ES2342083T3 - 3-piperidinilisocroman-5-oles como agonistas de dopamina. - Google Patents

Info

Publication number

ES2342083T3

ES2342083T3 ES05740005T ES05740005T ES2342083T3 ES 2342083 T3 ES2342083 T3 ES 2342083T3 ES 05740005 T ES05740005 T ES 05740005T ES 05740005 T ES05740005 T ES 05740005T ES 2342083 T3 ES2342083 T3 ES 2342083T3

Authority

ES

Spain

Prior art keywords

methyl

piperidin

isochroman

aminomethyl

alkyl

Prior art date

2004-04-29

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 - Lifetime

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003136 dopamine receptor stimulating agent Substances 0.000 title description 12
• 229940052760 dopamine agonists Drugs 0.000 title description 6
• -1 naphthyloxycarbonyl Chemical group 0.000 claims abstract description 238
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 179
• 150000001875 compounds Chemical class 0.000 claims abstract description 152
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 55
• 239000001257 hydrogen Substances 0.000 claims abstract description 54
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims abstract description 36
• 239000004305 biphenyl Substances 0.000 claims abstract description 28
• 235000010290 biphenyl Nutrition 0.000 claims abstract description 28
• 150000003839 salts Chemical class 0.000 claims abstract description 28
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 24
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 22
• 150000002367 halogens Chemical class 0.000 claims abstract description 21
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 17
• 125000003342 alkenyl group Chemical group 0.000 claims abstract description 16
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims abstract description 14
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 14
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 14
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 13
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims abstract description 13
• 125000005010 perfluoroalkyl group Chemical group 0.000 claims abstract description 11
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 10
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 10
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 10
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 9
• 125000006267 biphenyl group Chemical group 0.000 claims abstract description 9
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 8
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims abstract description 8
• 125000001424 substituent group Chemical group 0.000 claims abstract description 8
• KZTYYGOKRVBIMI-UHFFFAOYSA-N diphenyl sulfone Chemical group C=1C=CC=CC=1S(=O)(=O)C1=CC=CC=C1 KZTYYGOKRVBIMI-UHFFFAOYSA-N 0.000 claims abstract description 7
• 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 claims abstract description 7
• 125000006678 phenoxycarbonyl group Chemical group 0.000 claims abstract description 7
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims abstract description 7
• 125000001624 naphthyl group Chemical group 0.000 claims abstract description 6
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims abstract description 5
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims abstract description 4
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 4
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 4
• 125000002541 furyl group Chemical group 0.000 claims abstract description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 4
• 125000001041 indolyl group Chemical group 0.000 claims abstract description 4
• 125000005956 isoquinolyl group Chemical group 0.000 claims abstract description 4
• 125000001786 isothiazolyl group Chemical group 0.000 claims abstract description 4
• 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 4
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 4
• 125000005493 quinolyl group Chemical group 0.000 claims abstract description 4
• 125000001544 thienyl group Chemical group 0.000 claims abstract description 4
• 239000002253 acid Substances 0.000 claims description 128
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 79
• BDWGHVFBRSMPDD-GJZGRUSLSA-N 4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidine-1-carboxylic acid Chemical compound C1([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN(C(O)=O)CC1 BDWGHVFBRSMPDD-GJZGRUSLSA-N 0.000 claims description 58
• 229960003638 dopamine Drugs 0.000 claims description 40
• 150000002148 esters Chemical class 0.000 claims description 29
• 150000002431 hydrogen Chemical class 0.000 claims description 28
• 239000003814 drug Substances 0.000 claims description 25
• 238000011282 treatment Methods 0.000 claims description 24
• 230000000694 effects Effects 0.000 claims description 19
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 claims description 10
• 208000018737 Parkinson disease Diseases 0.000 claims description 10
• 208000012902 Nervous system disease Diseases 0.000 claims description 8
• NHNXXLRZHRLWTI-IRXDYDNUSA-N n-[[(1r,3s)-5-methoxy-6-methyl-3-piperidin-4-yl-3,4-dihydro-1h-isochromen-1-yl]methyl]formamide Chemical compound C1([C@H]2O[C@@H](CNC=O)C=3C=CC(C)=C(C=3C2)OC)CCNCC1 NHNXXLRZHRLWTI-IRXDYDNUSA-N 0.000 claims description 8
• OLKAFFLKIMAYMJ-SQJZIBIZSA-N (1R,3S)-3-[1-(3-aminobutyl)piperidin-4-yl]-1-(aminomethyl)-6-methyl-3,4-dihydro-1H-isochromen-5-ol Chemical compound C1CN(CCC(N)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 OLKAFFLKIMAYMJ-SQJZIBIZSA-N 0.000 claims description 7
• 208000025966 Neurological disease Diseases 0.000 claims description 7
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 6
• OYNWTHUVMYDYGL-OALUTQOASA-N n-[[(1r,3s)-6-methyl-3-piperidin-4-yl-5-propan-2-yloxy-3,4-dihydro-1h-isochromen-1-yl]methyl]formamide Chemical compound C1([C@H]2O[C@@H](CNC=O)C=3C=CC(C)=C(C=3C2)OC(C)C)CCNCC1 OYNWTHUVMYDYGL-OALUTQOASA-N 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
• 239000000126 substance Substances 0.000 claims description 5
• WJOIIDIWPYVQKA-CNZKWUBKSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(1-phenylethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1C(C)C1=CC=CC=C1 WJOIIDIWPYVQKA-CNZKWUBKSA-N 0.000 claims description 4
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
• 230000001149 cognitive effect Effects 0.000 claims description 4
• ISPLQTPMNBBWRZ-VMPREFPWSA-N (1r,3s)-1-(aminomethyl)-3-[1-(2,2-diphenylethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC(C=1C=CC=CC=1)C1=CC=CC=C1 ISPLQTPMNBBWRZ-VMPREFPWSA-N 0.000 claims description 3
• AEFIJVQTTVJTTJ-ZEQRLZLVSA-N (1r,3s)-1-(ethylaminomethyl)-6-methyl-3-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNCC)CCN1CC1=CC=C(C(F)(F)F)C=C1 AEFIJVQTTVJTTJ-ZEQRLZLVSA-N 0.000 claims description 3
• CZLZPANEELQSMK-DQEYMECFSA-N (1r,3s)-1-[[ethyl(methyl)amino]methyl]-6-methyl-3-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CN(C)CC)CCN1CC1=CC=C(C(F)(F)F)C=C1 CZLZPANEELQSMK-DQEYMECFSA-N 0.000 claims description 3
• QOQNMLXBGPDAKG-DQEYMECFSA-N (1r,3s)-3-(1-benzylpiperidin-4-yl)-1-[[ethyl(methyl)amino]methyl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CN(C)CC)CCN1CC1=CC=CC=C1 QOQNMLXBGPDAKG-DQEYMECFSA-N 0.000 claims description 3
• NCYZQXDFUDUZJP-GOTSBHOMSA-N (1r,3s)-3-(1-benzylpiperidin-4-yl)-6-methyl-1-(methylaminomethyl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=CC=C1 NCYZQXDFUDUZJP-GOTSBHOMSA-N 0.000 claims description 3
• RVGKITHRHMXVPD-DQEYMECFSA-N (1r,3s)-3-(1-benzylpiperidin-4-yl)-6-methyl-1-(propylaminomethyl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNCCC)CCN1CC1=CC=CC=C1 RVGKITHRHMXVPD-DQEYMECFSA-N 0.000 claims description 3
• RMJZFVIGUQUPAT-UIOOFZCWSA-N (1r,3s)-3-(1-benzylpiperidin-4-yl)-6-methyl-1-(pyrrolidin-1-ylmethyl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C([C@H]1C2=CC=C(C(=C2C[C@H](O1)C1CCN(CC=2C=CC=CC=2)CC1)O)C)N1CCCC1 RMJZFVIGUQUPAT-UIOOFZCWSA-N 0.000 claims description 3
• CFYYWPYMSFBKGA-UIOOFZCWSA-N (1r,3s)-3-(1-benzylpiperidin-4-yl)-6-methyl-1-[[methyl(propyl)amino]methyl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CN(C)CCC)CCN1CC1=CC=CC=C1 CFYYWPYMSFBKGA-UIOOFZCWSA-N 0.000 claims description 3
• JUEANUAHZGBLJD-UIOOFZCWSA-N (1r,3s)-6-methyl-1-[[methyl(propyl)amino]methyl]-3-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CN(C)CCC)CCN1CC1=CC=C(C(F)(F)F)C=C1 JUEANUAHZGBLJD-UIOOFZCWSA-N 0.000 claims description 3
• MPXDWMFKYLXSCA-GOTSBHOMSA-N 1-[2-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethyl]-3-(4-fluorophenyl)urea Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCNC(=O)NC1=CC=C(F)C=C1 MPXDWMFKYLXSCA-GOTSBHOMSA-N 0.000 claims description 3
• DYSJMQABFPKAQM-UHFFFAOYSA-N 1-benzothiophene-2-carboxylic acid Chemical compound C1=CC=C2SC(C(=O)O)=CC2=C1 DYSJMQABFPKAQM-UHFFFAOYSA-N 0.000 claims description 3
• GYHILXUHOQKEMR-DQEYMECFSA-N 2-[4-[(1r,3s)-1-(ethylaminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-1-phenylethanone Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNCC)CCN1CC(=O)C1=CC=CC=C1 GYHILXUHOQKEMR-DQEYMECFSA-N 0.000 claims description 3
• UOBYKYZJUGYBDK-UHFFFAOYSA-N 2-naphthoic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-N 0.000 claims description 3
• CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 claims description 3
• NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 claims description 3
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
• WCYBYZBPWZTMDW-UHFFFAOYSA-N dibutylazanide Chemical compound CCCC[N-]CCCC WCYBYZBPWZTMDW-UHFFFAOYSA-N 0.000 claims description 3
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
• NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 claims description 3
• 150000004702 methyl esters Chemical class 0.000 claims description 3
• OLAHHVRNGLPLAS-PPLCUNABSA-N (1R)-1-[[4-[(1R,3S)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1H-isochromen-3-yl]piperidin-1-yl]sulfonylmethyl]-7,7-dimethylbicyclo[2.2.1]heptan-2-one Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C[C@]1(C2(C)C)C(=O)CC2CC1 OLAHHVRNGLPLAS-PPLCUNABSA-N 0.000 claims description 2
• BZWGHAQNOBMVFM-JUQRWGLSSA-N (1R,3S)-6-methyl-1-(methylaminomethyl)-3-[1-(1-phenylethyl)piperidin-4-yl]-3,4-dihydro-1H-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1C(C)C1=CC=CC=C1 BZWGHAQNOBMVFM-JUQRWGLSSA-N 0.000 claims description 2
• JCMGZTZNYJBGOG-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-(1-benzylpiperidin-4-yl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC=C1 JCMGZTZNYJBGOG-VXKWHMMOSA-N 0.000 claims description 2
• RUXMQAQPHCLAHN-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-(1-benzylsulfonylpiperidin-4-yl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)CC1=CC=CC=C1 RUXMQAQPHCLAHN-VXKWHMMOSA-N 0.000 claims description 2
• FPKTVQWFZCIWPU-OALUTQOASA-N (1r,3s)-1-(aminomethyl)-3-(1-butylpiperidin-4-yl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CN(CCCC)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 FPKTVQWFZCIWPU-OALUTQOASA-N 0.000 claims description 2
• YZRRWCPYASKLRL-ZEQRLZLVSA-N (1r,3s)-1-(aminomethyl)-3-[1-(1-benzofuran-2-ylmethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=C2OC(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC2=C1 YZRRWCPYASKLRL-ZEQRLZLVSA-N 0.000 claims description 2
• CEJVKVYLAVYIIS-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-3-[1-(1-benzothiophen-3-ylmethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=C2C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CSC2=C1 CEJVKVYLAVYIIS-GOTSBHOMSA-N 0.000 claims description 2
• WZOIZYRTPCTDBG-ZEQRLZLVSA-N (1r,3s)-1-(aminomethyl)-3-[1-(1h-indol-3-ylmethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=C2C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CNC2=C1 WZOIZYRTPCTDBG-ZEQRLZLVSA-N 0.000 claims description 2
• CIILVARJBBOHLY-OALUTQOASA-N (1r,3s)-1-(aminomethyl)-3-[1-(2,2-dimethylpropyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN(CC(C)(C)C)CC1 CIILVARJBBOHLY-OALUTQOASA-N 0.000 claims description 2
• GUBHHPKJGREISE-VMPREFPWSA-N (1r,3s)-1-(aminomethyl)-3-[1-(2,2-diphenylethylsulfonyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 GUBHHPKJGREISE-VMPREFPWSA-N 0.000 claims description 2
• UGECZCKVFKGAGA-ZEQRLZLVSA-N (1r,3s)-1-(aminomethyl)-3-[1-(2,3-dihydro-1h-inden-2-yl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1C2=CC=CC=C2CC1N(CC1)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 UGECZCKVFKGAGA-ZEQRLZLVSA-N 0.000 claims description 2
• VNCSCEMQMVQUAE-PMACEKPBSA-N (1r,3s)-1-(aminomethyl)-3-[1-(2,4-dichlorophenyl)sulfonylpiperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC=C(Cl)C=C1Cl VNCSCEMQMVQUAE-PMACEKPBSA-N 0.000 claims description 2
• DGDZQJQCRDBSDN-PMACEKPBSA-N (1r,3s)-1-(aminomethyl)-3-[1-(2,5-dichlorophenyl)sulfonylpiperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC(Cl)=CC=C1Cl DGDZQJQCRDBSDN-PMACEKPBSA-N 0.000 claims description 2
• SVLJTNQPHKXTSI-IRXDYDNUSA-N (1r,3s)-1-(aminomethyl)-3-[1-(2-hydroxyethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN(CCO)CC1 SVLJTNQPHKXTSI-IRXDYDNUSA-N 0.000 claims description 2
• YHODLJWMKZWBRO-SFTDATJTSA-N (1r,3s)-1-(aminomethyl)-3-[1-(3,4-dichlorophenyl)sulfonylpiperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC=C(Cl)C(Cl)=C1 YHODLJWMKZWBRO-SFTDATJTSA-N 0.000 claims description 2
• YOQOMPMDCZYGQX-ZEQRLZLVSA-N (1r,3s)-1-(aminomethyl)-3-[1-(3,4-dihydro-1h-isoquinolin-2-ylsulfonyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC2=CC=CC=C2CN1S(=O)(=O)N(CC1)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 YOQOMPMDCZYGQX-ZEQRLZLVSA-N 0.000 claims description 2
• FOLRFDBEPLCPAT-GMAHTHKFSA-N (1r,3s)-1-(aminomethyl)-3-[1-(3,4-dimethoxyphenyl)sulfonylpiperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 FOLRFDBEPLCPAT-GMAHTHKFSA-N 0.000 claims description 2
• AELGNNXBPYKOQB-SVBPBHIXSA-N (1r,3s)-1-(aminomethyl)-3-[1-(4-benzylpiperidin-1-yl)sulfonylpiperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)N(CC1)CCC1CC1=CC=CC=C1 AELGNNXBPYKOQB-SVBPBHIXSA-N 0.000 claims description 2
• YNTBUMALJNLLQH-SFTDATJTSA-N (1r,3s)-1-(aminomethyl)-3-[1-(4-chlorophenyl)sulfonylpiperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC=C(Cl)C=C1 YNTBUMALJNLLQH-SFTDATJTSA-N 0.000 claims description 2
• APSHRLPOALCGDX-ZEQRLZLVSA-N (1r,3s)-1-(aminomethyl)-3-[1-(4-tert-butylphenyl)sulfonylpiperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 APSHRLPOALCGDX-ZEQRLZLVSA-N 0.000 claims description 2
