JP5514804B2 - ドーパミン神経伝達のモジュレーター - Google Patents

Info

Publication number

JP5514804B2

JP5514804B2 JP2011506689A JP2011506689A JP5514804B2 JP 5514804 B2 JP5514804 B2 JP 5514804B2 JP 2011506689 A JP2011506689 A JP 2011506689A JP 2011506689 A JP2011506689 A JP 2011506689A JP 5514804 B2 JP5514804 B2 JP 5514804B2

Authority

JP

Japan

Prior art keywords

dihydro

methyl

methylsulfonyl

benzodioxin

amine

Prior art date

2008-04-29

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.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• Discuss

• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 title description 43
• 229960003638 dopamine Drugs 0.000 title description 21
• 230000005062 synaptic transmission Effects 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims description 184
• 239000000203 mixture Substances 0.000 claims description 96
• -1 3,3,3-trifluoropropyl Chemical group 0.000 claims description 46
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 46
• 150000003839 salts Chemical class 0.000 claims description 43
• 150000001204 N-oxides Chemical class 0.000 claims description 34
• 229910052757 nitrogen Inorganic materials 0.000 claims description 27
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
• 229910052739 hydrogen Inorganic materials 0.000 claims description 19
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• 208000035475 disorder Diseases 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 15
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 14
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 8
• 208000020016 psychiatric disease Diseases 0.000 claims description 7
• 201000000980 schizophrenia Diseases 0.000 claims description 7
• NFLCJVNIHXOFPL-VIFPVBQESA-N n-[[(2s)-5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCCC)COC2=C1F NFLCJVNIHXOFPL-VIFPVBQESA-N 0.000 claims description 6
• 210000003169 central nervous system Anatomy 0.000 claims description 5
• 208000012661 Dyskinesia Diseases 0.000 claims description 4
• 208000004547 Hallucinations Diseases 0.000 claims description 4
• 208000010877 cognitive disease Diseases 0.000 claims description 4
• 230000010249 dopaminergic function Effects 0.000 claims description 4
• CYBYLIMSZIVQTB-QMMMGPOBSA-N n-[[(2s)-5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCC)COC2=C1F CYBYLIMSZIVQTB-QMMMGPOBSA-N 0.000 claims description 4
• MAMVDUBLWPVXIQ-JTQLQIEISA-N n-[[(3s)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCCC)COC2=C1 MAMVDUBLWPVXIQ-JTQLQIEISA-N 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• CCAIFRVSMWLNEE-UHFFFAOYSA-N 1-(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)-n-methylmethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNC)COC2=C1F CCAIFRVSMWLNEE-UHFFFAOYSA-N 0.000 claims description 3
• PEOWPJFIOSDEAU-QMMMGPOBSA-N 1-[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]-n,n-dimethylmethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CN(C)C)COC2=C1Cl PEOWPJFIOSDEAU-QMMMGPOBSA-N 0.000 claims description 3
• RZUBLNVSYWTUNT-ZETCQYMHSA-N 1-[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]-n-methylmethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNC)COC2=C1Cl RZUBLNVSYWTUNT-ZETCQYMHSA-N 0.000 claims description 3
• CCAIFRVSMWLNEE-ZETCQYMHSA-N 1-[(2s)-5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]-n-methylmethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNC)COC2=C1F CCAIFRVSMWLNEE-ZETCQYMHSA-N 0.000 claims description 3
• OGXFHSKZILWLNO-NSHDSACASA-N 2,2-dimethyl-n-[[(3s)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCC(C)(C)C)COC2=C1 OGXFHSKZILWLNO-NSHDSACASA-N 0.000 claims description 3
• CGUICIFMMKFYRR-UHFFFAOYSA-N 2-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methylamino]ethanol Chemical compound O1CC(CNCCO)OC2=CC(S(=O)(=O)C)=CC(F)=C21 CGUICIFMMKFYRR-UHFFFAOYSA-N 0.000 claims description 3
• AYRSCENJQDTKKW-UHFFFAOYSA-N 2-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methylamino]ethanol Chemical compound O1CC(CNCCO)OC2=CC(S(=O)(=O)C)=CC=C21 AYRSCENJQDTKKW-UHFFFAOYSA-N 0.000 claims description 3
• QTSMGAUELLRMTQ-QMMMGPOBSA-N 2-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methylamino]ethanol Chemical compound O1C[C@H](CNCCO)OC2=CC(S(=O)(=O)C)=CC(Cl)=C21 QTSMGAUELLRMTQ-QMMMGPOBSA-N 0.000 claims description 3
• PZGIGAYLGVNPAM-UHFFFAOYSA-N 2-methoxy-n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCCOC)COC2=C1 PZGIGAYLGVNPAM-UHFFFAOYSA-N 0.000 claims description 3
• XZLUXENLKSWQTA-UHFFFAOYSA-N 2-methyl-n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCC(C)C)COC2=C1 XZLUXENLKSWQTA-UHFFFAOYSA-N 0.000 claims description 3
• XZLUXENLKSWQTA-LLVKDONJSA-N 2-methyl-n-[[(3r)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@H](CNCC(C)C)COC2=C1 XZLUXENLKSWQTA-LLVKDONJSA-N 0.000 claims description 3
• XZLUXENLKSWQTA-NSHDSACASA-N 2-methyl-n-[[(3s)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCC(C)C)COC2=C1 XZLUXENLKSWQTA-NSHDSACASA-N 0.000 claims description 3
• ICGHWPFOUQWXGY-QMMMGPOBSA-N 3,3,3-trifluoro-n-[[(2s)-5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]propan-1-amine Chemical compound O1C[C@H](CNCCC(F)(F)F)OC2=CC(S(=O)(=O)C)=CC(F)=C21 ICGHWPFOUQWXGY-QMMMGPOBSA-N 0.000 claims description 3
• YNQIUDXOEYHCHG-VIFPVBQESA-N 3,3,3-trifluoro-n-[[(3s)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]propan-1-amine Chemical compound O1C[C@H](CNCCC(F)(F)F)OC2=CC(S(=O)(=O)C)=CC=C21 YNQIUDXOEYHCHG-VIFPVBQESA-N 0.000 claims description 3
• 208000024827 Alzheimer disease Diseases 0.000 claims description 3
• 208000020925 Bipolar disease Diseases 0.000 claims description 3
• 206010020852 Hypertonia Diseases 0.000 claims description 3
• 208000002193 Pain Diseases 0.000 claims description 3
• 208000018737 Parkinson disease Diseases 0.000 claims description 3
• 230000000642 iatrogenic effect Effects 0.000 claims description 3
• IWCVJTWXFIQFKV-UHFFFAOYSA-N n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-2-methoxyethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCCOC)COC2=C1F IWCVJTWXFIQFKV-UHFFFAOYSA-N 0.000 claims description 3
• JMVMQHJFSAOHCU-UHFFFAOYSA-N n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-2-methylpropan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCC(C)C)COC2=C1F JMVMQHJFSAOHCU-UHFFFAOYSA-N 0.000 claims description 3
• KRJUEVQPCIMMHI-UHFFFAOYSA-N n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-n-methylethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(C)CC)COC2=C1F KRJUEVQPCIMMHI-UHFFFAOYSA-N 0.000 claims description 3
• COZAOGJDNDUOHZ-UHFFFAOYSA-N n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-n-methylpropan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(C)CCC)COC2=C1F COZAOGJDNDUOHZ-UHFFFAOYSA-N 0.000 claims description 3
• HGYAEVSVNVKZRE-UHFFFAOYSA-N n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-n-propylpropan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(CCC)CCC)COC2=C1F HGYAEVSVNVKZRE-UHFFFAOYSA-N 0.000 claims description 3
• IZLXMGUNKCDTRS-UHFFFAOYSA-N n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]butan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCCCC)COC2=C1F IZLXMGUNKCDTRS-UHFFFAOYSA-N 0.000 claims description 3
• CYBYLIMSZIVQTB-UHFFFAOYSA-N n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCC)COC2=C1F CYBYLIMSZIVQTB-UHFFFAOYSA-N 0.000 claims description 3
• SVQXADAXWJUALF-UHFFFAOYSA-N n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]propan-2-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNC(C)C)COC2=C1F SVQXADAXWJUALF-UHFFFAOYSA-N 0.000 claims description 3
• WQSMDWKWHVKCSV-UHFFFAOYSA-N n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]-n-propylpropan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(CCC)CCC)COC2=C1 WQSMDWKWHVKCSV-UHFFFAOYSA-N 0.000 claims description 3
• QYNCLOCTEVTRJW-UHFFFAOYSA-N n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]butan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCCCC)COC2=C1 QYNCLOCTEVTRJW-UHFFFAOYSA-N 0.000 claims description 3
