RU2577858C2 - НОВЫЕ ПРОИЗВОДНЫЕ ПИРРОЛО[3,2-d]ПИРИМИДИН-4-ОНА И ИХ ПРИМЕНЕНИЕ В ТЕРАПИИ - Google Patents

Info

Publication number

RU2577858C2

RU2577858C2 RU2010139806/04A RU2010139806A RU2577858C2 RU 2577858 C2 RU2577858 C2 RU 2577858C2 RU 2010139806/04 A RU2010139806/04 A RU 2010139806/04A RU 2010139806 A RU2010139806 A RU 2010139806A RU 2577858 C2 RU2577858 C2 RU 2577858C2

Authority

RU

Russia

Prior art keywords

pyrimidin

pyrrolo

thioxo

tetrahydro

alkoxy

Prior art date

2004-12-06

Links

• Espacenet
• Global Dossier
• Discuss

• 238000002560 therapeutic procedure Methods 0.000 title description 4
• XVHFAJKXXPJYDW-UHFFFAOYSA-N pyrrolo[3,2-d]pyrimidin-4-one Chemical class O=C1N=CN=C2C=CN=C12 XVHFAJKXXPJYDW-UHFFFAOYSA-N 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 169
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 71
• 102000003896 Myeloperoxidases Human genes 0.000 claims abstract description 61
• 108090000235 Myeloperoxidases Proteins 0.000 claims abstract description 61
• 150000003839 salts Chemical class 0.000 claims abstract description 53
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 36
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 35
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 29
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 24
• 150000002367 halogens Chemical class 0.000 claims abstract description 24
• 125000003118 aryl group Chemical group 0.000 claims abstract description 19
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 17
• 239000003814 drug Substances 0.000 claims abstract description 16
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 15
• 239000001257 hydrogen Substances 0.000 claims abstract description 12
• 239000003112 inhibitor Substances 0.000 claims abstract description 10
• 208000036110 Neuroinflammatory disease Diseases 0.000 claims abstract description 7
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 7
• FVJCUZCRPIMVLB-UHFFFAOYSA-N 1-(2-propan-2-yloxyethyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound O=C1NC(=S)N(CCOC(C)C)C2=C1NC=C2 FVJCUZCRPIMVLB-UHFFFAOYSA-N 0.000 claims abstract description 5
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
• 125000002950 monocyclic group Chemical group 0.000 claims abstract description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 42
• 201000010099 disease Diseases 0.000 claims description 29
• 238000000034 method Methods 0.000 claims description 29
• 229910052717 sulfur Inorganic materials 0.000 claims description 29
• 238000011282 treatment Methods 0.000 claims description 24
• CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 18
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 17
• 208000035475 disorder Diseases 0.000 claims description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims description 13
• 201000001320 Atherosclerosis Diseases 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 10
• 102000004190 Enzymes Human genes 0.000 claims description 9
• 108090000790 Enzymes Proteins 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
• 239000002671 adjuvant Substances 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 8
• 201000006417 multiple sclerosis Diseases 0.000 claims description 8
• XGZUURWEGKBYOK-UHFFFAOYSA-N 1-(piperidin-3-ylmethyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=2C=CNC=2C(=O)NC(=S)N1CC1CCCNC1 XGZUURWEGKBYOK-UHFFFAOYSA-N 0.000 claims description 7
• 230000005764 inhibitory process Effects 0.000 claims description 7
