KR20140095067A - 전압-게이팅 나트륨 채널에서의 선택적 활성을 갖는 벤족사졸리논 화합물 - Google Patents

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Publication number

KR20140095067A

KR20140095067A KR1020147013911A KR20147013911A KR20140095067A KR 20140095067 A KR20140095067 A KR 20140095067A KR 1020147013911 A KR1020147013911 A KR 1020147013911A KR 20147013911 A KR20147013911 A KR 20147013911A KR 20140095067 A KR20140095067 A KR 20140095067A

Authority

KR

South Korea

Prior art keywords

sulfonamide

dihydro

oxo

thiadiazol

benzoxazole

Prior art date

2011-10-28

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.)

Withdrawn

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• 230000000694 effects Effects 0.000 title claims description 25
• ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical class C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 title claims description 8
• 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 title description 4
• 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 252
• 150000003839 salts Chemical class 0.000 claims abstract description 73
• 238000000034 method Methods 0.000 claims abstract description 44
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
• 208000004296 neuralgia Diseases 0.000 claims abstract description 15
• 208000021722 neuropathic pain Diseases 0.000 claims abstract description 14
• 208000035475 disorder Diseases 0.000 claims abstract description 9
• -1 alkylaryl Alkoxy Chemical group 0.000 claims description 374
• 229940124530 sulfonamide Drugs 0.000 claims description 146
• 125000000217 alkyl group Chemical group 0.000 claims description 122
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 115
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 90
• 125000003118 aryl group Chemical group 0.000 claims description 86
• 229910052799 carbon Inorganic materials 0.000 claims description 82
• 229910052736 halogen Inorganic materials 0.000 claims description 75
• 150000002367 halogens Chemical class 0.000 claims description 73
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 72
• 239000011734 sodium Substances 0.000 claims description 45
• 150000001721 carbon Chemical group 0.000 claims description 43
• 125000003545 alkoxy group Chemical group 0.000 claims description 41
• 125000004432 carbon atom Chemical group C* 0.000 claims description 35
• 229910052739 hydrogen Inorganic materials 0.000 claims description 35
• 125000001072 heteroaryl group Chemical group 0.000 claims description 32
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
• 125000004429 atom Chemical group 0.000 claims description 28
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 26
• 108010052164 Sodium Channels Proteins 0.000 claims description 26
• 102000018674 Sodium Channels Human genes 0.000 claims description 26
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 26
• 125000000623 heterocyclic group Chemical group 0.000 claims description 25
• 229910052757 nitrogen Inorganic materials 0.000 claims description 23
• 125000004516 1,2,4-thiadiazol-5-yl group Chemical group S1N=CN=C1* 0.000 claims description 22
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 22
• 125000006413 ring segment Chemical group 0.000 claims description 18
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
• 229910052717 sulfur Inorganic materials 0.000 claims description 17
• IEYWAMQEEJSGKK-UHFFFAOYSA-N 4-(thiadiazol-5-yl)-2,3-dihydro-1,3-benzoxazole-6-sulfonamide Chemical compound NS(=O)(=O)C1=CC2=C(NCO2)C(=C1)C1=CN=NS1 IEYWAMQEEJSGKK-UHFFFAOYSA-N 0.000 claims description 16
• 239000000460 chlorine Substances 0.000 claims description 16
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