• XMHPZKPXIAVGLB-UHFFFAOYSA-N n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCC)COC2=C1 XMHPZKPXIAVGLB-UHFFFAOYSA-N 0.000 claims description 3
• KXLHMDZOCIYVOU-UHFFFAOYSA-N n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]prop-2-en-1-amine Chemical compound O1CC(CNCC=C)OC2=CC(S(=O)(=O)C)=CC=C21 KXLHMDZOCIYVOU-UHFFFAOYSA-N 0.000 claims description 3
• MAMVDUBLWPVXIQ-UHFFFAOYSA-N n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCCC)COC2=C1 MAMVDUBLWPVXIQ-UHFFFAOYSA-N 0.000 claims description 3
• AUAAOFMSOHILNS-UHFFFAOYSA-N n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]propan-2-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNC(C)C)COC2=C1 AUAAOFMSOHILNS-UHFFFAOYSA-N 0.000 claims description 3
• VHIGPNQUCBEFFA-VIFPVBQESA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-2-methoxyethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCCOC)COC2=C1Cl VHIGPNQUCBEFFA-VIFPVBQESA-N 0.000 claims description 3
• WVGMRJOHWGRXDB-JTQLQIEISA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-2-methylpropan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCC(C)C)COC2=C1Cl WVGMRJOHWGRXDB-JTQLQIEISA-N 0.000 claims description 3
• KYUKFUXUFQAWEO-JTQLQIEISA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-n-ethylethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CN(CC)CC)COC2=C1Cl KYUKFUXUFQAWEO-JTQLQIEISA-N 0.000 claims description 3
• OSKPEFIPFULJMA-NSHDSACASA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-n-ethylpropan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CN(CC)CCC)COC2=C1Cl OSKPEFIPFULJMA-NSHDSACASA-N 0.000 claims description 3
• NEYQEXHISQFWSO-VIFPVBQESA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-n-methylethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CN(C)CC)COC2=C1Cl NEYQEXHISQFWSO-VIFPVBQESA-N 0.000 claims description 3
• ZZZDEINEZALERV-JTQLQIEISA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-n-methylpropan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CN(C)CCC)COC2=C1Cl ZZZDEINEZALERV-JTQLQIEISA-N 0.000 claims description 3
• DXONWYZCKWNSQB-LBPRGKRZSA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-n-propylpropan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CN(CCC)CCC)COC2=C1Cl DXONWYZCKWNSQB-LBPRGKRZSA-N 0.000 claims description 3
• PWLZAFAPSSRHLY-JTQLQIEISA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]butan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCCCC)COC2=C1Cl PWLZAFAPSSRHLY-JTQLQIEISA-N 0.000 claims description 3
• AJMTVCBEYFDENY-QMMMGPOBSA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCC)COC2=C1Cl AJMTVCBEYFDENY-QMMMGPOBSA-N 0.000 claims description 3
• QSPLWPQCFSOAHQ-VIFPVBQESA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]prop-2-en-1-amine Chemical compound O1C[C@H](CNCC=C)OC2=CC(S(=O)(=O)C)=CC(Cl)=C21 QSPLWPQCFSOAHQ-VIFPVBQESA-N 0.000 claims description 3
• NGWLBYMNHLEBMB-VIFPVBQESA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCCC)COC2=C1Cl NGWLBYMNHLEBMB-VIFPVBQESA-N 0.000 claims description 3
• DENNJTQQOMENLP-VIFPVBQESA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]propan-2-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNC(C)C)COC2=C1Cl DENNJTQQOMENLP-VIFPVBQESA-N 0.000 claims description 3
• MAMVDUBLWPVXIQ-SNVBAGLBSA-N n-[[(3r)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@H](CNCCC)COC2=C1 MAMVDUBLWPVXIQ-SNVBAGLBSA-N 0.000 claims description 3
• NCEOXFQEEQSDNM-QMMMGPOBSA-N n-[[(3s)-5-fluoro-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C(F)=C2O[C@@H](CNCC)COC2=C1 NCEOXFQEEQSDNM-QMMMGPOBSA-N 0.000 claims description 3
• DWDCNTGCXVPWSD-QMMMGPOBSA-N n-[[(3s)-6-(trifluoromethylsulfonyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]ethanamine Chemical compound C1=C(S(=O)(=O)C(F)(F)F)C=C2O[C@@H](CNCC)COC2=C1 DWDCNTGCXVPWSD-QMMMGPOBSA-N 0.000 claims description 3
• KHWNHRMQYUBIMK-VIFPVBQESA-N n-[[(3s)-6-(trifluoromethylsulfonyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]propan-1-amine Chemical compound C1=C(S(=O)(=O)C(F)(F)F)C=C2O[C@@H](CNCCC)COC2=C1 KHWNHRMQYUBIMK-VIFPVBQESA-N 0.000 claims description 3
• XMHPZKPXIAVGLB-VIFPVBQESA-N n-[[(3s)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCC)COC2=C1 XMHPZKPXIAVGLB-VIFPVBQESA-N 0.000 claims description 3
• JIUTZSUQHJMGKF-UHFFFAOYSA-N n-ethyl-n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(CC)CC)COC2=C1F JIUTZSUQHJMGKF-UHFFFAOYSA-N 0.000 claims description 3
• KFYTWRPWAHGQKM-UHFFFAOYSA-N n-ethyl-n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(CC)CCC)COC2=C1F KFYTWRPWAHGQKM-UHFFFAOYSA-N 0.000 claims description 3
• HXMHPIGFBKHTLF-UHFFFAOYSA-N n-ethyl-n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(CC)CC)COC2=C1 HXMHPIGFBKHTLF-UHFFFAOYSA-N 0.000 claims description 3
• WSUXMRJVCYPXQL-UHFFFAOYSA-N n-methyl-1-(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNC)COC2=C1 WSUXMRJVCYPXQL-UHFFFAOYSA-N 0.000 claims description 3
• WSUXMRJVCYPXQL-QMMMGPOBSA-N n-methyl-1-[(3s)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methanamine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNC)COC2=C1 WSUXMRJVCYPXQL-QMMMGPOBSA-N 0.000 claims description 3
• VKHIPSWUAQBLPH-UHFFFAOYSA-N n-methyl-n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(C)CC)COC2=C1 VKHIPSWUAQBLPH-UHFFFAOYSA-N 0.000 claims description 3
• XSKZKXSGWYQLOS-UHFFFAOYSA-N n-methyl-n-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(C)CCC)COC2=C1 XSKZKXSGWYQLOS-UHFFFAOYSA-N 0.000 claims description 3
• 230000036407 pain Effects 0.000 claims description 3
• 208000019901 Anxiety disease Diseases 0.000 claims description 2
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 2
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 2
• 206010012289 Dementia Diseases 0.000 claims description 2
• 206010013654 Drug abuse Diseases 0.000 claims description 2
• 208000014094 Dystonic disease Diseases 0.000 claims description 2
• 208000030814 Eating disease Diseases 0.000 claims description 2
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 2
• 206010019233 Headaches Diseases 0.000 claims description 2
• 208000023105 Huntington disease Diseases 0.000 claims description 2
• WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 2
• WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 2
• 241000124008 Mammalia Species 0.000 claims description 2
• 208000019022 Mood disease Diseases 0.000 claims description 2
• 208000008589 Obesity Diseases 0.000 claims description 2
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 2
• 208000027089 Parkinsonian disease Diseases 0.000 claims description 2
• 206010034010 Parkinsonism Diseases 0.000 claims description 2
• 206010044565 Tremor Diseases 0.000 claims description 2
• 208000029560 autism spectrum disease Diseases 0.000 claims description 2
• 206010008129 cerebral palsy Diseases 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 235000014632 disordered eating Nutrition 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 208000010118 dystonia Diseases 0.000 claims description 2
• 231100000869 headache Toxicity 0.000 claims description 2
• VPONXHJUNCZNLJ-UHFFFAOYSA-N n-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]prop-2-en-1-amine Chemical compound O1CC(CNCC=C)OC2=CC(S(=O)(=O)C)=CC(F)=C21 VPONXHJUNCZNLJ-UHFFFAOYSA-N 0.000 claims description 2
• VLRJTIYKLYDRSN-JTQLQIEISA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-2,2-dimethylpropan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2O[C@@H](CNCC(C)(C)C)COC2=C1Cl VLRJTIYKLYDRSN-JTQLQIEISA-N 0.000 claims description 2
• MNWSMMIMVHLCNW-VIFPVBQESA-N n-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-3-fluoropropan-1-amine Chemical compound O1C[C@H](CNCCCF)OC2=CC(S(=O)(=O)C)=CC(Cl)=C21 MNWSMMIMVHLCNW-VIFPVBQESA-N 0.000 claims description 2
• XENWRVWPGWCBES-VIFPVBQESA-N n-[[(3s)-6-(trifluoromethylsulfonyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]propan-2-amine Chemical compound C1=C(S(=O)(=O)C(F)(F)F)C=C2O[C@@H](CNC(C)C)COC2=C1 XENWRVWPGWCBES-VIFPVBQESA-N 0.000 claims description 2
