RU2549546C2 - Аминогетероарильные производные в качестве блокаторов hcn - Google Patents

Info

Publication number

RU2549546C2

RU2549546C2 RU2012131279/04A RU2012131279A RU2549546C2 RU 2549546 C2 RU2549546 C2 RU 2549546C2 RU 2012131279/04 A RU2012131279/04 A RU 2012131279/04A RU 2012131279 A RU2012131279 A RU 2012131279A RU 2549546 C2 RU2549546 C2 RU 2549546C2

Authority

RU

Russia

Prior art keywords

alkyl

pyrimidin

ethyl

amine

formula

Prior art date

2009-12-22

Links

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• 125000005214 aminoheteroaryl group Chemical group 0.000 title claims abstract description 30
• 239000002981 blocking agent Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 169
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 43
• 150000002367 halogens Chemical class 0.000 claims abstract description 40
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 35
• 208000004296 neuralgia Diseases 0.000 claims abstract description 19
• 208000021722 neuropathic pain Diseases 0.000 claims abstract description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 15
• 150000003839 salts Chemical class 0.000 claims abstract description 15
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 12
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 10
• 229920006395 saturated elastomer Polymers 0.000 claims abstract description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
• 206010065390 Inflammatory pain Diseases 0.000 claims abstract description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 7
• 230000000694 effects Effects 0.000 claims abstract description 6
• 230000001404 mediated effect Effects 0.000 claims abstract description 5
• 239000003814 drug Substances 0.000 claims abstract description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 67
• 239000000203 mixture Substances 0.000 claims description 46
• -1 alkyl halogen Chemical class 0.000 claims description 27
• 238000000034 method Methods 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 6
• IVWOENWZBVIUFI-MRVPVSSYSA-N 4-[(1r)-1-(3-methoxypyridin-2-yl)oxyethyl]pyrimidin-2-amine Chemical compound COC1=CC=CN=C1O[C@H](C)C1=CC=NC(N)=N1 IVWOENWZBVIUFI-MRVPVSSYSA-N 0.000 claims description 5
• ICFLLTCXXSTBNA-SSDOTTSWSA-N 4-[(1r)-1-[3-(trifluoromethyl)pyridin-2-yl]oxyethyl]pyrimidin-2-amine Chemical compound O([C@H](C)C=1N=C(N)N=CC=1)C1=NC=CC=C1C(F)(F)F ICFLLTCXXSTBNA-SSDOTTSWSA-N 0.000 claims description 5
• CWQVTZBWZFEUCZ-ZCFIWIBFSA-N 4-[(1r)-1-[4-(trifluoromethyl)pyrimidin-2-yl]oxyethyl]pyrimidin-2-amine Chemical compound O([C@H](C)C=1N=C(N)N=CC=1)C1=NC=CC(C(F)(F)F)=N1 CWQVTZBWZFEUCZ-ZCFIWIBFSA-N 0.000 claims description 5
• BRDFFIWBTPFAGW-UHFFFAOYSA-N 4-[1-[3-(trifluoromethyl)pyridin-2-yl]sulfanylethyl]pyrimidin-2-amine Chemical compound C=1C=NC(N)=NC=1C(C)SC1=NC=CC=C1C(F)(F)F BRDFFIWBTPFAGW-UHFFFAOYSA-N 0.000 claims description 5
• FHTLKGVVDAFGRW-UHFFFAOYSA-N 4-[1-[[3-(trifluoromethyl)pyridin-2-yl]amino]ethyl]pyrimidin-2-amine Chemical compound C=1C=NC(N)=NC=1C(C)NC1=NC=CC=C1C(F)(F)F FHTLKGVVDAFGRW-UHFFFAOYSA-N 0.000 claims description 5
• 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 5
• 230000002981 neuropathic effect Effects 0.000 claims description 5
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