• UZASYDVRUNALQB-UHFFFAOYSA-N 1-(1h-benzimidazol-2-ylmethyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=CC=C2NC(CN3C(=S)NC(C=4NC=CC=43)=O)=NC2=C1 UZASYDVRUNALQB-UHFFFAOYSA-N 0.000 claims description 4
• USKMFODSLRKIFI-UHFFFAOYSA-N 1-(1h-imidazol-2-ylmethyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=2C=CNC=2C(=O)NC(=S)N1CC1=NC=CN1 USKMFODSLRKIFI-UHFFFAOYSA-N 0.000 claims description 4
• WHRSXLDXDSQADR-UHFFFAOYSA-N 1-(1h-indol-3-ylmethyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=CC=C2C(CN3C(=S)NC(C=4NC=CC=43)=O)=CNC2=C1 WHRSXLDXDSQADR-UHFFFAOYSA-N 0.000 claims description 4
• OGTLEZMDFONXBQ-UHFFFAOYSA-N 1-(2-methoxy-2-methylpropyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound O=C1NC(=S)N(CC(C)(C)OC)C2=C1NC=C2 OGTLEZMDFONXBQ-UHFFFAOYSA-N 0.000 claims description 4
• VAVUZMJQNFZLET-UHFFFAOYSA-N 1-(2-methylpropyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound O=C1NC(=S)N(CC(C)C)C2=C1NC=C2 VAVUZMJQNFZLET-UHFFFAOYSA-N 0.000 claims description 4
• ZZSTWOVLRXICHQ-UHFFFAOYSA-N 1-(3-chlorophenyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound ClC1=CC=CC(N2C(NC(=O)C=3NC=CC=32)=S)=C1 ZZSTWOVLRXICHQ-UHFFFAOYSA-N 0.000 claims description 4
• CLVIPEBFJWXCOH-UHFFFAOYSA-N 1-(piperidin-4-ylmethyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=2C=CNC=2C(=O)NC(=S)N1CC1CCNCC1 CLVIPEBFJWXCOH-UHFFFAOYSA-N 0.000 claims description 4
• SINJRLSDUJGDMZ-UHFFFAOYSA-N 1-(pyridin-2-ylmethyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=2C=CNC=2C(=O)NC(=S)N1CC1=CC=CC=N1 SINJRLSDUJGDMZ-UHFFFAOYSA-N 0.000 claims description 4
• IHGVZUSBTJMLGA-UHFFFAOYSA-N 1-[(2,4-dimethoxyphenyl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(OC)=CC=C1CN1C(=S)NC(=O)C2=C1C=CN2 IHGVZUSBTJMLGA-UHFFFAOYSA-N 0.000 claims description 4
• MQXBXSNNPZCGGS-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound FC1=CC=CC=C1CN1C(=S)NC(=O)C2=C1C=CN2 MQXBXSNNPZCGGS-UHFFFAOYSA-N 0.000 claims description 4
• LJCUZCGIZWLJJY-UHFFFAOYSA-N 1-[(2-methoxyphenyl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound COC1=CC=CC=C1CN1C(=S)NC(=O)C2=C1C=CN2 LJCUZCGIZWLJJY-UHFFFAOYSA-N 0.000 claims description 4
• NVTFAAMTTOCCBM-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound COC1=CC=CC(CN2C(NC(=O)C=3NC=CC=32)=S)=C1 NVTFAAMTTOCCBM-UHFFFAOYSA-N 0.000 claims description 4
• YQYWXKPRHIKWCA-UHFFFAOYSA-N 1-[(6-chloro-1h-benzimidazol-2-yl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N=1C2=CC(Cl)=CC=C2NC=1CN(C(NC1=O)=S)C2=C1NC=C2 YQYWXKPRHIKWCA-UHFFFAOYSA-N 0.000 claims description 4
• KFKPJKLDKLWRDW-UHFFFAOYSA-N 1-[(6-ethoxypyridin-2-yl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound CCOC1=CC=CC(CN2C(NC(=O)C=3NC=CC=32)=S)=N1 KFKPJKLDKLWRDW-UHFFFAOYSA-N 0.000 claims description 4
• VRNBKPSKZMIIKZ-UHFFFAOYSA-N 1-[2-hydroxy-2-(4-methoxyphenyl)ethyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1C(O)CN1C(=S)NC(=O)C2=C1C=CN2 VRNBKPSKZMIIKZ-UHFFFAOYSA-N 0.000 claims description 4
• TUQAXTAEZPIBTD-UHFFFAOYSA-N 1-[[2-(2-methoxyethoxy)-3-propoxyphenyl]methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound CCCOC1=CC=CC(CN2C(NC(=O)C=3NC=CC=32)=S)=C1OCCOC TUQAXTAEZPIBTD-UHFFFAOYSA-N 0.000 claims description 4
• IDMGWGAHVHCHCZ-UHFFFAOYSA-N 1-butyl-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound O=C1NC(=S)N(CCCC)C2=C1NC=C2 IDMGWGAHVHCHCZ-UHFFFAOYSA-N 0.000 claims description 4
• GWCPOASUTWKBIK-UHFFFAOYSA-N 7-bromo-1-(2-methylpropyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound O=C1NC(=S)N(CC(C)C)C2=C1NC=C2Br GWCPOASUTWKBIK-UHFFFAOYSA-N 0.000 claims description 4