• 235000020824 obesity Nutrition 0.000 claims description 2
• 208000012201 sexual and gender identity disease Diseases 0.000 claims description 2
• 208000015891 sexual disease Diseases 0.000 claims description 2
• 208000019116 sleep disease Diseases 0.000 claims description 2
• 208000011117 substance-related disease Diseases 0.000 claims description 2
• 208000011580 syndromic disease Diseases 0.000 claims description 2
• 208000029726 Neurodevelopmental disease Diseases 0.000 claims 1
• 230000006735 deficit Effects 0.000 claims 1
• 208000015122 neurodegenerative disease Diseases 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 347
• 238000002360 preparation method Methods 0.000 description 108
• 150000001412 amines Chemical class 0.000 description 44
• 238000003818 flash chromatography Methods 0.000 description 43
• 239000011734 sodium Substances 0.000 description 41
• 239000000243 solution Substances 0.000 description 41
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 34
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 34
• 239000012074 organic phase Substances 0.000 description 33
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
• NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 30
• JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 30
• VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 28
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
• 241000700159 Rattus Species 0.000 description 25
• 239000012267 brine Substances 0.000 description 24
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
• 230000005855 radiation Effects 0.000 description 23
• 238000000034 method Methods 0.000 description 22
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 21
• 230000000694 effects Effects 0.000 description 21
• CFFZDZCDUFSOFZ-UHFFFAOYSA-N 3,4-Dihydroxy-phenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C(O)=C1 CFFZDZCDUFSOFZ-UHFFFAOYSA-N 0.000 description 20
• 125000004433 nitrogen atom Chemical group N* 0.000 description 20
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 18
• KDGCEARGZKBUBI-GFCCVEGCSA-N [(2r)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1OC2=CC(S(C)(=O)=O)=CC(Cl)=C2OC1 KDGCEARGZKBUBI-GFCCVEGCSA-N 0.000 description 18
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 18
• 238000000746 purification Methods 0.000 description 17
• 238000012360 testing method Methods 0.000 description 17
• 239000012071 phase Substances 0.000 description 16
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• WBEFMISIPKWNPE-UHFFFAOYSA-N (5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1OC2=CC(S(C)(=O)=O)=CC(F)=C2OC1 WBEFMISIPKWNPE-UHFFFAOYSA-N 0.000 description 14
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 14
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
• 238000002474 experimental method Methods 0.000 description 14
• 239000000523 sample Substances 0.000 description 14
• DPXPSYDMCQULPQ-UHFFFAOYSA-N (7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1OC2=CC(S(C)(=O)=O)=CC=C2CC1 DPXPSYDMCQULPQ-UHFFFAOYSA-N 0.000 description 13
• 230000003291 dopaminomimetic effect Effects 0.000 description 13
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 12
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 12
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 12
• 210000004556 brain Anatomy 0.000 description 12
• 239000008194 pharmaceutical composition Substances 0.000 description 12
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 11
• 239000002253 acid Substances 0.000 description 11
• KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 10
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 10
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 9
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• 241001465754 Metazoa Species 0.000 description 9
• 230000003542 behavioural effect Effects 0.000 description 9
• 238000001727 in vivo Methods 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 8
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 8
• DUUGKQCEGZLZNO-UHFFFAOYSA-N 5-hydroxyindoleacetic acid Chemical compound C1=C(O)C=C2C(CC(=O)O)=CNC2=C1 DUUGKQCEGZLZNO-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 125000000623 heterocyclic group Chemical group 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 239000003381 stabilizer Substances 0.000 description 8
• 239000013543 active substance Substances 0.000 description 7
• 239000008346 aqueous phase Substances 0.000 description 7
• 239000000872 buffer Substances 0.000 description 7
• 229940079593 drug Drugs 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• QRMZSPFSDQBLIX-UHFFFAOYSA-N homovanillic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1O QRMZSPFSDQBLIX-UHFFFAOYSA-N 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 7
• 238000010992 reflux Methods 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• PFVPWLLPFSBVBC-UHFFFAOYSA-N (6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1OC2=CC(S(C)(=O)=O)=CC=C2OC1 PFVPWLLPFSBVBC-UHFFFAOYSA-N 0.000 description 6
• VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 6
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 6
• 229930182821 L-proline Natural products 0.000 description 6
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 238000001514 detection method Methods 0.000 description 6
• LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 239000008101 lactose Substances 0.000 description 6
• GVWISOJSERXQBM-UHFFFAOYSA-N n-methylpropan-1-amine Chemical compound CCCNC GVWISOJSERXQBM-UHFFFAOYSA-N 0.000 description 6
• 230000010412 perfusion Effects 0.000 description 6
• 229960002429 proline Drugs 0.000 description 6
• LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 6
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
• 229920002261 Corn starch Polymers 0.000 description 5
• NOQXXYIGRPAZJC-SECBINFHSA-N [(2r)-oxiran-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1OC1 NOQXXYIGRPAZJC-SECBINFHSA-N 0.000 description 5
• PFVPWLLPFSBVBC-CYBMUJFWSA-N [(3r)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1OC2=CC(S(C)(=O)=O)=CC=C2OC1 PFVPWLLPFSBVBC-CYBMUJFWSA-N 0.000 description 5
• 229940025084 amphetamine Drugs 0.000 description 5
• 239000008120 corn starch Substances 0.000 description 5
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 5
• 210000004185 liver Anatomy 0.000 description 5
• 210000001853 liver microsome Anatomy 0.000 description 5
• 125000004430 oxygen atom Chemical group O* 0.000 description 5
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• 230000000144 pharmacologic effect Effects 0.000 description 5
• 239000007787 solid Substances 0.000 description 5
• 239000007921 spray Substances 0.000 description 5
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 5
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
• DIVQKHQLANKJQO-UHFFFAOYSA-N 3-methoxytyramine Chemical compound COC1=CC(CCN)=CC=C1O DIVQKHQLANKJQO-UHFFFAOYSA-N 0.000 description 4
• RVWZUOPFHTYIEO-UHFFFAOYSA-N 5-hydroxyindoleacetic acid Natural products C1=C(O)C=C2C(C(=O)O)=CNC2=C1 RVWZUOPFHTYIEO-UHFFFAOYSA-N 0.000 description 4
• 239000003310 5-hydroxyindoleacetic acid Substances 0.000 description 4
• 125000004070 6 membered heterocyclic group Chemical group 0.000 description 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• 108010010803 Gelatin Proteins 0.000 description 4
• WBEFMISIPKWNPE-GFCCVEGCSA-N [(2r)-5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1OC2=CC(S(C)(=O)=O)=CC(F)=C2OC1 WBEFMISIPKWNPE-GFCCVEGCSA-N 0.000 description 4
• PFVPWLLPFSBVBC-ZDUSSCGKSA-N [(3s)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@H]1OC2=CC(S(C)(=O)=O)=CC=C2OC1 PFVPWLLPFSBVBC-ZDUSSCGKSA-N 0.000 description 4
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 238000000502 dialysis Methods 0.000 description 4
• 238000001704 evaporation Methods 0.000 description 4
