MXPA04009459A - Nuevos compuestos. - Google Patents

Info

Publication number

MXPA04009459A

MXPA04009459A MXPA04009459A MXPA04009459A MXPA04009459A MX PA04009459 A MXPA04009459 A MX PA04009459A MX PA04009459 A MXPA04009459 A MX PA04009459A MX PA04009459 A MXPA04009459 A MX PA04009459A MX PA04009459 A MXPA04009459 A MX PA04009459A

Authority

MX

Mexico

Prior art keywords

methyl

compound

formula

morpholin

oxadiazol

Prior art date

2002-03-28

Links

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• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims description 303
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 67
• 239000001257 hydrogen Substances 0.000 claims abstract description 57
• 150000003839 salts Chemical class 0.000 claims abstract description 45
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 39
• 239000012453 solvate Substances 0.000 claims abstract description 34
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 29
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 27
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 21
• 239000005557 antagonist Substances 0.000 claims abstract description 10
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 4
• 102100024167 C-C chemokine receptor type 3 Human genes 0.000 claims abstract description 3
• 101710149862 C-C chemokine receptor type 3 Proteins 0.000 claims abstract description 3
• -1 { [( { [4- (3,4-dichlorobenzyl) morpholin-2-yl] methyl} amino) carbonyl] -amino} methyl Chemical group 0.000 claims description 415
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 72
• 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 50
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 50
• 238000006243 chemical reaction Methods 0.000 claims description 50
• 125000000217 alkyl group Chemical group 0.000 claims description 48
• 238000000034 method Methods 0.000 claims description 42
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 38
• 239000004202 carbamide Substances 0.000 claims description 34
• 239000002253 acid Substances 0.000 claims description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
• 230000008569 process Effects 0.000 claims description 17
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 16
• 208000006673 asthma Diseases 0.000 claims description 16
• 125000001544 thienyl group Chemical group 0.000 claims description 15
• 239000000460 chlorine Substances 0.000 claims description 14
• 229910052801 chlorine Inorganic materials 0.000 claims description 14
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 14
• 238000002360 preparation method Methods 0.000 claims description 14
• 238000011282 treatment Methods 0.000 claims description 13
• 125000003118 aryl group Chemical group 0.000 claims description 11
• 206010039083 rhinitis Diseases 0.000 claims description 10
• 125000006239 protecting group Chemical group 0.000 claims description 9
• 229910052731 fluorine Chemical group 0.000 claims description 8
• 239000011737 fluorine Chemical group 0.000 claims description 8
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 7
• 230000004968 inflammatory condition Effects 0.000 claims description 7
• 229920005989 resin Polymers 0.000 claims description 7
• 239000011347 resin Substances 0.000 claims description 7
• HIMWHLGWENNHOO-RUINGEJQSA-N (4-nitrophenyl) n-[[(2s)-4-[1-(3,4-difluorophenyl)ethyl]morpholin-2-yl]methyl]carbamate Chemical compound C([C@@H]1OCCN(C1)C(C)C=1C=C(F)C(F)=CC=1)NC(=O)OC1=CC=C([N+]([O-])=O)C=C1 HIMWHLGWENNHOO-RUINGEJQSA-N 0.000 claims description 6
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 229920005990 polystyrene resin Polymers 0.000 claims description 6
• 229940124597 therapeutic agent Drugs 0.000 claims description 5
• 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 claims description 4
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
• 239000003480 eluent Substances 0.000 claims description 4
• 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 4
• CHFLRXHBQCODJY-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(1,3-thiazol-2-ylmethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCC=2SC=CN=2)OCC1 CHFLRXHBQCODJY-UHFFFAOYSA-N 0.000 claims description 3
• SOANXCFVMUFQHE-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[(4-methyl-1,3-thiazol-2-yl)methyl]urea Chemical compound CC1=CSC(CNC(=O)NCC2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=N1 SOANXCFVMUFQHE-UHFFFAOYSA-N 0.000 claims description 3
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
• FLDBJBTUVYXSJV-UHFFFAOYSA-N 5-(aminomethyl)-n-methylthiophene-3-carboxamide Chemical compound CNC(=O)C1=CSC(CN)=C1 FLDBJBTUVYXSJV-UHFFFAOYSA-N 0.000 claims description 3