• 238000011321 prophylaxis Methods 0.000 claims description 4
• UGGJWCCNZNSTJX-UHFFFAOYSA-N 1-(1h-imidazol-5-ylmethyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=2C=CNC=2C(=O)NC(=S)N1CC1=CN=CN1 UGGJWCCNZNSTJX-UHFFFAOYSA-N 0.000 claims description 3
• ZZTZYCUHURXEAQ-UHFFFAOYSA-N 1-(1h-indol-5-ylmethyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=C2NC=CC2=CC(CN2C(=S)NC(C=3NC=CC=32)=O)=C1 ZZTZYCUHURXEAQ-UHFFFAOYSA-N 0.000 claims description 3
• UGJJNUDJZWAVGF-UHFFFAOYSA-N 1-(1h-indol-6-ylmethyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=C2C=CNC2=CC(CN2C(=S)NC(C=3NC=CC=32)=O)=C1 UGJJNUDJZWAVGF-UHFFFAOYSA-N 0.000 claims description 3
• BTXGMJJTWCEMEM-UHFFFAOYSA-N 1-[(1-methylpiperidin-3-yl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1N(C)CCCC1CN1C(=S)NC(=O)C2=C1C=CN2 BTXGMJJTWCEMEM-UHFFFAOYSA-N 0.000 claims description 3
• ZKCQRRUUPOGGKZ-UHFFFAOYSA-N 1-[(3-chloropyridin-2-yl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound ClC1=CC=CN=C1CN1C(=S)NC(=O)C2=C1C=CN2 ZKCQRRUUPOGGKZ-UHFFFAOYSA-N 0.000 claims description 3
• LHDQQAXJOKHNQC-UHFFFAOYSA-N 1-[(4,5-dimethyl-1h-benzimidazol-2-yl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N=1C2=C(C)C(C)=CC=C2NC=1CN(C(NC1=O)=S)C2=C1NC=C2 LHDQQAXJOKHNQC-UHFFFAOYSA-N 0.000 claims description 3
• DKDZHCHXYMZOIK-UHFFFAOYSA-N 1-[(5-chloro-1h-indol-2-yl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C=1C2=CC(Cl)=CC=C2NC=1CN(C(NC1=O)=S)C2=C1NC=C2 DKDZHCHXYMZOIK-UHFFFAOYSA-N 0.000 claims description 3
• AWUPSBKDUQAAKD-UHFFFAOYSA-N 1-[(5-fluoro-1h-indol-2-yl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C=1C2=CC(F)=CC=C2NC=1CN(C(NC1=O)=S)C2=C1NC=C2 AWUPSBKDUQAAKD-UHFFFAOYSA-N 0.000 claims description 3
• GXVILYVZTYQCRZ-UHFFFAOYSA-N 1-[(5-fluoro-1h-indol-3-yl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C12=CC(F)=CC=C2NC=C1CN(C(NC1=O)=S)C2=C1NC=C2 GXVILYVZTYQCRZ-UHFFFAOYSA-N 0.000 claims description 3
• ATTWPJFBYSVNRF-UHFFFAOYSA-N 1-[(6-oxo-1h-pyridin-2-yl)methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N1C(=O)C=CC=C1CN1C(=S)NC(=O)C2=C1C=CN2 ATTWPJFBYSVNRF-UHFFFAOYSA-N 0.000 claims description 3
• VBUUWMSCDVWVJO-UHFFFAOYSA-N 1-[[3-(2-ethoxyethoxy)pyridin-2-yl]methyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound CCOCCOC1=CC=CN=C1CN1C(=S)NC(=O)C2=C1C=CN2 VBUUWMSCDVWVJO-UHFFFAOYSA-N 0.000 claims description 3
• AYPLZCFZXKZSLD-UHFFFAOYSA-N 1-butyl-4-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-2-one Chemical compound S=C1NC(=O)N(CCCC)C2=C1NC=C2 AYPLZCFZXKZSLD-UHFFFAOYSA-N 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• LDQWSIAUSUXRSA-UHFFFAOYSA-N 1-(2-ethoxy-2-methylpropyl)-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound O=C1NC(=S)N(CC(C)(C)OCC)C2=C1NC=C2 LDQWSIAUSUXRSA-UHFFFAOYSA-N 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 230000002401 inhibitory effect Effects 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 10
• 125000004356 hydroxy functional group Chemical group O* 0.000 abstract description 7
• 208000023504 respiratory system disease Diseases 0.000 abstract description 7
• 230000002526 effect on cardiovascular system Effects 0.000 abstract description 6
• 208000024172 Cardiovascular disease Diseases 0.000 abstract description 3
• 230000002314 neuroinflammatory effect Effects 0.000 abstract description 3
• 239000000126 substance Substances 0.000 abstract description 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
