NO311976B1 - Substituerte benzylaminer, deres anvendelse samt farmasöytisk formulering - Google Patents

Info

Publication number

NO311976B1

NO311976B1 NO19984836A NO984836A NO311976B1 NO 311976 B1 NO311976 B1 NO 311976B1 NO 19984836 A NO19984836 A NO 19984836A NO 984836 A NO984836 A NO 984836A NO 311976 B1 NO311976 B1 NO 311976B1

Authority

NO

Norway

Prior art keywords

benzisoxazol

benzenemethanamine

phenyl

formula

solution

Prior art date

1996-04-19

Links

• Espacenet
• Global Dossier
• Discuss

• 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
• 150000003939 benzylamines Chemical class 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 108
• 150000003839 salts Chemical class 0.000 claims description 42
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
• 239000001257 hydrogen Substances 0.000 claims description 35
• 229910052739 hydrogen Inorganic materials 0.000 claims description 35
• 239000012453 solvate Substances 0.000 claims description 27
• -1 cyano, carboxyl Chemical group 0.000 claims description 23
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• 125000000217 alkyl group Chemical group 0.000 claims description 15
• 150000002431 hydrogen Chemical class 0.000 claims description 15
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 150000002367 halogens Chemical group 0.000 claims description 14
• 125000001424 substituent group Chemical group 0.000 claims description 13
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
• 208000028017 Psychotic disease Diseases 0.000 claims description 7
• 208000019901 Anxiety disease Diseases 0.000 claims description 6
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 6
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 6
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
• AYDSLXXUAYWCBG-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine Chemical compound C=CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 AYDSLXXUAYWCBG-UHFFFAOYSA-N 0.000 claims description 4
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 125000000335 thiazolyl group Chemical group 0.000 claims description 4
• 206010002650 Anorexia nervosa and bulimia Diseases 0.000 claims description 3
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
• 206010012239 Delusion Diseases 0.000 claims description 3
• 208000030814 Eating disease Diseases 0.000 claims description 3
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 3
• 208000008589 Obesity Diseases 0.000 claims description 3
• 208000020114 Schizophrenia and other psychotic disease Diseases 0.000 claims description 3
• 208000019568 Shared Paranoid disease Diseases 0.000 claims description 3
• 208000028810 Shared psychotic disease Diseases 0.000 claims description 3
• 208000031674 Traumatic Acute Stress disease Diseases 0.000 claims description 3
• 208000030963 borderline personality disease Diseases 0.000 claims description 3
• 231100000868 delusion Toxicity 0.000 claims description 3
• 235000014632 disordered eating Nutrition 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 201000003631 narcolepsy Diseases 0.000 claims description 3
• 208000023046 narcolepsy-cataplexy syndrome Diseases 0.000 claims description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
• 235000020824 obesity Nutrition 0.000 claims description 3
• 208000022821 personality disease Diseases 0.000 claims description 3
• 208000019899 phobic disease Diseases 0.000 claims description 3
• 208000028173 post-traumatic stress disease Diseases 0.000 claims description 3
• 230000036299 sexual function Effects 0.000 claims description 3
• 208000019116 sleep disease Diseases 0.000 claims description 3
• 208000011117 substance-related disease Diseases 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• AYDSLXXUAYWCBG-OAHLLOKOSA-N (1r)-1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine Chemical compound C=CC[C@@H](N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 AYDSLXXUAYWCBG-OAHLLOKOSA-N 0.000 claims description 2
• AYDSLXXUAYWCBG-HNNXBMFYSA-N (1s)-1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine Chemical compound C=CC[C@H](N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 AYDSLXXUAYWCBG-HNNXBMFYSA-N 0.000 claims description 2
• IZNDXPPESHFDPI-HNNXBMFYSA-N (1s)-1-[2-(6-chloro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine Chemical compound C=CC[C@H](N)C1=CC=CC=C1C1=NOC2=CC(Cl)=CC=C12 IZNDXPPESHFDPI-HNNXBMFYSA-N 0.000 claims description 2
• STXXHVIERRTTMA-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-yn-1-amine Chemical compound C#CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 STXXHVIERRTTMA-UHFFFAOYSA-N 0.000 claims description 2
• SFZZDZHYEXQGAM-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]pentan-1-amine Chemical compound CCCCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 SFZZDZHYEXQGAM-UHFFFAOYSA-N 0.000 claims description 2
• GUFCVRPABUNDAS-UHFFFAOYSA-N 1-[2-(1-methylindazol-3-yl)phenyl]but-3-en-1-amine Chemical compound C12=CC=CC=C2N(C)N=C1C1=CC=CC=C1C(N)CC=C GUFCVRPABUNDAS-UHFFFAOYSA-N 0.000 claims description 2
• HEICKJFKEBRYFH-UHFFFAOYSA-N 1-[2-(6-chloro-1,2-benzoxazol-3-yl)phenyl]but-3-yn-1-amine Chemical compound C#CCC(N)C1=CC=CC=C1C1=NOC2=CC(Cl)=CC=C12 HEICKJFKEBRYFH-UHFFFAOYSA-N 0.000 claims description 2
• 208000021465 Brief psychotic disease Diseases 0.000 claims description 2
• KYWWWBAUGDMAJT-UHFFFAOYSA-N [2-(1,2-benzoxazol-3-yl)phenyl]methanamine Chemical compound NCC1=CC=CC=C1C1=NOC2=CC=CC=C12 KYWWWBAUGDMAJT-UHFFFAOYSA-N 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
• 125000001544 thienyl group Chemical group 0.000 claims description 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 142
• 239000000243 solution Substances 0.000 description 141
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 113
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 87
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
• 239000000203 mixture Substances 0.000 description 69
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 59