• BKUKIADILJRFEL-CONSDPRKSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(1-benzylindol-3-yl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC(C1=CC=CC=C11)=CN1CC1=CC=CC=C1 BKUKIADILJRFEL-CONSDPRKSA-N 0.000 claims description 2
• GHRLRZIGFWTIRF-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(2,4-dichlorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(Cl)C=C1Cl GHRLRZIGFWTIRF-VXKWHMMOSA-N 0.000 claims description 2
• DSZANASAFNZUBB-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(2,4-difluorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(F)C=C1F DSZANASAFNZUBB-VXKWHMMOSA-N 0.000 claims description 2
• WFMVDHNJDJZDSV-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(2-chlorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC=C1Cl WFMVDHNJDJZDSV-VXKWHMMOSA-N 0.000 claims description 2
• ICWRGXVYGWHJMF-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(2-fluorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC=C1F ICWRGXVYGWHJMF-VXKWHMMOSA-N 0.000 claims description 2
• OKJKOFVMFSMYQK-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(Cl)C(Cl)=C1 OKJKOFVMFSMYQK-VXKWHMMOSA-N 0.000 claims description 2
• CVKAWMSGTCXRDK-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3,4-dichlorophenyl)methylsulfonyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)CC1=CC=C(Cl)C(Cl)=C1 CVKAWMSGTCXRDK-VXKWHMMOSA-N 0.000 claims description 2
• WACIWQMIFIPFBM-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3,4-difluorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(F)C(F)=C1 WACIWQMIFIPFBM-VXKWHMMOSA-N 0.000 claims description 2
• DPEVOCZNTQEATI-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3-chlorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC(Cl)=C1 DPEVOCZNTQEATI-VXKWHMMOSA-N 0.000 claims description 2
• WQYNJHHSJLOYSJ-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3-fluorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC(F)=C1 WQYNJHHSJLOYSJ-VXKWHMMOSA-N 0.000 claims description 2
• HVJFNWREPXKNTP-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(Cl)C=C1 HVJFNWREPXKNTP-VXKWHMMOSA-N 0.000 claims description 2
• RGNDYJCYQSQOJH-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(4-fluorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(F)C=C1 RGNDYJCYQSQOJH-VXKWHMMOSA-N 0.000 claims description 2
• OZVOFCNULPJLIC-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(4-hydroxyphenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(O)C=C1 OZVOFCNULPJLIC-VXKWHMMOSA-N 0.000 claims description 2
• XJZPWIFYNIWNBM-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-3-[1-[2-(3-chlorophenyl)ethyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCC1=CC=CC(Cl)=C1 XJZPWIFYNIWNBM-GOTSBHOMSA-N 0.000 claims description 2
• BYNZLXJBRXPACD-MCLASIAMSA-N (1r,3s)-1-(aminomethyl)-3-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)butyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound FC1=CC=C2C(C(CCN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C)C(O)=C4C3)C)=NOC2=C1 BYNZLXJBRXPACD-MCLASIAMSA-N 0.000 claims description 2
• RLQXGNOFPBUAQC-CONSDPRKSA-N (1r,3s)-1-(aminomethyl)-3-[1-[4,4-bis(4-fluorophenyl)butyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCCC(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 RLQXGNOFPBUAQC-CONSDPRKSA-N 0.000 claims description 2
• XDUGTYRHGDWDNW-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2,5-bis(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC(C(F)(F)F)=CC=C1C(F)(F)F XDUGTYRHGDWDNW-VXKWHMMOSA-N 0.000 claims description 2
• XZKKMRVALJRMGR-SFTDATJTSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC(C(F)(F)F)=C1Cl XZKKMRVALJRMGR-SFTDATJTSA-N 0.000 claims description 2
• CFGYHYAPYCVAHI-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2-chloro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC(C(F)(F)F)=CC=C1Cl CFGYHYAPYCVAHI-VXKWHMMOSA-N 0.000 claims description 2
• GANOWGKKRFHIEC-SFTDATJTSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2-fluoro-3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC(C(F)(F)F)=C1F GANOWGKKRFHIEC-SFTDATJTSA-N 0.000 claims description 2
• SOTGJLZJYXWEAF-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(C(F)(F)F)C=C1F SOTGJLZJYXWEAF-VXKWHMMOSA-N 0.000 claims description 2
• CBKORAXSNALJFQ-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2-fluoro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC(C(F)(F)F)=CC=C1F CBKORAXSNALJFQ-VXKWHMMOSA-N 0.000 claims description 2
• QJEKQCVLLXLLHO-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[3,5-bis(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 QJEKQCVLLXLLHO-VXKWHMMOSA-N 0.000 claims description 2
• VWVPNFZCMDQFLI-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[3-fluoro-4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(C(F)(F)F)C(F)=C1 VWVPNFZCMDQFLI-VXKWHMMOSA-N 0.000 claims description 2
• ICFXJEFPVSDHMJ-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC(F)=CC(C(F)(F)F)=C1 ICFXJEFPVSDHMJ-VXKWHMMOSA-N 0.000 claims description 2
• BIPLNIWXALOOIX-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(Cl)C(C(F)(F)F)=C1 BIPLNIWXALOOIX-VXKWHMMOSA-N 0.000 claims description 2
• CJRBLZJWKCATMO-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[4-fluoro-3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(F)C(C(F)(F)F)=C1 CJRBLZJWKCATMO-VXKWHMMOSA-N 0.000 claims description 2
• UNNFTMMRMAUYHR-DQEYMECFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-(1-naphthalen-2-ylsulfonylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=CC2=CC(S(=O)(=O)N3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=C21 UNNFTMMRMAUYHR-DQEYMECFSA-N 0.000 claims description 2
• SZESCBBOZOCCSP-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-(1-octylsulfonylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CN(S(=O)(=O)CCCCCCCC)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 SZESCBBOZOCCSP-GOTSBHOMSA-N 0.000 claims description 2
• XAGCJRDFQAFCKK-PMACEKPBSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-(1-piperidin-1-ylsulfonylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)N1CCCCC1 XAGCJRDFQAFCKK-PMACEKPBSA-N 0.000 claims description 2
• IUOPQHKELGMZNR-ROUUACIJSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-(1-propan-2-ylsulfonylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CN(S(=O)(=O)C(C)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 IUOPQHKELGMZNR-ROUUACIJSA-N 0.000 claims description 2
• FBDHSKRDKJLUOI-JUQRWGLSSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(1-phenylpropan-2-yl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1C(C)CC1=CC=CC=C1 FBDHSKRDKJLUOI-JUQRWGLSSA-N 0.000 claims description 2
• QUKMHXRDYTVARU-HOTGVXAUSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(2,2,2-trifluoroethylsulfonyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN(S(=O)(=O)CC(F)(F)F)CC1 QUKMHXRDYTVARU-HOTGVXAUSA-N 0.000 claims description 2
• OOZFGRHMDAIHAM-SVBPBHIXSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(2-naphthalen-1-ylethylsulfonyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=C2C(CCS(=O)(=O)N3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=CC2=C1 OOZFGRHMDAIHAM-SVBPBHIXSA-N 0.000 claims description 2
• FNKKUYIEDYZOER-JUQRWGLSSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(2-phenylpropyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CC(C)C1=CC=CC=C1 FNKKUYIEDYZOER-JUQRWGLSSA-N 0.000 claims description 2
• YTPSNVCCUHTPNY-PMACEKPBSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(3-methylbutyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CN(CCC(C)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 YTPSNVCCUHTPNY-PMACEKPBSA-N 0.000 claims description 2
• FHJKGDBZAYPSAZ-MQTLACETSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(3-phenylbutyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)C1=CC=CC=C1 FHJKGDBZAYPSAZ-MQTLACETSA-N 0.000 claims description 2
• BLPYVXJLLZCHLQ-ZEQRLZLVSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(3-phenylpropyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCCC1=CC=CC=C1 BLPYVXJLLZCHLQ-ZEQRLZLVSA-N 0.000 claims description 2
• WQBWPBGCFBCYRC-SVBPBHIXSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(4-phenylphenyl)sulfonylpiperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C(C=C1)=CC=C1C1=CC=CC=C1 WQBWPBGCFBCYRC-SVBPBHIXSA-N 0.000 claims description 2
• JEFBHAFJWAKVSV-ZEQRLZLVSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(4-propan-2-ylphenyl)sulfonylpiperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC(C(C)C)=CC=C1S(=O)(=O)N1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 JEFBHAFJWAKVSV-ZEQRLZLVSA-N 0.000 claims description 2
• CUMQNWFEVBNNCW-UIOOFZCWSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(naphthalen-1-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=C2C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=CC2=C1 CUMQNWFEVBNNCW-UIOOFZCWSA-N 0.000 claims description 2
• KEHDEMTVYFRBKZ-UIOOFZCWSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(naphthalen-2-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=CC2=CC(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=C21 KEHDEMTVYFRBKZ-UIOOFZCWSA-N 0.000 claims description 2
• BAVDRXVYXVZMTQ-SFTDATJTSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC=N1 BAVDRXVYXVZMTQ-SFTDATJTSA-N 0.000 claims description 2
• RIQIWDXXNNVCHK-SFTDATJTSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(pyridin-3-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CN=C1 RIQIWDXXNNVCHK-SFTDATJTSA-N 0.000 claims description 2
• SDVGSDIVFSQWKE-SFTDATJTSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(pyridin-4-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=NC=C1 SDVGSDIVFSQWKE-SFTDATJTSA-N 0.000 claims description 2
• FWZBCJWTFGPHNP-DQEYMECFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(quinolin-2-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=CC2=NC(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=C21 FWZBCJWTFGPHNP-DQEYMECFSA-N 0.000 claims description 2
• HOXAHHFFWYQPMT-DQEYMECFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(quinolin-3-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=CC2=CC(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CN=C21 HOXAHHFFWYQPMT-DQEYMECFSA-N 0.000 claims description 2
• XVHBFLCPPSOZPJ-DQEYMECFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(quinolin-4-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=C2C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=NC2=C1 XVHBFLCPPSOZPJ-DQEYMECFSA-N 0.000 claims description 2
• QFJRJNPYOAQZIR-PMACEKPBSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(thiophen-2-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CS1 QFJRJNPYOAQZIR-PMACEKPBSA-N 0.000 claims description 2
• OVOGMLVELXBCCP-PMACEKPBSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(thiophen-3-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC=1C=CSC=1 OVOGMLVELXBCCP-PMACEKPBSA-N 0.000 claims description 2
• RNBDIBIXWYWWSX-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(1-methylbenzimidazol-2-yl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=C2N(C)C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=NC2=C1 RNBDIBIXWYWWSX-GOTSBHOMSA-N 0.000 claims description 2
• HSNBWXGNSFELIB-DQEYMECFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(1-methylindol-2-yl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=C2N(C)C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC2=C1 HSNBWXGNSFELIB-DQEYMECFSA-N 0.000 claims description 2
• FZCSMJCPESKKHG-DQEYMECFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(1-methylindol-3-yl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC=C2C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CN(C)C2=C1 FZCSMJCPESKKHG-DQEYMECFSA-N 0.000 claims description 2
• XYKRNFIPXVXEFN-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(2-methylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound CC1=CC=CC=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 XYKRNFIPXVXEFN-GOTSBHOMSA-N 0.000 claims description 2
• OSBSZGXTPWDZEW-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(2-nitrophenyl)methylsulfonyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)CC1=CC=CC=C1[N+]([O-])=O OSBSZGXTPWDZEW-VXKWHMMOSA-N 0.000 claims description 2
• KGQBWQXIEOGAEW-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(3-methyl-1-benzothiophen-2-yl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound S1C2=CC=CC=C2C(C)=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 KGQBWQXIEOGAEW-GOTSBHOMSA-N 0.000 claims description 2
• CGYXMTAMZKDSSV-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(3-methylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound CC1=CC=CC(CN2CCC(CC2)[C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)=C1 CGYXMTAMZKDSSV-GOTSBHOMSA-N 0.000 claims description 2
• FHMLDLYOWLWMOV-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(4-methylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC(C)=CC=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 FHMLDLYOWLWMOV-GOTSBHOMSA-N 0.000 claims description 2
• HUHHWGPOQMXEBM-NSOVKSMOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(4-phenylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC(C=C1)=CC=C1C1=CC=CC=C1 HUHHWGPOQMXEBM-NSOVKSMOSA-N 0.000 claims description 2
• ZMYGQIOWLKIFBO-DQEYMECFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(4-propan-2-ylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC(C(C)C)=CC=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 ZMYGQIOWLKIFBO-DQEYMECFSA-N 0.000 claims description 2
• JTXBKECSTHRGKL-PMACEKPBSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[2-(trifluoromethyl)phenyl]sulfonylpiperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC=CC=C1C(F)(F)F JTXBKECSTHRGKL-PMACEKPBSA-N 0.000 claims description 2
• AQBFDRGNZFPVLW-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[[2-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC=C1C(F)(F)F AQBFDRGNZFPVLW-VXKWHMMOSA-N 0.000 claims description 2
• BVIGEHJQWMSXJX-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[[3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC(C(F)(F)F)=C1 BVIGEHJQWMSXJX-VXKWHMMOSA-N 0.000 claims description 2
• DSHIBJZTINSGRG-VXKWHMMOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(C(F)(F)F)C=C1 DSHIBJZTINSGRG-VXKWHMMOSA-N 0.000 claims description 2
