BR112012012529B1 - Composto indol, composição farmacêutica, inibidores e agentes compreendendo o referido composto e seus usos - Google Patents

Info

Publication number

BR112012012529B1

BR112012012529B1 BR112012012529-0A BR112012012529A BR112012012529B1 BR 112012012529 B1 BR112012012529 B1 BR 112012012529B1 BR 112012012529 A BR112012012529 A BR 112012012529A BR 112012012529 B1 BR112012012529 B1 BR 112012012529B1

Authority

BR

Brazil

Prior art keywords

group

optionally substituted

compound

substituents selected

alkoxy

Prior art date

2009-11-25

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 286
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 15
• -1 INDOL COMPOUND Chemical class 0.000 title abstract description 185
• 239000003795 chemical substances by application Substances 0.000 title abstract description 34
• 239000003112 inhibitor Substances 0.000 title abstract description 10
• 150000003839 salts Chemical class 0.000 claims abstract description 85
• 238000011282 treatment Methods 0.000 claims abstract description 29
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 25
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 22
• 208000026935 allergic disease Diseases 0.000 claims abstract description 20
• 206010052779 Transplant rejections Diseases 0.000 claims abstract description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 170
• 125000001424 substituent group Chemical group 0.000 claims description 170
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 153
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 149
• 125000000623 heterocyclic group Chemical group 0.000 claims description 92
• 125000003118 aryl group Chemical group 0.000 claims description 60
• 125000004043 oxo group Chemical group O=* 0.000 claims description 59
• 125000003545 alkoxy group Chemical group 0.000 claims description 47
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
• 125000000217 alkyl group Chemical group 0.000 claims description 42
• 125000003277 amino group Chemical group 0.000 claims description 42
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 41
• 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 35
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 34
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 26
• 241000124008 Mammalia Species 0.000 claims description 24
• 238000000034 method Methods 0.000 claims description 24
• 125000004104 aryloxy group Chemical group 0.000 claims description 22
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 15
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 14
• 230000002401 inhibitory effect Effects 0.000 claims description 13
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 12
• 125000005843 halogen group Chemical group 0.000 claims description 12
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 12
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
• 238000002054 transplantation Methods 0.000 claims description 2
• 238000011321 prophylaxis Methods 0.000 abstract description 25
• 239000012453 solvate Substances 0.000 abstract description 21
• SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 9
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 abstract description 8
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 abstract description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 114
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 108
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
• 238000004519 manufacturing process Methods 0.000 description 83
• 239000000243 solution Substances 0.000 description 82
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 76
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
• 239000000203 mixture Substances 0.000 description 68
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
• 238000006243 chemical reaction Methods 0.000 description 60
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 60
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 57
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
• 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 48
• 239000002904 solvent Substances 0.000 description 47
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 41
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
• 239000000706 filtrate Substances 0.000 description 39
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
• 238000001816 cooling Methods 0.000 description 33
• 238000005160 1H NMR spectroscopy Methods 0.000 description 32
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
• 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 27
• 229910052757 nitrogen Inorganic materials 0.000 description 25
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 24
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
• 125000004433 nitrogen atom Chemical group N* 0.000 description 24
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 24
• 238000010438 heat treatment Methods 0.000 description 23
• 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
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 22
• 238000010898 silica gel chromatography Methods 0.000 description 22
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• 125000001041 indolyl group Chemical group 0.000 description 19
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 19
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 19
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 18
• KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 17
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 16
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 16
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 16
• 239000002253 acid Substances 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
• 239000004210 ether based solvent Substances 0.000 description 16
• 239000012046 mixed solvent Substances 0.000 description 16
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 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
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 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
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
• 125000002883 imidazolyl group Chemical group 0.000 description 15
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 14
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
• 239000012300 argon atmosphere Substances 0.000 description 13
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 13
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 13
• 238000002360 preparation method Methods 0.000 description 13
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 13
• 239000012312 sodium hydride Substances 0.000 description 13
• 229910000104 sodium hydride Inorganic materials 0.000 description 13
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• 229910052799 carbon Inorganic materials 0.000 description 12
• 150000001721 carbon Chemical group 0.000 description 12
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
• 235000019341 magnesium sulphate Nutrition 0.000 description 12
• 125000005936 piperidyl group Chemical group 0.000 description 12
• 125000003226 pyrazolyl group Chemical group 0.000 description 12
• 229910052717 sulfur Inorganic materials 0.000 description 12
• 125000004434 sulfur atom Chemical group 0.000 description 12
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 11
• 239000002798 polar solvent Substances 0.000 description 11
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 11
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
• 210000004241 Th2 cell Anatomy 0.000 description 10
• 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 10
• 210000003630 histaminocyte Anatomy 0.000 description 10
• 125000002632 imidazolidinyl group Chemical group 0.000 description 10
• 125000000160 oxazolidinyl group Chemical group 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• 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
• 210000001744 T-lymphocyte Anatomy 0.000 description 9
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 9
• 125000003725 azepanyl group Chemical group 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
• 230000000694 effects Effects 0.000 description 9
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 9
• 239000012299 nitrogen atmosphere Substances 0.000 description 9
• 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 8
• 239000005456 alcohol based solvent Substances 0.000 description 8
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 8
• 238000007796 conventional method Methods 0.000 description 8
• 125000000753 cycloalkyl group Chemical group 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 125000005842 heteroatom Chemical group 0.000 description 8
• 150000002430 hydrocarbons Chemical group 0.000 description 8
• 239000001257 hydrogen Substances 0.000 description 8
• 229910052739 hydrogen Inorganic materials 0.000 description 8
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 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
• UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 8
• 125000005554 pyridyloxy group Chemical group 0.000 description 8
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
• 230000004913 activation Effects 0.000 description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
• 125000004432 carbon atom Chemical group C* 0.000 description 7
• 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 7
• 229940079593 drug Drugs 0.000 description 7
• 229910052731 fluorine Inorganic materials 0.000 description 7
• 125000001153 fluoro group Chemical group F* 0.000 description 7
• 125000000842 isoxazolyl group Chemical group 0.000 description 7
• 239000010410 layer Substances 0.000 description 7
• 229910052763 palladium Inorganic materials 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
• 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
• VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 6
• 229950008138 carmellose Drugs 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• 239000013078 crystal Substances 0.000 description 6
• 238000010511 deprotection reaction Methods 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
• 229930195733 hydrocarbon Natural products 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• 125000006239 protecting group Chemical group 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 239000000741 silica gel Substances 0.000 description 6
• 229910002027 silica gel Inorganic materials 0.000 description 6
• 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 6
• 150000003512 tertiary amines Chemical class 0.000 description 6
• 239000008096 xylene Substances 0.000 description 6
• IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 5
• 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• 108090000695 Cytokines Proteins 0.000 description 5
• 102000004127 Cytokines Human genes 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 230000020411 cell activation Effects 0.000 description 5
• 235000015165 citric acid Nutrition 0.000 description 5
• 125000002541 furyl group Chemical group 0.000 description 5
• 229960001340 histamine Drugs 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• 125000003831 tetrazolyl group Chemical group 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
• 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 4
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 4
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
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