• 230000008020 evaporation Effects 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• 239000007789 gas Substances 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 239000008273 gelatin Substances 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• 235000011852 gelatine desserts Nutrition 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 235000019359 magnesium stearate Nutrition 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 229960002748 norepinephrine Drugs 0.000 description 4
• SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 4
• 230000003287 optical effect Effects 0.000 description 4
• DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 4
• 229960002695 phenobarbital Drugs 0.000 description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 108020003175 receptors Proteins 0.000 description 4
• 102000005962 receptors Human genes 0.000 description 4
• 230000002441 reversible effect Effects 0.000 description 4
• 239000000377 silicon dioxide Substances 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 230000007306 turnover Effects 0.000 description 4
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
• 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 description 3
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 3
• HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 229920002785 Croscarmellose sodium Polymers 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
• PPQNQXQZIWHJRB-UHFFFAOYSA-N Methylcholanthrene Chemical compound C1=CC=C2C3=CC4=CC=C(C)C(CC5)=C4C5=C3C=CC2=C1 PPQNQXQZIWHJRB-UHFFFAOYSA-N 0.000 description 3
• 208000012902 Nervous system disease Diseases 0.000 description 3
• 208000025966 Neurological disease Diseases 0.000 description 3
• 241001327647 Oncorhynchus mykiss gairdneri Species 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• MLGNSKURLVNJRX-GFCCVEGCSA-N [(3r)-6-(trifluoromethylsulfonyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1OC2=CC(S(=O)(=O)C(F)(F)F)=CC=C2OC1 MLGNSKURLVNJRX-GFCCVEGCSA-N 0.000 description 3
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 239000000164 antipsychotic agent Substances 0.000 description 3
• 229940005529 antipsychotics Drugs 0.000 description 3
• 230000006399 behavior Effects 0.000 description 3
• BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical class C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 3
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 3
• 238000004364 calculation method Methods 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 208000015114 central nervous system disease Diseases 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 229960001681 croscarmellose sodium Drugs 0.000 description 3
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
• 229960000632 dexamfetamine Drugs 0.000 description 3
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
• 125000004311 dioxin-2-yl group Chemical group [H]C1=C([H])OC(*)=C([H])O1 0.000 description 3
• WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 3
• 235000013305 food Nutrition 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 239000000543 intermediate Substances 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
• 210000005171 mammalian brain Anatomy 0.000 description 3
• 230000004060 metabolic process Effects 0.000 description 3
• 238000001690 micro-dialysis Methods 0.000 description 3
• XCVNDBIXFPGMIW-UHFFFAOYSA-N n-ethylpropan-1-amine Chemical compound CCCNCC XCVNDBIXFPGMIW-UHFFFAOYSA-N 0.000 description 3
• 210000001577 neostriatum Anatomy 0.000 description 3
• 230000000926 neurological effect Effects 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 239000000825 pharmaceutical preparation Substances 0.000 description 3
• 239000000651 prodrug Substances 0.000 description 3
• 229940002612 prodrug Drugs 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• RWPCQJOZQXSJGQ-UHFFFAOYSA-N (4-bromo-2-chlorophenyl) acetate Chemical compound CC(=O)OC1=CC=C(Br)C=C1Cl RWPCQJOZQXSJGQ-UHFFFAOYSA-N 0.000 description 2
• UKOKLZNUIOTMJU-UHFFFAOYSA-N (4-bromo-2-fluorophenyl) acetate Chemical compound CC(=O)OC1=CC=C(Br)C=C1F UKOKLZNUIOTMJU-UHFFFAOYSA-N 0.000 description 2
• NBDDFAKYVVDWPU-UHFFFAOYSA-N 1-(5-bromo-3-fluoro-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(Br)=CC(F)=C1O NBDDFAKYVVDWPU-UHFFFAOYSA-N 0.000 description 2
• ACSYJWICJIGNLM-UHFFFAOYSA-N 1-(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)-n,n-dimethylmethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(C)C)COC2=C1F ACSYJWICJIGNLM-UHFFFAOYSA-N 0.000 description 2
• NUIPPHWBYVORHW-UHFFFAOYSA-N 1-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]azetidine Chemical compound O1C2=CC(S(=O)(=O)C)=CC(F)=C2OCC1CN1CCC1 NUIPPHWBYVORHW-UHFFFAOYSA-N 0.000 description 2
• NWDJQBPQRBURCK-UHFFFAOYSA-N 1-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]pyrrolidine Chemical compound O1C2=CC(S(=O)(=O)C)=CC(F)=C2OCC1CN1CCCC1 NWDJQBPQRBURCK-UHFFFAOYSA-N 0.000 description 2
• VWZYPYQIYSAIMK-UHFFFAOYSA-N 1-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]azetidine Chemical compound O1C2=CC(S(=O)(=O)C)=CC=C2OCC1CN1CCC1 VWZYPYQIYSAIMK-UHFFFAOYSA-N 0.000 description 2
• YMYCYPLFBJAPSA-UHFFFAOYSA-N 1-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]piperidine Chemical compound O1C2=CC(S(=O)(=O)C)=CC=C2OCC1CN1CCCCC1 YMYCYPLFBJAPSA-UHFFFAOYSA-N 0.000 description 2
• MZCVJTWBVVJSPU-UHFFFAOYSA-N 1-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]pyrrolidine Chemical compound O1C2=CC(S(=O)(=O)C)=CC=C2OCC1CN1CCCC1 MZCVJTWBVVJSPU-UHFFFAOYSA-N 0.000 description 2
• MDPRCZLYVCMHCH-UHFFFAOYSA-N 1-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]azetidine Chemical compound O1C2=CC(S(=O)(=O)C)=CC=C2CCC1CN1CCC1 MDPRCZLYVCMHCH-UHFFFAOYSA-N 0.000 description 2
• DRKJABUWGLAFKY-UHFFFAOYSA-N 1-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]piperidine Chemical compound O1C2=CC(S(=O)(=O)C)=CC=C2CCC1CN1CCCCC1 DRKJABUWGLAFKY-UHFFFAOYSA-N 0.000 description 2
• PQZPJSJBBOGKFA-UHFFFAOYSA-N 1-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]pyrrolidine Chemical compound O1C2=CC(S(=O)(=O)C)=CC=C2CCC1CN1CCCC1 PQZPJSJBBOGKFA-UHFFFAOYSA-N 0.000 description 2
• UPPBQQQGJDYDAE-VIFPVBQESA-N 1-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]azetidine Chemical compound C([C@H]1COC2=C(Cl)C=C(C=C2O1)S(=O)(=O)C)N1CCC1 UPPBQQQGJDYDAE-VIFPVBQESA-N 0.000 description 2
• KMNLDFWCAPNJMO-NSHDSACASA-N 1-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]piperidine Chemical compound C([C@H]1COC2=C(Cl)C=C(C=C2O1)S(=O)(=O)C)N1CCCCC1 KMNLDFWCAPNJMO-NSHDSACASA-N 0.000 description 2
• JZQRHSKASKRFLH-JTQLQIEISA-N 1-[[(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]pyrrolidine Chemical compound C([C@H]1COC2=C(Cl)C=C(C=C2O1)S(=O)(=O)C)N1CCCC1 JZQRHSKASKRFLH-JTQLQIEISA-N 0.000 description 2
• YMYCYPLFBJAPSA-GFCCVEGCSA-N 1-[[(3r)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]piperidine Chemical compound C([C@@H]1COC2=CC=C(C=C2O1)S(=O)(=O)C)N1CCCCC1 YMYCYPLFBJAPSA-GFCCVEGCSA-N 0.000 description 2
• YMYCYPLFBJAPSA-LBPRGKRZSA-N 1-[[(3s)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]piperidine Chemical compound C([C@H]1COC2=CC=C(C=C2O1)S(=O)(=O)C)N1CCCCC1 YMYCYPLFBJAPSA-LBPRGKRZSA-N 0.000 description 2
• RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-Tetramethylpiperidine Substances CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 2
• XDIAMRVROCPPBK-UHFFFAOYSA-N 2,2-dimethylpropan-1-amine Chemical compound CC(C)(C)CN XDIAMRVROCPPBK-UHFFFAOYSA-N 0.000 description 2
• JHNURUNMNRSGRO-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-3-ylmethanamine Chemical class C1=CC=C2OC(CN)COC2=C1 JHNURUNMNRSGRO-UHFFFAOYSA-N 0.000 description 2
• UFXCPZGYIFTGBV-UHFFFAOYSA-N 2-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methylamino]ethanol Chemical compound C1CC(CNCCO)OC2=CC(S(=O)(=O)C)=CC=C21 UFXCPZGYIFTGBV-UHFFFAOYSA-N 0.000 description 2
• DTYYIKTYZUMRGL-UHFFFAOYSA-N 2-methoxy-n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCCOC)CCC2=C1 DTYYIKTYZUMRGL-UHFFFAOYSA-N 0.000 description 2
• NJOVSKINYLLZJB-UHFFFAOYSA-N 2-methyl-n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCC(C)C)CCC2=C1 NJOVSKINYLLZJB-UHFFFAOYSA-N 0.000 description 2