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 54
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 43
• 230000002829 reductive effect Effects 0.000 description 42
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 41
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 38
• 238000000034 method Methods 0.000 description 36
• 239000007787 solid Substances 0.000 description 36
• 239000012044 organic layer Substances 0.000 description 35
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 27
• 235000019341 magnesium sulphate Nutrition 0.000 description 27
• 238000005481 NMR spectroscopy Methods 0.000 description 23
• 238000006243 chemical reaction Methods 0.000 description 23
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 238000003756 stirring Methods 0.000 description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
• TXRRCHZIDGBYSJ-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)benzaldehyde Chemical compound O=CC1=CC=CC=C1C1=NOC2=CC=CC=C12 TXRRCHZIDGBYSJ-UHFFFAOYSA-N 0.000 description 19
• 239000000706 filtrate Substances 0.000 description 19
• 239000000725 suspension Substances 0.000 description 19
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
• 229910052938 sodium sulfate Inorganic materials 0.000 description 18
• 235000011152 sodium sulphate Nutrition 0.000 description 18
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
• 239000012267 brine Substances 0.000 description 16
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
• 239000003921 oil Substances 0.000 description 15
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 12
• 239000000460 chlorine Substances 0.000 description 12
• 238000002360 preparation method Methods 0.000 description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
• 239000002244 precipitate Substances 0.000 description 11
• 238000005160 1H NMR spectroscopy Methods 0.000 description 10
• ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 10
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• 238000003818 flash chromatography Methods 0.000 description 10
• 229910052757 nitrogen Inorganic materials 0.000 description 10
• 239000011347 resin Substances 0.000 description 10
• 229920005989 resin Polymers 0.000 description 10
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 238000002844 melting Methods 0.000 description 9
• 230000008018 melting Effects 0.000 description 9
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• 229910000029 sodium carbonate Inorganic materials 0.000 description 8
• 239000002904 solvent Substances 0.000 description 8
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
• APDGYQVYBWGBSD-UHFFFAOYSA-N 1-bromo-2-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC=CC=C1Br APDGYQVYBWGBSD-UHFFFAOYSA-N 0.000 description 7
• MYANOPGERSSIQJ-UHFFFAOYSA-N 2-(6-chloro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound N=1OC2=CC(Cl)=CC=C2C=1C1=CC=CC=C1C=O MYANOPGERSSIQJ-UHFFFAOYSA-N 0.000 description 7
• WWEPCBKULBKDCS-UHFFFAOYSA-N 2-fluoro-n-methoxy-n-methylbenzamide Chemical compound CON(C)C(=O)C1=CC=CC=C1F WWEPCBKULBKDCS-UHFFFAOYSA-N 0.000 description 7
• IVYGPMQYLKQFNP-UHFFFAOYSA-N 4-methyl-2,6,7-trioxabicyclo[2.2.2]octane Chemical compound C1OC2OCC1(C)CO2 IVYGPMQYLKQFNP-UHFFFAOYSA-N 0.000 description 7
• 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 7
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 7
• 239000007864 aqueous solution Substances 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 238000001704 evaporation Methods 0.000 description 7
• 230000008020 evaporation Effects 0.000 description 7
• 230000008570 general process Effects 0.000 description 7
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 7
• IUIQFAFNPZXCBL-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]ethanol Chemical compound CC(O)C1=CC=CC=C1C1=NOC2=CC=CC=C12 IUIQFAFNPZXCBL-UHFFFAOYSA-N 0.000 description 6
• GYECROLIZPLTMN-UHFFFAOYSA-N 4-chloro-2-fluoro-n-methoxy-n-methylbenzamide Chemical compound CON(C)C(=O)C1=CC=C(Cl)C=C1F GYECROLIZPLTMN-UHFFFAOYSA-N 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 230000007062 hydrolysis Effects 0.000 description 6
• 238000006460 hydrolysis reaction Methods 0.000 description 6
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 239000002808 molecular sieve Substances 0.000 description 6
• SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 6
• 239000012279 sodium borohydride Substances 0.000 description 6
• 229910000033 sodium borohydride Inorganic materials 0.000 description 6
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 150000001299 aldehydes Chemical class 0.000 description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
• 229910052794 bromium Inorganic materials 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• 150000002466 imines Chemical class 0.000 description 5
• DQEUYIQDSMINEY-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C=C DQEUYIQDSMINEY-UHFFFAOYSA-M 0.000 description 5
• 125000002524 organometallic group Chemical group 0.000 description 5
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
• CBYQEJJGMLIWMW-UHFFFAOYSA-N 1-bromo-2-(diethoxymethyl)-4-fluorobenzene Chemical compound CCOC(OCC)C1=CC(F)=CC=C1Br CBYQEJJGMLIWMW-UHFFFAOYSA-N 0.000 description 4
• SEISRZQKXBZVCG-UHFFFAOYSA-N 2,5-difluoro-n-methoxy-n-methylbenzamide Chemical compound CON(C)C(=O)C1=CC(F)=CC=C1F SEISRZQKXBZVCG-UHFFFAOYSA-N 0.000 description 4
• PXMPCSSNJZZAJR-UHFFFAOYSA-N 2-(6-fluoro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound N=1OC2=CC(F)=CC=C2C=1C1=CC=CC=C1C=O PXMPCSSNJZZAJR-UHFFFAOYSA-N 0.000 description 4
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
• DHPSVWWHCBZFLP-UHFFFAOYSA-N 2-bromo-1-(diethoxymethyl)-4-fluorobenzene Chemical compound CCOC(OCC)C1=CC=C(F)C=C1Br DHPSVWWHCBZFLP-UHFFFAOYSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• ZPIRRBYBHGWDRV-UHFFFAOYSA-N [2-(6-fluoro-1,2-benzoxazol-3-yl)phenyl]-phenylmethanone Chemical compound N=1OC2=CC(F)=CC=C2C=1C1=CC=CC=C1C(=O)C1=CC=CC=C1 ZPIRRBYBHGWDRV-UHFFFAOYSA-N 0.000 description 4