• 125000005843 halogen group Chemical group 0.000 claims description 16
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
• 239000001257 hydrogen Substances 0.000 claims description 15
• 125000003342 alkenyl group Chemical group 0.000 claims description 14
• 238000011282 treatment Methods 0.000 claims description 14
• 125000004122 cyclic group Chemical group 0.000 claims description 13
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 13
• 125000003386 piperidinyl group Chemical group 0.000 claims description 13
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 11
• RLSSLKRGSUZGIB-UHFFFAOYSA-N 3-(1,3-thiazol-2-yl)-2H-1,3-benzoxazole-6-sulfonamide Chemical compound S1C(=NC=C1)N1COC2=C1C=CC(=C2)S(=O)(=O)N RLSSLKRGSUZGIB-UHFFFAOYSA-N 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• HZPJOYCUMMIWSJ-UHFFFAOYSA-N 2,3-dihydro-1,3-benzoxazole-6-sulfonamide 1,2,4-thiadiazole Chemical compound O1CNC2=C1C=C(C=C2)S(=O)(=O)N.S2N=CN=C2 HZPJOYCUMMIWSJ-UHFFFAOYSA-N 0.000 claims description 9
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 238000005859 coupling reaction Methods 0.000 claims description 8
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 8
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 8
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 8
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 7
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 7
• 230000008878 coupling Effects 0.000 claims description 7
• 238000010168 coupling process Methods 0.000 claims description 7
• YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 claims description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
• 229910052801 chlorine Inorganic materials 0.000 claims description 6
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 6
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 6
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
• RXRRMVXMEDFOIK-UHFFFAOYSA-N 2-oxo-n-(1,2,4-thiadiazol-5-yl)-3h-1,3-benzoxazole-6-sulfonamide Chemical compound C1=C2OC(=O)NC2=CC=C1S(=O)(=O)NC1=NC=NS1 RXRRMVXMEDFOIK-UHFFFAOYSA-N 0.000 claims description 5
• 125000002252 acyl group Chemical group 0.000 claims description 5
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 5
• 150000001412 amines Chemical class 0.000 claims description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 5
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
• YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 4
• GACNWTKCHJLFJU-UHFFFAOYSA-N 2-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1,3-benzoxazole-6-sulfonamide Chemical compound O1C2=CC(S(=O)(=O)N)=CC=C2NC1C1=NC=NS1 GACNWTKCHJLFJU-UHFFFAOYSA-N 0.000 claims description 4
• VGNXPEYAJVASMT-GFCCVEGCSA-N 2-oxo-3-[(1r)-1-phenylethyl]-n-(1,3-thiazol-2-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound C1([C@@H](C)N2C(OC3=CC(=CC=C32)S(=O)(=O)NC=2SC=CN=2)=O)=CC=CC=C1 VGNXPEYAJVASMT-GFCCVEGCSA-N 0.000 claims description 4
• HLHIGROOBCDZPJ-GFCCVEGCSA-N 3-[(1r)-1-isoquinolin-8-ylethyl]-2-oxo-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound C1=C2OC(=O)N([C@@H](C=3C4=CN=CC=C4C=CC=3)C)C2=CC=C1S(=O)(=O)NC1=NC=NS1 HLHIGROOBCDZPJ-GFCCVEGCSA-N 0.000 claims description 4
• OSOXNNWCUNIVCU-LLVKDONJSA-N 5-bromo-2-oxo-3-[(1r)-1-(1,2,3,4-tetrahydroisoquinolin-8-yl)ethyl]-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound C1=C2OC(=O)N([C@@H](C=3C=4CNCCC=4C=CC=3)C)C2=CC(Br)=C1S(=O)(=O)NC1=NC=NS1 OSOXNNWCUNIVCU-LLVKDONJSA-N 0.000 claims description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
• 125000004104 aryloxy group Chemical group 0.000 claims description 4
• 125000000524 functional group Chemical group 0.000 claims description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