• SFLFCQJQOIZMHF-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)CCC2=C1 SFLFCQJQOIZMHF-UHFFFAOYSA-N 0.000 description 2
• YTHVGJSPULXGNY-UHFFFAOYSA-N 3-fluoropropan-1-amine Chemical compound NCCCF YTHVGJSPULXGNY-UHFFFAOYSA-N 0.000 description 2
• HMTHTJXBHPRKIF-ZGTCLIOFSA-N 3-methyl-1-[[(3r)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]piperidine Chemical compound C1C(C)CCCN1C[C@H]1OC2=CC(S(C)(=O)=O)=CC=C2OC1 HMTHTJXBHPRKIF-ZGTCLIOFSA-N 0.000 description 2
• QIMAGFLOKOCZDJ-UHFFFAOYSA-N 4-[(5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]morpholine Chemical compound O1C2=CC(S(=O)(=O)C)=CC(F)=C2OCC1CN1CCOCC1 QIMAGFLOKOCZDJ-UHFFFAOYSA-N 0.000 description 2
• KOFNOWRXIDSMAA-UHFFFAOYSA-N 4-[(6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]morpholine Chemical compound O1C2=CC(S(=O)(=O)C)=CC=C2OCC1CN1CCOCC1 KOFNOWRXIDSMAA-UHFFFAOYSA-N 0.000 description 2
• JDCIBHCASSGJOB-UHFFFAOYSA-N 4-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]morpholine Chemical compound O1C2=CC(S(=O)(=O)C)=CC=C2CCC1CN1CCOCC1 JDCIBHCASSGJOB-UHFFFAOYSA-N 0.000 description 2
• QIMAGFLOKOCZDJ-JTQLQIEISA-N 4-[[(2s)-5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]morpholine Chemical compound C([C@H]1COC2=C(F)C=C(C=C2O1)S(=O)(=O)C)N1CCOCC1 QIMAGFLOKOCZDJ-JTQLQIEISA-N 0.000 description 2
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• 229920000945 Amylopectin Polymers 0.000 description 2
• KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 2
• 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• 208000016285 Movement disease Diseases 0.000 description 2
• 241000277275 Oncorhynchus mykiss Species 0.000 description 2
• KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 208000028017 Psychotic disease Diseases 0.000 description 2
• 229910021607 Silver chloride Inorganic materials 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• BGDLLFQXXLFRCM-LURJTMIESA-N [(2s)-5-chloro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methanol Chemical compound O1C[C@H](CO)OC2=CC(S(=O)(=O)C)=CC(Cl)=C21 BGDLLFQXXLFRCM-LURJTMIESA-N 0.000 description 2
• XHWQUQYIUMKLDB-LURJTMIESA-N [(2s)-5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methanamine Chemical compound O1C[C@H](CN)OC2=CC(S(=O)(=O)C)=CC(F)=C21 XHWQUQYIUMKLDB-LURJTMIESA-N 0.000 description 2
• PHZVNKOZALOXOU-LURJTMIESA-N [(2s)-5-fluoro-7-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-2-yl]methanol Chemical compound O1C[C@H](CO)OC2=CC(S(=O)(=O)C)=CC(F)=C21 PHZVNKOZALOXOU-LURJTMIESA-N 0.000 description 2
• CUFFXDXORSUSBS-LURJTMIESA-N [(2s)-7-bromo-5-fluoro-2,3-dihydro-1,4-benzodioxin-2-yl]methanol Chemical compound C1=C(Br)C=C2O[C@@H](CO)COC2=C1F CUFFXDXORSUSBS-LURJTMIESA-N 0.000 description 2
• XRHOOAVKNINMDW-GFCCVEGCSA-N [(3r)-5-fluoro-2,3-dihydro-1,4-benzodioxin-3-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1OC2=C(F)C=CC=C2OC1 XRHOOAVKNINMDW-GFCCVEGCSA-N 0.000 description 2
• FJGPKNZNSQTEAL-SSDOTTSWSA-N [(3r)-6-bromo-2,3-dihydro-1,4-benzodioxin-3-yl]methanol Chemical compound C1=C(Br)C=C2O[C@H](CO)COC2=C1 FJGPKNZNSQTEAL-SSDOTTSWSA-N 0.000 description 2
• GHFSOMFFPIXDPZ-ZETCQYMHSA-N [(3s)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methanol Chemical compound O1C[C@H](CO)OC2=CC(S(=O)(=O)C)=CC=C21 GHFSOMFFPIXDPZ-ZETCQYMHSA-N 0.000 description 2
• BGEOAJGTGTXLTD-UHFFFAOYSA-N [4-(trifluoromethylsulfonyl)phenyl] acetate Chemical compound CC(=O)OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 BGEOAJGTGTXLTD-UHFFFAOYSA-N 0.000 description 2
• OGGVYZPOGSIZFD-UHFFFAOYSA-N [5-bromo-2-(oxiran-2-ylmethoxy)phenyl] formate Chemical compound O=COC1=CC(Br)=CC=C1OCC1OC1 OGGVYZPOGSIZFD-UHFFFAOYSA-N 0.000 description 2
• OGGVYZPOGSIZFD-QMMMGPOBSA-N [5-bromo-2-[[(2s)-oxiran-2-yl]methoxy]phenyl] formate Chemical compound O=COC1=CC(Br)=CC=C1OC[C@H]1OC1 OGGVYZPOGSIZFD-QMMMGPOBSA-N 0.000 description 2
• ZEKYQEJXQWMEMI-UHFFFAOYSA-N [5-bromo-3-chloro-2-(oxiran-2-ylmethoxy)phenyl] acetate Chemical compound CC(=O)OC1=CC(Br)=CC(Cl)=C1OCC1OC1 ZEKYQEJXQWMEMI-UHFFFAOYSA-N 0.000 description 2
• OGZNFRWLUMFESE-UHFFFAOYSA-N [5-bromo-3-fluoro-2-(oxiran-2-ylmethoxy)phenyl] acetate Chemical compound CC(=O)OC1=CC(Br)=CC(F)=C1OCC1OC1 OGZNFRWLUMFESE-UHFFFAOYSA-N 0.000 description 2
• IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 230000001174 ascending effect Effects 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 230000003925 brain function Effects 0.000 description 2
• 208000029028 brain injury Diseases 0.000 description 2
• 125000004432 carbon atom Chemical group C* 0.000 description 2
• 125000002091 cationic group Chemical group 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 230000000295 complement effect Effects 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 235000013681 dietary sucrose Nutrition 0.000 description 2
• QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 2
• 239000003210 dopamine receptor blocking agent Substances 0.000 description 2
• 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
• 208000013843 drug-induced mental disease Diseases 0.000 description 2
• 238000000835 electrochemical detection Methods 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 2
• KPXZTRUTSLXORO-UHFFFAOYSA-N ethyl 7-hydroxy-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C1=C(O)C=C2OC(C(=O)OCC)CCC2=C1 KPXZTRUTSLXORO-UHFFFAOYSA-N 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 238000003384 imaging method Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000005342 ion exchange Methods 0.000 description 2
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
• 230000006742 locomotor activity Effects 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
• 230000003228 microsomal effect Effects 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 230000007659 motor function Effects 0.000 description 2
• QVVXSAIFIWLFAB-UHFFFAOYSA-N n,n-dimethyl-1-(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(C)C)CCC2=C1 QVVXSAIFIWLFAB-UHFFFAOYSA-N 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• BMVUMEMDCRNOSK-UHFFFAOYSA-N n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]-n-propylpropan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(CCC)CCC)CCC2=C1 BMVUMEMDCRNOSK-UHFFFAOYSA-N 0.000 description 2
• JUKYRQPWRKYMEH-UHFFFAOYSA-N n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]butan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCCCC)CCC2=C1 JUKYRQPWRKYMEH-UHFFFAOYSA-N 0.000 description 2
• WIVADSNAUYDWFY-UHFFFAOYSA-N n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNCC)CCC2=C1 WIVADSNAUYDWFY-UHFFFAOYSA-N 0.000 description 2
• DPQXIDNQWGFQAA-UHFFFAOYSA-N n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]prop-2-en-1-amine Chemical compound C1CC(CNCC=C)OC2=CC(S(=O)(=O)C)=CC=C21 DPQXIDNQWGFQAA-UHFFFAOYSA-N 0.000 description 2
• BHNSRSOJVPQCHH-UHFFFAOYSA-N n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]propan-2-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNC(C)C)CCC2=C1 BHNSRSOJVPQCHH-UHFFFAOYSA-N 0.000 description 2
• JSKTWSDFQLGSCS-UHFFFAOYSA-N n-ethyl-n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(CC)CC)CCC2=C1 JSKTWSDFQLGSCS-UHFFFAOYSA-N 0.000 description 2
• XYKUQSBFOINJJP-UHFFFAOYSA-N n-ethyl-n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(CC)CCC)CCC2=C1 XYKUQSBFOINJJP-UHFFFAOYSA-N 0.000 description 2
• MGYNLGKVKLYWQS-UHFFFAOYSA-N n-methyl-1-(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CNC)CCC2=C1 MGYNLGKVKLYWQS-UHFFFAOYSA-N 0.000 description 2
• DMEIURQIMNPMOQ-UHFFFAOYSA-N n-methyl-n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]ethanamine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(C)CC)CCC2=C1 DMEIURQIMNPMOQ-UHFFFAOYSA-N 0.000 description 2
• GTOBKTAKGUERFM-UHFFFAOYSA-N n-methyl-n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]propan-1-amine Chemical compound C1=C(S(C)(=O)=O)C=C2OC(CN(C)CCC)CCC2=C1 GTOBKTAKGUERFM-UHFFFAOYSA-N 0.000 description 2