• PJQKEGSMTMAYPS-UHFFFAOYSA-N [2-(diethoxymethyl)phenyl]-(2-fluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC=CC=C1C(=O)C1=CC=CC=C1F PJQKEGSMTMAYPS-UHFFFAOYSA-N 0.000 description 4
• 239000003377 acid catalyst Substances 0.000 description 4
• 150000007513 acids Chemical class 0.000 description 4
• 235000019270 ammonium chloride Nutrition 0.000 description 4
• 239000000010 aprotic solvent Substances 0.000 description 4
• 239000002585 base Chemical class 0.000 description 4
• 150000008366 benzophenones Chemical class 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
• 238000004821 distillation Methods 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 4
• 125000005843 halogen group Chemical group 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
• 239000012299 nitrogen atmosphere Substances 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 229920006395 saturated elastomer Polymers 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• 229910052725 zinc Inorganic materials 0.000 description 4
• 239000011701 zinc Substances 0.000 description 4
• GHLOTOLVNNONDS-UHFFFAOYSA-N (4-chloro-2-fluorophenyl)-[2-(diethoxymethyl)phenyl]methanone Chemical compound CCOC(OCC)C1=CC=CC=C1C(=O)C1=CC=C(Cl)C=C1F GHLOTOLVNNONDS-UHFFFAOYSA-N 0.000 description 3
• KJILCQFEWBDJES-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-en-1-ol Chemical compound C=CCC(O)C1=CC=CC=C1C1=NOC2=CC=CC=C12 KJILCQFEWBDJES-UHFFFAOYSA-N 0.000 description 3
• WBWOPMKSGUSGIZ-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]ethanamine;hydrochloride Chemical compound Cl.CC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 WBWOPMKSGUSGIZ-UHFFFAOYSA-N 0.000 description 3
• JGGYFFMOVGYCDX-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]ethanone Chemical compound CC(=O)C1=CC=CC=C1C1=NOC2=CC=CC=C12 JGGYFFMOVGYCDX-UHFFFAOYSA-N 0.000 description 3
• PJMWTTMOXWPIRW-UHFFFAOYSA-N 2-(1-methylindazol-3-yl)benzaldehyde Chemical compound C12=CC=CC=C2N(C)N=C1C1=CC=CC=C1C=O PJMWTTMOXWPIRW-UHFFFAOYSA-N 0.000 description 3
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 3
• IPFLQRPIASGXMM-WLHGVMLRSA-N 2-[2-(1,2-benzoxazol-3-yl)phenyl]pent-4-en-2-amine (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C=CCC(N)(C)C1=CC=CC=C1C1=NOC2=CC=CC=C12 IPFLQRPIASGXMM-WLHGVMLRSA-N 0.000 description 3
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 3
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 3
• DSOLAYKMBAIBMT-UHFFFAOYSA-N 3-[2-(1-azidobut-3-ynyl)phenyl]-1,2-benzoxazole Chemical compound [N-]=[N+]=NC(CC#C)C1=CC=CC=C1C1=NOC2=CC=CC=C12 DSOLAYKMBAIBMT-UHFFFAOYSA-N 0.000 description 3
• XRMNXSCMCIZTDA-UHFFFAOYSA-N 3-[2-(1-azidoethyl)phenyl]-1,2-benzoxazole Chemical compound [N-]=[N+]=NC(C)C1=CC=CC=C1C1=NOC2=CC=CC=C12 XRMNXSCMCIZTDA-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
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
• 208000020401 Depressive disease Diseases 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• 208000019022 Mood disease Diseases 0.000 description 3
• HZFDKBPTVOENNB-GAFUQQFSSA-N N-[(2S)-1-[2-[(2R)-2-chloro-2-fluoroacetyl]-2-[[(3S)-2-oxopyrrolidin-3-yl]methyl]hydrazinyl]-3-(1-methylcyclopropyl)-1-oxopropan-2-yl]-5-(difluoromethyl)-1,2-oxazole-3-carboxamide Chemical compound CC1(C[C@@H](C(NN(C[C@H](CCN2)C2=O)C([C@H](F)Cl)=O)=O)NC(C2=NOC(C(F)F)=C2)=O)CC1 HZFDKBPTVOENNB-GAFUQQFSSA-N 0.000 description 3
• XMOURLICDSXKGC-UHFFFAOYSA-N [2-(1,2-benzoxazol-3-yl)phenyl]methanol Chemical compound OCC1=CC=CC=C1C1=NOC2=CC=CC=C12 XMOURLICDSXKGC-UHFFFAOYSA-N 0.000 description 3
• YNEOKYRXLBACLE-UHFFFAOYSA-N [2-(6-fluoro-1,2-benzoxazol-3-yl)phenyl]-phenylmethanamine;hydrochloride Chemical compound Cl.C=1C=CC=C(C=2C3=CC=C(F)C=C3ON=2)C=1C(N)C1=CC=CC=C1 YNEOKYRXLBACLE-UHFFFAOYSA-N 0.000 description 3
• FKACLIMREISUOY-UHFFFAOYSA-N [2-(diethoxymethyl)phenyl]-(2-fluorophenyl)methanol Chemical compound CCOC(OCC)C1=CC=CC=C1C(O)C1=CC=CC=C1F FKACLIMREISUOY-UHFFFAOYSA-N 0.000 description 3
• PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 229940024606 amino acid Drugs 0.000 description 3
• 235000001014 amino acid Nutrition 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 229940117975 chromium trioxide Drugs 0.000 description 3
• WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 3
• GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 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
• 239000002274 desiccant Substances 0.000 description 3
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 229920001971 elastomer Polymers 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 3
• SZOVCEDQZHNGSM-UHFFFAOYSA-N ethyl 2-[2-(1,2-benzoxazol-3-yl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC=C1C1=NOC2=CC=CC=C12 SZOVCEDQZHNGSM-UHFFFAOYSA-N 0.000 description 3
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 239000011976 maleic acid Substances 0.000 description 3
• CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 239000000047 product Substances 0.000 description 3
• YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 238000006722 reduction reaction Methods 0.000 description 3
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
• XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 3
• 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 3
• NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
• LGNCTBFOSSNVRK-XFULWGLBSA-N (1r)-1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CC[C@@H](N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 LGNCTBFOSSNVRK-XFULWGLBSA-N 0.000 description 2
• LGNCTBFOSSNVRK-RSAXXLAASA-N (1s)-1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CC[C@H](N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 LGNCTBFOSSNVRK-RSAXXLAASA-N 0.000 description 2
• TVAQKPOCPLOHKU-UHFFFAOYSA-N (4-chloro-2-fluorophenyl)-[2-(diethoxymethyl)-4-fluorophenyl]methanone Chemical compound CCOC(OCC)C1=CC(F)=CC=C1C(=O)C1=CC=C(Cl)C=C1F TVAQKPOCPLOHKU-UHFFFAOYSA-N 0.000 description 2
