ES2635067T3 - Compuesto de sulfamato de fenilalquilo y composición de relajante muscular que comprende el mismo - Google Patents

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Publication number

ES2635067T3

ES2635067T3 ES13803704.9T ES13803704T ES2635067T3 ES 2635067 T3 ES2635067 T3 ES 2635067T3 ES 13803704 T ES13803704 T ES 13803704T ES 2635067 T3 ES2635067 T3 ES 2635067T3

Authority

ES

Spain

Prior art keywords

methyl

preparation example

dioxolan

methyl sulfamate

sulfamate

Prior art date

2012-06-15

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 640
• -1 phenylalkyl sulfamate Chemical compound 0.000 title claims description 457
• 239000000203 mixture Substances 0.000 title claims description 60
• 239000003158 myorelaxant agent Substances 0.000 title description 10
• 150000003839 salts Chemical class 0.000 claims abstract description 29
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 19
• 239000001257 hydrogen Substances 0.000 claims abstract description 17
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 10
• 150000002431 hydrogen Chemical class 0.000 claims abstract description 10
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims abstract description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
• 125000003277 amino group Chemical group 0.000 claims abstract description 5
• 150000001721 carbon Chemical group 0.000 claims abstract description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims abstract description 3
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
• 150000002367 halogens Chemical group 0.000 claims abstract description 3
• 238000000034 method Methods 0.000 claims description 511
• FIYXUOWXHWJDAM-UHFFFAOYSA-N methyl sulfamate Chemical compound COS(N)(=O)=O FIYXUOWXHWJDAM-UHFFFAOYSA-N 0.000 claims description 109
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 57
• 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 56
• 239000000460 chlorine Substances 0.000 claims description 41
• 239000002253 acid Substances 0.000 claims description 30
• BGGQCYYULFFRLC-UHFFFAOYSA-N ethyl sulfamate Chemical compound CCOS(N)(=O)=O BGGQCYYULFFRLC-UHFFFAOYSA-N 0.000 claims description 30
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
• 208000005392 Spasm Diseases 0.000 claims description 20
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 19
• 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 claims description 19
• 208000007101 Muscle Cramp Diseases 0.000 claims description 19
• 201000010099 disease Diseases 0.000 claims description 19
• 206010021118 Hypotonia Diseases 0.000 claims description 17
• 230000036640 muscle relaxation Effects 0.000 claims description 17
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 13
• 238000005906 dihydroxylation reaction Methods 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• 239000007800 oxidant agent Substances 0.000 claims description 7
• RZMCTLKVIWUBPA-UHFFFAOYSA-N [5-(2-chlorophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(C)(C)OC(COS(N)(=O)=O)C1C1=CC=CC=C1Cl RZMCTLKVIWUBPA-UHFFFAOYSA-N 0.000 claims description 6
• 230000001590 oxidative effect Effects 0.000 claims description 6
• 210000000278 spinal cord Anatomy 0.000 claims description 6
• 206010019196 Head injury Diseases 0.000 claims description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• BAPAOLGFWMELPD-UHFFFAOYSA-N [5-(2-nitrophenyl)-2-oxo-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound NS(=O)(=O)OCC1OC(=O)OC1C1=CC=CC=C1[N+]([O-])=O BAPAOLGFWMELPD-UHFFFAOYSA-N 0.000 claims description 5
• 239000003638 chemical reducing agent Substances 0.000 claims description 5
• 206010041415 Spastic paralysis Diseases 0.000 claims description 4
• 206010041591 Spinal osteoarthritis Diseases 0.000 claims description 4
• QWOWRIOCXVQFRR-UHFFFAOYSA-N [5-(2,6-dichlorophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(C)(C)OC(COS(N)(=O)=O)C1C1=C(Cl)C=CC=C1Cl QWOWRIOCXVQFRR-UHFFFAOYSA-N 0.000 claims description 4