• 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 3
• MYWZAJHQYKKYCH-UHFFFAOYSA-N 3-benzyl-5-fluoro-2-oxo-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound O=C1OC=2C=C(S(=O)(=O)NC=3SN=CN=3)C(F)=CC=2N1CC1=CC=CC=C1 MYWZAJHQYKKYCH-UHFFFAOYSA-N 0.000 claims description 3
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 3
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
• 125000004414 alkyl thio group Chemical group 0.000 claims description 3
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
• 125000005110 aryl thio group Chemical group 0.000 claims description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
• 125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 3
• 125000005368 heteroarylthio group Chemical group 0.000 claims description 3
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 2
• 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 2
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
• YHCUZRJTNSWYCY-UHFFFAOYSA-N 2,3,4,7-tetrahydro-1h-azepine Chemical compound C1CNCC=CC1 YHCUZRJTNSWYCY-UHFFFAOYSA-N 0.000 claims description 2
• VGNXPEYAJVASMT-UHFFFAOYSA-N 2-oxo-3-(1-phenylethyl)-n-(1,3-thiazol-2-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound C12=CC=C(S(=O)(=O)NC=3SC=CN=3)C=C2OC(=O)N1C(C)C1=CC=CC=C1 VGNXPEYAJVASMT-UHFFFAOYSA-N 0.000 claims description 2
• SOPCEYMWSZYBKO-UHFFFAOYSA-N 2-oxo-3-(1-phenylpropyl)-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound C12=CC=C(S(=O)(=O)NC=3SN=CN=3)C=C2OC(=O)N1C(CC)C1=CC=CC=C1 SOPCEYMWSZYBKO-UHFFFAOYSA-N 0.000 claims description 2
• 125000001847 2-phenylcyclopropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1([H])C([H])([H])C1([H])* 0.000 claims description 2
• SCYZBCAHDHMJSM-JTQLQIEISA-N 3-[(1s)-1-(2-iodophenyl)ethyl]-2-oxo-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound C1([C@H](C)N2C(OC3=CC(=CC=C32)S(=O)(=O)NC=2SN=CN=2)=O)=CC=CC=C1I SCYZBCAHDHMJSM-JTQLQIEISA-N 0.000 claims description 2
• OZXXFTCTSNMOGT-UHFFFAOYSA-N 3-benzhydryl-2-oxo-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound O=C1OC=2C=C(S(=O)(=O)NC=3SN=CN=3)C=CC=2N1C(C=1C=CC=CC=1)C1=CC=CC=C1 OZXXFTCTSNMOGT-UHFFFAOYSA-N 0.000 claims description 2
• XUNWLSIZOQCHMX-UHFFFAOYSA-N 4-(1,2,3,4-tetrahydronaphthalen-2-yl)morpholine Chemical compound C1COCCN1C1CC2=CC=CC=C2CC1 XUNWLSIZOQCHMX-UHFFFAOYSA-N 0.000 claims description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
• HZUDJNNEZVMPSO-UHFFFAOYSA-N 5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-3-[[7-(2,2,2-trifluoroethylamino)-5,6,7,8-tetrahydronaphthalen-1-yl]methyl]-1,3-benzoxazole-6-sulfonamide Chemical compound Fc1cc2n(Cc3cccc4CCC(Cc34)NCC(F)(F)F)c(=O)oc2cc1S(=O)(=O)Nc1ncns1 HZUDJNNEZVMPSO-UHFFFAOYSA-N 0.000 claims description 2
• ONJMZYVZWJUJRH-UHFFFAOYSA-N 5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-3H-1,3-benzoxazole-6-sulfonamide Chemical compound FC1=CC=2NC(=O)OC=2C=C1S(=O)(=O)NC1=NC=NS1 ONJMZYVZWJUJRH-UHFFFAOYSA-N 0.000 claims description 2
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 2
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
• 125000003435 aroyl group Chemical group 0.000 claims description 2
• 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 2
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
• 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
• RZZFOJKGQIYSBE-UHFFFAOYSA-N cyclopropyl carbamate Chemical compound NC(=O)OC1CC1 RZZFOJKGQIYSBE-UHFFFAOYSA-N 0.000 claims description 2
• LOCAIGRSOJUCTB-UHFFFAOYSA-N indazol-3-one Chemical compound C1=CC=C2C(=O)N=NC2=C1 LOCAIGRSOJUCTB-UHFFFAOYSA-N 0.000 claims description 2