• JDSFRKFCLIOIID-ZEQRLZLVSA-N (1r,3s)-1-[(dimethylamino)methyl]-6-methyl-3-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CN(C)C)CCN1CC1=CC=C(C(F)(F)F)C=C1 JDSFRKFCLIOIID-ZEQRLZLVSA-N 0.000 claims description 2
• UZIYVHWKAPTLIM-GOTSBHOMSA-N (1r,3s)-3-[1-(cyclohexylmethyl)piperidin-4-yl]-6-methyl-1-(methylaminomethyl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1CCCCC1 UZIYVHWKAPTLIM-GOTSBHOMSA-N 0.000 claims description 2
• QKOIEBXTHJUZTJ-GOTSBHOMSA-N (1r,3s)-3-[1-[(3,4-difluorophenyl)methyl]piperidin-4-yl]-6-methyl-1-(methylaminomethyl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(F)C(F)=C1 QKOIEBXTHJUZTJ-GOTSBHOMSA-N 0.000 claims description 2
• FNIYMCLMIFKUEQ-GOTSBHOMSA-N (1r,3s)-3-[1-[(4-fluorophenyl)methyl]piperidin-4-yl]-6-methyl-1-(methylaminomethyl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(F)C=C1 FNIYMCLMIFKUEQ-GOTSBHOMSA-N 0.000 claims description 2
• DMPUCMGWNGRQJO-ZEQRLZLVSA-N (1r,3s)-3-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-6-methyl-1-(methylaminomethyl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(OC)C=C1 DMPUCMGWNGRQJO-ZEQRLZLVSA-N 0.000 claims description 2
• MBWROEPUMJSIIK-IRXDYDNUSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-(1-methylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN(C)CC1 MBWROEPUMJSIIK-IRXDYDNUSA-N 0.000 claims description 2
• PUJWGCPTXQMICM-RBCOLISLSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-[1-(2-phenylbutyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CNC)C3=CC=C(C)C(O)=C3C2)CCN1CC(CC)C1=CC=CC=C1 PUJWGCPTXQMICM-RBCOLISLSA-N 0.000 claims description 2
• HQBATKZCCGLDHC-ZEQRLZLVSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-[1-[(4-methylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(C)C=C1 HQBATKZCCGLDHC-ZEQRLZLVSA-N 0.000 claims description 2
• CSLNIYHOVWNBFK-VMPREFPWSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-[1-[(4-phenylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC(C=C1)=CC=C1C1=CC=CC=C1 CSLNIYHOVWNBFK-VMPREFPWSA-N 0.000 claims description 2
• CQMNENXLLSABNA-UIOOFZCWSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-[1-[(4-propan-2-ylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(C(C)C)C=C1 CQMNENXLLSABNA-UIOOFZCWSA-N 0.000 claims description 2
• QCDCUTGCURHFGT-GOTSBHOMSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(C(F)(F)F)C=C1 QCDCUTGCURHFGT-GOTSBHOMSA-N 0.000 claims description 2
• OLAHHVRNGLPLAS-CWKMGFASSA-N (4s)-4-[[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]sulfonylmethyl]-7,7-dimethylbicyclo[2.2.1]heptan-3-one Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C[C@@]1(C2(C)C)C(=O)CC2CC1 OLAHHVRNGLPLAS-CWKMGFASSA-N 0.000 claims description 2
• NJSYHLKGARRBGS-GOTSBHOMSA-N 1-[2-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethyl]-3-phenylurea Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCNC(=O)NC1=CC=CC=C1 NJSYHLKGARRBGS-GOTSBHOMSA-N 0.000 claims description 2
• SRWXAAISFUFMBO-VXKWHMMOSA-N 1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-2-phenylethanone Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)CC1=CC=CC=C1 SRWXAAISFUFMBO-VXKWHMMOSA-N 0.000 claims description 2
• FHXJRPKCODIORW-OALUTQOASA-N 1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-3-methylbutan-1-one Chemical compound C1CN(C(=O)CC(C)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 FHXJRPKCODIORW-OALUTQOASA-N 0.000 claims description 2
• OJXCFRRNVYLJNM-GOTSBHOMSA-N 1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-3-phenylpropan-1-one Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)CCC1=CC=CC=C1 OJXCFRRNVYLJNM-GOTSBHOMSA-N 0.000 claims description 2
• CTOKPZPVKRHVEP-ROUUACIJSA-N 1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-1-one Chemical compound C1CN(C(=O)CCC)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 CTOKPZPVKRHVEP-ROUUACIJSA-N 0.000 claims description 2
• MZUQSFJVCKMDSM-IRXDYDNUSA-N 1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 MZUQSFJVCKMDSM-IRXDYDNUSA-N 0.000 claims description 2
• XBLDUOXNGORQLX-LGTSYYJHSA-N 2-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-2-phenylacetic acid Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(C(O)=O)C1=CC=CC=C1 XBLDUOXNGORQLX-LGTSYYJHSA-N 0.000 claims description 2
• CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 claims description 2
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
• DRKWGMXFFCPZLW-UHFFFAOYSA-N 2-fluoro-5-(trifluoromethyl)aniline Chemical compound NC1=CC(C(F)(F)F)=CC=C1F DRKWGMXFFCPZLW-UHFFFAOYSA-N 0.000 claims description 2
• FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical compound NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
• KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 claims description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 2
• AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 claims description 2
• IEOYREJEGGRZES-SFTDATJTSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(2-hydroxyphenyl)methanone Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C1=CC=CC=C1O IEOYREJEGGRZES-SFTDATJTSA-N 0.000 claims description 2
• POAZCUQXIWLLCB-SFTDATJTSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(4-bromophenyl)methanone Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C1=CC=C(Br)C=C1 POAZCUQXIWLLCB-SFTDATJTSA-N 0.000 claims description 2
• BXOKUGWYJZKEAC-SFTDATJTSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(4-chlorophenyl)methanone Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C1=CC=C(Cl)C=C1 BXOKUGWYJZKEAC-SFTDATJTSA-N 0.000 claims description 2
• BATOQBAOQKIKQZ-SFTDATJTSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C1=CC=C(F)C=C1 BATOQBAOQKIKQZ-SFTDATJTSA-N 0.000 claims description 2
• RZBBIMJDVSZYCT-VXKWHMMOSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)N1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 RZBBIMJDVSZYCT-VXKWHMMOSA-N 0.000 claims description 2
• SWSAOGBVXZMDTI-SVBPBHIXSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(4-phenylphenyl)methanone Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 SWSAOGBVXZMDTI-SVBPBHIXSA-N 0.000 claims description 2
• OVWTWTOZFMYVSD-OALUTQOASA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-morpholin-4-ylmethanone Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)N1CCOCC1 OVWTWTOZFMYVSD-OALUTQOASA-N 0.000 claims description 2
• BBMGISNNTLJMLS-DQEYMECFSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-phenothiazin-10-ylmethanone Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1C(=O)N(CC1)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 BBMGISNNTLJMLS-DQEYMECFSA-N 0.000 claims description 2
• DJMGRWWQKFYIRW-SFTDATJTSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-phenylmethanone Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C1=CC=CC=C1 DJMGRWWQKFYIRW-SFTDATJTSA-N 0.000 claims description 2
• UPHIXZJETRWMFG-PMACEKPBSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-piperidin-1-ylmethanone Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)N1CCCCC1 UPHIXZJETRWMFG-PMACEKPBSA-N 0.000 claims description 2
• MFXHAIOXZVIBTA-OALUTQOASA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-pyrrolidin-1-ylmethanone Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)N1CCCC1 MFXHAIOXZVIBTA-OALUTQOASA-N 0.000 claims description 2
• IRAHRCHBTDAYLL-VEMKCTPSSA-N n-[1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-2-methylpentan-3-yl]-4-methylbenzamide Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CC(C)C(CC)NC(=O)C1=CC=C(C)C=C1 IRAHRCHBTDAYLL-VEMKCTPSSA-N 0.000 claims description 2
• YRNYJWRGFDFXDT-GOTSBHOMSA-N n-[2-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethyl]-4-fluorobenzamide Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCNC(=O)C1=CC=C(F)C=C1 YRNYJWRGFDFXDT-GOTSBHOMSA-N 0.000 claims description 2
• DCJPDNSPDFAPST-ZEQRLZLVSA-N n-[2-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethyl]-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NCCN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 DCJPDNSPDFAPST-ZEQRLZLVSA-N 0.000 claims description 2
• QYSVGCVWHXVGHC-GOTSBHOMSA-N n-[2-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethyl]benzamide Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCNC(=O)C1=CC=CC=C1 QYSVGCVWHXVGHC-GOTSBHOMSA-N 0.000 claims description 2
• VJOHTYSVUHBOJW-GSIQFNFPSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-2,4-dichlorobenzamide Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=C(Cl)C=C1Cl VJOHTYSVUHBOJW-GSIQFNFPSA-N 0.000 claims description 2
• COQHPUOEOYEUOW-MQTLACETSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-4-bromobenzamide Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=C(Br)C=C1 COQHPUOEOYEUOW-MQTLACETSA-N 0.000 claims description 2
• SYWVQTHZDXAOLR-MQTLACETSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-4-chlorobenzamide Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=C(Cl)C=C1 SYWVQTHZDXAOLR-MQTLACETSA-N 0.000 claims description 2
• MJGWSOZOTWHZBI-MQTLACETSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-4-fluorobenzamide Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=C(F)C=C1 MJGWSOZOTWHZBI-MQTLACETSA-N 0.000 claims description 2
• MLMGHZCMANPFMX-MQTLACETSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-4-nitrobenzamide Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=C([N+]([O-])=O)C=C1 MLMGHZCMANPFMX-MQTLACETSA-N 0.000 claims description 2
• BTFMOHVFKIFMHA-MTSQGGNFSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]benzamide Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=CC=C1 BTFMOHVFKIFMHA-MTSQGGNFSA-N 0.000 claims description 2
• 239000003176 neuroleptic agent Substances 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 2
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims 2
• 238000004519 manufacturing process Methods 0.000 claims 2
• HASIZRCMXSGWPU-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(2-methoxyphenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound COC1=CC=CC=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 HASIZRCMXSGWPU-GOTSBHOMSA-N 0.000 claims 1
• BAHPHSJGRDWLDW-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3-methoxyphenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound COC1=CC=CC(CN2CCC(CC2)[C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)=C1 BAHPHSJGRDWLDW-GOTSBHOMSA-N 0.000 claims 1
• DZXZXIDJMYENCB-GOTSBHOMSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1=CC(OC)=CC=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 DZXZXIDJMYENCB-GOTSBHOMSA-N 0.000 claims 1
• DXGWAHYCISADTJ-GJZGRUSLSA-N 4-[(1R,3S)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1H-isochromen-3-yl]piperidine-1-sulfonic acid Chemical compound NC[C@@H]1O[C@@H](CC2=C(C(=CC=C12)C)O)C1CCN(CC1)S(=O)(=O)O DXGWAHYCISADTJ-GJZGRUSLSA-N 0.000 claims 1
• PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 claims 1
• UZBQIPPOMKBLAS-UHFFFAOYSA-N diethylazanide Chemical compound CC[N-]CC UZBQIPPOMKBLAS-UHFFFAOYSA-N 0.000 claims 1
• DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 claims 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 12
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 148
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
• 239000002904 solvent Substances 0.000 description 57
• 238000006243 chemical reaction Methods 0.000 description 56
• 239000000203 mixture Substances 0.000 description 49
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
• 210000004027 cell Anatomy 0.000 description 37
• 239000000243 solution Substances 0.000 description 36
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
• 238000000034 method Methods 0.000 description 28
• 235000019439 ethyl acetate Nutrition 0.000 description 25
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• 239000000047 product Substances 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 24
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 23
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 23
• 229940079593 drug Drugs 0.000 description 22
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 239000007983 Tris buffer Substances 0.000 description 21
• 230000014509 gene expression Effects 0.000 description 21
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 21
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
• 239000000872 buffer Substances 0.000 description 19
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
• 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 18
• 239000003960 organic solvent Substances 0.000 description 18
• 230000000638 stimulation Effects 0.000 description 17
• 238000012360 testing method Methods 0.000 description 17
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
• 102000005962 receptors Human genes 0.000 description 16
• 108020003175 receptors Proteins 0.000 description 16
• 230000027455 binding Effects 0.000 description 15
• 208000035475 disorder Diseases 0.000 description 15
• ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 15
• 239000003921 oil Substances 0.000 description 15
• 235000019198 oils Nutrition 0.000 description 15
• 239000003153 chemical reaction reagent Substances 0.000 description 14
• 239000000741 silica gel Substances 0.000 description 14
• 229910002027 silica gel Inorganic materials 0.000 description 14
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
• 239000002585 base Substances 0.000 description 12
• 108090000623 proteins and genes Proteins 0.000 description 12
• 229920005989 resin Polymers 0.000 description 12
• 239000011347 resin Substances 0.000 description 12
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
• 239000000556 agonist Substances 0.000 description 11
• 150000004820 halides Chemical class 0.000 description 11
• 239000002609 medium Substances 0.000 description 11
• 239000012074 organic phase Substances 0.000 description 11
• 102000004169 proteins and genes Human genes 0.000 description 11
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• 235000008504 concentrate Nutrition 0.000 description 10
• 239000012141 concentrate Substances 0.000 description 10
• 239000012043 crude product Substances 0.000 description 10
• BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 10
• 230000009467 reduction Effects 0.000 description 10
• 238000006722 reduction reaction Methods 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• 238000004587 chromatography analysis Methods 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 239000012091 fetal bovine serum Substances 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 7