• 239000006199 nebulizer Substances 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• 229940049953 phenylacetate Drugs 0.000 description 2
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 229920001592 potato starch Polymers 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 238000002953 preparative HPLC Methods 0.000 description 2
• 239000003380 propellant Substances 0.000 description 2
• 239000011541 reaction mixture Substances 0.000 description 2
• 239000002464 receptor antagonist Substances 0.000 description 2
• 229940044551 receptor antagonist Drugs 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000002098 selective ion monitoring Methods 0.000 description 2
• 229940076279 serotonin Drugs 0.000 description 2
• HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 2
• 239000001509 sodium citrate Substances 0.000 description 2
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 235000010356 sorbitol Nutrition 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• 238000010254 subcutaneous injection Methods 0.000 description 2
• 239000007929 subcutaneous injection Substances 0.000 description 2
• 125000001424 substituent group Chemical group 0.000 description 2
• 229960004793 sucrose Drugs 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 229940095064 tartrate Drugs 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 238000003325 tomography Methods 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
• 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• 239000002699 waste material Substances 0.000 description 2
• JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 2
• KPWKPGFLZGMMFX-VHSXEESVSA-N (-)-camphanic acid Chemical compound C1C[C@]2(C(O)=O)OC(=O)[C@@]1(C)C2(C)C KPWKPGFLZGMMFX-VHSXEESVSA-N 0.000 description 1
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
• KPWKPGFLZGMMFX-ZJUUUORDSA-N (1s,4r)-1,7,7-trimethyl-2-oxo-3-oxabicyclo[2.2.1]heptane-4-carboxylic acid Chemical compound C1C[C@@]2(C(O)=O)OC(=O)[C@]1(C)C2(C)C KPWKPGFLZGMMFX-ZJUUUORDSA-N 0.000 description 1
• MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
• FJGPKNZNSQTEAL-UHFFFAOYSA-N (6-bromo-2,3-dihydro-1,4-benzodioxin-3-yl)methanol Chemical compound C1=C(Br)C=C2OC(CO)COC2=C1 FJGPKNZNSQTEAL-UHFFFAOYSA-N 0.000 description 1
• YTAQGBMBBWJTOY-UHFFFAOYSA-N (7-bromo-5-chloro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol Chemical compound C1=C(Br)C=C2OC(CO)COC2=C1Cl YTAQGBMBBWJTOY-UHFFFAOYSA-N 0.000 description 1
• CUFFXDXORSUSBS-UHFFFAOYSA-N (7-bromo-5-fluoro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol Chemical compound C1=C(Br)C=C2OC(CO)COC2=C1F CUFFXDXORSUSBS-UHFFFAOYSA-N 0.000 description 1
• UWSRZYRNBFXTMP-UHFFFAOYSA-N (7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methanol Chemical compound C1CC(CO)OC2=CC(S(=O)(=O)C)=CC=C21 UWSRZYRNBFXTMP-UHFFFAOYSA-N 0.000 description 1
• WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 1
• LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
• ULIYQAUQKZDZOX-UHFFFAOYSA-N 1,1,1-trifluoro-3-iodopropane Chemical compound FC(F)(F)CCI ULIYQAUQKZDZOX-UHFFFAOYSA-N 0.000 description 1
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical class C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
• HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
• ALJXTLQDUCCTJV-UHFFFAOYSA-N 1-(2-methoxy-4-methylsulfanylphenyl)ethanone Chemical compound COC1=CC(SC)=CC=C1C(C)=O ALJXTLQDUCCTJV-UHFFFAOYSA-N 0.000 description 1
• JPNKIDWQXJZFDV-UHFFFAOYSA-N 1-(5-bromo-3-chloro-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(Br)=CC(Cl)=C1O JPNKIDWQXJZFDV-UHFFFAOYSA-N 0.000 description 1
• XRZSVBLCAJMDBM-MRVPVSSYSA-N 1-[2-[[(2r)-oxiran-2-yl]methoxy]-5-(trifluoromethylsulfonyl)phenyl]ethanone Chemical compound CC(=O)C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1OC[C@@H]1OC1 XRZSVBLCAJMDBM-MRVPVSSYSA-N 0.000 description 1
• VTUCFRRLCPDGON-UHFFFAOYSA-N 1-[2-hydroxy-5-(trifluoromethylsulfonyl)phenyl]ethanone Chemical compound CC(=O)C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1O VTUCFRRLCPDGON-UHFFFAOYSA-N 0.000 description 1
• LRFQWAZWNOFREC-MRVPVSSYSA-N 1-[5-bromo-3-fluoro-2-[[(2r)-oxiran-2-yl]methoxy]phenyl]ethanone Chemical compound CC(=O)C1=CC(Br)=CC(F)=C1OC[C@@H]1OC1 LRFQWAZWNOFREC-MRVPVSSYSA-N 0.000 description 1
• KVGOXGQSTGQXDD-UHFFFAOYSA-N 1-decane-sulfonic-acid Chemical compound CCCCCCCCCCS(O)(=O)=O KVGOXGQSTGQXDD-UHFFFAOYSA-N 0.000 description 1
• MHVSMFDBVMPRGT-UHFFFAOYSA-N 1-methoxyethanamine Chemical compound COC(C)N MHVSMFDBVMPRGT-UHFFFAOYSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• BAEAJWASBASFOC-UHFFFAOYSA-N 2-[(3-fluoro-2-phenylmethoxyphenoxy)methyl]oxirane Chemical compound C=1C=CC=CC=1COC=1C(F)=CC=CC=1OCC1CO1 BAEAJWASBASFOC-UHFFFAOYSA-N 0.000 description 1
• MGMNHOZTKDEFRM-UHFFFAOYSA-N 2-fluoro-6-(oxiran-2-ylmethoxy)phenol Chemical compound OC1=C(F)C=CC=C1OCC1OC1 MGMNHOZTKDEFRM-UHFFFAOYSA-N 0.000 description 1
• 125000004228 2H-chromen-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C([H])(*)OC2=C1[H] 0.000 description 1
• CLYDIKMXAKTMKM-UHFFFAOYSA-N 3-(3-ethylsulfonylphenyl)-1-propylpiperidine Chemical compound C1N(CCC)CCCC1C1=CC=CC(S(=O)(=O)CC)=C1 CLYDIKMXAKTMKM-UHFFFAOYSA-N 0.000 description 1
• GWMUJBNCVXBBPS-UHFFFAOYSA-N 3-(morpholin-4-ylmethyl)-2,3-dihydro-1,4-benzodioxine-6-carbonitrile Chemical compound O1C2=CC(C#N)=CC=C2OCC1CN1CCOCC1 GWMUJBNCVXBBPS-UHFFFAOYSA-N 0.000 description 1
• GFWBHWDNEMMCLC-UHFFFAOYSA-N 3-fluoro-2-phenylmethoxyphenol Chemical compound OC1=CC=CC(F)=C1OCC1=CC=CC=C1 GFWBHWDNEMMCLC-UHFFFAOYSA-N 0.000 description 1
• ZWYFYDRACZPCHR-UHFFFAOYSA-N 3-fluoro-n-[(7-methylsulfonyl-3,4-dihydro-2h-chromen-2-yl)methyl]propan-1-amine Chemical compound C1CC(CNCCCF)OC2=CC(S(=O)(=O)C)=CC=C21 ZWYFYDRACZPCHR-UHFFFAOYSA-N 0.000 description 1
• JEGMWWXJUXDNJN-UHFFFAOYSA-N 3-methylpiperidine Chemical compound CC1CCCNC1 JEGMWWXJUXDNJN-UHFFFAOYSA-N 0.000 description 1
• 125000001963 4 membered heterocyclic group Chemical group 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• OXNUKWVRLVKGOB-UHFFFAOYSA-N 4-(trifluoromethylsulfanyl)phenol 4-(trifluoromethylsulfonyl)phenol Chemical compound FC(SC1=CC=C(C=C1)O)(F)F.FC(S(=O)(=O)C1=CC=C(C=C1)O)(F)F OXNUKWVRLVKGOB-UHFFFAOYSA-N 0.000 description 1
• FGVZAVSVXFMGIK-UHFFFAOYSA-N 4-(trifluoromethylsulfonyl)phenol Chemical compound OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 FGVZAVSVXFMGIK-UHFFFAOYSA-N 0.000 description 1
• VIBJPUXLAKVICD-UHFFFAOYSA-N 4-bromo-2-chlorophenol Chemical compound OC1=CC=C(Br)C=C1Cl VIBJPUXLAKVICD-UHFFFAOYSA-N 0.000 description 1
• RYVOZMPTISNBDB-UHFFFAOYSA-N 4-bromo-2-fluorophenol Chemical compound OC1=CC=C(Br)C=C1F RYVOZMPTISNBDB-UHFFFAOYSA-N 0.000 description 1
• JKTORXLUQLQJCM-UHFFFAOYSA-N 4-phosphonobutylphosphonic acid Chemical compound OP(O)(=O)CCCCP(O)(O)=O JKTORXLUQLQJCM-UHFFFAOYSA-N 0.000 description 1
• 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
• 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 1
• 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
• 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
• 108091005435 5-HT6 receptors Proteins 0.000 description 1
• OLUSWBYEPIMASF-UHFFFAOYSA-N 5-bromo-2-(oxiran-2-ylmethoxy)benzaldehyde Chemical compound O=CC1=CC(Br)=CC=C1OCC1OC1 OLUSWBYEPIMASF-UHFFFAOYSA-N 0.000 description 1
• OLUSWBYEPIMASF-SECBINFHSA-N 5-bromo-2-[[(2r)-oxiran-2-yl]methoxy]benzaldehyde Chemical compound O=CC1=CC(Br)=CC=C1OC[C@@H]1OC1 OLUSWBYEPIMASF-SECBINFHSA-N 0.000 description 1
• OLUSWBYEPIMASF-VIFPVBQESA-N 5-bromo-2-[[(2s)-oxiran-2-yl]methoxy]benzaldehyde Chemical compound O=CC1=CC(Br)=CC=C1OC[C@H]1OC1 OLUSWBYEPIMASF-VIFPVBQESA-N 0.000 description 1
• RMOGFQRZGSQGOU-UHFFFAOYSA-N 7-phenylmethoxy-3,4-bis(trifluoromethyl)chromen-2-one Chemical compound C1=CC=2C(C(F)(F)F)=C(C(F)(F)F)C(=O)OC=2C=C1OCC1=CC=CC=C1 RMOGFQRZGSQGOU-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 108060003345 Adrenergic Receptor Proteins 0.000 description 1
• 102000017910 Adrenergic receptor Human genes 0.000 description 1