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• GIKWERIUUJADFI-UHFFFAOYSA-N n-methylthiophene-3-carboxamide Chemical compound CNC(=O)C=1C=CSC=1 GIKWERIUUJADFI-UHFFFAOYSA-N 0.000 claims description 3
• 229960003966 nicotinamide Drugs 0.000 claims description 3
• 235000005152 nicotinamide Nutrition 0.000 claims description 3
• 239000011570 nicotinamide Substances 0.000 claims description 3
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 3
• 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims description 3
• DJVBYKUXZPCRCL-INIZCTEOSA-N (4-nitrophenyl) n-[[(2s)-4-[(3-chloro-4-fluorophenyl)methyl]morpholin-2-yl]methyl]carbamate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)NC[C@@H]1OCCN(CC=2C=C(Cl)C(F)=CC=2)C1 DJVBYKUXZPCRCL-INIZCTEOSA-N 0.000 claims description 2
• LJQCWQGMVJGSKQ-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(1h-indol-4-ylmethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCC=2C=3C=CNC=3C=CC=2)OCC1 LJQCWQGMVJGSKQ-UHFFFAOYSA-N 0.000 claims description 2
• PONVDQFSFUCTIN-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[(6-methoxypyridin-3-yl)methyl]urea Chemical compound C1=NC(OC)=CC=C1CNC(=O)NCC1OCCN(CC=2C=C(Cl)C(Cl)=CC=2)C1 PONVDQFSFUCTIN-UHFFFAOYSA-N 0.000 claims description 2
• VKJDDBJDNJOXOP-UHFFFAOYSA-N 2-(5-methyl-1,3,4-oxadiazol-2-yl)ethanamine Chemical compound CC1=NN=C(CCN)O1 VKJDDBJDNJOXOP-UHFFFAOYSA-N 0.000 claims description 2
• 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
• HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical group CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 claims description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
• SHWHZSUZZGMZID-UHFFFAOYSA-N 5-(aminomethyl)-n-methyl-1,3,4-oxadiazole-2-carboxamide;hydrochloride Chemical compound Cl.CNC(=O)C1=NN=C(CN)O1 SHWHZSUZZGMZID-UHFFFAOYSA-N 0.000 claims description 2
• FWJJBJSRDWAPHW-UHFFFAOYSA-N 5-(aminomethyl)-n-methylfuran-3-carboxamide Chemical compound CNC(=O)C1=COC(CN)=C1 FWJJBJSRDWAPHW-UHFFFAOYSA-N 0.000 claims description 2
• 229920001367 Merrifield resin Polymers 0.000 claims description 2
• 241001465754 Metazoa Species 0.000 claims description 2
• HWRGSZBKNXDGBP-UHFFFAOYSA-N [4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methylurea Chemical compound ClC=1C=C(CN2CC(OCC2)CNC(=O)N)C=CC=1Cl HWRGSZBKNXDGBP-UHFFFAOYSA-N 0.000 claims description 2
• 125000004532 benzofuran-3-yl group Chemical group O1C=C(C2=C1C=CC=C2)* 0.000 claims description 2
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 2
• 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 2
• FSKWRNINWRUSHD-UHFFFAOYSA-N methyl 2-(aminomethyl)-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(CN)=N1 FSKWRNINWRUSHD-UHFFFAOYSA-N 0.000 claims description 2
• BNCNNWWRGRSEDP-UHFFFAOYSA-N n-methyl-5-[[(2,2,2-trifluoroacetyl)amino]methyl]furan-3-carboxamide Chemical compound CNC(=O)C1=COC(CNC(=O)C(F)(F)F)=C1 BNCNNWWRGRSEDP-UHFFFAOYSA-N 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• 230000001681 protective effect Effects 0.000 claims description 2
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims description 2
• UNHWIEGKCBNIBF-UHFFFAOYSA-N tert-butyl n-[2-(5-methyl-1,3,4-oxadiazol-2-yl)ethyl]carbamate Chemical compound CC1=NN=C(CCNC(=O)OC(C)(C)C)O1 UNHWIEGKCBNIBF-UHFFFAOYSA-N 0.000 claims description 2
• CUTTVDFLPQWLBT-UHFFFAOYSA-N tert-butyl n-[3-(2-acetylhydrazinyl)-3-oxopropyl]carbamate Chemical compound CC(=O)NNC(=O)CCNC(=O)OC(C)(C)C CUTTVDFLPQWLBT-UHFFFAOYSA-N 0.000 claims description 2
• HWTMFHDEXRMMSD-PYMCNQPYSA-N tert-butyl n-[[(2s)-4-[1-(3,4-difluorophenyl)ethyl]morpholin-2-yl]methyl]carbamate Chemical compound C=1C=C(F)C(F)=CC=1C(C)N1CCO[C@@H](CNC(=O)OC(C)(C)C)C1 HWTMFHDEXRMMSD-PYMCNQPYSA-N 0.000 claims description 2
• VIYRXFZMEZXIIV-SFHVURJKSA-N tert-butyl n-[[5-[[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methylcarbamoylamino]methyl]furan-3-carbonyl]amino]carbamate Chemical compound CC(C)(C)OC(=O)NNC(=O)C1=COC(CNC(=O)NC[C@@H]2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=C1 VIYRXFZMEZXIIV-SFHVURJKSA-N 0.000 claims description 2
• 101100456896 Drosophila melanogaster metl gene Proteins 0.000 claims 2
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims 1
• SOANXCFVMUFQHE-AWEZNQCLSA-N 1-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[(4-methyl-1,3-thiazol-2-yl)methyl]urea Chemical compound CC1=CSC(CNC(=O)NC[C@@H]2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=N1 SOANXCFVMUFQHE-AWEZNQCLSA-N 0.000 claims 1
• KDICWNXUQADMTF-RSAXXLAASA-N 1-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[[4-(hydrazinecarbonyl)furan-2-yl]methyl]urea;hydrochloride Chemical compound Cl.NNC(=O)C1=COC(CNC(=O)NC[C@@H]2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=C1 KDICWNXUQADMTF-RSAXXLAASA-N 0.000 claims 1