• XHAGRJPHZXUFFK-UHFFFAOYSA-N [5-(2-chlorophenyl)-2,2-diethyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(CC)(CC)OC(COS(N)(=O)=O)C1C1=CC=CC=C1Cl XHAGRJPHZXUFFK-UHFFFAOYSA-N 0.000 claims description 4
• ZJTMPSSKRYNKNG-UHFFFAOYSA-N [5-(2-chlorophenyl)-2-methyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound S(N)(OCC1OC(OC1C1=C(C=CC=C1)Cl)C)(=O)=O ZJTMPSSKRYNKNG-UHFFFAOYSA-N 0.000 claims description 4
• 206010008129 cerebral palsy Diseases 0.000 claims description 4
• 208000036319 cervical spondylosis Diseases 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• 208000020431 spinal cord injury Diseases 0.000 claims description 4
• 208000005801 spondylosis Diseases 0.000 claims description 4
• 208000019553 vascular disease Diseases 0.000 claims description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 3
• 206010008025 Cerebellar ataxia Diseases 0.000 claims description 3
• 208000003618 Intervertebral Disc Displacement Diseases 0.000 claims description 3
• 206010050296 Intervertebral disc protrusion Diseases 0.000 claims description 3
• 208000010112 Spinocerebellar Degenerations Diseases 0.000 claims description 3
• 229910052783 alkali metal Inorganic materials 0.000 claims description 3
• 150000001340 alkali metals Chemical class 0.000 claims description 3
• 150000001413 amino acids Chemical class 0.000 claims description 3
• 150000007522 mineralic acids Chemical class 0.000 claims description 3
• 150000007524 organic acids Chemical class 0.000 claims description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
• 230000019635 sulfation Effects 0.000 claims description 3
• 238000005670 sulfation reaction Methods 0.000 claims description 3
• KSMPNKLYNWJXNI-UHFFFAOYSA-N (5-benzyl-2,2-diethyl-1,3-dioxolan-4-yl)methyl sulfamate Chemical compound S(N)(OCC1OC(OC1CC1=CC=CC=C1)(CC)CC)(=O)=O KSMPNKLYNWJXNI-UHFFFAOYSA-N 0.000 claims description 2
• GPQXADGDQZYFMV-UHFFFAOYSA-N (5-benzyl-2,2-dimethyl-1,3-dioxolan-4-yl)methyl sulfamate Chemical compound S(N)(OCC1OC(OC1CC1=CC=CC=C1)(C)C)(=O)=O GPQXADGDQZYFMV-UHFFFAOYSA-N 0.000 claims description 2
• CSXDJPXXSIMJBX-UHFFFAOYSA-N 2-(5-benzyl-2,2-diethyl-1,3-dioxolan-4-yl)ethyl sulfamate Chemical compound O1C(CC)(CC)OC(CCOS(N)(=O)=O)C1CC1=CC=CC=C1 CSXDJPXXSIMJBX-UHFFFAOYSA-N 0.000 claims description 2
• SFNZSFGVNUSPAU-UHFFFAOYSA-N 2-(5-benzyl-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl sulfamate Chemical compound O1C(C)(C)OC(CCOS(N)(=O)=O)C1CC1=CC=CC=C1 SFNZSFGVNUSPAU-UHFFFAOYSA-N 0.000 claims description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
• 206010033799 Paralysis Diseases 0.000 claims description 2
• XNPNIYWWVGGUIK-UHFFFAOYSA-N [5-(2,4-dichlorophenyl)-2,2-diethyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(CC)(CC)OC(COS(N)(=O)=O)C1C1=CC=C(Cl)C=C1Cl XNPNIYWWVGGUIK-UHFFFAOYSA-N 0.000 claims description 2
• PZJPBLBSIBZHEU-UHFFFAOYSA-N [5-(2,4-dichlorophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(C)(C)OC(COS(N)(=O)=O)C1C1=CC=C(Cl)C=C1Cl PZJPBLBSIBZHEU-UHFFFAOYSA-N 0.000 claims description 2
• VAYHBFLVNBUIQJ-UHFFFAOYSA-N [5-(2,4-dichlorophenyl)-2-methyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(C)OC(COS(N)(=O)=O)C1C1=CC=C(Cl)C=C1Cl VAYHBFLVNBUIQJ-UHFFFAOYSA-N 0.000 claims description 2
• QPUZPKPURUDSKT-UHFFFAOYSA-N [5-(2,4-dichlorophenyl)-2-phenyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound NS(=O)(=O)OCC1OC(C=2C=CC=CC=2)OC1C1=CC=C(Cl)C=C1Cl QPUZPKPURUDSKT-UHFFFAOYSA-N 0.000 claims description 2
• VATHXICLBXMRAO-UHFFFAOYSA-N [5-(2,6-dichlorophenyl)-2,2-diethyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(CC)(CC)OC(COS(N)(=O)=O)C1C1=C(Cl)C=CC=C1Cl VATHXICLBXMRAO-UHFFFAOYSA-N 0.000 claims description 2
• ZCCGKLLDFDGOMF-UHFFFAOYSA-N [5-(2,6-dichlorophenyl)-2-methyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(C)OC(COS(N)(=O)=O)C1C1=C(Cl)C=CC=C1Cl ZCCGKLLDFDGOMF-UHFFFAOYSA-N 0.000 claims description 2
