NO329669B1 - Piperazinylacylpiperidinderivater, deres fremstilling og terapeutiske anvendelse - Google Patents

Info

Publication number

NO329669B1

NO329669B1 NO20045331A NO20045331A NO329669B1 NO 329669 B1 NO329669 B1 NO 329669B1 NO 20045331 A NO20045331 A NO 20045331A NO 20045331 A NO20045331 A NO 20045331A NO 329669 B1 NO329669 B1 NO 329669B1

Authority

NO

Norway

Prior art keywords

compound

formula

methyl

trifluoromethyl

radical

Prior art date

2002-06-07

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• 238000002360 preparation method Methods 0.000 title claims description 94
• 230000001225 therapeutic effect Effects 0.000 title abstract description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 408
• -1 trifluoromethoxy radical Chemical class 0.000 claims abstract description 146
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 29
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 24
• 125000005843 halogen group Chemical group 0.000 claims abstract description 23
• WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims abstract description 22
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 21
• 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 11
• 125000003118 aryl group Chemical group 0.000 claims abstract description 10
• 150000003254 radicals Chemical class 0.000 claims abstract description 10
• 125000001424 substituent group Chemical group 0.000 claims abstract description 5
• 238000000034 method Methods 0.000 claims description 69
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
• 150000003839 salts Chemical class 0.000 claims description 26
• 239000002253 acid Substances 0.000 claims description 21
• 229910052801 chlorine Inorganic materials 0.000 claims description 19
• 239000012453 solvate Substances 0.000 claims description 18
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
• 238000011282 treatment Methods 0.000 claims description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 150000001412 amines Chemical group 0.000 claims description 10
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
• 229910052794 bromium Inorganic materials 0.000 claims description 8
• 239000000460 chlorine Substances 0.000 claims description 8
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• 230000006870 function Effects 0.000 claims description 6
• 208000014674 injury Diseases 0.000 claims description 6
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 6
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 6
• 230000008733 trauma Effects 0.000 claims description 6
• 238000010511 deprotection reaction Methods 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 229910052739 hydrogen Inorganic materials 0.000 claims description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 5
• 229910052757 nitrogen Inorganic materials 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 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
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 206010028980 Neoplasm Diseases 0.000 claims description 4
• 229940079593 drug Drugs 0.000 claims description 4
• 239000001257 hydrogen Substances 0.000 claims description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
• 230000008569 process Effects 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
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 3
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
• WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• 230000002093 peripheral effect Effects 0.000 claims description 3
• 230000002265 prevention Effects 0.000 claims description 3
• XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical group N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims description 2
• 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
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
• 206010065390 Inflammatory pain Diseases 0.000 claims description 2
• 206010027476 Metastases Diseases 0.000 claims description 2
• 208000031481 Pathologic Constriction Diseases 0.000 claims description 2
• 231100000360 alopecia Toxicity 0.000 claims description 2
• 230000001684 chronic effect Effects 0.000 claims description 2
• 230000006378 damage Effects 0.000 claims description 2
• 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 208000032839 leukemia Diseases 0.000 claims description 2
• 208000004296 neuralgia Diseases 0.000 claims description 2
• 230000002981 neuropathic effect Effects 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
• 230000037390 scarring Effects 0.000 claims description 2
• 210000000278 spinal cord Anatomy 0.000 claims description 2
• DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims 2
• 201000011510 cancer Diseases 0.000 claims 1
• 230000004770 neurodegeneration Effects 0.000 claims 1
• 208000015122 neurodegenerative disease Diseases 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 abstract description 59
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 252
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 224
• 239000000203 mixture Substances 0.000 description 213
• 239000000047 product Substances 0.000 description 141
• 239000000243 solution Substances 0.000 description 127
• 239000002904 solvent Substances 0.000 description 99
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 99
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 93
• 238000003756 stirring Methods 0.000 description 84
• 229910001868 water Inorganic materials 0.000 description 80
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
• 239000012074 organic phase Substances 0.000 description 76
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 63
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
• 239000011734 sodium Substances 0.000 description 48
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 44
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
• 239000000741 silica gel Substances 0.000 description 40
• 229910002027 silica gel Inorganic materials 0.000 description 40