• PHMMAHLAVAGBGI-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(1h-pyrrolo[2,3-b]pyridin-3-ylmethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCC=2C3=CC=CN=C3NC=2)OCC1 PHMMAHLAVAGBGI-UHFFFAOYSA-N 0.000 claims 1
• YESMWHHSKLCUDO-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(2-thiophen-2-ylethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCCC=2SC=CC=2)OCC1 YESMWHHSKLCUDO-UHFFFAOYSA-N 0.000 claims 1
• 125000004803 chlorobenzyl group Chemical group 0.000 claims 1
• 150000002431 hydrogen Chemical group 0.000 claims 1
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 1
• GACCYZRDGNSLGQ-INIZCTEOSA-N n-[[5-[[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methylcarbamoylamino]methyl]furan-3-carbonyl]amino]formamide Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1C[C@H](CNC(=O)NCC=2OC=C(C=2)C(=O)NNC=O)OCC1 GACCYZRDGNSLGQ-INIZCTEOSA-N 0.000 claims 1
• 125000003107 substituted aryl group Chemical group 0.000 abstract description 2
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 326
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
• 239000000243 solution Substances 0.000 description 107
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 95
• 239000000203 mixture Substances 0.000 description 90
• 239000002904 solvent Substances 0.000 description 74
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 61
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
• 125000001424 substituent group Chemical group 0.000 description 45
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 38
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 37
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
• 239000007787 solid Substances 0.000 description 35
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
• 239000000725 suspension Substances 0.000 description 32
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 28
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
• 229910021529 ammonia Inorganic materials 0.000 description 26
• 229910052757 nitrogen Inorganic materials 0.000 description 25
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• 238000005342 ion exchange Methods 0.000 description 22
• 238000001819 mass spectrum Methods 0.000 description 22
• 238000010992 reflux Methods 0.000 description 22
• 125000005843 halogen group Chemical group 0.000 description 19
• BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 19
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
• 239000003921 oil Substances 0.000 description 17
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
• 210000004027 cell Anatomy 0.000 description 16
• 239000012074 organic phase Substances 0.000 description 16
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
• 210000003979 eosinophil Anatomy 0.000 description 15
• 238000001704 evaporation Methods 0.000 description 15
• 239000000047 product Substances 0.000 description 15
• 239000002585 base Substances 0.000 description 14
• 201000010099 disease Diseases 0.000 description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 13
• 230000008020 evaporation Effects 0.000 description 13
• 239000000377 silicon dioxide Substances 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• 238000010189 synthetic method Methods 0.000 description 13
• 125000003831 tetrazolyl group Chemical group 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical group ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 11
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 11
• 125000000842 isoxazolyl group Chemical group 0.000 description 11
• 125000001715 oxadiazolyl group Chemical group 0.000 description 11
• 229920006395 saturated elastomer Polymers 0.000 description 11
• 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 11
• 125000003545 alkoxy group Chemical group 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 125000000623 heterocyclic group Chemical group 0.000 description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
• 238000005481 NMR spectroscopy Methods 0.000 description 9
• 235000011114 ammonium hydroxide Nutrition 0.000 description 9
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 9
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 9
• 238000002414 normal-phase solid-phase extraction Methods 0.000 description 9
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• 102000019034 Chemokines Human genes 0.000 description 8
• 108010012236 Chemokines Proteins 0.000 description 8
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• 230000004913 activation Effects 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 238000003818 flash chromatography Methods 0.000 description 8
• 125000002541 furyl group Chemical group 0.000 description 8
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
• 210000000265 leukocyte Anatomy 0.000 description 8
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