• 229910052740 iodine Inorganic materials 0.000 claims description 4
• YYEYMXDRGTXIIZ-SSDOTTSWSA-N 4-[(1r)-1-(2,4-difluorophenoxy)ethyl]pyrimidin-2-amine Chemical compound O([C@H](C)C=1N=C(N)N=CC=1)C1=CC=C(F)C=C1F YYEYMXDRGTXIIZ-SSDOTTSWSA-N 0.000 claims description 3
• OCGVPGIOKVTCBH-SSDOTTSWSA-N 4-[(1r)-1-(2,5-difluorophenoxy)ethyl]pyrimidin-2-amine Chemical compound O([C@H](C)C=1N=C(N)N=CC=1)C1=CC(F)=CC=C1F OCGVPGIOKVTCBH-SSDOTTSWSA-N 0.000 claims description 3
• RPQVMJSHJBPMOL-SSDOTTSWSA-N 4-[(1r)-1-(2-chloro-5-fluorophenoxy)ethyl]pyrimidin-2-amine Chemical compound O([C@H](C)C=1N=C(N)N=CC=1)C1=CC(F)=CC=C1Cl RPQVMJSHJBPMOL-SSDOTTSWSA-N 0.000 claims description 3
• YIIPERPMWRNKSL-MRVPVSSYSA-N 4-[(1r)-1-(3-fluorophenoxy)ethyl]pyrimidin-2-amine Chemical compound O([C@H](C)C=1N=C(N)N=CC=1)C1=CC=CC(F)=C1 YIIPERPMWRNKSL-MRVPVSSYSA-N 0.000 claims description 3
• OCGVPGIOKVTCBH-ZETCQYMHSA-N 4-[(1s)-1-(2,5-difluorophenoxy)ethyl]pyrimidin-2-amine Chemical compound O([C@@H](C)C=1N=C(N)N=CC=1)C1=CC(F)=CC=C1F OCGVPGIOKVTCBH-ZETCQYMHSA-N 0.000 claims description 3
• YIIPERPMWRNKSL-QMMMGPOBSA-N 4-[(1s)-1-(3-fluorophenoxy)ethyl]pyrimidin-2-amine Chemical compound O([C@@H](C)C=1N=C(N)N=CC=1)C1=CC=CC(F)=C1 YIIPERPMWRNKSL-QMMMGPOBSA-N 0.000 claims description 3
• FWRGXFQZCMCDER-UHFFFAOYSA-N 4-[1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]sulfanylethyl]pyrimidin-2-amine Chemical compound C=1C=NC(N)=NC=1C(C)SC1=NC=C(C(F)(F)F)C=C1Cl FWRGXFQZCMCDER-UHFFFAOYSA-N 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
• 239000000126 substance Substances 0.000 abstract description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 11
• 125000001072 heteroaryl group Chemical group 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
• 239000000243 solution Substances 0.000 description 50
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
• 239000003153 chemical reaction reagent Substances 0.000 description 32
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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 23
• 239000007787 solid Substances 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 20
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
• 210000004027 cell Anatomy 0.000 description 17
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
• 208000002193 Pain Diseases 0.000 description 16
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 15
• GRCYXPAUEDBQEP-UHFFFAOYSA-N 1-(2-aminopyrimidin-4-yl)ethanol Chemical compound CC(O)C1=CC=NC(N)=N1 GRCYXPAUEDBQEP-UHFFFAOYSA-N 0.000 description 13
• 108091006146 Channels Proteins 0.000 description 13
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• GRCYXPAUEDBQEP-SCSAIBSYSA-N (1r)-1-(2-aminopyrimidin-4-yl)ethanol Chemical compound C[C@@H](O)C1=CC=NC(N)=N1 GRCYXPAUEDBQEP-SCSAIBSYSA-N 0.000 description 11
• 229910052751 metal Inorganic materials 0.000 description 11
• 239000002184 metal Substances 0.000 description 11
• 239000000377 silicon dioxide Substances 0.000 description 11
• IGYXYGDEYHNFFT-UHFFFAOYSA-N 2-chloro-4-fluorophenol Chemical compound OC1=CC=C(F)C=C1Cl IGYXYGDEYHNFFT-UHFFFAOYSA-N 0.000 description 10
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 229910052938 sodium sulfate Inorganic materials 0.000 description 10
• 235000011152 sodium sulphate Nutrition 0.000 description 10