• 241000282414 Homo sapiens Species 0.000 description 7
• AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 7
• 239000007832 Na2SO4 Substances 0.000 description 7
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
• 150000001350 alkyl halides Chemical class 0.000 description 7
• 230000003935 attention Effects 0.000 description 7
• 210000004556 brain Anatomy 0.000 description 7
• 239000012267 brine Substances 0.000 description 7
• 239000012528 membrane Substances 0.000 description 7
• 239000012044 organic layer Substances 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• 229910052938 sodium sulfate Inorganic materials 0.000 description 7
• 235000011152 sodium sulphate Nutrition 0.000 description 7
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
• 230000004913 activation Effects 0.000 description 6
• 150000001299 aldehydes Chemical class 0.000 description 6
• 125000005090 alkenylcarbonyl group Chemical group 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 210000003169 central nervous system Anatomy 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 229940125773 compound 10 Drugs 0.000 description 6
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• 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 6
• 150000002576 ketones Chemical class 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 239000012071 phase Substances 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000011550 stock solution Substances 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class 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 5
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• 229920002873 Polyethylenimine Polymers 0.000 description 5
• 235000011054 acetic acid Nutrition 0.000 description 5
• 102000030621 adenylate cyclase Human genes 0.000 description 5
• 108060000200 adenylate cyclase Proteins 0.000 description 5
• 230000001476 alcoholic effect Effects 0.000 description 5
• 150000001298 alcohols Chemical class 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 229910052796 boron Inorganic materials 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 238000010790 dilution Methods 0.000 description 5
• 239000012895 dilution Substances 0.000 description 5
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
• 229940005501 dopaminergic agent Drugs 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
• 229940098779 methanesulfonic acid Drugs 0.000 description 5
• 239000002953 phosphate buffered saline Substances 0.000 description 5
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
• 201000009032 substance abuse Diseases 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• JGLWVWKHYTTXCC-YKHYUQSHSA-N (1R,3S)-3-[1-(3-aminobutyl)piperidin-4-yl]-1-(aminomethyl)-6-methyl-3,4-dihydro-1H-isochromen-5-ol dihydrochloride Chemical compound Cl.Cl.C1CN(CCC(N)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 JGLWVWKHYTTXCC-YKHYUQSHSA-N 0.000 description 4
• HVUWYURNADYGGL-HPLSCNMKSA-N (1r,3s)-1-(aminomethyl)-3-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)-2-methylpropyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.FC1=CC=C2C(CC(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C)C(O)=C4C3)C)=NOC2=C1 HVUWYURNADYGGL-HPLSCNMKSA-N 0.000 description 4
• REGRYQONWXUVDJ-AWEZNQCLSA-N (1s)-2-(2-methoxy-3-methylphenyl)-1-piperidin-4-ylethanol Chemical compound COC1=C(C)C=CC=C1C[C@H](O)C1CCNCC1 REGRYQONWXUVDJ-AWEZNQCLSA-N 0.000 description 4
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
• 239000002841 Lewis acid Substances 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 230000006399 behavior Effects 0.000 description 4
• 238000009835 boiling Methods 0.000 description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 229910052799 carbon Inorganic materials 0.000 description 4
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
• 229910052681 coesite Inorganic materials 0.000 description 4
• 229910052906 cristobalite Inorganic materials 0.000 description 4
• 230000007812 deficiency Effects 0.000 description 4
• 238000001514 detection method Methods 0.000 description 4
• 201000010099 disease Diseases 0.000 description 4
• 239000003937 drug carrier Substances 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 4
• 239000012948 isocyanate Substances 0.000 description 4
• 150000002513 isocyanates Chemical class 0.000 description 4
• 150000007517 lewis acids Chemical class 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 239000012299 nitrogen atmosphere Substances 0.000 description 4
• 150000007524 organic acids Chemical class 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 238000006268 reductive amination reaction Methods 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• 235000012239 silicon dioxide Nutrition 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 229910052682 stishovite Inorganic materials 0.000 description 4
• 229960005322 streptomycin Drugs 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 4
• 229910052905 tridymite Inorganic materials 0.000 description 4
• UXTRSEZMEXKCQO-INIZCTEOSA-N (1s)-2-(3-methyl-2-propan-2-yloxyphenyl)-1-piperidin-4-ylethanol Chemical compound CC(C)OC1=C(C)C=CC=C1C[C@H](O)C1CCNCC1 UXTRSEZMEXKCQO-INIZCTEOSA-N 0.000 description 3
• XTCDOSHTXMEERU-INIZCTEOSA-N (1s)-2-(3-methyl-2-propan-2-yloxyphenyl)-1-pyridin-4-ylethanol Chemical compound CC(C)OC1=C(C)C=CC=C1C[C@H](O)C1=CC=NC=C1 XTCDOSHTXMEERU-INIZCTEOSA-N 0.000 description 3
• IJFAUIBWMSPSIV-UHFFFAOYSA-N 2-(3-methyl-2-propan-2-yloxyphenyl)-1-pyridin-4-ylethanone Chemical compound CC(C)OC1=C(C)C=CC=C1CC(=O)C1=CC=NC=C1 IJFAUIBWMSPSIV-UHFFFAOYSA-N 0.000 description 3
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
• VNSQYSFEIBZPHF-UHFFFAOYSA-N 2-methoxy-3-methylbenzaldehyde Chemical compound COC1=C(C)C=CC=C1C=O VNSQYSFEIBZPHF-UHFFFAOYSA-N 0.000 description 3
• 125000003890 2-phenylbutyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 3
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 3
• MVYBGIGBXXPTOD-UHFFFAOYSA-N 3-methyl-2-propan-2-yloxybenzaldehyde Chemical compound CC(C)OC1=C(C)C=CC=C1C=O MVYBGIGBXXPTOD-UHFFFAOYSA-N 0.000 description 3
• 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 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 3
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
• WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 3
• WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 3
• ZZJYIKPMDIWRSN-HWBMXIPRSA-N LSM-20934 Chemical compound C12=CC=CC=C2CCC2=CC=CC3=C2[C@H]1CN1CC[C@](C(C)(C)C)(O)C[C@H]13 ZZJYIKPMDIWRSN-HWBMXIPRSA-N 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 208000019022 Mood disease Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• GOTMKOSCLKVOGG-UHFFFAOYSA-N SCH 23390 Chemical compound C1N(C)CCC2=CC(Cl)=C(O)C=C2C1C1=CC=CC=C1 GOTMKOSCLKVOGG-UHFFFAOYSA-N 0.000 description 3
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
• 229910052782 aluminium Inorganic materials 0.000 description 3
• 239000000908 ammonium hydroxide Substances 0.000 description 3
• 239000000935 antidepressant agent Substances 0.000 description 3
• 239000000164 antipsychotic agent Substances 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
• 239000003849 aromatic solvent Substances 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 3
• 229960002802 bromocriptine Drugs 0.000 description 3
• 239000001110 calcium chloride Substances 0.000 description 3
• 235000011148 calcium chloride Nutrition 0.000 description 3
• 229910001628 calcium chloride Inorganic materials 0.000 description 3
• 238000004364 calculation method Methods 0.000 description 3
• 239000003638 chemical reducing agent Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 229940125846 compound 25 Drugs 0.000 description 3
• 229940125898 compound 5 Drugs 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
• 238000005984 hydrogenation reaction Methods 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 229910052500 inorganic mineral Inorganic materials 0.000 description 3
• HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical compound C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 229910001629 magnesium chloride Inorganic materials 0.000 description 3
• 108020004999 messenger RNA Proteins 0.000 description 3
• 239000011707 mineral Substances 0.000 description 3
• 235000010755 mineral Nutrition 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• ASDUWISQIKGSCT-OALUTQOASA-N n-[[(1r,3s)-3-[1-(2-aminoethyl)piperidin-4-yl]-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-1-yl]methyl]formamide Chemical compound C1([C@H]2O[C@@H](CNC=O)C=3C=CC(C)=C(C=3C2)OC)CCN(CCN)CC1 ASDUWISQIKGSCT-OALUTQOASA-N 0.000 description 3
• JQXPHYOWEXVUGV-UHFFFAOYSA-N n-[[3-[1-[(4-fluorophenyl)methyl]piperidin-4-yl]-6-methyl-5-propan-2-yloxy-3,4-dihydro-1h-isochromen-1-yl]methyl]formamide Chemical compound C1C=2C(OC(C)C)=C(C)C=CC=2C(CNC=O)OC1C(CC1)CCN1CC1=CC=C(F)C=C1 JQXPHYOWEXVUGV-UHFFFAOYSA-N 0.000 description 3
• 239000002858 neurotransmitter agent Substances 0.000 description 3
• 229910052757 nitrogen Inorganic materials 0.000 description 3
• 230000009871 nonspecific binding Effects 0.000 description 3
• 230000008447 perception Effects 0.000 description 3
• 230000002093 peripheral effect Effects 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 235000019260 propionic acid Nutrition 0.000 description 3
• 208000020016 psychiatric disease Diseases 0.000 description 3
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
• 201000000980 schizophrenia Diseases 0.000 description 3
• 239000012679 serum free medium Substances 0.000 description 3
• 239000012279 sodium borohydride Substances 0.000 description 3
• 229910000033 sodium borohydride Inorganic materials 0.000 description 3
• 230000009870 specific binding Effects 0.000 description 3
• 231100000736 substance abuse Toxicity 0.000 description 3
• 208000011117 substance-related disease Diseases 0.000 description 3
• 238000012546 transfer Methods 0.000 description 3
• 239000008096 xylene Substances 0.000 description 3
• 150000003738 xylenes Chemical class 0.000 description 3
• LODHNBGJNBYCPG-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(4-fluorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(F)C=C1 LODHNBGJNBYCPG-IXOXMDGESA-N 0.000 description 2
• ZQHIZUHWKITBPZ-ZEQRLZLVSA-N (1r,3s)-3-(1-benzylpiperidin-4-yl)-1-(ethylaminomethyl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNCC)CCN1CC1=CC=CC=C1 ZQHIZUHWKITBPZ-ZEQRLZLVSA-N 0.000 description 2
• ISKIMXCSQPYIPR-AWEZNQCLSA-N (1s)-2-(2-methoxy-3-methylphenyl)-1-pyridin-4-ylethanol Chemical compound COC1=C(C)C=CC=C1C[C@H](O)C1=CC=NC=C1 ISKIMXCSQPYIPR-AWEZNQCLSA-N 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
• JUDKOGFHZYMDMF-UHFFFAOYSA-N 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol Chemical compound C1=2C=C(O)C(O)=CC=2CCNCC1C1=CC=CC=C1 JUDKOGFHZYMDMF-UHFFFAOYSA-N 0.000 description 2
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 2
• VPIRMHDMNJNFAZ-UHFFFAOYSA-N 2-(2-methoxy-3-methylphenyl)-1-pyridin-4-ylethanone Chemical compound COC1=C(C)C=CC=C1CC(=O)C1=CC=NC=C1 VPIRMHDMNJNFAZ-UHFFFAOYSA-N 0.000 description 2
• NMPVEAUIHMEAQP-UHFFFAOYSA-N 2-Bromoacetaldehyde Chemical compound BrCC=O NMPVEAUIHMEAQP-UHFFFAOYSA-N 0.000 description 2
• VMFILRXPIRWNCW-UHFFFAOYSA-N 2-oxoethylcarbamic acid Chemical compound OC(=O)NCC=O VMFILRXPIRWNCW-UHFFFAOYSA-N 0.000 description 2
• 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 2
• BYJXGCRAXIIOLC-UHFFFAOYSA-N 3,4-dihydro-1h-isochromen-5-ol Chemical compound C1OCCC2=C1C=CC=C2O BYJXGCRAXIIOLC-UHFFFAOYSA-N 0.000 description 2
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
• IPPQNXSAJZOTJZ-UHFFFAOYSA-N 3-methylsalicylaldehyde Chemical compound CC1=CC=CC(C=O)=C1O IPPQNXSAJZOTJZ-UHFFFAOYSA-N 0.000 description 2
• OUHFZFAWSLFFSN-HOTGVXAUSA-N 4-[(1r,3s)-1-(bromomethyl)-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidine Chemical compound C1([C@H]2O[C@@H](CBr)C=3C=CC(C)=C(C=3C2)OC)CCNCC1 OUHFZFAWSLFFSN-HOTGVXAUSA-N 0.000 description 2
• UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 2
• AADCDMQTJNYOSS-LBPRGKRZSA-N 5-chloro-3-ethyl-N-[[(2S)-1-ethyl-2-pyrrolidinyl]methyl]-2-hydroxy-6-methoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(CC)=CC(Cl)=C1OC AADCDMQTJNYOSS-LBPRGKRZSA-N 0.000 description 2
• 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 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 2
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• HBBTZQCLSOKRMG-KFTXQHHCSA-N C(C)(C)OC1=C2C[C@H](O[C@H](C2=CC=C1C)CNC)C1CCN(CC1)C(C)C1=CC=CC=C1 Chemical compound C(C)(C)OC1=C2C[C@H](O[C@H](C2=CC=C1C)CNC)C1CCN(CC1)C(C)C1=CC=CC=C1 HBBTZQCLSOKRMG-KFTXQHHCSA-N 0.000 description 2
• IEWLVFCESBTRJS-OJSMNCEXSA-N CC1=C(C2=C(C=C1)[C@@H](O[C@@H](C2)C3CCN(CC3)C(C4=CC=CC=C4)C(=O)O)CNC=O)O Chemical compound CC1=C(C2=C(C=C1)[C@@H](O[C@@H](C2)C3CCN(CC3)C(C4=CC=CC=C4)C(=O)O)CNC=O)O IEWLVFCESBTRJS-OJSMNCEXSA-N 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• XZTUTTFLYRVZFU-QBANDZAYSA-N Cl.Cl.C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1C(C)C1=CC=CC=C1 Chemical compound Cl.Cl.C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1C(C)C1=CC=CC=C1 XZTUTTFLYRVZFU-QBANDZAYSA-N 0.000 description 2
• 208000028698 Cognitive impairment Diseases 0.000 description 2
• 101150049660 DRD2 gene Proteins 0.000 description 2
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 108050004812 Dopamine receptor Proteins 0.000 description 2
• 102000015554 Dopamine receptor Human genes 0.000 description 2
• 208000012661 Dyskinesia Diseases 0.000 description 2
• 208000030814 Eating disease Diseases 0.000 description 2
• GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 2
• 208000019454 Feeding and Eating disease Diseases 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
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 206010019280 Heart failures Diseases 0.000 description 2
• 101000931925 Homo sapiens D(1A) dopamine receptor Proteins 0.000 description 2
• 101000931901 Homo sapiens D(2) dopamine receptor Proteins 0.000 description 2
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
• 241000713869 Moloney murine leukemia virus Species 0.000 description 2
• 206010027951 Mood swings Diseases 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
