 0.000 description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
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