• QRDCDSPGTCAMDD-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-[2-(6-chloro-1,2-benzoxazol-3-yl)phenyl]but-3-yn-1-amine Chemical compound OC(=O)\C=C\C(O)=O.C#CCC(N)C1=CC=CC=C1C1=NOC2=CC(Cl)=CC=C12 QRDCDSPGTCAMDD-WLHGVMLRSA-N 0.000 description 2
• KKVIGLAEPYIGJS-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-2-(4-fluorophenyl)ethanamine;hydrochloride Chemical compound Cl.C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C(N)CC1=CC=C(F)C=C1 KKVIGLAEPYIGJS-UHFFFAOYSA-N 0.000 description 2
• LDWQSOCRDRZSJE-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1=CC=CC=C1C1=NOC2=CC=CC=C12 LDWQSOCRDRZSJE-UHFFFAOYSA-N 0.000 description 2
• FGESCCXVHDSWBF-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-[[2-(1,2-benzoxazol-3-yl)phenyl]methyl]methanamine Chemical compound C1=CC=C2C(C3=CC=CC=C3CNCC=3C(=CC=CC=3)C=3C4=CC=CC=C4ON=3)=NOC2=C1 FGESCCXVHDSWBF-UHFFFAOYSA-N 0.000 description 2
• LGNCTBFOSSNVRK-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 LGNCTBFOSSNVRK-UHFFFAOYSA-N 0.000 description 2
• RKQOJGJWCZENQD-UHFFFAOYSA-N 1-[2-(1-methylindazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(C)N=C1C1=CC=CC=C1C(N)CC=C RKQOJGJWCZENQD-UHFFFAOYSA-N 0.000 description 2
• KDHRJLQXMOBXRV-UHFFFAOYSA-N 1-bromo-3-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC=CC(Br)=C1 KDHRJLQXMOBXRV-UHFFFAOYSA-N 0.000 description 2
• BFSNEBVTOODGHZ-UHFFFAOYSA-N 1-bromo-4-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC=C(Br)C=C1 BFSNEBVTOODGHZ-UHFFFAOYSA-N 0.000 description 2
• BVZHAPSCOYXAMU-UHFFFAOYSA-N 1-bromo-4-chloro-2-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC(Cl)=CC=C1Br BVZHAPSCOYXAMU-UHFFFAOYSA-N 0.000 description 2
• UTSSEXHZQHZWED-UHFFFAOYSA-N 2,4-difluoro-n-methoxy-n-methylbenzamide Chemical compound CON(C)C(=O)C1=CC=C(F)C=C1F UTSSEXHZQHZWED-UHFFFAOYSA-N 0.000 description 2
• HAGRVLNZAGKTAQ-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(C=2C3=CC=CC=C3ON=2)=C1 HAGRVLNZAGKTAQ-UHFFFAOYSA-N 0.000 description 2
• TZXZGFVNRMFJSE-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)-5-chlorobenzaldehyde Chemical compound O=CC1=CC(Cl)=CC=C1C1=NOC2=CC=CC=C12 TZXZGFVNRMFJSE-UHFFFAOYSA-N 0.000 description 2
• VJTCTVTZJGGKHN-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)-5-fluorobenzaldehyde Chemical compound O=CC1=CC(F)=CC=C1C1=NOC2=CC=CC=C12 VJTCTVTZJGGKHN-UHFFFAOYSA-N 0.000 description 2
• NSKUSGAFNOEGIO-UHFFFAOYSA-N 2-(5-fluoro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound C12=CC(F)=CC=C2ON=C1C1=CC=CC=C1C=O NSKUSGAFNOEGIO-UHFFFAOYSA-N 0.000 description 2
• CRBBEKVLXLCCMY-UHFFFAOYSA-N 2-(6-chloro-1,2-benzoxazol-3-yl)-5-fluorobenzaldehyde Chemical compound O=CC1=CC(F)=CC=C1C1=NOC2=CC(Cl)=CC=C12 CRBBEKVLXLCCMY-UHFFFAOYSA-N 0.000 description 2
• AWSHJABBFJHIDH-UHFFFAOYSA-N 2-[2-(1,2-benzoxazol-3-yl)phenyl]-2-methylpent-4-enoic acid Chemical compound C=CCC(C)(C(O)=O)C1=CC=CC=C1C1=NOC2=CC=CC=C12 AWSHJABBFJHIDH-UHFFFAOYSA-N 0.000 description 2
• KJCDMXWQQNCOPE-UHFFFAOYSA-N 2-[[2-(1,2-benzoxazol-3-yl)phenyl]methyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC1=CC=CC=C1C1=NOC2=CC=CC=C12 KJCDMXWQQNCOPE-UHFFFAOYSA-N 0.000 description 2
• YEHHOAGIGIHPBL-UHFFFAOYSA-N 2-[[2-(1,2-benzoxazol-3-yl)phenyl]methylamino]-3-phenylpropanamide Chemical compound C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1CNC(C(=O)N)CC1=CC=CC=C1 YEHHOAGIGIHPBL-UHFFFAOYSA-N 0.000 description 2
• NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 2
• NOUPPELZOLDUCK-UHFFFAOYSA-N 2-fluoro-n-methoxy-n-methyl-4-(trifluoromethyl)benzamide Chemical compound CON(C)C(=O)C1=CC=C(C(F)(F)F)C=C1F NOUPPELZOLDUCK-UHFFFAOYSA-N 0.000 description 2
• RHPUTIYHXQQPBX-UHFFFAOYSA-N 3-(1,2-benzoxazol-3-yl)benzaldehyde Chemical compound O=CC1=CC=CC(C=2C3=CC=CC=C3ON=2)=C1 RHPUTIYHXQQPBX-UHFFFAOYSA-N 0.000 description 2
• POCCWZYCZJRTQM-UHFFFAOYSA-N 3-phenyl-1,2-benzoxazole Chemical compound C1=CC=CC=C1C1=NOC2=CC=CC=C12 POCCWZYCZJRTQM-UHFFFAOYSA-N 0.000 description 2
• JPUSSXAJGZPWFC-UHFFFAOYSA-N 4-fluoro-2-(5-fluoro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound FC1=CC=C(C=O)C(C=2C3=CC(F)=CC=C3ON=2)=C1 JPUSSXAJGZPWFC-UHFFFAOYSA-N 0.000 description 2
• NXAMQNZFUKJXAE-UHFFFAOYSA-N 5-fluoro-2-(5-fluoro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound O=CC1=CC(F)=CC=C1C1=NOC2=CC=C(F)C=C12 NXAMQNZFUKJXAE-UHFFFAOYSA-N 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• HMCIFWLUJNALST-UHFFFAOYSA-N OC(=O)C(O)=O.C#CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 Chemical compound OC(=O)C(O)=O.C#CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 HMCIFWLUJNALST-UHFFFAOYSA-N 0.000 description 2
• MUBZPKHOEPUJKR-UHFFFAOYSA-L Oxalate Chemical compound [O-]C(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-L 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• GWZDMHSFLUQFQE-UHFFFAOYSA-N [2-(1,2-benzoxazol-3-yl)phenyl]-cyclohex-3-en-1-ylmethanamine;hydrochloride Chemical compound Cl.C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C(N)C1CCC=CC1 GWZDMHSFLUQFQE-UHFFFAOYSA-N 0.000 description 2
• JHFMTEKQJGALPU-UHFFFAOYSA-N [2-(1,2-benzoxazol-3-yl)phenyl]methanamine;hydrochloride Chemical compound Cl.NCC1=CC=CC=C1C1=NOC2=CC=CC=C12 JHFMTEKQJGALPU-UHFFFAOYSA-N 0.000 description 2
• OHYLHVJPGXOWIZ-UHFFFAOYSA-N [2-(diethoxymethyl)-4-fluorophenyl]-(2,5-difluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC(F)=CC=C1C(=O)C1=CC(F)=CC=C1F OHYLHVJPGXOWIZ-UHFFFAOYSA-N 0.000 description 2
• DEUBFGMRUMBUBG-UHFFFAOYSA-N [2-(diethoxymethyl)-4-fluorophenyl]-(2-fluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC(F)=CC=C1C(=O)C1=CC=CC=C1F DEUBFGMRUMBUBG-UHFFFAOYSA-N 0.000 description 2
• XWKCOOSOTMQMLV-UHFFFAOYSA-N [2-(diethoxymethyl)-5-fluorophenyl]-(2,5-difluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC=C(F)C=C1C(=O)C1=CC(F)=CC=C1F XWKCOOSOTMQMLV-UHFFFAOYSA-N 0.000 description 2
• LWLFHYJBPHZTBZ-UHFFFAOYSA-N [2-(diethoxymethyl)-5-fluorophenyl]-(2-fluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC=C(F)C=C1C(=O)C1=CC=CC=C1F LWLFHYJBPHZTBZ-UHFFFAOYSA-N 0.000 description 2