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
• 239000003054 catalyst Substances 0.000 description 9
• 238000004440 column chromatography Methods 0.000 description 9
• 125000006239 protecting group Chemical group 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• 238000003818 flash chromatography Methods 0.000 description 8
• 230000002829 reductive effect Effects 0.000 description 8
• 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 8
• SJTBRFHBXDZMPS-UHFFFAOYSA-N 3-fluorophenol Chemical compound OC1=CC=CC(F)=C1 SJTBRFHBXDZMPS-UHFFFAOYSA-N 0.000 description 7
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 7
• 239000007868 Raney catalyst Substances 0.000 description 7
• 229910000564 Raney nickel Inorganic materials 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 229910052786 argon Inorganic materials 0.000 description 7
• 125000005843 halogen group Chemical group 0.000 description 7
• 239000012299 nitrogen atmosphere Substances 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• GRCYXPAUEDBQEP-BYPYZUCNSA-N (1s)-1-(2-aminopyrimidin-4-yl)ethanol Chemical compound C[C@H](O)C1=CC=NC(N)=N1 GRCYXPAUEDBQEP-BYPYZUCNSA-N 0.000 description 6
• XDKSEDDZHXZRKQ-UHFFFAOYSA-N 1-(2-aminopyrimidin-4-yl)ethanone Chemical compound CC(=O)C1=CC=NC(N)=N1 XDKSEDDZHXZRKQ-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 229910052739 hydrogen Inorganic materials 0.000 description 6
• 239000001257 hydrogen Substances 0.000 description 6
• 239000000543 intermediate Substances 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• 125000002524 organometallic group Chemical group 0.000 description 6
• YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical compound [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 description 6
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• FASZWOLPNJDCCV-UHFFFAOYSA-N 1-(2-aminopyrimidin-4-yl)propan-2-one Chemical compound CC(=O)CC1=CC=NC(N)=N1 FASZWOLPNJDCCV-UHFFFAOYSA-N 0.000 description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
• 208000004454 Hyperalgesia Diseases 0.000 description 5
• 238000006254 arylation reaction Methods 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 239000010410 layer Substances 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• UWJBSSXERIXLCT-ZCFIWIBFSA-N (1r)-1-(2-aminopyrimidin-4-yl)propan-1-ol Chemical compound CC[C@@H](O)C1=CC=NC(N)=N1 UWJBSSXERIXLCT-ZCFIWIBFSA-N 0.000 description 4
• UWJBSSXERIXLCT-LURJTMIESA-N (1s)-1-(2-aminopyrimidin-4-yl)propan-1-ol Chemical compound CC[C@H](O)C1=CC=NC(N)=N1 UWJBSSXERIXLCT-LURJTMIESA-N 0.000 description 4
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 4
• GCMMYIYEKSCNRT-UHFFFAOYSA-N 1-(2-aminopyridin-4-yl)ethanol Chemical compound CC(O)C1=CC=NC(N)=C1 GCMMYIYEKSCNRT-UHFFFAOYSA-N 0.000 description 4
• JGPUNUZKILMJDR-UHFFFAOYSA-N 1-[2-(methylamino)pyrimidin-4-yl]ethanol Chemical compound CNC1=NC=CC(C(C)O)=N1 JGPUNUZKILMJDR-UHFFFAOYSA-N 0.000 description 4
• JSTJKIRLQHXBFE-SECBINFHSA-N 2-bromo-6-[(1r)-1-(3-fluorophenoxy)ethyl]pyridine Chemical compound O([C@H](C)C=1N=C(Br)C=CC=1)C1=CC=CC(F)=C1 JSTJKIRLQHXBFE-SECBINFHSA-N 0.000 description 4
• UTAQOVYPSZIDTK-UHFFFAOYSA-N 2-fluoro-3-(trifluoromethyl)pyridine Chemical compound FC1=NC=CC=C1C(F)(F)F UTAQOVYPSZIDTK-UHFFFAOYSA-N 0.000 description 4
