TWI450899B - 被取代之螺環環已烷衍生物 - Google Patents

Info

Publication number

TWI450899B

TWI450899B TW098109648A TW98109648A TWI450899B TW I450899 B TWI450899 B TW I450899B TW 098109648 A TW098109648 A TW 098109648A TW 98109648 A TW98109648 A TW 98109648A TW I450899 B TWI450899 B TW I450899B

Authority

TW

Taiwan

Prior art keywords

group

cyclohexane

amine

indole

phenyl

Prior art date

2008-03-27

Links

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• 125000000113 cyclohexyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 title claims description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims description 258
• -1 oxythio Chemical group 0.000 claims description 176
• 125000001931 aliphatic group Chemical group 0.000 claims description 161
• 150000001875 compounds Chemical class 0.000 claims description 153
• 239000000203 mixture Substances 0.000 claims description 124
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 121
• 125000003118 aryl group Chemical group 0.000 claims description 116
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 93
• 229910052757 nitrogen Inorganic materials 0.000 claims description 91
• 125000001072 heteroaryl group Chemical group 0.000 claims description 67
• 229910052731 fluorine Inorganic materials 0.000 claims description 54
• 229910052801 chlorine Inorganic materials 0.000 claims description 49
• RERZNCLIYCABFS-UHFFFAOYSA-N harmaline Chemical compound C1CN=C(C)C2=C1C1=CC=C(OC)C=C1N2 RERZNCLIYCABFS-UHFFFAOYSA-N 0.000 claims description 49
• 239000000460 chlorine Substances 0.000 claims description 48
• 239000011737 fluorine Substances 0.000 claims description 48
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 47
• 125000001424 substituent group Chemical group 0.000 claims description 44
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 37
• 150000002430 hydrocarbons Chemical group 0.000 claims description 37
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 35
• 229910052794 bromium Inorganic materials 0.000 claims description 35
• 150000001338 aliphatic hydrocarbons Chemical group 0.000 claims description 34
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 33
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 32
• 125000004043 oxo group Chemical group O=* 0.000 claims description 32
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
• 125000003277 amino group Chemical group 0.000 claims description 28
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 28
• 229920006395 saturated elastomer Polymers 0.000 claims description 28
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
• 150000003839 salts Chemical class 0.000 claims description 26
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 25
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
• 125000005842 heteroatom Chemical group 0.000 claims description 21
• 239000001257 hydrogen Substances 0.000 claims description 21
• 229910052739 hydrogen Inorganic materials 0.000 claims description 21
• 239000003814 drug Substances 0.000 claims description 18
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 17
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
• 208000002193 Pain Diseases 0.000 claims description 16
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 16
• 229940127240 opiate Drugs 0.000 claims description 16
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 16
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 16
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 15
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
• 125000004149 thio group Chemical group *S* 0.000 claims description 15
• 150000007942 carboxylates Chemical group 0.000 claims description 14
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 14
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 14
• 238000006467 substitution reaction Methods 0.000 claims description 14
• 125000004429 atom Chemical group 0.000 claims description 13
• 238000002360 preparation method Methods 0.000 claims description 13
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 125000001153 fluoro group Chemical group F* 0.000 claims description 12
• 125000000623 heterocyclic group Chemical group 0.000 claims description 12
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 11
• 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 11
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 10
• 229940079593 drug Drugs 0.000 claims description 10
• 229930195733 hydrocarbon Natural products 0.000 claims description 10
• 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 10
• 229910052760 oxygen Inorganic materials 0.000 claims description 10
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 10
• 239000004215 Carbon black (E152) Substances 0.000 claims description 9
• QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical group C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 claims description 9
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
• 239000001301 oxygen Substances 0.000 claims description 9
• 125000003367 polycyclic group Chemical group 0.000 claims description 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 9
• 125000001302 tertiary amino group Chemical group 0.000 claims description 9
• 150000001412 amines Chemical class 0.000 claims description 8
• 125000004122 cyclic group Chemical group 0.000 claims description 8