• OEETZXCOMYWIRN-UHFFFAOYSA-N [2-(diethoxymethyl)phenyl]-(2,4-difluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC=CC=C1C(=O)C1=CC=C(F)C=C1F OEETZXCOMYWIRN-UHFFFAOYSA-N 0.000 description 2
• PKTBXSWGSBLVDT-UHFFFAOYSA-N [2-(diethoxymethyl)phenyl]-(2,5-difluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC=CC=C1C(=O)C1=CC(F)=CC=C1F PKTBXSWGSBLVDT-UHFFFAOYSA-N 0.000 description 2
• 229910052783 alkali metal Inorganic materials 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• 230000029936 alkylation Effects 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 239000000935 antidepressant agent Substances 0.000 description 2
• 229940005513 antidepressants Drugs 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
• RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 238000004296 chiral HPLC Methods 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 229940043279 diisopropylamine Drugs 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• VGAOWLDYXGZTPH-UHFFFAOYSA-N ethyl 2-[2-(1,2-benzoxazol-3-yl)phenyl]-2-methylpent-4-enoate Chemical compound CCOC(=O)C(C)(CC=C)C1=CC=CC=C1C1=NOC2=CC=CC=C12 VGAOWLDYXGZTPH-UHFFFAOYSA-N 0.000 description 2
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 2
• 239000001530 fumaric acid Substances 0.000 description 2
• 229960002598 fumaric acid Drugs 0.000 description 2
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
• PHTQWCKDNZKARW-UHFFFAOYSA-N isopentyl alcohol Natural products CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• FJLKKYOPIZBXSA-UHFFFAOYSA-N n-[1-[2-(1,2-benzoxazol-3-yl)phenyl]-2-(4-fluorophenyl)ethyl]-1,1-diphenylmethanimine Chemical compound C1=CC(F)=CC=C1CC(C=1C(=CC=CC=1)C=1C2=CC=CC=C2ON=1)N=C(C=1C=CC=CC=1)C1=CC=CC=C1 FJLKKYOPIZBXSA-UHFFFAOYSA-N 0.000 description 2
• GMIQHRLTWCTQSZ-UHFFFAOYSA-N n-benzhydryl-1-[2-(1,2-benzoxazol-3-yl)phenyl]methanimine Chemical compound C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C=NC(C=1C=CC=CC=1)C1=CC=CC=C1 GMIQHRLTWCTQSZ-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000006408 oxalic acid Nutrition 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• WLJVXDMOQOGPHL-UHFFFAOYSA-M phenylacetate Chemical compound [O-]C(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-M 0.000 description 2
• AFDMODCXODAXLC-UHFFFAOYSA-N phenylmethanimine Chemical compound N=CC1=CC=CC=C1 AFDMODCXODAXLC-UHFFFAOYSA-N 0.000 description 2
• 239000002798 polar solvent Substances 0.000 description 2
• 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• 239000007790 solid phase Substances 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
• 229940075966 (+)- menthol Drugs 0.000 description 1
• NOOLISFMXDJSKH-AEJSXWLSSA-N (+)-menthol Chemical compound CC(C)[C@H]1CC[C@H](C)C[C@@H]1O NOOLISFMXDJSKH-AEJSXWLSSA-N 0.000 description 1
• MFOVJVCJIWVUAE-YAKGRJRBSA-N (1S)-1-[2-(1,2-benzoxazol-3-yl)-4-fluorophenyl]but-3-en-1-amine (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C=CC[C@H](N)C1=CC=C(F)C=C1C1=NOC2=CC=CC=C12 MFOVJVCJIWVUAE-YAKGRJRBSA-N 0.000 description 1
• HGIQFKOCBOTADE-XFULWGLBSA-N (1r)-1-[2-(6-chloro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CC[C@@H](N)C1=CC=CC=C1C1=NOC2=CC(Cl)=CC=C12 HGIQFKOCBOTADE-XFULWGLBSA-N 0.000 description 1
• IBOICUDCOMQAHW-XFULWGLBSA-N (1r)-1-[2-(6-fluoro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CC[C@@H](N)C1=CC=CC=C1C1=NOC2=CC(F)=CC=C12 IBOICUDCOMQAHW-XFULWGLBSA-N 0.000 description 1
• HGIQFKOCBOTADE-RSAXXLAASA-N (1s)-1-[2-(6-chloro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CC[C@H](N)C1=CC=CC=C1C1=NOC2=CC(Cl)=CC=C12 HGIQFKOCBOTADE-RSAXXLAASA-N 0.000 description 1
• IBOICUDCOMQAHW-RSAXXLAASA-N (1s)-1-[2-(6-fluoro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CC[C@H](N)C1=CC=CC=C1C1=NOC2=CC(F)=CC=C12 IBOICUDCOMQAHW-RSAXXLAASA-N 0.000 description 1
• NLQMSBJFLQPLIJ-UHFFFAOYSA-N (3-methyloxetan-3-yl)methanol Chemical compound OCC1(C)COC1 NLQMSBJFLQPLIJ-UHFFFAOYSA-N 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• STGNLGBPLOVYMA-MAZDBSFSSA-N (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O STGNLGBPLOVYMA-MAZDBSFSSA-N 0.000 description 1
• PGMOPEQXBVJOOW-YAKGRJRBSA-N (E)-but-2-enedioic acid (1S)-1-[2-(6-fluoro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine Chemical compound OC(=O)\C=C\C(O)=O.C=CC[C@H](N)C1=CC=CC=C1C1=NOC2=CC(F)=CC=C12 PGMOPEQXBVJOOW-YAKGRJRBSA-N 0.000 description 1
• HWSCZDFDKWWZMD-WLHGVMLRSA-N (E)-but-2-enedioic acid 1-[2-[6-(trifluoromethyl)-1,2-benzoxazol-3-yl]phenyl]but-3-en-1-amine Chemical compound OC(=O)\C=C\C(O)=O.C=CCC(N)C1=CC=CC=C1C1=NOC2=CC(C(F)(F)F)=CC=C12 HWSCZDFDKWWZMD-WLHGVMLRSA-N 0.000 description 1
• TWODIMDXIYXFDU-WLHGVMLRSA-N (E)-but-2-enedioic acid 1-[4-fluoro-2-(5-fluoro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine Chemical compound OC(=O)\C=C\C(O)=O.C=CCC(N)C1=CC=C(F)C=C1C1=NOC2=CC=C(F)C=C12 TWODIMDXIYXFDU-WLHGVMLRSA-N 0.000 description 1
• LLKKGKBBAPHCGH-WLHGVMLRSA-N (E)-but-2-enedioic acid 1-[5-fluoro-2-(5-fluoro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine Chemical compound OC(=O)\C=C\C(O)=O.C=CCC(N)C1=CC(F)=CC=C1C1=NOC2=CC=C(F)C=C12 LLKKGKBBAPHCGH-WLHGVMLRSA-N 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
• KXSAGWSBYKFVNZ-BTJKTKAUSA-N (Z)-but-2-enedioic acid 1-[2-(6-chloro-1,2-benzoxazol-3-yl)-5-fluorophenyl]but-3-en-1-amine Chemical compound OC(=O)\C=C/C(O)=O.C=CCC(N)C1=CC(F)=CC=C1C1=NOC2=CC(Cl)=CC=C12 KXSAGWSBYKFVNZ-BTJKTKAUSA-N 0.000 description 1
• AVMHMVJVHYGDOO-NSCUHMNNSA-N (e)-1-bromobut-2-ene Chemical compound C\C=C\CBr AVMHMVJVHYGDOO-NSCUHMNNSA-N 0.000 description 1
• FQDIANVAWVHZIR-UPHRSURJSA-N (z)-1,4-dichlorobut-2-ene Chemical compound ClC\C=C/CCl FQDIANVAWVHZIR-UPHRSURJSA-N 0.000 description 1
• STGNLGBPLOVYMA-TZKOHIRVSA-N (z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O STGNLGBPLOVYMA-TZKOHIRVSA-N 0.000 description 1
• LNDGACQEAYKNOI-UHFFFAOYSA-N 1,1,1-trifluoro-4-iodobutane Chemical compound FC(F)(F)CCCI LNDGACQEAYKNOI-UHFFFAOYSA-N 0.000 description 1
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
• NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 1
