TWI491591B - 吲哚化合物及其醫藥用途 - Google Patents

Info

Publication number

TWI491591B

TWI491591B TW099140715A TW99140715A TWI491591B TW I491591 B TWI491591 B TW I491591B TW 099140715 A TW099140715 A TW 099140715A TW 99140715 A TW99140715 A TW 99140715A TW I491591 B TWI491591 B TW I491591B

Authority

TW

Taiwan

Prior art keywords

group

substituted

alkoxy

alkyl

substituents selected

Prior art date

2009-11-25

Links

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• 150000001622 bismuth compounds Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 228
• -1 cyclic amine Chemical class 0.000 claims description 199
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 183
• 125000001424 substituent group Chemical group 0.000 claims description 181
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 178
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 157
• 125000003118 aryl group Chemical group 0.000 claims description 114
• 125000000623 heterocyclic group Chemical group 0.000 claims description 113
• 150000003839 salts Chemical class 0.000 claims description 82
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 79
• 125000000217 alkyl group Chemical group 0.000 claims description 55
• 125000003545 alkoxy group Chemical group 0.000 claims description 53
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 51
• 125000003277 amino group Chemical group 0.000 claims description 48
• 238000004519 manufacturing process Methods 0.000 claims description 48
• 238000002360 preparation method Methods 0.000 claims description 48
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 44
• 108010075324 emt protein-tyrosine kinase Proteins 0.000 claims description 40
• 229910052757 nitrogen Inorganic materials 0.000 claims description 35
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 30
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 29
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 26
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 26
• 125000004104 aryloxy group Chemical group 0.000 claims description 24
• 208000023275 Autoimmune disease Diseases 0.000 claims description 22
• 206010061218 Inflammation Diseases 0.000 claims description 22
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 230000004054 inflammatory process Effects 0.000 claims description 22
• 208000026935 allergic disease Diseases 0.000 claims description 19
• 150000001335 aliphatic alkanes Chemical group 0.000 claims description 18
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 17
• 239000003112 inhibitor Substances 0.000 claims description 15
• 206010052779 Transplant rejections Diseases 0.000 claims description 14
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 13
• 125000005843 halogen group Chemical group 0.000 claims description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims description 13
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000005577 anthracene group Chemical group 0.000 claims description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
• 125000004122 cyclic group Chemical group 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 151
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 127
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 115
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 80
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
• 239000000243 solution Substances 0.000 description 72
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 64
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
• 238000006243 chemical reaction Methods 0.000 description 61
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 60
• 235000019439 ethyl acetate Nutrition 0.000 description 59
• 239000000203 mixture Substances 0.000 description 58
• 239000002904 solvent Substances 0.000 description 56
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 50
• 229910052938 sodium sulfate Inorganic materials 0.000 description 50
• 235000011152 sodium sulphate Nutrition 0.000 description 50
• 239000012044 organic layer Substances 0.000 description 46
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
• 239000002585 base Substances 0.000 description 41
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 41
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 34
• 239000011541 reaction mixture Substances 0.000 description 34
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
• 238000005160 1H NMR spectroscopy Methods 0.000 description 32
• 238000001914 filtration Methods 0.000 description 32
• 239000000706 filtrate Substances 0.000 description 31
• 238000000034 method Methods 0.000 description 31
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• 238000001816 cooling Methods 0.000 description 30
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 27
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 23
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical group CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 22
• 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 22
• 239000012453 solvate Substances 0.000 description 21
• 241000124008 Mammalia Species 0.000 description 20
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 19
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
• 210000003423 ankle Anatomy 0.000 description 17
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 17
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 17
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 17
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 16
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 16
• 125000003386 piperidinyl group Chemical group 0.000 description 16
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 16
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
• 239000003795 chemical substances by application Substances 0.000 description 15
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 15
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
• 125000002883 imidazolyl group Chemical group 0.000 description 14
• 230000002401 inhibitory effect Effects 0.000 description 14
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 14