• 206010047139 Vasoconstriction Diseases 0.000 description 2
• 206010047700 Vomiting Diseases 0.000 description 2
• YDMGSWCNRVDDSN-UHFFFAOYSA-N [anilino(pyridin-4-yl)methyl]phosphonic acid Chemical compound C=1C=NC=CC=1C(P(O)(=O)O)NC1=CC=CC=C1 YDMGSWCNRVDDSN-UHFFFAOYSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• 230000000561 anti-psychotic effect Effects 0.000 description 2
• 229940005513 antidepressants Drugs 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 229960005070 ascorbic acid Drugs 0.000 description 2
• 230000003542 behavioural effect Effects 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 230000000035 biogenic effect Effects 0.000 description 2
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 229950006479 butaclamol Drugs 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
• 150000001805 chlorine compounds Chemical class 0.000 description 2
• UHZZMRAGKVHANO-UHFFFAOYSA-M chlormequat chloride Chemical compound [Cl-].C[N+](C)(C)CCCl UHZZMRAGKVHANO-UHFFFAOYSA-M 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
• 230000019771 cognition Effects 0.000 description 2
• 208000010877 cognitive disease Diseases 0.000 description 2
• 230000002860 competitive effect Effects 0.000 description 2
• 239000002299 complementary DNA Substances 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
• 235000014632 disordered eating Nutrition 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• 238000006073 displacement reaction Methods 0.000 description 2
• 238000004090 dissolution Methods 0.000 description 2
• 239000003210 dopamine receptor blocking agent Substances 0.000 description 2
• 230000003291 dopaminomimetic effect Effects 0.000 description 2
• 238000009509 drug development Methods 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
• 239000012055 enteric layer Substances 0.000 description 2
• 229950007535 eticlopride Drugs 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 239000012065 filter cake Substances 0.000 description 2
• 239000001963 growth medium Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 229960003878 haloperidol Drugs 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• QRMZSPFSDQBLIX-UHFFFAOYSA-N homovanillic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1O QRMZSPFSDQBLIX-UHFFFAOYSA-N 0.000 description 2
• 102000057752 human DRD2 Human genes 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 150000003840 hydrochlorides Chemical class 0.000 description 2
• 208000013403 hyperactivity Diseases 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 239000013067 intermediate product Substances 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000011968 lewis acid catalyst Substances 0.000 description 2
• 239000012280 lithium aluminium hydride Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 238000012423 maintenance Methods 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 229910052987 metal hydride Inorganic materials 0.000 description 2
• 150000004681 metal hydrides Chemical class 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• HDUUXJJYVSFMOK-YPSJUKSRSA-N n-[2-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethyl]-4-fluorobenzamide;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCNC(=O)C1=CC=C(F)C=C1 HDUUXJJYVSFMOK-YPSJUKSRSA-N 0.000 description 2
• KBOORQWDIBSTNF-UYSMMYKSSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-4-chlorobenzamide;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=C(Cl)C=C1 KBOORQWDIBSTNF-UYSMMYKSSA-N 0.000 description 2
• YWFIMALOIFCZJF-SVBPBHIXSA-N n-[[(1r,3s)-6-methyl-3-[1-(2-phenylethyl)piperidin-4-yl]-5-propan-2-yloxy-3,4-dihydro-1h-isochromen-1-yl]methyl]formamide Chemical compound C1CC([C@H]2O[C@@H](CNC=O)C=3C=CC(C)=C(C=3C2)OC(C)C)CCN1CCC1=CC=CC=C1 YWFIMALOIFCZJF-SVBPBHIXSA-N 0.000 description 2
• 239000013642 negative control Substances 0.000 description 2
• 210000001577 neostriatum Anatomy 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 210000001428 peripheral nervous system Anatomy 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
• DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 2
• 229910003446 platinum oxide Inorganic materials 0.000 description 2
• 239000013641 positive control Substances 0.000 description 2
• 229910052700 potassium Chemical class 0.000 description 2
• 239000011591 potassium Chemical class 0.000 description 2
• 235000015320 potassium carbonate Nutrition 0.000 description 2
• 150000003141 primary amines Chemical class 0.000 description 2
• 230000002035 prolonged effect Effects 0.000 description 2
• 229940044551 receptor antagonist Drugs 0.000 description 2
• 239000002464 receptor antagonist Substances 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 238000005096 rolling process Methods 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 239000013049 sediment Substances 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
• 230000035939 shock Effects 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• 230000000707 stereoselective effect Effects 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 150000003512 tertiary amines Chemical class 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
• FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 2
• RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 2
• 229960000281 trometamol Drugs 0.000 description 2
• 230000025033 vasoconstriction Effects 0.000 description 2
• 239000013598 vector Substances 0.000 description 2
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• CJUUXMZGIUATKN-YJKKXFLHSA-N (1R)-1-[[4-[(1R,3S)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1H-isochromen-3-yl]piperidin-1-yl]sulfonylmethyl]-7,7-dimethylbicyclo[2.2.1]heptan-2-one hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C[C@]1(C2(C)C)C(=O)CC2CC1 CJUUXMZGIUATKN-YJKKXFLHSA-N 0.000 description 1
• FGBVMEFLDMYIGV-WIZOSFNBSA-N (1R,3S)-1-(aminomethyl)-6-methyl-3-[1-(1-phenylethyl)piperidin-4-yl]-3,4-dihydro-1H-isochromen-5-ol dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1C(C)C1=CC=CC=C1 FGBVMEFLDMYIGV-WIZOSFNBSA-N 0.000 description 1
• RNCCTZSCEKHREN-USLJDWOKSA-N (1R,3S)-1-(aminomethyl)-6-methyl-3-[1-[(1-methylbenzimidazol-2-yl)methyl]piperidin-4-yl]-3,4-dihydro-1H-isochromen-5-ol trihydrochloride Chemical compound Cl.Cl.Cl.C1=CC=C2N(C)C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=NC2=C1 RNCCTZSCEKHREN-USLJDWOKSA-N 0.000 description 1
• UWNAWBDOPMVTQT-FQFBWUQZSA-N (1R,3S)-1-(aminomethyl)-6-methyl-3-[1-[(1-methylindol-3-yl)methyl]piperidin-4-yl]-3,4-dihydro-1H-isochromen-5-ol trihydrochloride Chemical compound Cl.Cl.Cl.C1=CC=C2C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CN(C)C2=C1 UWNAWBDOPMVTQT-FQFBWUQZSA-N 0.000 description 1
• CJUUXMZGIUATKN-TXLCXATLSA-N (1S)-1-[[4-[(1R,3S)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1H-isochromen-3-yl]piperidin-1-yl]sulfonylmethyl]-7,7-dimethylbicyclo[2.2.1]heptan-2-one hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C[C@@]1(C2(C)C)C(=O)CC2CC1 CJUUXMZGIUATKN-TXLCXATLSA-N 0.000 description 1
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
• FBNREZBXSPKZAV-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-(1-benzylpiperidin-4-yl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC=C1 FBNREZBXSPKZAV-IXOXMDGESA-N 0.000 description 1
• RZDMBBKXHPSREQ-VROPFNGYSA-N (1r,3s)-1-(aminomethyl)-3-(1-benzylsulfonylpiperidin-4-yl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)CC1=CC=CC=C1 RZDMBBKXHPSREQ-VROPFNGYSA-N 0.000 description 1
• QRNWOVHIGKUADJ-JYRWABTFSA-N (1r,3s)-1-(aminomethyl)-3-(1-butylpiperidin-4-yl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CN(CCCC)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 QRNWOVHIGKUADJ-JYRWABTFSA-N 0.000 description 1
• QZOJKYSWGFYCIY-OALUTQOASA-N (1r,3s)-1-(aminomethyl)-3-(1-butylsulfonylpiperidin-4-yl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CN(S(=O)(=O)CCCC)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 QZOJKYSWGFYCIY-OALUTQOASA-N 0.000 description 1
• UQHIOHUCAWGTHR-HLRBRJAUSA-N (1r,3s)-1-(aminomethyl)-3-(1-butylsulfonylpiperidin-4-yl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CN(S(=O)(=O)CCCC)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 UQHIOHUCAWGTHR-HLRBRJAUSA-N 0.000 description 1
• IVTPNYYUYXTGHX-IRXDYDNUSA-N (1r,3s)-1-(aminomethyl)-3-(1-ethylsulfonylpiperidin-4-yl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CN(S(=O)(=O)CC)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 IVTPNYYUYXTGHX-IRXDYDNUSA-N 0.000 description 1
• KYRPLEWNSGPBRQ-QJHJCNPRSA-N (1r,3s)-1-(aminomethyl)-3-(1-ethylsulfonylpiperidin-4-yl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CN(S(=O)(=O)CC)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 KYRPLEWNSGPBRQ-QJHJCNPRSA-N 0.000 description 1
• XWWDHWQDKSEFND-YPSJUKSRSA-N (1r,3s)-1-(aminomethyl)-3-[1-(1-benzothiophen-3-ylmethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1=CC=C2C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CSC2=C1 XWWDHWQDKSEFND-YPSJUKSRSA-N 0.000 description 1
• LKZMWGCDPWFCEK-GDUXWEAWSA-N (1r,3s)-1-(aminomethyl)-3-[1-(2,2-diphenylethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC(C=1C=CC=CC=1)C1=CC=CC=C1 LKZMWGCDPWFCEK-GDUXWEAWSA-N 0.000 description 1
• SNWQTEFVRHXJGN-WLKYSPGFSA-N (1r,3s)-1-(aminomethyl)-3-[1-(2,3-dihydro-1h-inden-2-yl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1C2=CC=CC=C2CC1N(CC1)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 SNWQTEFVRHXJGN-WLKYSPGFSA-N 0.000 description 1
• RGVKHSKZIZNDMH-FKLPMGAJSA-N (1r,3s)-1-(aminomethyl)-3-[1-(2,5-dichlorophenyl)sulfonylpiperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC(Cl)=CC=C1Cl RGVKHSKZIZNDMH-FKLPMGAJSA-N 0.000 description 1
• DXKGUJKNZYWFHZ-SZKOKKDDSA-N (1r,3s)-1-(aminomethyl)-3-[1-(2-hydroxyethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN(CCO)CC1 DXKGUJKNZYWFHZ-SZKOKKDDSA-N 0.000 description 1
• NHRIKODWRNHLPH-UKOKCHKQSA-N (1r,3s)-1-(aminomethyl)-3-[1-(3,4-dihydro-1h-isoquinolin-2-ylsulfonyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2CN1S(=O)(=O)N(CC1)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 NHRIKODWRNHLPH-UKOKCHKQSA-N 0.000 description 1
• HYXQAPNJVYDGNV-IUQUCOCYSA-N (1r,3s)-1-(aminomethyl)-3-[1-(3,4-dimethoxyphenyl)sulfonylpiperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 HYXQAPNJVYDGNV-IUQUCOCYSA-N 0.000 description 1
• WVFREWMYFIQRHH-UKOKCHKQSA-N (1r,3s)-1-(aminomethyl)-3-[1-(4-tert-butylphenyl)sulfonylpiperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 WVFREWMYFIQRHH-UKOKCHKQSA-N 0.000 description 1
• ISZDRKXEFUPQGJ-SFTDATJTSA-N (1r,3s)-1-(aminomethyl)-3-[1-(benzenesulfonyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC=CC=C1 ISZDRKXEFUPQGJ-SFTDATJTSA-N 0.000 description 1
• BEDUOAIDFCKKDF-GUTACTQSSA-N (1r,3s)-1-(aminomethyl)-3-[1-(benzenesulfonyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC=CC=C1 BEDUOAIDFCKKDF-GUTACTQSSA-N 0.000 description 1
• VDVTZMBYVQYKFD-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-(cyclohexylmethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1CCCCC1 VDVTZMBYVQYKFD-IXOXMDGESA-N 0.000 description 1
• AXGQDQOXXIBHNE-JYRWABTFSA-N (1r,3s)-1-(aminomethyl)-3-[1-(cyclopropylmethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1CC1 AXGQDQOXXIBHNE-JYRWABTFSA-N 0.000 description 1
• RFNAOFQSECSMRX-TULUPMBKSA-N (1r,3s)-1-(aminomethyl)-3-[1-(furan-3-ylmethyl)piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC=1C=COC=1 RFNAOFQSECSMRX-TULUPMBKSA-N 0.000 description 1
• ANEQVUKOPOAFSK-YBZGWEFGSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(1-benzylindol-3-yl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC(C1=CC=CC=C11)=CN1CC1=CC=CC=C1 ANEQVUKOPOAFSK-YBZGWEFGSA-N 0.000 description 1
• SPKLAFBRQOMSRQ-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(2,4-dichlorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(Cl)C=C1Cl SPKLAFBRQOMSRQ-IXOXMDGESA-N 0.000 description 1
• AJKXVRZSVJKSFG-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(2,4-difluorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(F)C=C1F AJKXVRZSVJKSFG-IXOXMDGESA-N 0.000 description 1
• SVGCTUDOPYSUQD-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(2-chlorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC=C1Cl SVGCTUDOPYSUQD-IXOXMDGESA-N 0.000 description 1
• LWWOFOXYUHQGAE-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(2-fluorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC=C1F LWWOFOXYUHQGAE-IXOXMDGESA-N 0.000 description 1
• BCMGJGLIDOSHEB-YPSJUKSRSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(2-methoxyphenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.COC1=CC=CC=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 BCMGJGLIDOSHEB-YPSJUKSRSA-N 0.000 description 1
• DTSAENPYLLDUHO-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(Cl)C(Cl)=C1 DTSAENPYLLDUHO-IXOXMDGESA-N 0.000 description 1
• UQHOKYAIQBBBPA-VROPFNGYSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3,4-dichlorophenyl)methylsulfonyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)CC1=CC=C(Cl)C(Cl)=C1 UQHOKYAIQBBBPA-VROPFNGYSA-N 0.000 description 1
• FECFZMVKPBRIFI-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3,4-difluorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(F)C(F)=C1 FECFZMVKPBRIFI-IXOXMDGESA-N 0.000 description 1
• PCFOTDOFNDPTQI-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3-chlorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC(Cl)=C1 PCFOTDOFNDPTQI-IXOXMDGESA-N 0.000 description 1
• ZULBJWYZOTVDOH-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3-fluorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC(F)=C1 ZULBJWYZOTVDOH-IXOXMDGESA-N 0.000 description 1
• XBYADTHKXPWOKZ-YPSJUKSRSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(3-methoxyphenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.COC1=CC=CC(CN2CCC(CC2)[C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)=C1 XBYADTHKXPWOKZ-YPSJUKSRSA-N 0.000 description 1
• ZNPSMOWBKMDEFX-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(Cl)C=C1 ZNPSMOWBKMDEFX-IXOXMDGESA-N 0.000 description 1
• IAGPUSUYEKFSGT-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[(4-hydroxyphenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(O)C=C1 IAGPUSUYEKFSGT-IXOXMDGESA-N 0.000 description 1