• UDZGOSZSFMSKDM-UHFFFAOYSA-N [5-(2,6-dichlorophenyl)-2-phenyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound NS(=O)(=O)OCC1OC(C=2C=CC=CC=2)OC1C1=C(Cl)C=CC=C1Cl UDZGOSZSFMSKDM-UHFFFAOYSA-N 0.000 claims description 2
• MOUITVGTOGQRGR-UHFFFAOYSA-N [5-(2-aminophenyl)-2,2-diethyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(CC)(CC)OC(COS(N)(=O)=O)C1C1=CC=CC=C1N MOUITVGTOGQRGR-UHFFFAOYSA-N 0.000 claims description 2
• PPMVXZLGSOOHNV-UHFFFAOYSA-N [5-(2-aminophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(C)(C)OC(COS(N)(=O)=O)C1C1=CC=CC=C1N PPMVXZLGSOOHNV-UHFFFAOYSA-N 0.000 claims description 2
• PKNWMDOCDWBNCK-UHFFFAOYSA-N [5-(2-aminophenyl)-2-phenyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound NC1=CC=CC=C1C1C(COS(N)(=O)=O)OC(C=2C=CC=CC=2)O1 PKNWMDOCDWBNCK-UHFFFAOYSA-N 0.000 claims description 2
• UANGRXRESSDGEE-UHFFFAOYSA-N [5-(2-chlorophenyl)-2-phenyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound NS(=O)(=O)OCC1OC(C=2C=CC=CC=2)OC1C1=CC=CC=C1Cl UANGRXRESSDGEE-UHFFFAOYSA-N 0.000 claims description 2
• ANYUUFVAPYZBOM-UHFFFAOYSA-N [5-(2-fluorophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(C)(C)OC(COS(N)(=O)=O)C1C1=CC=CC=C1F ANYUUFVAPYZBOM-UHFFFAOYSA-N 0.000 claims description 2
• ZUBCNBYVKBJOHW-UHFFFAOYSA-N [5-(2-fluorophenyl)-2-methyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound S(N)(OCC1OC(OC1C1=C(C=CC=C1)F)C)(=O)=O ZUBCNBYVKBJOHW-UHFFFAOYSA-N 0.000 claims description 2
• PGKJDCCMJALRSH-UHFFFAOYSA-N [5-(2-fluorophenyl)-2-phenyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound NS(=O)(=O)OCC1OC(C=2C=CC=CC=2)OC1C1=CC=CC=C1F PGKJDCCMJALRSH-UHFFFAOYSA-N 0.000 claims description 2
• DVWFSTVNQGCQOW-UHFFFAOYSA-N [5-(2-iodophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(C)(C)OC(COS(N)(=O)=O)C1C1=CC=CC=C1I DVWFSTVNQGCQOW-UHFFFAOYSA-N 0.000 claims description 2
• SSQLUTKYINNSAY-UHFFFAOYSA-N [5-(2-iodophenyl)-2-methyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound S(N)(OCC1OC(OC1C1=C(C=CC=C1)I)C)(=O)=O SSQLUTKYINNSAY-UHFFFAOYSA-N 0.000 claims description 2
• BDHJUEFXZRDXKT-UHFFFAOYSA-N [5-(2-iodophenyl)-2-phenyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound NS(=O)(=O)OCC1OC(C=2C=CC=CC=2)OC1C1=CC=CC=C1I BDHJUEFXZRDXKT-UHFFFAOYSA-N 0.000 claims description 2
• LFJHTCHBWSCVIF-UHFFFAOYSA-N [5-(2-methylphenyl)-2-phenyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound CC1=CC=CC=C1C1C(COS(N)(=O)=O)OC(C=2C=CC=CC=2)O1 LFJHTCHBWSCVIF-UHFFFAOYSA-N 0.000 claims description 2
• QXXREHAVUAFLBD-UHFFFAOYSA-N [5-(2-nitrophenyl)-2-phenyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound NS(=O)(=O)OCC1OC(C=2C=CC=CC=2)OC1C1=CC=CC=C1[N+]([O-])=O QXXREHAVUAFLBD-UHFFFAOYSA-N 0.000 claims description 2
• 239000004480 active ingredient Substances 0.000 claims description 2
• 229910052801 chlorine Inorganic materials 0.000 claims description 2
• 239000011737 fluorine Substances 0.000 claims description 2
• 229910052731 fluorine Inorganic materials 0.000 claims description 2
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
• IQUJYITYUVTFDO-UHFFFAOYSA-N 2-[5-(2-chlorophenyl)-2,2-diethyl-1,3-dioxolan-4-yl]ethyl sulfamate Chemical compound O1C(CC)(CC)OC(CCOS(N)(=O)=O)C1C1=CC=CC=C1Cl IQUJYITYUVTFDO-UHFFFAOYSA-N 0.000 claims 1
• JANMWWVANVYISM-UHFFFAOYSA-N 2-[5-(2-chlorophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl sulfamate Chemical compound O1C(C)(C)OC(CCOS(N)(=O)=O)C1C1=CC=CC=C1Cl JANMWWVANVYISM-UHFFFAOYSA-N 0.000 claims 1
• LNUSHCOTFXLBNS-UHFFFAOYSA-N [5-(2-aminophenyl)-2-methyl-1,3-dioxolan-4-yl]methyl sulfamate Chemical compound O1C(C)OC(COS(N)(=O)=O)C1C1=CC=CC=C1N LNUSHCOTFXLBNS-UHFFFAOYSA-N 0.000 claims 1
• 230000001148 spastic effect Effects 0.000 claims 1
• 238000002360 preparation method Methods 0.000 description 1225
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 600