• JOUIIVTUJAFSNJ-WLHGVMLRSA-N 1-[2-(1,2-benzoxazol-3-yl)-5-fluorophenyl]but-3-en-1-amine (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C=CCC(N)C1=CC(F)=CC=C1C1=NOC2=CC=CC=C12 JOUIIVTUJAFSNJ-WLHGVMLRSA-N 0.000 description 1
• RQGHLRIVZXVWGV-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-2-cyclopropylethanamine;hydrochloride Chemical compound Cl.C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C(N)CC1CC1 RQGHLRIVZXVWGV-UHFFFAOYSA-N 0.000 description 1
• QBHDOOUVKVSZNM-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-2-phenylethanamine;hydrochloride Chemical compound Cl.C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C(N)CC1=CC=CC=C1 QBHDOOUVKVSZNM-UHFFFAOYSA-N 0.000 description 1
• RSZRRDOFNQJNBB-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-3-chlorobut-2-en-1-amine;hydrochloride Chemical compound Cl.CC(Cl)=CC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 RSZRRDOFNQJNBB-UHFFFAOYSA-N 0.000 description 1
• UGEBYTMKGHXYEA-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-3-methylbut-3-en-1-amine;hydrochloride Chemical compound Cl.CC(=C)CC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 UGEBYTMKGHXYEA-UHFFFAOYSA-N 0.000 description 1
• CEZAXYGJGJXKNU-WLHGVMLRSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-5,5,5-trifluoropentan-1-amine (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.FC(F)(F)CCCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 CEZAXYGJGJXKNU-WLHGVMLRSA-N 0.000 description 1
• GYPSOQXGUMIDHK-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-(2-phenylethyl)but-3-en-1-amine Chemical compound C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C(CC=C)NCCC1=CC=CC=C1 GYPSOQXGUMIDHK-UHFFFAOYSA-N 0.000 description 1
• CQJXOOHZZUZJLA-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-benzylbut-3-en-1-amine Chemical compound C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1C(CC=C)NCC1=CC=CC=C1 CQJXOOHZZUZJLA-UHFFFAOYSA-N 0.000 description 1
• MFOHBIQMJQLTBF-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-methylbut-3-en-1-amine Chemical compound C=CCC(NC)C1=CC=CC=C1C1=NOC2=CC=CC=C12 MFOHBIQMJQLTBF-UHFFFAOYSA-N 0.000 description 1
• QCVIRLPMPWMQPU-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]-n-methylmethanamine;hydrochloride Chemical compound Cl.CNCC1=CC=CC=C1C1=NOC2=CC=CC=C12 QCVIRLPMPWMQPU-UHFFFAOYSA-N 0.000 description 1
• XSHGGLYVZZOGME-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]butan-1-amine;hydrochloride Chemical compound Cl.CCCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 XSHGGLYVZZOGME-UHFFFAOYSA-N 0.000 description 1
• PIBNHFICKJXHLK-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]pent-3-en-1-amine;hydrochloride Chemical compound Cl.CC=CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 PIBNHFICKJXHLK-UHFFFAOYSA-N 0.000 description 1
• GJADGPUOQOSQRP-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]pent-4-en-1-amine;hydrochloride Chemical compound Cl.C=CCCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 GJADGPUOQOSQRP-UHFFFAOYSA-N 0.000 description 1
• JHIJTVWLHKHPGD-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]pentan-1-amine;hydrochloride Chemical compound Cl.CCCCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 JHIJTVWLHKHPGD-UHFFFAOYSA-N 0.000 description 1
• YXJSHDHTVZGSGH-UHFFFAOYSA-N 1-[2-(1,2-benzoxazol-3-yl)phenyl]propan-1-amine;hydrochloride Chemical compound Cl.CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 YXJSHDHTVZGSGH-UHFFFAOYSA-N 0.000 description 1
• ZWQNKMLDIFXXRU-UHFFFAOYSA-N 1-[2-(5-fluoro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CCC(N)C1=CC=CC=C1C1=NOC2=CC=C(F)C=C12 ZWQNKMLDIFXXRU-UHFFFAOYSA-N 0.000 description 1
• HGIQFKOCBOTADE-UHFFFAOYSA-N 1-[2-(6-chloro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CCC(N)C1=CC=CC=C1C1=NOC2=CC(Cl)=CC=C12 HGIQFKOCBOTADE-UHFFFAOYSA-N 0.000 description 1
• DQDPUBAEMBNSEU-UHFFFAOYSA-N 1-[2-(6-chloro-1,2-benzoxazol-3-yl)phenyl]but-3-yn-1-amine;hydrochloride Chemical compound Cl.C#CCC(N)C1=CC=CC=C1C1=NOC2=CC(Cl)=CC=C12 DQDPUBAEMBNSEU-UHFFFAOYSA-N 0.000 description 1
• CKAWEVLAGISELS-UHFFFAOYSA-N 1-[2-(6-chloro-1,2-benzoxazol-3-yl)phenyl]pentan-1-amine;hydrochloride Chemical compound Cl.CCCCC(N)C1=CC=CC=C1C1=NOC2=CC(Cl)=CC=C12 CKAWEVLAGISELS-UHFFFAOYSA-N 0.000 description 1
• RHQITXSWKCUONY-UHFFFAOYSA-N 1-[2-(6-fluoro-1,2-benzoxazol-3-yl)phenyl]-3-methylbut-3-en-1-amine;hydrochloride Chemical compound Cl.CC(=C)CC(N)C1=CC=CC=C1C1=NOC2=CC(F)=CC=C12 RHQITXSWKCUONY-UHFFFAOYSA-N 0.000 description 1
• IBOICUDCOMQAHW-UHFFFAOYSA-N 1-[2-(6-fluoro-1,2-benzoxazol-3-yl)phenyl]but-3-en-1-amine;hydrochloride Chemical compound Cl.C=CCC(N)C1=CC=CC=C1C1=NOC2=CC(F)=CC=C12 IBOICUDCOMQAHW-UHFFFAOYSA-N 0.000 description 1
• LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 1
• SFOYQZYQTQDRIY-UHFFFAOYSA-N 1-chloro-3-iodopropane Chemical compound ClCCCI SFOYQZYQTQDRIY-UHFFFAOYSA-N 0.000 description 1
• 125000006021 1-methyl-2-propenyl group Chemical group 0.000 description 1
• FALCMQXTWHPRIH-UHFFFAOYSA-N 2,3-dichloroprop-1-ene Chemical compound ClCC(Cl)=C FALCMQXTWHPRIH-UHFFFAOYSA-N 0.000 description 1
• DWXSYDKEWORWBT-UHFFFAOYSA-N 2-(2-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1Br DWXSYDKEWORWBT-UHFFFAOYSA-N 0.000 description 1
• RFPBUXOVSZEMSW-UHFFFAOYSA-N 2-(2-bromophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1Br RFPBUXOVSZEMSW-UHFFFAOYSA-N 0.000 description 1
• RXWOHFUULDINMC-UHFFFAOYSA-N 2-(3-nitrothiophen-2-yl)acetic acid Chemical compound OC(=O)CC=1SC=CC=1[N+]([O-])=O RXWOHFUULDINMC-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• FZKIUZJAGILULP-UHFFFAOYSA-N 2-[6-(trifluoromethyl)-1,2-benzoxazol-3-yl]benzaldehyde Chemical compound N=1OC2=CC(C(F)(F)F)=CC=C2C=1C1=CC=CC=C1C=O FZKIUZJAGILULP-UHFFFAOYSA-N 0.000 description 1
• QGBDJNZREUSXCZ-UHFFFAOYSA-N 2-bromo-4-chloro-1-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC=C(Cl)C=C1Br QGBDJNZREUSXCZ-UHFFFAOYSA-N 0.000 description 1
• AJOAHIKYBSZIEV-UHFFFAOYSA-N 2-bromo-4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C(Br)=C1 AJOAHIKYBSZIEV-UHFFFAOYSA-N 0.000 description 1
