MX2012006017A - Compuestos de indol y su uso farmaceutico. - Google Patents

Info

Publication number

MX2012006017A

MX2012006017A MX2012006017A MX2012006017A MX2012006017A MX 2012006017 A MX2012006017 A MX 2012006017A MX 2012006017 A MX2012006017 A MX 2012006017A MX 2012006017 A MX2012006017 A MX 2012006017A MX 2012006017 A MX2012006017 A MX 2012006017A

Authority

MX

Mexico

Prior art keywords

group

optionally substituted

substituents selected

alkoxy

compound

Prior art date

2009-11-25

Links

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• -1 Indole compound Chemical class 0.000 title claims description 182
• SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title description 11
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title description 8
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title description 8
• 150000001875 compounds Chemical class 0.000 claims abstract description 254
• 150000003839 salts Chemical class 0.000 claims abstract description 89
• 239000003795 chemical substances by application Substances 0.000 claims abstract description 38
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 26
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 25
• 208000026935 allergic disease Diseases 0.000 claims abstract description 21
• 238000002054 transplantation Methods 0.000 claims abstract description 12
• 125000000217 alkyl group Chemical group 0.000 claims description 199
• 125000003545 alkoxy group Chemical group 0.000 claims description 185
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 183
• 125000001424 substituent group Chemical group 0.000 claims description 181
• 125000003118 aryl group Chemical group 0.000 claims description 123
• 125000000623 heterocyclic group Chemical group 0.000 claims description 63
• 125000004043 oxo group Chemical group O=* 0.000 claims description 59
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 52
• 125000003277 amino group Chemical group 0.000 claims description 50
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 40
• 229920006395 saturated elastomer Polymers 0.000 claims description 37
• 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 34
• 238000011282 treatment Methods 0.000 claims description 32
• 241000124008 Mammalia Species 0.000 claims description 29
• 238000000034 method Methods 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 26
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 24
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 24
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
• 125000004432 carbon atom Chemical group C* 0.000 claims description 20
• 125000001041 indolyl group Chemical group 0.000 claims description 19
• 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 18
• 230000002401 inhibitory effect Effects 0.000 claims description 18
• 230000002265 prevention Effects 0.000 claims description 18
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 16
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 16
• 229910052799 carbon Inorganic materials 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 14
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
• 125000005843 halogen group Chemical group 0.000 claims description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims description 13
• 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 claims description 9
• 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 9
• 239000003112 inhibitor Substances 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 1
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims 1
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
• 239000012453 solvate Substances 0.000 abstract description 22
• 230000000069 prophylactic effect Effects 0.000 abstract description 2
• 210000000056 organ Anatomy 0.000 abstract 1
• 230000001225 therapeutic effect Effects 0.000 abstract 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 113
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 110
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
• 238000004519 manufacturing process Methods 0.000 description 86
• 239000000243 solution Substances 0.000 description 74
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 71
• ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 71
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
• 239000000203 mixture Substances 0.000 description 68
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 67
• 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
• 230000002829 reductive effect Effects 0.000 description 52
• 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
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
• 239000000706 filtrate Substances 0.000 description 39
• 238000001914 filtration Methods 0.000 description 39
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 38
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
• 108010075324 emt protein-tyrosine kinase Proteins 0.000 description 35
• 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 31
• 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
• 239000000741 silica gel Substances 0.000 description 27
• 229910002027 silica gel Inorganic materials 0.000 description 27
• 238000004587 chromatography analysis Methods 0.000 description 25
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 25
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
• 238000010438 heat treatment Methods 0.000 description 23
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound 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
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
• 229910052739 hydrogen Inorganic materials 0.000 description 21
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 19
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 18
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 17
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 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
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 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
• 125000005936 piperidyl 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
• 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 15
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
• 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
• 125000002883 imidazolyl group Chemical group 0.000 description 15
• 125000002757 morpholinyl group Chemical group 0.000 description 15
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-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
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 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
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 14
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 13
• 125000003718 tetrahydrofuranyl group Chemical group 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
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
• 235000019341 magnesium sulphate Nutrition 0.000 description 12
• 238000011321 prophylaxis Methods 0.000 description 12
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 12
• 239000012312 sodium hydride Substances 0.000 description 12
• 229910000104 sodium hydride Inorganic materials 0.000 description 12
• 229910052717 sulfur Inorganic materials 0.000 description 12
• 125000004434 sulfur atom Chemical group 0.000 description 12
• 210000004241 Th2 cell Anatomy 0.000 description 11
• 239000002253 acid Substances 0.000 description 11
• 239000007864 aqueous solution Substances 0.000 description 11
• 239000002798 polar solvent Substances 0.000 description 11
• 238000002360 preparation method Methods 0.000 description 11
• 125000003226 pyrazolyl group Chemical group 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
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 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
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 10
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-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
• 230000004913 activation Effects 0.000 description 9
• 239000012300 argon atmosphere Substances 0.000 description 9
• 239000012298 atmosphere Substances 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
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 9
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 9
• 239000012299 nitrogen atmosphere Substances 0.000 description 9
• 125000006239 protecting group Chemical group 0.000 description 9
• 125000005554 pyridyloxy group Chemical group 0.000 description 9
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-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
• 238000010511 deprotection reaction Methods 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
• 125000005842 heteroatom Chemical group 0.000 description 8
• 150000002430 hydrocarbons Chemical group 0.000 description 8
• 239000010410 layer Substances 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
• YMWUJEATGCHHMB-UHFFFAOYSA-N methylene chloride Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
• 108090000695 Cytokines Proteins 0.000 description 7
• 102000004127 Cytokines Human genes 0.000 description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
• 210000001744 T-lymphocyte Anatomy 0.000 description 7
• 239000000872 buffer Substances 0.000 description 7
• 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 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
• 229910000029 sodium carbonate Inorganic materials 0.000 description 7
• 235000017550 sodium carbonate Nutrition 0.000 description 7
• IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 6
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• 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
• 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
• 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
• 229950008138 carmellose Drugs 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• 238000009833 condensation Methods 0.000 description 6
• 230000005494 condensation Effects 0.000 description 6
• 239000000470 constituent Substances 0.000 description 6
• 239000013078 crystal Substances 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 6
• 229930195733 hydrocarbon Natural products 0.000 description 6
• 239000001257 hydrogen Substances 0.000 description 6
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 239000000725 suspension Substances 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
• 125000000335 thiazolyl group Chemical group 0.000 description 6
• 239000008096 xylene Substances 0.000 description 6
• 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
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
• 235000015165 citric acid Nutrition 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 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
• 239000000047 product Substances 0.000 description 5
• 125000000168 pyrrolyl group Chemical group 0.000 description 5
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• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1
• 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