• YCQYQEBSTZJGAH-YPSJUKSRSA-N (1r,3s)-1-(aminomethyl)-3-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1=CC(OC)=CC=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 YCQYQEBSTZJGAH-YPSJUKSRSA-N 0.000 description 1
• GDJBEHPNVFRXBT-YPSJUKSRSA-N (1r,3s)-1-(aminomethyl)-3-[1-[2-(3-chlorophenyl)ethyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCC1=CC=CC(Cl)=C1 GDJBEHPNVFRXBT-YPSJUKSRSA-N 0.000 description 1
• UIBZSNOFBJGVEJ-NVDYSTOVSA-N (1r,3s)-1-(aminomethyl)-3-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)-2-methylpropyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound FC1=CC=C2C(CC(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C)C(O)=C4C3)C)=NOC2=C1 UIBZSNOFBJGVEJ-NVDYSTOVSA-N 0.000 description 1
• BZZIQFLYXAOKNK-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2,5-bis(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC(C(F)(F)F)=CC=C1C(F)(F)F BZZIQFLYXAOKNK-IXOXMDGESA-N 0.000 description 1
• ROYPJDWIBCWVIH-HRIAXCGHSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC(C(F)(F)F)=C1Cl ROYPJDWIBCWVIH-HRIAXCGHSA-N 0.000 description 1
• GZKSRFQZWAGSLX-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2-chloro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC(C(F)(F)F)=CC=C1Cl GZKSRFQZWAGSLX-IXOXMDGESA-N 0.000 description 1
• PHIAICCHGIIHPU-HRIAXCGHSA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2-fluoro-3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC(C(F)(F)F)=C1F PHIAICCHGIIHPU-HRIAXCGHSA-N 0.000 description 1
• NHIGVNRZXOHQPN-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(C(F)(F)F)C=C1F NHIGVNRZXOHQPN-IXOXMDGESA-N 0.000 description 1
• UVYLZJINPMHLNN-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[[2-fluoro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC(C(F)(F)F)=CC=C1F UVYLZJINPMHLNN-IXOXMDGESA-N 0.000 description 1
• PFUCCOOEOVYWHX-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[[3-fluoro-4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(C(F)(F)F)C(F)=C1 PFUCCOOEOVYWHX-IXOXMDGESA-N 0.000 description 1
• DYKIAKGWPLPKGQ-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC(F)=CC(C(F)(F)F)=C1 DYKIAKGWPLPKGQ-IXOXMDGESA-N 0.000 description 1
• PKIJIPBSKKNXNZ-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(Cl)C(C(F)(F)F)=C1 PKIJIPBSKKNXNZ-IXOXMDGESA-N 0.000 description 1
• AURKRYGBCPJXFA-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-3-[1-[[4-fluoro-3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(F)C(C(F)(F)F)=C1 AURKRYGBCPJXFA-IXOXMDGESA-N 0.000 description 1
• WQCYSRKRYFDSAW-DKIIUIKKSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-(1-naphthalen-2-ylsulfonylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1=CC=CC2=CC(S(=O)(=O)N3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=C21 WQCYSRKRYFDSAW-DKIIUIKKSA-N 0.000 description 1
• WCBJOQFNHYUPMR-SJEIDVEUSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-(1-octylsulfonylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CN(S(=O)(=O)CCCCCCCC)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 WCBJOQFNHYUPMR-SJEIDVEUSA-N 0.000 description 1
• WJESREZLLGPWMU-FKLPMGAJSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-(1-piperidin-1-ylsulfonylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)N1CCCCC1 WJESREZLLGPWMU-FKLPMGAJSA-N 0.000 description 1
• PFCVDBMNNMIPQT-ROUUACIJSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-(1-propan-2-ylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CN(C(C)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 PFCVDBMNNMIPQT-ROUUACIJSA-N 0.000 description 1
• AHPZHEYQUUEBJT-MPGISEFESA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-(1-propan-2-ylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CN(C(C)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 AHPZHEYQUUEBJT-MPGISEFESA-N 0.000 description 1
• LKZAVLRPBJLZLW-APTPAJQOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-(1-propan-2-ylsulfonylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CN(S(=O)(=O)C(C)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 LKZAVLRPBJLZLW-APTPAJQOSA-N 0.000 description 1
• CJPIZJGNIUPEIG-WIZOSFNBSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(1-phenylethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1C(C)C1=CC=CC=C1 CJPIZJGNIUPEIG-WIZOSFNBSA-N 0.000 description 1
• XKZQIYALKCXTIW-QBANDZAYSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(1-phenylpropan-2-yl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1C(C)CC1=CC=CC=C1 XKZQIYALKCXTIW-QBANDZAYSA-N 0.000 description 1
• GCAHTIVERRMHFF-MOGJOVFKSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(2,2,2-trifluoroethylsulfonyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN(S(=O)(=O)CC(F)(F)F)CC1 GCAHTIVERRMHFF-MOGJOVFKSA-N 0.000 description 1
• XEYSFZRGOKEOHD-OALUTQOASA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(2-methylpropyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CN(CC(C)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 XEYSFZRGOKEOHD-OALUTQOASA-N 0.000 description 1
• FZVCLQXIHVKITF-JYRWABTFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(2-methylpropyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CN(CC(C)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 FZVCLQXIHVKITF-JYRWABTFSA-N 0.000 description 1
• VUJAYYMAZVQUFA-WMXJXTQLSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(2-naphthalen-1-ylethylsulfonyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1=CC=C2C(CCS(=O)(=O)N3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=CC2=C1 VUJAYYMAZVQUFA-WMXJXTQLSA-N 0.000 description 1
• SPXYDOTZXCVUKU-QBANDZAYSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(2-phenylpropyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CC(C)C1=CC=CC=C1 SPXYDOTZXCVUKU-QBANDZAYSA-N 0.000 description 1
• XDWXYDFYIIQAKL-TULUPMBKSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(3-methylbutyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CN(CCC(C)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 XDWXYDFYIIQAKL-TULUPMBKSA-N 0.000 description 1
• WHQGRJCQWHRMHY-UYSMMYKSSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(3-phenylbutyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)C1=CC=CC=C1 WHQGRJCQWHRMHY-UYSMMYKSSA-N 0.000 description 1
• SYMUTJXKSHIQDJ-WLKYSPGFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(3-phenylpropyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCCC1=CC=CC=C1 SYMUTJXKSHIQDJ-WLKYSPGFSA-N 0.000 description 1
• FBDORJBAFZGURI-UKOKCHKQSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(4-propan-2-ylphenyl)sulfonylpiperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1=CC(C(C)C)=CC=C1S(=O)(=O)N1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 FBDORJBAFZGURI-UKOKCHKQSA-N 0.000 description 1
• BUPHNVJIGNSPIB-HWTGJJCHSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(naphthalen-1-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1=CC=C2C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=CC2=C1 BUPHNVJIGNSPIB-HWTGJJCHSA-N 0.000 description 1
• LHPDNPFIDCPMTR-HWTGJJCHSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(naphthalen-2-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1=CC=CC2=CC(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=C21 LHPDNPFIDCPMTR-HWTGJJCHSA-N 0.000 description 1
• RUOGIFVUDFKGQE-HRIAXCGHSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC=N1 RUOGIFVUDFKGQE-HRIAXCGHSA-N 0.000 description 1
• FWMCXSSJTSLXQN-HRIAXCGHSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(pyridin-3-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CN=C1 FWMCXSSJTSLXQN-HRIAXCGHSA-N 0.000 description 1
• MZDFSUPASOASTD-HRIAXCGHSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(pyridin-4-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=NC=C1 MZDFSUPASOASTD-HRIAXCGHSA-N 0.000 description 1
• NLEZOVZRSFSMJA-LXTBHBSOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(quinolin-2-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1=CC=CC2=NC(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=C21 NLEZOVZRSFSMJA-LXTBHBSOSA-N 0.000 description 1
• CTFXUQKKCLAIIM-LXTBHBSOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(quinolin-3-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1=CC=CC2=CC(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CN=C21 CTFXUQKKCLAIIM-LXTBHBSOSA-N 0.000 description 1
• YFAMKHIISMTSIQ-LXTBHBSOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(quinolin-4-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1=CC=C2C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC=NC2=C1 YFAMKHIISMTSIQ-LXTBHBSOSA-N 0.000 description 1
• BFZCRQVFSWLRPG-TULUPMBKSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(thiophen-2-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CS1 BFZCRQVFSWLRPG-TULUPMBKSA-N 0.000 description 1
• UHEHJAGJTNXCDI-TULUPMBKSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-(thiophen-3-ylmethyl)piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC=1C=CSC=1 UHEHJAGJTNXCDI-TULUPMBKSA-N 0.000 description 1
• XMEHQDQJXIPICR-LXTBHBSOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(1-methylindol-2-yl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1=CC=C2N(C)C(CN3CCC(CC3)[C@H]3O[C@@H](CN)C4=CC=C(C(=C4C3)O)C)=CC2=C1 XMEHQDQJXIPICR-LXTBHBSOSA-N 0.000 description 1
• AZCHDUNUNAYKRY-YPSJUKSRSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(2-methylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.CC1=CC=CC=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 AZCHDUNUNAYKRY-YPSJUKSRSA-N 0.000 description 1
• JHDNHWLKIAEXAU-VROPFNGYSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(2-nitrophenyl)methylsulfonyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)CC1=CC=CC=C1[N+]([O-])=O JHDNHWLKIAEXAU-VROPFNGYSA-N 0.000 description 1
• NBBYWYOYSHTXKM-YPSJUKSRSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(3-methyl-1-benzothiophen-2-yl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.S1C2=CC=CC=C2C(C)=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 NBBYWYOYSHTXKM-YPSJUKSRSA-N 0.000 description 1
• TZJSPMLDUHFWTQ-YPSJUKSRSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(3-methylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.CC1=CC=CC(CN2CCC(CC2)[C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)=C1 TZJSPMLDUHFWTQ-YPSJUKSRSA-N 0.000 description 1
• LTXSLBFQIINDBK-YPSJUKSRSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(4-methylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1=CC(C)=CC=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 LTXSLBFQIINDBK-YPSJUKSRSA-N 0.000 description 1
• CLLNIZRGMNIZEW-NSOVKSMOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(4-phenoxyphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC(C=C1)=CC=C1OC1=CC=CC=C1 CLLNIZRGMNIZEW-NSOVKSMOSA-N 0.000 description 1
• FIGGZBJFSFIIDU-QLBXQKMFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(4-phenoxyphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC(C=C1)=CC=C1OC1=CC=CC=C1 FIGGZBJFSFIIDU-QLBXQKMFSA-N 0.000 description 1
• LYOUVKUOOKWGCY-QLBXQKMFSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(4-phenylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC(C=C1)=CC=C1C1=CC=CC=C1 LYOUVKUOOKWGCY-QLBXQKMFSA-N 0.000 description 1
• QAXJQPLSVXODLM-LXTBHBSOSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[(4-propan-2-ylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1=CC(C(C)C)=CC=C1CN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 QAXJQPLSVXODLM-LXTBHBSOSA-N 0.000 description 1
• LRFRRSVLRIGQHJ-FKLPMGAJSA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[2-(trifluoromethyl)phenyl]sulfonylpiperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1S(=O)(=O)C1=CC=CC=C1C(F)(F)F LRFRRSVLRIGQHJ-FKLPMGAJSA-N 0.000 description 1
• ZHOXZLKDSMWAPC-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[[2-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC=C1C(F)(F)F ZHOXZLKDSMWAPC-IXOXMDGESA-N 0.000 description 1
• FCKVIASBOCOOPG-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[[3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=CC(C(F)(F)F)=C1 FCKVIASBOCOOPG-IXOXMDGESA-N 0.000 description 1
• REJXLHVHWOIZNP-IXOXMDGESA-N (1r,3s)-1-(aminomethyl)-6-methyl-3-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CC1=CC=C(C(F)(F)F)C=C1 REJXLHVHWOIZNP-IXOXMDGESA-N 0.000 description 1
• OJGFVNGKSLRIBZ-UIOOFZCWSA-N (1r,3s)-3-(1-benzylpiperidin-4-yl)-1-(diethylaminomethyl)-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CN(CC)CC)CCN1CC1=CC=CC=C1 OJGFVNGKSLRIBZ-UIOOFZCWSA-N 0.000 description 1
• ARMBTBRZUSBEGS-UIOOFZCWSA-N (1r,3s)-3-(1-benzylpiperidin-4-yl)-1-[(cyclobutylamino)methyl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C([C@H]1C2=CC=C(C(=C2C[C@H](O1)C1CCN(CC=2C=CC=CC=2)CC1)O)C)NC1CCC1 ARMBTBRZUSBEGS-UIOOFZCWSA-N 0.000 description 1
• ROUWUDWWWUOBOZ-ZEQRLZLVSA-N (1r,3s)-3-(1-benzylpiperidin-4-yl)-1-[(dimethylamino)methyl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol Chemical compound C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CN(C)C)CCN1CC1=CC=CC=C1 ROUWUDWWWUOBOZ-ZEQRLZLVSA-N 0.000 description 1
• ZIQRGTOPAXBCCU-QLBXQKMFSA-N (1r,3s)-3-(1-benzylpiperidin-4-yl)-1-[(dipropylamino)methyl]-6-methyl-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CN(CCC)CCC)CCN1CC1=CC=CC=C1 ZIQRGTOPAXBCCU-QLBXQKMFSA-N 0.000 description 1
• MNDTWSMYLFFVDA-YPSJUKSRSA-N (1r,3s)-3-[1-[(3,4-difluorophenyl)methyl]piperidin-4-yl]-6-methyl-1-(methylaminomethyl)-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(F)C(F)=C1 MNDTWSMYLFFVDA-YPSJUKSRSA-N 0.000 description 1
• RFDWQELVPFPUTL-YPSJUKSRSA-N (1r,3s)-3-[1-[(4-fluorophenyl)methyl]piperidin-4-yl]-6-methyl-1-(methylaminomethyl)-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(F)C=C1 RFDWQELVPFPUTL-YPSJUKSRSA-N 0.000 description 1
• HIHOSEXQUYVNEZ-WLKYSPGFSA-N (1r,3s)-3-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-6-methyl-1-(methylaminomethyl)-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(OC)C=C1 HIHOSEXQUYVNEZ-WLKYSPGFSA-N 0.000 description 1
• WGVMBJHHARYYKF-SZKOKKDDSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-(1-methylpiperidin-4-yl)-3,4-dihydro-1h-isochromen-5-ol;dihydrobromide Chemical compound Br.Br.C1([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN(C)CC1 WGVMBJHHARYYKF-SZKOKKDDSA-N 0.000 description 1
• KQPQNXFHJVVSIF-WLKYSPGFSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-[1-[(4-methylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(C)C=C1 KQPQNXFHJVVSIF-WLKYSPGFSA-N 0.000 description 1