• 239000011541 reaction mixture Substances 0.000 description 39
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 36
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 36
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
• 239000000706 filtrate Substances 0.000 description 29
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
• 238000010828 elution Methods 0.000 description 26
• 239000002244 precipitate Substances 0.000 description 26
• 239000007832 Na2SO4 Substances 0.000 description 24
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
• 229910052938 sodium sulfate Inorganic materials 0.000 description 24
• 235000011152 sodium sulphate Nutrition 0.000 description 24
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 22
• 102100029946 Sialic acid-binding Ig-like lectin 7 Human genes 0.000 description 21
• 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 description 21
• 238000010992 reflux Methods 0.000 description 21
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
• 229910000027 potassium carbonate Inorganic materials 0.000 description 19
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 18
• 102000005962 receptors Human genes 0.000 description 18
• 108020003175 receptors Proteins 0.000 description 18
• 238000001953 recrystallisation Methods 0.000 description 17
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
• 238000001819 mass spectrum Methods 0.000 description 16
• 108010025020 Nerve Growth Factor Proteins 0.000 description 15
• 239000002585 base Substances 0.000 description 15
• 230000006907 apoptotic process Effects 0.000 description 14
• LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 13
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 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
• 210000004027 cell Anatomy 0.000 description 11
• 238000006243 chemical reaction Methods 0.000 description 11
• 102000015336 Nerve Growth Factor Human genes 0.000 description 10
• 239000008346 aqueous phase Substances 0.000 description 10
• 229940053128 nerve growth factor Drugs 0.000 description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 230000027455 binding Effects 0.000 description 9
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
• 239000007868 Raney catalyst Substances 0.000 description 8
• 229910000564 Raney nickel Inorganic materials 0.000 description 8
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 8
• 238000007796 conventional method Methods 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• 239000012312 sodium hydride Substances 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 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
• SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• 235000011114 ammonium hydroxide Nutrition 0.000 description 6
• 239000000543 intermediate Substances 0.000 description 6
• 239000011777 magnesium Substances 0.000 description 6
• 229910052749 magnesium Inorganic materials 0.000 description 6
• 235000006408 oxalic acid Nutrition 0.000 description 6
• 125000006239 protecting group Chemical group 0.000 description 6
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• 238000005481 NMR spectroscopy Methods 0.000 description 5
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• 125000000217 alkyl group Chemical group 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
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• 208000024827 Alzheimer disease Diseases 0.000 description 4
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• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
• 101000801254 Homo sapiens Tumor necrosis factor receptor superfamily member 16 Proteins 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 230000030833 cell death Effects 0.000 description 4
• 239000013078 crystal Substances 0.000 description 4
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
• 238000000605 extraction Methods 0.000 description 4
• 239000012458 free base Substances 0.000 description 4
• 239000001963 growth medium Substances 0.000 description 4
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
• 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 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 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
• 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
• 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
• 241000282412 Homo Species 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 206010029260 Neuroblastoma Diseases 0.000 description 3
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• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
• 229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
• 150000008041 alkali metal carbonates Chemical class 0.000 description 3
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 3
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 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
• 239000007853 buffer solution Substances 0.000 description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 239000012280 lithium aluminium hydride Substances 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 3
• 208000031225 myocardial ischemia Diseases 0.000 description 3
• PGYJLGNVBKZLNC-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]piperidin-4-yl]acetamide;hydrochloride Chemical compound Cl.C=1C=C(Cl)C(C(F)(F)F)=CC=1C1(NC(=O)C)CCNCC1 PGYJLGNVBKZLNC-UHFFFAOYSA-N 0.000 description 3
• 210000002569 neuron Anatomy 0.000 description 3
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• 230000008929 regeneration Effects 0.000 description 3
• 238000011069 regeneration method Methods 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
• 235000011149 sulphuric acid Nutrition 0.000 description 3
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 3
• 230000000699 topical effect Effects 0.000 description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
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