• 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• PMPXWZGIXZFSBV-UHFFFAOYSA-N B(Br)(Br)Br.OC1=C(C=CC(=C1)SC)C(C)=O Chemical compound B(Br)(Br)Br.OC1=C(C=CC(=C1)SC)C(C)=O PMPXWZGIXZFSBV-UHFFFAOYSA-N 0.000 description 1
• FAWFVLGGEQDGTR-UHFFFAOYSA-N BrC=1C=C(C(=C(C1)C(C)=O)O)Cl.BrC=1C=C(C(=C(C1)C(C)=O)OCC1OC1)Cl Chemical compound BrC=1C=C(C(=C(C1)C(C)=O)O)Cl.BrC=1C=C(C(=C(C1)C(C)=O)OCC1OC1)Cl FAWFVLGGEQDGTR-UHFFFAOYSA-N 0.000 description 1
• NJBDZMYDJRDLGR-UHFFFAOYSA-N BrC=1C=C(C(=C(C1)C(C)=O)O)F.BrC=1C=C(C(=C(C1)C(C)=O)OCC1OC1)F Chemical compound BrC=1C=C(C(=C(C1)C(C)=O)O)F.BrC=1C=C(C(=C(C1)C(C)=O)OCC1OC1)F NJBDZMYDJRDLGR-UHFFFAOYSA-N 0.000 description 1
• ZNKKPKYKVAEODS-UHFFFAOYSA-N BrC=1C=C(C2=C(OC(CO2)CO)C1)F.FC1=CC(=CC=2OC(COC21)CO)S(=O)(=O)C Chemical compound BrC=1C=C(C2=C(OC(CO2)CO)C1)F.FC1=CC(=CC=2OC(COC21)CO)S(=O)(=O)C ZNKKPKYKVAEODS-UHFFFAOYSA-N 0.000 description 1
• JQLLJCSCTUXHIW-UHFFFAOYSA-N BrC=1C=CC(=C(C=O)C1)O.BrC=1C=CC(=C(C=O)C1)OCC1OC1 Chemical compound BrC=1C=CC(=C(C=O)C1)O.BrC=1C=CC(=C(C=O)C1)OCC1OC1 JQLLJCSCTUXHIW-UHFFFAOYSA-N 0.000 description 1
• JQLLJCSCTUXHIW-SBSPUUFOSA-N BrC=1C=CC(=C(C=O)C1)O.BrC=1C=CC(=C(C=O)C1)OC[C@@H]1OC1 Chemical compound BrC=1C=CC(=C(C=O)C1)O.BrC=1C=CC(=C(C=O)C1)OC[C@@H]1OC1 JQLLJCSCTUXHIW-SBSPUUFOSA-N 0.000 description 1
• JQLLJCSCTUXHIW-FVGYRXGTSA-N BrC=1C=CC(=C(C=O)C1)O.BrC=1C=CC(=C(C=O)C1)OC[C@H]1OC1 Chemical compound BrC=1C=CC(=C(C=O)C1)O.BrC=1C=CC(=C(C=O)C1)OC[C@H]1OC1 JQLLJCSCTUXHIW-FVGYRXGTSA-N 0.000 description 1
• OILNOXXQROVQCY-UHFFFAOYSA-N BrC=1C=CC2=C(OC(CO2)CO)C1.CS(=O)(=O)C=1C=CC2=C(OC(CO2)CO)C1 Chemical compound BrC=1C=CC2=C(OC(CO2)CO)C1.CS(=O)(=O)C=1C=CC2=C(OC(CO2)CO)C1 OILNOXXQROVQCY-UHFFFAOYSA-N 0.000 description 1
• WLGUCYQXTUBTHU-RSAXXLAASA-N C(C)(=O)O.C(C1=CC=CC=C1)N(CC)C[C@H]1COC2=C(O1)C(=C(C=C2)S(=O)(=O)C)F Chemical compound C(C)(=O)O.C(C1=CC=CC=C1)N(CC)C[C@H]1COC2=C(O1)C(=C(C=C2)S(=O)(=O)C)F WLGUCYQXTUBTHU-RSAXXLAASA-N 0.000 description 1
• IJGISFZUSYGIRN-HJIBXMCBSA-N C(C1=CC=CC=C1)N(CC)C[C@H]1COC2=C(O1)C(=CC=C2)F.C(C2=CC=CC=C2)N(CC)C[C@H]2COC1=C(O2)C(=C(C=C1)SC)F Chemical compound C(C1=CC=CC=C1)N(CC)C[C@H]1COC2=C(O1)C(=CC=C2)F.C(C2=CC=CC=C2)N(CC)C[C@H]2COC1=C(O2)C(=C(C=C1)SC)F IJGISFZUSYGIRN-HJIBXMCBSA-N 0.000 description 1
• RBMALSBJBVBPIJ-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=C(C=CC=C1F)Cl.C(C1=CC=CC=C1)OC1=C(C=CC=C1F)O Chemical compound C(C1=CC=CC=C1)OC1=C(C=CC=C1F)Cl.C(C1=CC=CC=C1)OC1=C(C=CC=C1F)O RBMALSBJBVBPIJ-UHFFFAOYSA-N 0.000 description 1
• ITTSPPSDIMYMGO-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=C(OCC2OC2)C=CC=C1F.FC1=C(C(=CC=C1)OCC1OC1)O Chemical compound C(C1=CC=CC=C1)OC1=C(OCC2OC2)C=CC=C1F.FC1=C(C(=CC=C1)OCC1OC1)O ITTSPPSDIMYMGO-UHFFFAOYSA-N 0.000 description 1
• 0 CC1(*)C(C(*)(N(*)*)S)OC2=CC(*)=C*(*)C=C2*C1 Chemical compound CC1(*)C(C(*)(N(*)*)S)OC2=CC(*)=C*(*)C=C2*C1 0.000 description 1
• NBBFSQUCUFBUDP-UHFFFAOYSA-N CC1=C(C=CC(=C1)C)S(=O)(=O)OC1COC2=C(O1)C=C(C=C2F)S(=O)(=O)C.FC2=CC(=CC=1OC(COC12)CNCC=C)S(=O)(=O)C Chemical compound CC1=C(C=CC(=C1)C)S(=O)(=O)OC1COC2=C(O1)C=C(C=C2F)S(=O)(=O)C.FC2=CC(=CC=1OC(COC12)CNCC=C)S(=O)(=O)C NBBFSQUCUFBUDP-UHFFFAOYSA-N 0.000 description 1
• IHMXVSZXHFTOFN-UHFFFAOYSA-N CCC1OCCC1 Chemical compound CCC1OCCC1 IHMXVSZXHFTOFN-UHFFFAOYSA-N 0.000 description 1
• WEBRDDDJKLAXTO-UHFFFAOYSA-N CCC1OCCO1 Chemical compound CCC1OCCO1 WEBRDDDJKLAXTO-UHFFFAOYSA-N 0.000 description 1
• DQRRKICOYYCWQS-JTQLQIEISA-N CS(=O)(=O)C=1C=CC2=C(O[C@@H](CO2)NC)C1 Chemical compound CS(=O)(=O)C=1C=CC2=C(O[C@@H](CO2)NC)C1 DQRRKICOYYCWQS-JTQLQIEISA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• DHZDJHYFQCJADG-UHFFFAOYSA-N ClC1=C(C(=CC=C1)F)O.C(C1=CC=CC=C1)OC1=C(C=CC=C1F)Cl Chemical compound ClC1=C(C(=CC=C1)F)O.C(C1=CC=CC=C1)OC1=C(C=CC=C1F)Cl DHZDJHYFQCJADG-UHFFFAOYSA-N 0.000 description 1
• NYNKCGWJPNZJMI-UHFFFAOYSA-N Clebopride malate Chemical compound [O-]C(=O)C(O)CC(O)=O.COC1=CC(N)=C(Cl)C=C1C(=O)NC1CC[NH+](CC=2C=CC=CC=2)CC1 NYNKCGWJPNZJMI-UHFFFAOYSA-N 0.000 description 1
• 208000028698 Cognitive impairment Diseases 0.000 description 1
• 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 1
• 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 1
• ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 description 1
• 102000015554 Dopamine receptor Human genes 0.000 description 1
• 108050004812 Dopamine receptor Proteins 0.000 description 1
• 208000027534 Emotional disease Diseases 0.000 description 1
• RBCPWHCBLDZACH-TZTJCCGVSA-N FC1=CC=CC2=C1O[C@H](CO2)CNCC.C(C2=CC=CC=C2)N(CC)C[C@H]2COC1=C(O2)C(=CC=C1)F Chemical compound FC1=CC=CC2=C1O[C@H](CO2)CNCC.C(C2=CC=CC=C2)N(CC)C[C@H]2COC1=C(O2)C(=CC=C1)F RBCPWHCBLDZACH-TZTJCCGVSA-N 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 101150104779 HTR2A gene Proteins 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 208000030990 Impulse-control disease Diseases 0.000 description 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 229910004803 Na2 WO4.2H2 O Inorganic materials 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• YNYAYWLBAHXHLL-UHFFFAOYSA-N Normetanephrine Chemical compound COC1=CC(C(O)CN)=CC=C1O YNYAYWLBAHXHLL-UHFFFAOYSA-N 0.000 description 1
• YNYAYWLBAHXHLL-MRVPVSSYSA-N Normetanephrine Natural products COC1=CC([C@H](O)CN)=CC=C1O YNYAYWLBAHXHLL-MRVPVSSYSA-N 0.000 description 1
• BUILTDLMVSANBJ-UHFFFAOYSA-N O1C(C(O)=O)=CC(=O)C=2C1=CC(S(=O)(=O)C)=CC=2 Chemical compound O1C(C(O)=O)=CC(=O)C=2C1=CC(S(=O)(=O)C)=CC=2 BUILTDLMVSANBJ-UHFFFAOYSA-N 0.000 description 1
• RUVGKLUCKIVWAF-UHFFFAOYSA-N OC1=C(C=CC(=C1)SC)C(C)=O.OC1=C(C=CC(=C1)S(=O)(=O)C)C(C)=O Chemical compound OC1=C(C=CC(=C1)SC)C(C)=O.OC1=C(C=CC(=C1)S(=O)(=O)C)C(C)=O RUVGKLUCKIVWAF-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 239000005662 Paraffin oil Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 206010037211 Psychomotor hyperactivity Diseases 0.000 description 1
• 208000005793 Restless legs syndrome Diseases 0.000 description 1
• 239000012891 Ringer solution Substances 0.000 description 1
• 241000277331 Salmonidae Species 0.000 description 1
• 238000000692 Student's t-test Methods 0.000 description 1
• 244000028419 Styrax benzoin Species 0.000 description 1
• 235000000126 Styrax benzoin Nutrition 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 235000008411 Sumatra benzointree Nutrition 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• NOQXXYIGRPAZJC-VIFPVBQESA-N [(2s)-oxiran-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@H]1OC1 NOQXXYIGRPAZJC-VIFPVBQESA-N 0.000 description 1
• GMPCGVPMZQXOTB-CYBMUJFWSA-N [(3r)-6-(trifluoromethyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1OC2=CC(C(F)(F)F)=CC=C2OC1 GMPCGVPMZQXOTB-CYBMUJFWSA-N 0.000 description 1
• XCEWPVHFPPXOSA-LURJTMIESA-N [(3s)-5-fluoro-2,3-dihydro-1,4-benzodioxin-3-yl]methanol Chemical compound C1=CC(F)=C2O[C@@H](CO)COC2=C1 XCEWPVHFPPXOSA-LURJTMIESA-N 0.000 description 1
• YNGINRKEIBVVLE-LURJTMIESA-N [(3s)-6-(trifluoromethylsulfonyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methanol Chemical compound C1=C(S(=O)(=O)C(F)(F)F)C=C2O[C@@H](CO)COC2=C1 YNGINRKEIBVVLE-LURJTMIESA-N 0.000 description 1
• FJGPKNZNSQTEAL-ZETCQYMHSA-N [(3s)-6-bromo-2,3-dihydro-1,4-benzodioxin-3-yl]methanol Chemical compound C1=C(Br)C=C2O[C@@H](CO)COC2=C1 FJGPKNZNSQTEAL-ZETCQYMHSA-N 0.000 description 1
• YHLJBNMWXXGKBX-ZETCQYMHSA-N [(3s)-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methanamine Chemical compound O1C[C@H](CN)OC2=CC(S(=O)(=O)C)=CC=C21 YHLJBNMWXXGKBX-ZETCQYMHSA-N 0.000 description 1
• IIASINAUOVMXHK-MRVPVSSYSA-N [2-[[(2r)-oxiran-2-yl]methoxy]-5-(trifluoromethylsulfonyl)phenyl] acetate Chemical compound CC(=O)OC1=CC(S(=O)(=O)C(F)(F)F)=CC=C1OC[C@@H]1OC1 IIASINAUOVMXHK-MRVPVSSYSA-N 0.000 description 1
• OGGVYZPOGSIZFD-MRVPVSSYSA-N [5-bromo-2-[[(2r)-oxiran-2-yl]methoxy]phenyl] formate Chemical compound O=COC1=CC(Br)=CC=C1OC[C@@H]1OC1 OGGVYZPOGSIZFD-MRVPVSSYSA-N 0.000 description 1
• OGZNFRWLUMFESE-MRVPVSSYSA-N [5-bromo-3-fluoro-2-[[(2r)-oxiran-2-yl]methoxy]phenyl] acetate Chemical compound CC(=O)OC1=CC(Br)=CC(F)=C1OC[C@@H]1OC1 OGZNFRWLUMFESE-MRVPVSSYSA-N 0.000 description 1