• GNHWZRZIPQSPAM-UHFFFAOYSA-N 4-(1,1-dimethoxyethyl)pyrimidin-2-amine Chemical compound COC(C)(OC)C1=CC=NC(N)=N1 GNHWZRZIPQSPAM-UHFFFAOYSA-N 0.000 description 4
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
• 0 CC(C(*)(O*)O*)=*C(N(*)*)=*C=* Chemical compound CC(C(*)(O*)O*)=*C(N(*)*)=*C=* 0.000 description 4
• 101001009074 Homo sapiens Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Proteins 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 238000007792 addition Methods 0.000 description 4
• 125000001118 alkylidene group Chemical group 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 239000012267 brine Substances 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 238000010511 deprotection reaction Methods 0.000 description 4
• 229960000789 guanidine hydrochloride Drugs 0.000 description 4
• PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 4
• 238000005984 hydrogenation reaction Methods 0.000 description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
• 235000019341 magnesium sulphate Nutrition 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 239000012312 sodium hydride Substances 0.000 description 4
• 229910000104 sodium hydride Inorganic materials 0.000 description 4
• 238000001356 surgical procedure Methods 0.000 description 4
• VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 4
• 230000009466 transformation Effects 0.000 description 4
• 238000000844 transformation Methods 0.000 description 4
• WXWFPQXHEKFXJZ-UHFFFAOYSA-N 1-(4-amino-6-methylsulfanyl-1,3,5-triazin-2-yl)ethanol Chemical compound CSC1=NC(N)=NC(C(C)O)=N1 WXWFPQXHEKFXJZ-UHFFFAOYSA-N 0.000 description 3
• OVRSIQWVIJSERH-UHFFFAOYSA-N 1-(dimethylamino)-4,4-dimethoxypent-1-en-3-one Chemical compound COC(C)(OC)C(=O)C=CN(C)C OVRSIQWVIJSERH-UHFFFAOYSA-N 0.000 description 3
• LQJNIKQNMJEMOZ-UHFFFAOYSA-N 1-[2-(methylamino)pyrimidin-4-yl]ethanone Chemical compound CNC1=NC=CC(C(C)=O)=N1 LQJNIKQNMJEMOZ-UHFFFAOYSA-N 0.000 description 3
• OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 3
• KMYPLSMWYXTSCA-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-2-(2-chloro-4-fluorophenoxy)ethanol Chemical compound NC1=NC=CC(C(CO)OC=2C(=CC(F)=CC=2)Cl)=N1 KMYPLSMWYXTSCA-UHFFFAOYSA-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
• RXATZPCCMYMPME-UHFFFAOYSA-N 2-chloro-3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CN=C1Cl RXATZPCCMYMPME-UHFFFAOYSA-N 0.000 description 3
• FZRBTBCCMVNZBD-UHFFFAOYSA-N 2-chloro-4-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=CC=NC(Cl)=N1 FZRBTBCCMVNZBD-UHFFFAOYSA-N 0.000 description 3
• ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 3
• LAKNMIMTKJEVGW-SSDOTTSWSA-N 4-[(1r)-1-(6-fluoropyridin-2-yl)oxyethyl]pyrimidin-2-amine Chemical compound O([C@H](C)C=1N=C(N)N=CC=1)C1=CC=CC(F)=N1 LAKNMIMTKJEVGW-SSDOTTSWSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• 239000007995 HEPES buffer Substances 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 208000028389 Nerve injury Diseases 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 238000005903 acid hydrolysis reaction Methods 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 150000001721 carbon Chemical group 0.000 description 3
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