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 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 description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 2
• SITJYVQPZVJMQR-UHFFFAOYSA-N 2h-1,3-benzoxazole-3-carboxamide Chemical class C1=CC=C2N(C(=O)N)COC2=C1 SITJYVQPZVJMQR-UHFFFAOYSA-N 0.000 claims 2
• UWQNWXMVIFOIBT-UHFFFAOYSA-N 2-oxo-3-(1-phenylethyl)-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound C12=CC=C(S(=O)(=O)NC=3SN=CN=3)C=C2OC(=O)N1C(C)C1=CC=CC=C1 UWQNWXMVIFOIBT-UHFFFAOYSA-N 0.000 claims 1
• FOHGHYYKTOULOL-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-2-oxo-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound ClC1=CC=CC=C1CN1C(=O)OC2=CC(S(=O)(=O)NC=3SN=CN=3)=CC=C21 FOHGHYYKTOULOL-UHFFFAOYSA-N 0.000 claims 1
• WWIBYNJIUUFFEX-UHFFFAOYSA-N 3-[(3-chlorophenyl)methyl]-2-oxo-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound ClC1=CC=CC(CN2C(OC3=CC(=CC=C32)S(=O)(=O)NC=2SN=CN=2)=O)=C1 WWIBYNJIUUFFEX-UHFFFAOYSA-N 0.000 claims 1
• QZZRWMKVMGKCBZ-UHFFFAOYSA-N 3-[(4-chlorophenyl)methyl]-2-oxo-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound C1=CC(Cl)=CC=C1CN1C(=O)OC2=CC(S(=O)(=O)NC=3SN=CN=3)=CC=C21 QZZRWMKVMGKCBZ-UHFFFAOYSA-N 0.000 claims 1
• IPVXYZBOUDDZMD-KRWDZBQOSA-N 3-[[(7s)-7-(1,1-dioxo-1,4-thiazinan-4-yl)-5,6,7,8-tetrahydronaphthalen-1-yl]methyl]-5-fluoro-2-oxo-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound N1([C@H]2CCC=3C=CC=C(C=3C2)CN2C=3C=C(C(=CC=3OC2=O)S(=O)(=O)NC=2SN=CN=2)F)CCS(=O)(=O)CC1 IPVXYZBOUDDZMD-KRWDZBQOSA-N 0.000 claims 1
• PSIPRNWCGIUIOK-UHFFFAOYSA-N 3-[cyclopropyl(phenyl)methyl]-2-oxo-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound O=C1OC=2C=C(S(=O)(=O)NC=3SN=CN=3)C=CC=2N1C(C=1C=CC=CC=1)C1CC1 PSIPRNWCGIUIOK-UHFFFAOYSA-N 0.000 claims 1
• HMJMQGPOPAKICS-UHFFFAOYSA-N 3-benzyl-2-oxo-n-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide Chemical compound O=C1OC=2C=C(S(=O)(=O)NC=3SN=CN=3)C=CC=2N1CC1=CC=CC=C1 HMJMQGPOPAKICS-UHFFFAOYSA-N 0.000 claims 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
• 125000005122 aminoalkylamino group Chemical group 0.000 claims 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims 1
• 210000002569 neuron Anatomy 0.000 abstract description 5
• 230000000903 blocking effect Effects 0.000 abstract description 3
• 230000002889 sympathetic effect Effects 0.000 abstract description 3
• 102000004310 Ion Channels Human genes 0.000 abstract 1
• 230000002093 peripheral effect Effects 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 252
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• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 146
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
• 235000019439 ethyl acetate Nutrition 0.000 description 124
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• 239000000243 solution Substances 0.000 description 120
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• 238000003756 stirring Methods 0.000 description 64
• 238000000746 purification Methods 0.000 description 58
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• 125000001424 substituent group Chemical group 0.000 description 48
• 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 48
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• 239000000758 substrate Substances 0.000 description 35
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
• 229910052938 sodium sulfate Inorganic materials 0.000 description 34
• 235000011152 sodium sulphate Nutrition 0.000 description 34
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 31
• 239000012267 brine Substances 0.000 description 30
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
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