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
• 125000003172 aldehyde group Chemical group 0.000 claims description 6
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 6
• 150000004702 methyl esters Chemical class 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 239000011593 sulfur Substances 0.000 claims description 6
• 125000004354 sulfur functional group Chemical group 0.000 claims description 6
• 208000024891 symptom Diseases 0.000 claims description 6
• ZWVMLYRJXORSEP-LURJTMIESA-N (2s)-hexane-1,2,6-triol Chemical compound OCCCC[C@H](O)CO ZWVMLYRJXORSEP-LURJTMIESA-N 0.000 claims description 5
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
• 239000005977 Ethylene Substances 0.000 claims description 5
• 230000003444 anaesthetic effect Effects 0.000 claims description 5
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 5
• 150000002923 oximes Chemical class 0.000 claims description 5
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
• 125000005496 phosphonium group Chemical group 0.000 claims description 4
• 230000001105 regulatory effect Effects 0.000 claims description 4
• 208000011117 substance-related disease Diseases 0.000 claims description 4
• FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 claims description 3
• 208000024827 Alzheimer disease Diseases 0.000 claims description 3
• 208000019901 Anxiety disease Diseases 0.000 claims description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
• 239000000654 additive Substances 0.000 claims description 3
• 239000002671 adjuvant Substances 0.000 claims description 3
• 230000036506 anxiety Effects 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
• 208000035475 disorder Diseases 0.000 claims description 3
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 claims description 3
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 3
• 239000011734 sodium Substances 0.000 claims description 3
• 229910052708 sodium Inorganic materials 0.000 claims description 3
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 claims description 2
• 208000032841 Bulimia Diseases 0.000 claims description 2
• 206010006550 Bulimia nervosa Diseases 0.000 claims description 2
• 206010006895 Cachexia Diseases 0.000 claims description 2
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
• 208000028698 Cognitive impairment Diseases 0.000 claims description 2
• 206010012335 Dependence Diseases 0.000 claims description 2
• 206010012735 Diarrhoea Diseases 0.000 claims description 2
• 206010013654 Drug abuse Diseases 0.000 claims description 2
• 208000012661 Dyskinesia Diseases 0.000 claims description 2
• 208000030814 Eating disease Diseases 0.000 claims description 2
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 2
• 206010020772 Hypertension Diseases 0.000 claims description 2
• 208000001953 Hypotension Diseases 0.000 claims description 2
• 208000020358 Learning disease Diseases 0.000 claims description 2
• 208000026139 Memory disease Diseases 0.000 claims description 2
• 208000019695 Migraine disease Diseases 0.000 claims description 2
• 208000003251 Pruritus Diseases 0.000 claims description 2
• 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
• 208000009205 Tinnitus Diseases 0.000 claims description 2
• 206010046543 Urinary incontinence Diseases 0.000 claims description 2
• 125000003545 alkoxy group Chemical group 0.000 claims description 2
• 230000000202 analgesic effect Effects 0.000 claims description 2
• 208000022531 anorexia Diseases 0.000 claims description 2
• 230000001773 anti-convulsant effect Effects 0.000 claims description 2
• 239000001961 anticonvulsive agent Substances 0.000 claims description 2
• 229960003965 antiepileptics Drugs 0.000 claims description 2
• 208000010877 cognitive disease Diseases 0.000 claims description 2
• 206010061428 decreased appetite Diseases 0.000 claims description 2
• 235000014632 disordered eating Nutrition 0.000 claims description 2
• 230000001882 diuretic effect Effects 0.000 claims description 2
• 206010013663 drug dependence Diseases 0.000 claims description 2
• 206010015037 epilepsy Diseases 0.000 claims description 2
• 230000036543 hypotension Effects 0.000 claims description 2
• JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims description 2
• 201000003723 learning disability Diseases 0.000 claims description 2
• 206010027599 migraine Diseases 0.000 claims description 2
• 239000003158 myorelaxant agent Substances 0.000 claims description 2
• 230000004770 neurodegeneration Effects 0.000 claims description 2
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
• 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims description 2
• 231100000886 tinnitus Toxicity 0.000 claims description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 8
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims 3
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 3
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
• FATSCUUTULBVQD-UHFFFAOYSA-N 3-carbonoperoxoylpentanedioic acid Chemical compound OOC(=O)C(CC(O)=O)CC(O)=O FATSCUUTULBVQD-UHFFFAOYSA-N 0.000 claims 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
• 206010011878 Deafness Diseases 0.000 claims 1
• 206010012289 Dementia Diseases 0.000 claims 1
• RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical group NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 claims 1
• YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims 1
• 239000002934 diuretic Substances 0.000 claims 1
• 230000010370 hearing loss Effects 0.000 claims 1
• 231100000888 hearing loss Toxicity 0.000 claims 1
• 208000016354 hearing loss disease Diseases 0.000 claims 1
• 230000037023 motor activity Effects 0.000 claims 1
• 239000002858 neurotransmitter agent Substances 0.000 claims 1
• 230000001777 nootropic effect Effects 0.000 claims 1
• 229940005483 opioid analgesics Drugs 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 181
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 141
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 126
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 102
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 87
• 239000012074 organic phase Substances 0.000 description 85
• 239000000243 solution Substances 0.000 description 84
• 239000011541 reaction mixture Substances 0.000 description 72
• 235000019439 ethyl acetate Nutrition 0.000 description 62
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 43
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
• 238000000034 method Methods 0.000 description 38
• 238000002844 melting Methods 0.000 description 37
• 230000008018 melting Effects 0.000 description 37
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 36
• 238000005481 NMR spectroscopy Methods 0.000 description 31
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 30
• 239000007864 aqueous solution Substances 0.000 description 29
• 239000002904 solvent Substances 0.000 description 28
• 108090000137 Opioid Receptors Proteins 0.000 description 26
• 102000003840 Opioid Receptors Human genes 0.000 description 26
• 238000004587 chromatography analysis Methods 0.000 description 25
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
• 239000007787 solid Substances 0.000 description 24
• 238000006243 chemical reaction Methods 0.000 description 23
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 22
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
• 235000019341 magnesium sulphate Nutrition 0.000 description 20
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
• 125000000217 alkyl group Chemical group 0.000 description 19
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 19
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 18
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 18
• 125000001544 thienyl group Chemical group 0.000 description 18
• 239000002585 base Substances 0.000 description 17
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
• 239000011343 solid material Substances 0.000 description 16
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
• MBBOMCVGYCRMEA-UHFFFAOYSA-N Tryptophol Natural products C1=CC=C2C(CCO)=CNC2=C1 MBBOMCVGYCRMEA-UHFFFAOYSA-N 0.000 description 14
• ONVGARFWQRCLML-UHFFFAOYSA-N Tryptophol [xylosyl-(1->6)-glucoside] Chemical compound OC1C(O)C(O)COC1OCC1C(O)C(O)C(O)C(OCCC=2C3=CC=CC=C3NC=2)O1 ONVGARFWQRCLML-UHFFFAOYSA-N 0.000 description 14
• 239000012071 phase Substances 0.000 description 14
• 229920001296 polysiloxane Polymers 0.000 description 14
• 125000004076 pyridyl group Chemical group 0.000 description 14
• 239000000126 substance Substances 0.000 description 14
• FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 14
• APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 14
• 239000002253 acid Substances 0.000 description 13
• 239000008346 aqueous phase Substances 0.000 description 13
• 238000011097 chromatography purification Methods 0.000 description 13
• 238000000746 purification Methods 0.000 description 13
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
• 230000015572 biosynthetic process Effects 0.000 description 12
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
• 239000002244 precipitate Substances 0.000 description 12
• 238000003756 stirring Methods 0.000 description 12
• 238000001914 filtration Methods 0.000 description 11
• 239000011521 glass Substances 0.000 description 11
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 11
• 235000019270 ammonium chloride Nutrition 0.000 description 10
• 230000000052 comparative effect Effects 0.000 description 10
• 102000005962 receptors Human genes 0.000 description 10
• 108020003175 receptors Proteins 0.000 description 10
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
• 230000002378 acidificating effect Effects 0.000 description 9
• 238000001556 precipitation Methods 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• 125000000335 thiazolyl group Chemical group 0.000 description 9
• 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 8
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 8
• 150000001299 aldehydes Chemical class 0.000 description 8
• 229910052786 argon Inorganic materials 0.000 description 8
• 150000004945 aromatic hydrocarbons Chemical group 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
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• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
• BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
• LLZRNZOLAXHGLL-UHFFFAOYSA-J titanic acid Chemical compound O[Ti](O)(O)O LLZRNZOLAXHGLL-UHFFFAOYSA-J 0.000 description 1
• XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
• 150000003672 ureas Chemical class 0.000 description 1
• 210000001835 viscera Anatomy 0.000 description 1