• HFKPUHISOKPWDL-GDUXWEAWSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-[1-[(4-phenylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC(C=C1)=CC=C1C1=CC=CC=C1 HFKPUHISOKPWDL-GDUXWEAWSA-N 0.000 description 1
• WYFSNLOQKUETAB-HWTGJJCHSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-[1-[(4-propan-2-ylphenyl)methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(C(C)C)C=C1 WYFSNLOQKUETAB-HWTGJJCHSA-N 0.000 description 1
• ZMNSHLBGDKKVCG-SJEIDVEUSA-N (1r,3s)-6-methyl-1-(methylaminomethyl)-3-[1-[[4-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-3,4-dihydro-1h-isochromen-5-ol;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@H](C3=CC=C(C)C(O)=C3C2)CNC)CCN1CC1=CC=C(C(F)(F)F)C=C1 ZMNSHLBGDKKVCG-SJEIDVEUSA-N 0.000 description 1
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• VIYKYVYAKVNDPS-HKGPVOKGSA-N (2s)-2-azanyl-3-[3,4-bis(oxidanyl)phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 VIYKYVYAKVNDPS-HKGPVOKGSA-N 0.000 description 1
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• ZNBQMNLJFTYCHC-UHFFFAOYSA-N 1,1'-biphenyl;isocyanic acid Chemical class N=C=O.C1=CC=CC=C1C1=CC=CC=C1 ZNBQMNLJFTYCHC-UHFFFAOYSA-N 0.000 description 1
• UEMGWPRHOOEKTA-UHFFFAOYSA-N 1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1 UEMGWPRHOOEKTA-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
• WTADFWDVNWBPPA-YPSJUKSRSA-N 1-[2-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethyl]-3-(4-fluorophenyl)urea;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCNC(=O)NC1=CC=C(F)C=C1 WTADFWDVNWBPPA-YPSJUKSRSA-N 0.000 description 1
• IGMVYHODUVARJG-YPSJUKSRSA-N 1-[2-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethyl]-3-phenylurea;dihydrobromide Chemical compound Br.Br.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1CCNC(=O)NC1=CC=CC=C1 IGMVYHODUVARJG-YPSJUKSRSA-N 0.000 description 1
• IGWPBXRYAGVTGT-VROPFNGYSA-N 1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-2-phenylethanone;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)CC1=CC=CC=C1 IGWPBXRYAGVTGT-VROPFNGYSA-N 0.000 description 1
• CYUSLHNVEBHPFZ-HLRBRJAUSA-N 1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-3-methylbutan-1-one;hydrochloride Chemical compound Cl.C1CN(C(=O)CC(C)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 CYUSLHNVEBHPFZ-HLRBRJAUSA-N 0.000 description 1
• HYWQIYIUULSCOW-SJEIDVEUSA-N 1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-3-phenylpropan-1-one;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)CCC1=CC=CC=C1 HYWQIYIUULSCOW-SJEIDVEUSA-N 0.000 description 1
• YNHQWNJVVXUFPA-APTPAJQOSA-N 1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-1-one;hydrochloride Chemical compound Cl.C1CN(C(=O)CCC)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 YNHQWNJVVXUFPA-APTPAJQOSA-N 0.000 description 1
• WWNBSOGZQHCRKH-QJHJCNPRSA-N 1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethanone;hydrochloride Chemical compound Cl.C1CN(C(=O)C)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 WWNBSOGZQHCRKH-QJHJCNPRSA-N 0.000 description 1
• WMPHRIOTAXWHAN-GOTSBHOMSA-N 1-benzyl-4-[(1r,3s)-1-(bromomethyl)-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidine Chemical compound C1CC([C@H]2O[C@@H](CBr)C=3C=CC(C)=C(C=3C2)OC)CCN1CC1=CC=CC=C1 WMPHRIOTAXWHAN-GOTSBHOMSA-N 0.000 description 1
• ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 1
• RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
• QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
• JHKKTXXMAQLGJB-UHFFFAOYSA-N 2-(methylamino)phenol Chemical compound CNC1=CC=CC=C1O JHKKTXXMAQLGJB-UHFFFAOYSA-N 0.000 description 1
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
• QUDZAFKCASPJLX-UHFFFAOYSA-N 2-aminophenol;hydron;chloride Chemical compound Cl.NC1=CC=CC=C1O QUDZAFKCASPJLX-UHFFFAOYSA-N 0.000 description 1
• SMKOMPIOXYJADT-UHFFFAOYSA-N 2-fluoro-5-(trifluoromethyl)aniline hydrobromide Chemical compound Br.NC1=CC(C(F)(F)F)=CC=C1F SMKOMPIOXYJADT-UHFFFAOYSA-N 0.000 description 1
• HDBRUGFOHGDYRJ-UHFFFAOYSA-N 2-fluoroaniline;hydrochloride Chemical compound Cl.NC1=CC=CC=C1F HDBRUGFOHGDYRJ-UHFFFAOYSA-N 0.000 description 1
• 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
• WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
• QGXMHCMPIAYMGT-UHFFFAOYSA-N 2-phenylbutanoyl chloride Chemical compound CCC(C(Cl)=O)C1=CC=CC=C1 QGXMHCMPIAYMGT-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 1
• 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
• DFATXMYLKPCSCX-UHFFFAOYSA-N 3-methylsuccinic anhydride Chemical compound CC1CC(=O)OC1=O DFATXMYLKPCSCX-UHFFFAOYSA-N 0.000 description 1
• RYQIICZFDGUUPG-GOTSBHOMSA-N 4-[(1r,3s)-1-(bromomethyl)-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]-1-[[4-(trifluoromethyl)phenyl]methyl]piperidine Chemical compound C1CC([C@H]2O[C@@H](CBr)C=3C=CC(C)=C(C=3C2)OC)CCN1CC1=CC=C(C(F)(F)F)C=C1 RYQIICZFDGUUPG-GOTSBHOMSA-N 0.000 description 1
• YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• CIURLBZXVDEBCC-UHFFFAOYSA-N 4-chloro-n-(4-oxobutan-2-yl)benzamide Chemical compound O=CCC(C)NC(=O)C1=CC=C(Cl)C=C1 CIURLBZXVDEBCC-UHFFFAOYSA-N 0.000 description 1
• WTOPXWFQIAYEHN-MPEZEPLXSA-N 4-chloro-n-[4-[4-[(1r,3s)-1-(formamidomethyl)-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]benzamide Chemical compound C1CC([C@H]2O[C@@H](CNC=O)C=3C=CC(C)=C(C=3C2)OC)CCN1CCC(C)NC(=O)C1=CC=C(Cl)C=C1 WTOPXWFQIAYEHN-MPEZEPLXSA-N 0.000 description 1
• WTOPXWFQIAYEHN-UHFFFAOYSA-N 4-chloro-n-[4-[4-[1-(formamidomethyl)-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]benzamide Chemical compound C1C=2C(OC)=C(C)C=CC=2C(CNC=O)OC1C(CC1)CCN1CCC(C)NC(=O)C1=CC=C(Cl)C=C1 WTOPXWFQIAYEHN-UHFFFAOYSA-N 0.000 description 1
• KGOSTQLVRCHXQG-DQEYMECFSA-N 4-fluoro-n-[2-[4-[(1r,3s)-1-(formamidomethyl)-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethyl]benzamide Chemical compound C1CC([C@H]2O[C@@H](CNC=O)C=3C=CC(C)=C(C=3C2)OC)CCN1CCNC(=O)C1=CC=C(F)C=C1 KGOSTQLVRCHXQG-DQEYMECFSA-N 0.000 description 1
• RQCWFLTXPVGHLK-UHFFFAOYSA-N 4-fluoroaniline;hydrochloride Chemical compound Cl.NC1=CC=C(F)C=C1 RQCWFLTXPVGHLK-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 description 1
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-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
• 208000017194 Affective disease Diseases 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• 102000009027 Albumins Human genes 0.000 description 1
• 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 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
• 208000037157 Azotemia Diseases 0.000 description 1
• 229910015844 BCl3 Inorganic materials 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• TURBNCFREGSEBU-UHFFFAOYSA-N C1(=CC=C(C=C1)S(=O)(=O)O)C.OCCS(=O)(=O)O Chemical compound C1(=CC=C(C=C1)S(=O)(=O)O)C.OCCS(=O)(=O)O TURBNCFREGSEBU-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 206010007559 Cardiac failure congestive Diseases 0.000 description 1
• 206010048610 Cardiotoxicity Diseases 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 208000013641 Cerebrofacial arteriovenous metameric syndrome Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000022497 Cocaine-Related disease Diseases 0.000 description 1
• 229940126657 Compound 17 Drugs 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 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 1
• 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 1
• 101150101796 D2L gene Proteins 0.000 description 1
• 206010012397 Depression suicidal Diseases 0.000 description 1
• 208000020401 Depressive disease Diseases 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 102000004980 Dopamine D2 Receptors Human genes 0.000 description 1
• 108090001111 Dopamine D2 Receptors Proteins 0.000 description 1
• 229940121891 Dopamine receptor antagonist Drugs 0.000 description 1
• 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 1
• 241000282326 Felis catus Species 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 208000005577 Gastroenteritis Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 208000031361 Hiccup Diseases 0.000 description 1
• 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
• 208000023105 Huntington disease Diseases 0.000 description 1
• 208000001953 Hypotension Diseases 0.000 description 1
• 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 1
• 229910010082 LiAlH Inorganic materials 0.000 description 1
• 229910015853 MSO4 Inorganic materials 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 206010026749 Mania Diseases 0.000 description 1
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
• 208000016285 Movement disease Diseases 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• YFRLGISFXFWINL-MCFYZFDISA-N N-methyl-1-[(1R,3S)-6-methyl-3-[1-(2-phenylbutyl)piperidin-4-yl]-5-propan-2-yloxy-3,4-dihydro-1H-isochromen-1-yl]methanamine Chemical compound C1CC([C@H]2O[C@@H](CNC)C3=C(C(=C(C)C=C3)OC(C)C)C2)CCN1CC(CC)C1=CC=CC=C1 YFRLGISFXFWINL-MCFYZFDISA-N 0.000 description 1
• 206010057852 Nicotine dependence Diseases 0.000 description 1
• IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 229920001774 Perfluoroether Polymers 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 208000028017 Psychotic disease Diseases 0.000 description 1
• 206010061921 Psychotic disorder due to a general medical condition Diseases 0.000 description 1
• 229910019020 PtO2 Inorganic materials 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 239000002262 Schiff base Substances 0.000 description 1
• 150000004753 Schiff bases Chemical class 0.000 description 1
• 206010039897 Sedation Diseases 0.000 description 1
• 244000000231 Sesamum indicum Species 0.000 description 1
• 235000003434 Sesamum indicum Nutrition 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 208000014584 Specific learning disability Diseases 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 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 1
• 229930006000 Sucrose Natural products 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 208000025569 Tobacco Use disease Diseases 0.000 description 1
• 208000000323 Tourette Syndrome Diseases 0.000 description 1
• 208000016620 Tourette disease Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 102000004142 Trypsin Human genes 0.000 description 1
• 108090000631 Trypsin Proteins 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
• XSVCMOQTBXMEJT-GUTACTQSSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(2-hydroxyphenyl)methanone;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C1=CC=CC=C1O XSVCMOQTBXMEJT-GUTACTQSSA-N 0.000 description 1
• ZHRDLDVFUMKTJW-GUTACTQSSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(4-bromophenyl)methanone;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C1=CC=C(Br)C=C1 ZHRDLDVFUMKTJW-GUTACTQSSA-N 0.000 description 1
• IVDGDSRWPGTJFK-GUTACTQSSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(4-chlorophenyl)methanone;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C1=CC=C(Cl)C=C1 IVDGDSRWPGTJFK-GUTACTQSSA-N 0.000 description 1
• PPIYHKFDQYRQLD-GUTACTQSSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(4-fluorophenyl)methanone;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C1=CC=C(F)C=C1 PPIYHKFDQYRQLD-GUTACTQSSA-N 0.000 description 1
• IWHUFXLAORJIPL-VROPFNGYSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(4-methoxyphenyl)methanone;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C(=O)N1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 IWHUFXLAORJIPL-VROPFNGYSA-N 0.000 description 1
• XLKAGLVHGVHBGL-WMXJXTQLSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-(4-phenylphenyl)methanone;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 XLKAGLVHGVHBGL-WMXJXTQLSA-N 0.000 description 1
• BDKCSWBROROJIS-HLRBRJAUSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-morpholin-4-ylmethanone;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)N1CCOCC1 BDKCSWBROROJIS-HLRBRJAUSA-N 0.000 description 1
• DNUBLZSBYSESJL-DKIIUIKKSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-phenothiazin-10-ylmethanone;hydrochloride Chemical compound Cl.C12=CC=CC=C2SC2=CC=CC=C2N1C(=O)N(CC1)CCC1[C@H]1O[C@@H](CN)C2=CC=C(C)C(O)=C2C1 DNUBLZSBYSESJL-DKIIUIKKSA-N 0.000 description 1
• NTFNUWSDWAPXFE-GUTACTQSSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-phenylmethanone;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)C1=CC=CC=C1 NTFNUWSDWAPXFE-GUTACTQSSA-N 0.000 description 1
• UBDSUARPNUOTFF-FKLPMGAJSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-piperidin-1-ylmethanone;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)N1CCCCC1 UBDSUARPNUOTFF-FKLPMGAJSA-N 0.000 description 1
• XTCCCYDBWVKAPI-HLRBRJAUSA-N [4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-pyrrolidin-1-ylmethanone;hydrochloride Chemical compound Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C(=C3C2)O)C)CCN1C(=O)N1CCCC1 XTCCCYDBWVKAPI-HLRBRJAUSA-N 0.000 description 1
• XWGFTYTXKZMCRC-UHFFFAOYSA-K [Ru+3].CC([O-])=O.CC([O-])=O.CC([O-])=O.C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 Chemical compound [Ru+3].CC([O-])=O.CC([O-])=O.CC([O-])=O.C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 XWGFTYTXKZMCRC-UHFFFAOYSA-K 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
• 159000000021 acetate salts Chemical class 0.000 description 1
• LSTDYDRCKUBPDI-UHFFFAOYSA-N acetic acid cetyl ester Natural products CCCCCCCCCCCCCCCCOC(C)=O LSTDYDRCKUBPDI-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 238000010306 acid treatment Methods 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
• 230000001464 adherent effect Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 239000005456 alcohol based solvent Substances 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
• 150000008041 alkali metal carbonates Chemical class 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• 125000000304 alkynyl group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• VCDGSBJCRYTLNU-AZWGFFAPSA-N alpine borane Chemical compound C1CCC2CCCC1B2[C@@H]1C[C@H](C2(C)C)C[C@H]2[C@H]1C VCDGSBJCRYTLNU-AZWGFFAPSA-N 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 238000005576 amination reaction Methods 0.000 description 1
• 125000004103 aminoalkyl group Chemical group 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 230000002547 anomalous effect Effects 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000001078 anti-cholinergic effect Effects 0.000 description 1