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 563
• 238000005160 1H NMR spectroscopy Methods 0.000 description 531
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 107
• CSXVIDKEWQWVHS-GHMZBOCLSA-N [(4r,5r)-5-(2-chlorophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol Chemical compound O1C(C)(C)O[C@H](CO)[C@H]1C1=CC=CC=C1Cl CSXVIDKEWQWVHS-GHMZBOCLSA-N 0.000 description 103
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 100
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 82
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 76
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 72
• FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 64
• 239000000243 solution Substances 0.000 description 46
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
• 229950010765 pivalate Drugs 0.000 description 42
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 41
• 235000019439 ethyl acetate Nutrition 0.000 description 40
• 125000001309 chloro group Chemical group Cl* 0.000 description 38
• 239000011541 reaction mixture Substances 0.000 description 33
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 31
• 235000019341 magnesium sulphate Nutrition 0.000 description 31
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 30
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 30
• 239000000741 silica gel Substances 0.000 description 30
• 229910002027 silica gel Inorganic materials 0.000 description 30
• 238000012360 testing method Methods 0.000 description 29
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 26
• XANDIZUBPVRBDO-UHFFFAOYSA-N 3-(2-chlorophenyl)-2,3-dihydroxypropanoic acid Chemical compound C1=CC=C(C(=C1)C(C(C(=O)O)O)O)Cl XANDIZUBPVRBDO-UHFFFAOYSA-N 0.000 description 24
• 230000000694 effects Effects 0.000 description 21
• UJUPWGLGIULAPW-UHFFFAOYSA-N 5-(2-chlorophenyl)-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid Chemical compound ClC1=C(C=CC=C1)C1C(OC(O1)(C)C)C(=O)O UJUPWGLGIULAPW-UHFFFAOYSA-N 0.000 description 20
• HHEIMYAXCOIQCJ-UHFFFAOYSA-N ethyl 2,2-dimethylpropanoate Chemical compound CCOC(=O)C(C)(C)C HHEIMYAXCOIQCJ-UHFFFAOYSA-N 0.000 description 20
• 239000012044 organic layer Substances 0.000 description 20
• 239000010410 layer Substances 0.000 description 17
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
• 125000000068 chlorophenyl group Chemical group 0.000 description 16
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 14
• SAOSCTYRONNFTC-UHFFFAOYSA-N 2-methyl-decanoic acid Chemical compound CCCCCCCCC(C)C(O)=O SAOSCTYRONNFTC-UHFFFAOYSA-N 0.000 description 13
• 238000005481 NMR spectroscopy Methods 0.000 description 13
• SBVWZRBKTDOSDR-GQCTYLIASA-N 1-chloro-2-[(e)-3-(methoxymethoxy)prop-1-enyl]benzene Chemical compound COCOC\C=C\C1=CC=CC=C1Cl SBVWZRBKTDOSDR-GQCTYLIASA-N 0.000 description 12
• LTUCVZZJUOHZJL-UHFFFAOYSA-N 5-(2-iodophenyl)-2-methyl-1,3-dioxolane-4-carboxylic acid Chemical compound CC1OC(C(O1)C(=O)O)C2=CC=CC=C2I LTUCVZZJUOHZJL-UHFFFAOYSA-N 0.000 description 12
• 241000699670 Mus sp. Species 0.000 description 12
• DIIPEABOGNNQOT-UHFFFAOYSA-N 5-(2-chlorophenyl)-2,2-diethyl-1,3-dioxolane-4-carboxylic acid Chemical compound ClC1=C(C=CC=C1)C1C(OC(O1)(CC)CC)C(=O)O DIIPEABOGNNQOT-UHFFFAOYSA-N 0.000 description 11
• 239000008194 pharmaceutical composition Substances 0.000 description 11
• ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 10
• UBHZUDXTHNMNLD-UHFFFAOYSA-N dimethylsilane Chemical compound C[SiH2]C UBHZUDXTHNMNLD-UHFFFAOYSA-N 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 9
• DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 8
• JVVDMVUMEQHWTD-UHFFFAOYSA-N 5-[(2-chlorophenyl)methyl]-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid Chemical compound ClC1=C(CC2C(OC(O2)(C)C)C(=O)O)C=CC=C1 JVVDMVUMEQHWTD-UHFFFAOYSA-N 0.000 description 8
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