• SFGFOJPGCOYQJK-UHFFFAOYSA-N 2-bromo-4-fluoro-1-methylbenzene Chemical compound CC1=CC=C(F)C=C1Br SFGFOJPGCOYQJK-UHFFFAOYSA-N 0.000 description 1
• OPZDXMCOWFPQPE-UHFFFAOYSA-N 2-bromo-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(Br)=C1 OPZDXMCOWFPQPE-UHFFFAOYSA-N 0.000 description 1
• CJUCIKJLMFVWIS-UHFFFAOYSA-N 2-bromo-5-fluorobenzaldehyde Chemical compound FC1=CC=C(Br)C(C=O)=C1 CJUCIKJLMFVWIS-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• VTUKKVHSZDBIPA-UHFFFAOYSA-N 3,5,8-trioxabicyclo[2.2.2]octane Chemical compound O1CC2COC1OC2 VTUKKVHSZDBIPA-UHFFFAOYSA-N 0.000 description 1
• FXIUNHPOEYCWEO-UHFFFAOYSA-N 3-(2-pyrrolidin-2-ylphenyl)-1,2-benzoxazole Chemical compound C1CCNC1C1=CC=CC=C1C1=NOC2=CC=CC=C12 FXIUNHPOEYCWEO-UHFFFAOYSA-N 0.000 description 1
• KBWHYRUAHXHHFO-UHFFFAOYSA-N 3-(bromomethyl)thiophene Chemical compound BrCC=1C=CSC=1 KBWHYRUAHXHHFO-UHFFFAOYSA-N 0.000 description 1
• DVNHHFOMVKVCJM-UHFFFAOYSA-N 3-[2-(1,2,3,6-tetrahydropyridin-2-yl)phenyl]-1,2-benzoxazole Chemical compound C1C=CCNC1C1=CC=CC=C1C1=NOC2=CC=CC=C12 DVNHHFOMVKVCJM-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 description 1
• AJKDUJRRWLQXHM-UHFFFAOYSA-N 3-bromocyclohexene Chemical compound BrC1CCCC=C1 AJKDUJRRWLQXHM-UHFFFAOYSA-N 0.000 description 1
• KJPURSPTLWQLOM-UHFFFAOYSA-N 3-propyl-1,2-benzoxazole Chemical class C1=CC=C2C(CCC)=NOC2=C1 KJPURSPTLWQLOM-UHFFFAOYSA-N 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• KFPDQYAPXSRACF-UHFFFAOYSA-N 4-(1,2-benzoxazol-3-yl)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=NOC2=CC=CC=C12 KFPDQYAPXSRACF-UHFFFAOYSA-N 0.000 description 1
• ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
• ZLPXBWMVZANJJQ-UHFFFAOYSA-N 4-chloro-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1F ZLPXBWMVZANJJQ-UHFFFAOYSA-N 0.000 description 1
• VUSYNHBKPCGGCI-UHFFFAOYSA-N 4-iodobut-1-ene Chemical compound ICCC=C VUSYNHBKPCGGCI-UHFFFAOYSA-N 0.000 description 1
• QVXKELCLFMYEPC-UHFFFAOYSA-N 5-chloro-2-(6-chloro-1,2-benzoxazol-3-yl)benzaldehyde Chemical compound O=CC1=CC(Cl)=CC=C1C1=NOC2=CC(Cl)=CC=C12 QVXKELCLFMYEPC-UHFFFAOYSA-N 0.000 description 1
• RRMIIFIMXCQQOK-UHFFFAOYSA-N 5-fluoro-2-[6-(trifluoromethyl)-1,2-benzoxazol-3-yl]benzaldehyde Chemical compound O=CC1=CC(F)=CC=C1C1=NOC2=CC(C(F)(F)F)=CC=C12 RRMIIFIMXCQQOK-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
• 208000020925 Bipolar disease Diseases 0.000 description 1
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 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
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 238000006824 Eschweiler-Clarke methylation reaction Methods 0.000 description 1
• 241000400611 Eucalyptus deanei Species 0.000 description 1
• 238000007167 Hofmann rearrangement reaction Methods 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• FFKZOUIEAHOBHW-UHFFFAOYSA-N N,4-dimethyl-N-nitrosobenzenesulfonamide Chemical compound O=NN(C)S(=O)(=O)C1=CC=C(C)C=C1 FFKZOUIEAHOBHW-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• YQLIMZPELWZLSY-UHFFFAOYSA-N OC(=O)C(O)=O.C(NCc1ccccc1-c1noc2ccccc12)c1ccccc1 Chemical compound OC(=O)C(O)=O.C(NCc1ccccc1-c1noc2ccccc12)c1ccccc1 YQLIMZPELWZLSY-UHFFFAOYSA-N 0.000 description 1
• SHOBNMHVIMCQFQ-UHFFFAOYSA-N OC(=O)C(O)=O.COc1ccccc1CNCc1ccccc1-c1noc2ccccc12 Chemical compound OC(=O)C(O)=O.COc1ccccc1CNCc1ccccc1-c1noc2ccccc12 SHOBNMHVIMCQFQ-UHFFFAOYSA-N 0.000 description 1
• SBWXOAXQBQRTEK-BTJKTKAUSA-N OC(=O)\C=C/C(O)=O.CC(C)=CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 Chemical compound OC(=O)\C=C/C(O)=O.CC(C)=CCC(N)C1=CC=CC=C1C1=NOC2=CC=CC=C12 SBWXOAXQBQRTEK-BTJKTKAUSA-N 0.000 description 1
• JOUIIVTUJAFSNJ-YAKGRJRBSA-N OC(=O)\C=C\C(O)=O.C=CC[C@H](N)C1=CC(F)=CC=C1C1=NOC2=CC=CC=C12 Chemical compound OC(=O)\C=C\C(O)=O.C=CC[C@H](N)C1=CC(F)=CC=C1C1=NOC2=CC=CC=C12 JOUIIVTUJAFSNJ-YAKGRJRBSA-N 0.000 description 1
• XZMVZNINGCRABV-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.CC(C)CC(N)C1=CC=CC=C1C1=NOC2=CC(F)=CC=C12 Chemical compound OC(=O)\C=C\C(O)=O.CC(C)CC(N)C1=CC=CC=C1C1=NOC2=CC(F)=CC=C12 XZMVZNINGCRABV-WLHGVMLRSA-N 0.000 description 1
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
• BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 241000700157 Rattus norvegicus Species 0.000 description 1
• 238000006085 Schmidt reaction Methods 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 238000007059 Strecker synthesis reaction Methods 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
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
• 238000003833 Wallach reaction Methods 0.000 description 1
• 239000003875 Wang resin Substances 0.000 description 1
• NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
• YXBCNYAUIKVHCT-UHFFFAOYSA-N [4-chloro-2-(diethoxymethyl)phenyl]-(2-fluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC(Cl)=CC=C1C(=O)C1=CC=CC=C1F YXBCNYAUIKVHCT-UHFFFAOYSA-N 0.000 description 1
• LVLGOFCAKHPSNE-UHFFFAOYSA-N [4-chloro-2-(diethoxymethyl)phenyl]-(4-chloro-2-fluorophenyl)methanone Chemical compound CCOC(OCC)C1=CC(Cl)=CC=C1C(=O)C1=CC=C(Cl)C=C1F LVLGOFCAKHPSNE-UHFFFAOYSA-N 0.000 description 1
• PGVHQMHLQMUDPY-UHFFFAOYSA-M [Br-].CC(=C)C[Mg+] Chemical compound [Br-].CC(=C)C[Mg+] PGVHQMHLQMUDPY-UHFFFAOYSA-M 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 150000005215 alkyl ethers Chemical class 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
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 230000000202 analgesic effect Effects 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• HYTACLVSJIFYBY-UHFFFAOYSA-N azane;dichloromethane;methanol Chemical compound N.OC.ClCCl HYTACLVSJIFYBY-UHFFFAOYSA-N 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 229960004365 benzoic acid Drugs 0.000 description 1
• 229960004217 benzyl alcohol Drugs 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 229910000085 borane Inorganic materials 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
• KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 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