• YNGINRKEIBVVLE-UHFFFAOYSA-N [6-(trifluoromethylsulfonyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methanol Chemical compound C1=C(S(=O)(=O)C(F)(F)F)C=C2OC(CO)COC2=C1 YNGINRKEIBVVLE-UHFFFAOYSA-N 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 229940022663 acetate Drugs 0.000 description 1
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 229940091179 aconitate Drugs 0.000 description 1
• GTZCVFVGUGFEME-UHFFFAOYSA-N aconitic acid Chemical compound OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 125000000129 anionic group Chemical group 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
• 230000036528 appetite Effects 0.000 description 1
• 235000019789 appetite Nutrition 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 229940090047 auto-injector Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 230000006931 brain damage Effects 0.000 description 1
• 231100000874 brain damage Toxicity 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 239000007963 capsule composition Substances 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 238000005341 cation exchange Methods 0.000 description 1
• 210000004027 cell Anatomy 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 150000001793 charged compounds Chemical class 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical class C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 229940114081 cinnamate Drugs 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 230000001149 cognitive effect Effects 0.000 description 1
• 230000003920 cognitive function Effects 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 238000002591 computed tomography Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 239000003479 dental cement Substances 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 238000002405 diagnostic procedure Methods 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
• 230000009699 differential effect Effects 0.000 description 1
• 210000002249 digestive system Anatomy 0.000 description 1
• 150000004683 dihydrates Chemical class 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 150000002012 dioxanes Chemical class 0.000 description 1
• LBOJYSIDWZQNJS-CVEARBPZSA-N dizocilpine Chemical compound C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 LBOJYSIDWZQNJS-CVEARBPZSA-N 0.000 description 1
• 229940052760 dopamine agonists Drugs 0.000 description 1
• 210000001029 dorsal striatum Anatomy 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 230000008406 drug-drug interaction Effects 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 229950005627 embonate Drugs 0.000 description 1
• 230000002996 emotional effect Effects 0.000 description 1
• 231100000317 environmental toxin Toxicity 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• RKIMFICEWCXBCE-UHFFFAOYSA-N ethyl 7-hydroxy-4-oxochromene-2-carboxylate Chemical compound C1=C(O)C=C2OC(C(=O)OCC)=CC(=O)C2=C1 RKIMFICEWCXBCE-UHFFFAOYSA-N 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 239000000834 fixative Substances 0.000 description 1
• 229940044170 formate Drugs 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 238000013467 fragmentation Methods 0.000 description 1
• 238000006062 fragmentation reaction Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 210000001652 frontal lobe Anatomy 0.000 description 1
• 229910021397 glassy carbon Inorganic materials 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000005484 gravity Effects 0.000 description 1
• 235000019382 gum benzoic Nutrition 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
• 238000000265 homogenisation Methods 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 208000013403 hyperactivity Diseases 0.000 description 1
• 230000001146 hypoxic effect Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 230000002427 irreversible effect Effects 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-O lysinium(1+) Chemical compound [NH3+]CCCCC([NH3+])C([O-])=O KDXKERNSBIXSRK-UHFFFAOYSA-O 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 238000002595 magnetic resonance imaging Methods 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 230000003340 mental effect Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• 239000011859 microparticle Substances 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 230000000897 modulatory effect Effects 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 150000004682 monohydrates Chemical class 0.000 description 1
• 230000036651 mood Effects 0.000 description 1
• WWLPVRXRPMRFSG-QMMMGPOBSA-N n-[[(3s)-5-fluoro-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]ethanamine Chemical compound C1=CC(F)=C2O[C@@H](CNCC)COC2=C1 WWLPVRXRPMRFSG-QMMMGPOBSA-N 0.000 description 1
• LQLCPBNRRGUCOE-HNNXBMFYSA-N n-benzyl-n-[[(3s)-5-fluoro-6-methylsulfanyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]ethanamine Chemical compound C([C@@H]1OC2=C(F)C(SC)=CC=C2OC1)N(CC)CC1=CC=CC=C1 LQLCPBNRRGUCOE-HNNXBMFYSA-N 0.000 description 1
• CVRRRHVIIZIEJC-INIZCTEOSA-N n-benzyl-n-[[(3s)-5-fluoro-6-methylsulfonyl-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]propan-1-amine Chemical compound C([C@@H]1OC2=C(F)C(=CC=C2OC1)S(C)(=O)=O)N(CCC)CC1=CC=CC=C1 CVRRRHVIIZIEJC-INIZCTEOSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 201000003631 narcolepsy Diseases 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 239000004031 partial agonist Substances 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 150000004965 peroxy acids Chemical class 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
• 238000011202 physical detection method Methods 0.000 description 1
• LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 229920002239 polyacrylonitrile Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 210000002442 prefrontal cortex Anatomy 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 210000004129 prosencephalon Anatomy 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 239000003368 psychostimulant agent Substances 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 150000003248 quinolines Chemical class 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
• 229960001860 salicylate Drugs 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 230000001953 sensory effect Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 238000002603 single-photon emission computed tomography Methods 0.000 description 1
• 230000007958 sleep Effects 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• YSWQFZZFQUYBJI-UHFFFAOYSA-M sodium methanethiolate 1-(2-methoxy-4-methylsulfanylphenyl)ethanone Chemical compound C[S-].[Na+].COC1=C(C=CC(=C1)SC)C(C)=O YSWQFZZFQUYBJI-UHFFFAOYSA-M 0.000 description 1
• 239000012439 solid excipient Substances 0.000 description 1
• 229940075554 sorbate Drugs 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 229940114926 stearate Drugs 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 229940086735 succinate Drugs 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 239000007916 tablet composition Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 150000004685 tetrahydrates Chemical class 0.000 description 1
• WEMNATFLVGEPEW-UHFFFAOYSA-N thiophene Chemical compound C=1C=CSC=1.C=1C=CSC=1 WEMNATFLVGEPEW-UHFFFAOYSA-N 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• 235000010215 titanium dioxide Nutrition 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• 230000000472 traumatic effect Effects 0.000 description 1
• CPKHFNMJTBLKLK-UHFFFAOYSA-N tri(propan-2-yl)-sulfanylsilane Chemical compound CC(C)[Si](S)(C(C)C)C(C)C CPKHFNMJTBLKLK-UHFFFAOYSA-N 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
• 229940029284 trichlorofluoromethane Drugs 0.000 description 1
• 150000004684 trihydrates Chemical class 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 239000002351 wastewater Substances 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1