• 230000001430 anti-depressive effect Effects 0.000 description 1
• 230000002932 anti-schizophrenic effect Effects 0.000 description 1
• 229940005529 antipsychotics Drugs 0.000 description 1
• 230000036506 anxiety Effects 0.000 description 1
• VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
• 229960004046 apomorphine Drugs 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000011260 aqueous acid Substances 0.000 description 1
• 239000012223 aqueous fraction Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 150000003934 aromatic aldehydes Chemical class 0.000 description 1
• 238000013528 artificial neural network Methods 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000004658 aryl carbonyl amino group Chemical group 0.000 description 1
• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 210000003192 autonomic ganglia Anatomy 0.000 description 1
• JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
• OVLHQUWQINALPR-UHFFFAOYSA-N azane;dichloromethane Chemical compound N.ClCCl OVLHQUWQINALPR-UHFFFAOYSA-N 0.000 description 1
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
• DLGYNVMUCSTYDQ-UHFFFAOYSA-N azane;pyridine Chemical compound N.C1=CC=NC=C1 DLGYNVMUCSTYDQ-UHFFFAOYSA-N 0.000 description 1
• 210000004227 basal ganglia Anatomy 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical class ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 239000012455 biphasic mixture Substances 0.000 description 1
• 208000028683 bipolar I disease Diseases 0.000 description 1
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 229910000085 borane Inorganic materials 0.000 description 1
• MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
• 239000012888 bovine serum Substances 0.000 description 1
• 150000001649 bromium compounds Chemical class 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 231100000259 cardiotoxicity Toxicity 0.000 description 1
• 239000002327 cardiovascular agent Substances 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000003833 cell viability Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 229940049297 cetyl acetate Drugs 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 229920001429 chelating resin Polymers 0.000 description 1
• 238000000451 chemical ionisation Methods 0.000 description 1
• 239000007810 chemical reaction solvent Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 229960003920 cocaine Drugs 0.000 description 1
• 201000006145 cocaine dependence Diseases 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 230000003920 cognitive function Effects 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 239000002131 composite material Substances 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 229940125797 compound 12 Drugs 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940126142 compound 16 Drugs 0.000 description 1
• 229940125782 compound 2 Drugs 0.000 description 1
• 229940125961 compound 24 Drugs 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• 229940125877 compound 31 Drugs 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• 238000013211 curve analysis Methods 0.000 description 1
• 125000001316 cycloalkyl 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
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([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
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical class CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000000994 depressogenic effect Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 125000005117 dialkylcarbamoyl group Chemical group 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
• KUMNEOGIHFCNQW-UHFFFAOYSA-N diphenyl phosphite Chemical compound C=1C=CC=CC=1OP([O-])OC1=CC=CC=C1 KUMNEOGIHFCNQW-UHFFFAOYSA-N 0.000 description 1
• QPOWUYJWCJRLEE-UHFFFAOYSA-N dipyridin-2-ylmethanone Chemical compound C=1C=CC=NC=1C(=O)C1=CC=CC=N1 QPOWUYJWCJRLEE-UHFFFAOYSA-N 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• 239000000510 dopamine 1 receptor stimulating agent Substances 0.000 description 1
• 239000002804 dopamine agent Substances 0.000 description 1
• 206010013663 drug dependence Diseases 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 229920001971 elastomer Polymers 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 230000000095 emetic effect Effects 0.000 description 1
• 230000008451 emotion Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 125000001033 ether group Chemical group 0.000 description 1
• MZQXAVZPEZUJIJ-UHFFFAOYSA-N ethyl 2-(2-bromophenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC=C1Br MZQXAVZPEZUJIJ-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000004744 fabric Substances 0.000 description 1
• 235000021050 feed intake Nutrition 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 235000020375 flavoured syrup Nutrition 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 150000003948 formamides Chemical group 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• 230000008014 freezing Effects 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 210000005153 frontal cortex Anatomy 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 238000007306 functionalization reaction Methods 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 238000003306 harvesting Methods 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 210000005003 heart tissue Anatomy 0.000 description 1
• 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
• 125000006038 hexenyl group Chemical group 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• 230000036543 hypotension Effects 0.000 description 1
• 208000036260 idiopathic disease Diseases 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 230000010365 information processing Effects 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 150000004694 iodide salts Chemical class 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Substances CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 1
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
• 229910000103 lithium hydride Inorganic materials 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 208000024714 major depressive disease Diseases 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
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 210000005171 mammalian brain Anatomy 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
• 229910052753 mercury Inorganic materials 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 230000008450 motivation Effects 0.000 description 1
• 230000007659 motor function Effects 0.000 description 1
• HHRBHXDVRRCGQY-UHFFFAOYSA-N n-(2,2-dimethoxyethyl)formamide Chemical compound COC(OC)CNC=O HHRBHXDVRRCGQY-UHFFFAOYSA-N 0.000 description 1
• ZVHSEBGCZGEVGS-QLIGFRAYSA-N n-[1-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]-2-methylpentan-3-yl]-4-methylbenzamide;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CC(C)C(CC)NC(=O)C1=CC=C(C)C=C1 ZVHSEBGCZGEVGS-QLIGFRAYSA-N 0.000 description 1
• FEYPFSYZBDNBFM-WLKYSPGFSA-N n-[2-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]ethyl]-4-methylbenzamide;dihydrobromide Chemical compound Br.Br.C1=CC(C)=CC=C1C(=O)NCCN1CCC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CC1 FEYPFSYZBDNBFM-WLKYSPGFSA-N 0.000 description 1
• VGWJXSAGRJRVAQ-HEPGPWGBSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-2,4-dichlorobenzamide;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=C(Cl)C=C1Cl VGWJXSAGRJRVAQ-HEPGPWGBSA-N 0.000 description 1
• RXCDPSHTZFJFLV-UYSMMYKSSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-4-bromobenzamide;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=C(Br)C=C1 RXCDPSHTZFJFLV-UYSMMYKSSA-N 0.000 description 1
• MBGVPRPAYCIAOX-UYSMMYKSSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-4-fluorobenzamide;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=C(F)C=C1 MBGVPRPAYCIAOX-UYSMMYKSSA-N 0.000 description 1
• XGEKBHPTULVWMG-UYSMMYKSSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-4-nitrobenzamide;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=C([N+]([O-])=O)C=C1 XGEKBHPTULVWMG-UYSMMYKSSA-N 0.000 description 1
• UGICZONIGXTVJW-DCGLWWNUSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-hydroxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]benzamide;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H]2O[C@@H](CN)C3=CC=C(C)C(O)=C3C2)CCN1CCC(C)NC(=O)C1=CC=CC=C1 UGICZONIGXTVJW-DCGLWWNUSA-N 0.000 description 1
• RNJLQDKWMWPVRT-AIKKUKTPSA-N n-[4-[4-[(1r,3s)-1-(aminomethyl)-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-3-yl]piperidin-1-yl]butan-2-yl]-4-chlorobenzamide Chemical compound C1CC([C@H]2O[C@@H](CN)C=3C=CC(C)=C(C=3C2)OC)CCN1CCC(C)NC(=O)C1=CC=C(Cl)C=C1 RNJLQDKWMWPVRT-AIKKUKTPSA-N 0.000 description 1
• WMULIYTYTUDZBG-ZEQRLZLVSA-N n-[[(1r,3s)-3-(1-benzylpiperidin-4-yl)-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-1-yl]methyl]formamide Chemical compound C1CC([C@H]2O[C@@H](CNC=O)C=3C=CC(C)=C(C=3C2)OC)CCN1CC1=CC=CC=C1 WMULIYTYTUDZBG-ZEQRLZLVSA-N 0.000 description 1
• CLRKYKKTNDWFHB-JYRWABTFSA-N n-[[(1r,3s)-3-[1-(2-aminoethyl)piperidin-4-yl]-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-1-yl]methyl]formamide;dihydrochloride Chemical compound Cl.Cl.C1([C@H]2O[C@@H](CNC=O)C=3C=CC(C)=C(C=3C2)OC)CCN(CCN)CC1 CLRKYKKTNDWFHB-JYRWABTFSA-N 0.000 description 1
• UAWTZTBTCAMQKX-DQEYMECFSA-N n-[[(1r,3s)-3-[1-[2-[(4-fluorophenyl)carbamoylamino]ethyl]piperidin-4-yl]-5-methoxy-6-methyl-3,4-dihydro-1h-isochromen-1-yl]methyl]formamide Chemical compound C1CC([C@H]2O[C@@H](CNC=O)C=3C=CC(C)=C(C=3C2)OC)CCN1CCNC(=O)NC1=CC=C(F)C=C1 UAWTZTBTCAMQKX-DQEYMECFSA-N 0.000 description 1
• OQAGEPBRHVZAMW-ACFUZCEKSA-N n-[[(1r,3s)-6-methyl-3-[1-(2-phenylbutanoyl)piperidin-4-yl]-5-propan-2-yloxy-3,4-dihydro-1h-isochromen-1-yl]methyl]formamide Chemical compound C1CC([C@H]2O[C@@H](CNC=O)C3=CC=C(C)C(OC(C)C)=C3C2)CCN1C(=O)C(CC)C1=CC=CC=C1 OQAGEPBRHVZAMW-ACFUZCEKSA-N 0.000 description 1
• LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 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
• 230000001537 neural effect Effects 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
• 125000005246 nonafluorobutyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
• 229960002748 norepinephrine Drugs 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000013110 organic ligand Substances 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• BDOLXPFAFMNDOK-UHFFFAOYSA-N oxazaborolidine Chemical class B1CCON1 BDOLXPFAFMNDOK-UHFFFAOYSA-N 0.000 description 1
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 229910003445 palladium oxide Inorganic materials 0.000 description 1
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 239000003182 parenteral nutrition solution Substances 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• 125000006194 pentinyl group Chemical group 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
• DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical class O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
• 229940100595 phenylacetaldehyde Drugs 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000002985 plastic film Substances 0.000 description 1
• 229920006255 plastic film Polymers 0.000 description 1
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 230000002028 premature Effects 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 238000004321 preservation Methods 0.000 description 1
• 230000003518 presynaptic effect Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
• IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 238000002731 protein assay Methods 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 210000002637 putamen Anatomy 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 239000012429 reaction media Substances 0.000 description 1
• 230000003014 reinforcing effect Effects 0.000 description 1
• 210000005084 renal tissue Anatomy 0.000 description 1
• 238000009256 replacement therapy Methods 0.000 description 1
• 229910052703 rhodium Inorganic materials 0.000 description 1
• 239000010948 rhodium Substances 0.000 description 1
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
• 229910052707 ruthenium Inorganic materials 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 238000007790 scraping Methods 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 230000036280 sedation Effects 0.000 description 1
• XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
• 229940076279 serotonin Drugs 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 238000002633 shock therapy Methods 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 230000011273 social behavior Effects 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• VDZXAOBGHPKGCS-UHFFFAOYSA-M sodium;1,4-dioxane;hydroxide Chemical compound [OH-].[Na+].C1COCCO1 VDZXAOBGHPKGCS-UHFFFAOYSA-M 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 1
• 229950001675 spiperone Drugs 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000003461 sulfonyl halides Chemical class 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000004114 suspension culture Methods 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 238000002636 symptomatic treatment Methods 0.000 description 1
• 208000011580 syndromic disease Diseases 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
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical class O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
• 238000011287 therapeutic dose Methods 0.000 description 1
• 230000004797 therapeutic response Effects 0.000 description 1
• XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
• 125000005490 tosylate group Chemical group 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000003146 transient transfection Methods 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• 208000009852 uremia Diseases 0.000 description 1
• 239000002996 urinary tract agent Substances 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 230000024883 vasodilation Effects 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000008673 vomiting Effects 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• CITILBVTAYEWKR-UHFFFAOYSA-L zinc trifluoromethanesulfonate Chemical compound [Zn+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F CITILBVTAYEWKR-UHFFFAOYSA-L 0.000 description 1