• 229960005069 calcium Drugs 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 150000001728 carbonyl compounds Chemical class 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 239000003518 caustics Substances 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 229910052804 chromium Inorganic materials 0.000 description 1
• 239000011651 chromium Substances 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 208000035195 congenital hypomyelinating 3 neuropathy Diseases 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 125000004093 cyano group Chemical group *C#N 0.000 description 1
• 125000000392 cycloalkenyl group Chemical group 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
• 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
• 239000012024 dehydrating agents‎ Substances 0.000 description 1
• 230000003001 depressive effect Effects 0.000 description 1
• 230000005595 deprotonation Effects 0.000 description 1
• 238000010537 deprotonation reaction Methods 0.000 description 1
• 150000008049 diazo compounds Chemical class 0.000 description 1
• NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• DKWOHBPRFZIUQL-UHFFFAOYSA-N dimethyl-methylidene-oxo-$l^{6}-sulfane Chemical compound C[S+](C)([CH2-])=O DKWOHBPRFZIUQL-UHFFFAOYSA-N 0.000 description 1
• XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
• MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
• 201000010099 disease Diseases 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 239000000428 dust Substances 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 238000000537 electroencephalography Methods 0.000 description 1
• ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940095399 enema Drugs 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 239000004744 fabric Substances 0.000 description 1
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 150000003948 formamides Chemical class 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 238000004817 gas chromatography Methods 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 229950006191 gluconic acid Drugs 0.000 description 1
• 229960004275 glycolic acid Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• KWHDXJHBFYQOTK-UHFFFAOYSA-N heptane;toluene Chemical compound CCCCCCC.CC1=CC=CC=C1 KWHDXJHBFYQOTK-UHFFFAOYSA-N 0.000 description 1
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
• 125000006038 hexenyl group Chemical group 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000001077 hypotensive effect Effects 0.000 description 1
• 125000004245 indazol-3-yl group Chemical group [H]N1N=C(*)C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 150000002485 inorganic esters Chemical class 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 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
• JHKJQWFHNIOUKY-UHFFFAOYSA-N iodomethylcyclopropane Chemical compound ICC1CC1 JHKJQWFHNIOUKY-UHFFFAOYSA-N 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229960004873 levomenthol Drugs 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• XQAMFOKVRXJOGD-UHFFFAOYSA-M magnesium;but-1-ene;chloride Chemical compound [Mg+2].[Cl-].CC=C[CH2-] XQAMFOKVRXJOGD-UHFFFAOYSA-M 0.000 description 1
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
• QGEFGPVWRJCFQP-UHFFFAOYSA-M magnesium;methanidylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1=CC=CC=C1 QGEFGPVWRJCFQP-UHFFFAOYSA-M 0.000 description 1
• SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 239000004579 marble Substances 0.000 description 1
• 238000013160 medical therapy Methods 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• KUGLDBMQKZTXPW-JEDNCBNOSA-N methyl (2s)-2-amino-3-methylbutanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)C(C)C KUGLDBMQKZTXPW-JEDNCBNOSA-N 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
• SFHBPNGZDICHEI-UHFFFAOYSA-N n-[[2-(1,2-benzoxazol-3-yl)phenyl]methyl]-1-pyridin-3-ylmethanamine;dihydrochloride Chemical compound Cl.Cl.C=1C=CC=C(C=2C3=CC=CC=C3ON=2)C=1CNCC1=CC=CN=C1 SFHBPNGZDICHEI-UHFFFAOYSA-N 0.000 description 1
• FWXABJFJEXZRDG-UHFFFAOYSA-N n-[[2-(1,2-benzoxazol-3-yl)phenyl]methyl]prop-2-en-1-amine;hydrochloride Chemical compound Cl.C=CCNCC1=CC=CC=C1C1=NOC2=CC=CC=C12 FWXABJFJEXZRDG-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([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
• 230000036403 neuro physiology Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• LURABKZOEVFURH-UHFFFAOYSA-N nitromethanesulfonic acid Chemical compound OS(=O)(=O)C[N+]([O-])=O LURABKZOEVFURH-UHFFFAOYSA-N 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 150000002905 orthoesters Chemical class 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
• 125000005489 p-toluenesulfonic acid group Chemical class 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
• ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 239000000902 placebo Substances 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 229940095574 propionic acid Drugs 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
• 208000020016 psychiatric disease Diseases 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 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 1
• 238000005932 reductive alkylation reaction Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 229910001927 ruthenium tetroxide Inorganic materials 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000007958 sleep Effects 0.000 description 1
• 208000022925 sleep disturbance Diseases 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 238000010532 solid phase synthesis reaction Methods 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000001384 succinic acid Substances 0.000 description 1
• 229960005137 succinic acid Drugs 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 238000003420 transacetalization reaction Methods 0.000 description 1
• 238000005809 transesterification reaction Methods 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
• 229960004295 valine Drugs 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1