• 125000002757 morpholinyl group Chemical group 0.000 description 14
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 14
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 13
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• 150000001721 carbon Chemical group 0.000 description 13
• 239000004210 ether based solvent Substances 0.000 description 13
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 13
• 239000012046 mixed solvent Substances 0.000 description 13
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 13
• 125000003226 pyrazolyl group Chemical group 0.000 description 13
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 12
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
• 235000019341 magnesium sulphate Nutrition 0.000 description 12
• 239000012312 sodium hydride Substances 0.000 description 12
• 229910000104 sodium hydride Inorganic materials 0.000 description 12
• 238000006467 substitution reaction Methods 0.000 description 12
• 229910052717 sulfur Inorganic materials 0.000 description 12
• 125000004434 sulfur atom Chemical group 0.000 description 12
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 11
• 210000004241 Th2 cell Anatomy 0.000 description 11
• 230000004913 activation Effects 0.000 description 11
• 238000010438 heat treatment Methods 0.000 description 11
• 239000002798 polar solvent Substances 0.000 description 11
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 10
• 239000003814 drug Substances 0.000 description 10
• 210000003630 histaminocyte Anatomy 0.000 description 10
• 239000001257 hydrogen Substances 0.000 description 10
• 229910052739 hydrogen Inorganic materials 0.000 description 10
• 125000002632 imidazolidinyl group Chemical group 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 9
• 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 9
• 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 description 9
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 9
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
• 229910052763 palladium Inorganic materials 0.000 description 9
• 125000005554 pyridyloxy group Chemical group 0.000 description 9
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 125000003943 azolyl group Chemical group 0.000 description 8
• 238000007796 conventional method Methods 0.000 description 8
• 125000005842 heteroatom Chemical group 0.000 description 8
• 150000002430 hydrocarbons Chemical group 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 150000002829 nitrogen Chemical group 0.000 description 8
• 230000000069 prophylactic effect Effects 0.000 description 8
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
• 230000001225 therapeutic effect Effects 0.000 description 8
• 210000001744 T-lymphocyte Anatomy 0.000 description 7
• PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 7
• 239000001768 carboxy methyl cellulose Substances 0.000 description 7
• 238000010511 deprotection reaction Methods 0.000 description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
• 229940079593 drug Drugs 0.000 description 7
• 125000001153 fluoro group Chemical group F* 0.000 description 7
• 239000010410 layer Substances 0.000 description 7
• 239000012299 nitrogen atmosphere Substances 0.000 description 7
• 229910000029 sodium carbonate Inorganic materials 0.000 description 7
• 235000017550 sodium carbonate Nutrition 0.000 description 7
• 239000004215 Carbon black (E152) Substances 0.000 description 6
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 6
• 108090000695 Cytokines Proteins 0.000 description 6
• 102000004127 Cytokines Human genes 0.000 description 6
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 6
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 6
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 6
• 229940105329 carboxymethylcellulose Drugs 0.000 description 6
• 239000013078 crystal Substances 0.000 description 6
• 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 6
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 6
• 229930195733 hydrocarbon Natural products 0.000 description 6
• 230000005764 inhibitory process Effects 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
• 125000000168 pyrrolyl group Chemical group 0.000 description 6
• 150000003512 tertiary amines Chemical class 0.000 description 6
• 239000008096 xylene Substances 0.000 description 6
• 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 5
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 5
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 235000011054 acetic acid Nutrition 0.000 description 5
• 229910052786 argon Inorganic materials 0.000 description 5
• 239000012300 argon atmosphere Substances 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 229960004106 citric acid Drugs 0.000 description 5
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• 201000010099 disease Diseases 0.000 description 5
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• 230000006870 function Effects 0.000 description 5
• 125000002541 furyl group Chemical group 0.000 description 5
• 229960001340 histamine Drugs 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• 150000003536 tetrazoles Chemical class 0.000 description 5
• 125000000335 thiazolyl group Chemical group 0.000 description 5
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
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• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• RRHONYZEMUNMJX-UHFFFAOYSA-N N-[5-[[5-[(4-acetyl-1-piperazinyl)-oxomethyl]-4-methoxy-2-methylphenyl]thio]-2-thiazolyl]-4-[(3-methylbutan-2-ylamino)methyl]benzamide Chemical compound C1=C(C(=O)N2CCN(CC2)C(C)=O)C(OC)=CC(C)=C1SC(S1)=CN=C1NC(=O)C1=CC=C(CNC(C)C(C)C)C=C1 RRHONYZEMUNMJX-UHFFFAOYSA-N 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 239000002168 alkylating agent Substances 0.000 description 4
• 229940100198 alkylating agent Drugs 0.000 description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
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• 239000011592 zinc chloride Substances 0.000 description 1
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• OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1