• 239000000203 mixture Substances 0.000 description 91
• 239000007787 solid Substances 0.000 description 46
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
• 239000011541 reaction mixture Substances 0.000 description 32
• 239000002904 solvent Substances 0.000 description 32
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 28
• 229910052760 oxygen Inorganic materials 0.000 description 28
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 26
• 239000000243 solution Substances 0.000 description 26
• -1 aromatic amino acids Chemical class 0.000 description 22
• 238000006243 chemical reaction Methods 0.000 description 22
• 239000012043 crude product Substances 0.000 description 22
• SPNDLEQTZLQLTA-UHFFFAOYSA-N ethyl 3-amino-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC=CC=1N SPNDLEQTZLQLTA-UHFFFAOYSA-N 0.000 description 22
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• BDTDECDAHYOJRO-UHFFFAOYSA-N ethyl n-(sulfanylidenemethylidene)carbamate Chemical group CCOC(=O)N=C=S BDTDECDAHYOJRO-UHFFFAOYSA-N 0.000 description 20
• 238000003818 flash chromatography Methods 0.000 description 20
• 238000007429 general method Methods 0.000 description 20
• 239000000047 product Substances 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 230000003143 atherosclerotic effect Effects 0.000 description 18
• 239000003921 oil Substances 0.000 description 18
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
• 229910052757 nitrogen Inorganic materials 0.000 description 17
• 238000002953 preparative HPLC Methods 0.000 description 15
• 238000000746 purification Methods 0.000 description 15
• 229910021529 ammonia Inorganic materials 0.000 description 14
• 238000003756 stirring Methods 0.000 description 14
• 230000003902 lesion Effects 0.000 description 13
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• 230000004048 modification Effects 0.000 description 11
• 238000012986 modification Methods 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 10
• 239000000543 intermediate Substances 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 229910004373 HOAc Inorganic materials 0.000 description 9
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
• 229940088598 enzyme Drugs 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 230000002265 prevention Effects 0.000 description 9
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
• AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
• 239000012044 organic layer Substances 0.000 description 8
• 239000012074 organic phase Substances 0.000 description 8
• 239000001301 oxygen Substances 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 7
• QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 7
• 210000004072 lung Anatomy 0.000 description 7
• 210000002540 macrophage Anatomy 0.000 description 7
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 7
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
• 108091005804 Peptidases Proteins 0.000 description 6
• 102000035195 Peptidases Human genes 0.000 description 6
• 239000004365 Protease Substances 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
• 208000006673 asthma Diseases 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 239000012267 brine Substances 0.000 description 6
• 125000004432 carbon atom Chemical group C* 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 230000006378 damage Effects 0.000 description 6
• MWWQOUGXCWIOSR-UHFFFAOYSA-N ethyl 3-amino-1h-pyrrole-2-carboxylate;hydrochloride Chemical compound [Cl-].CCOC(=O)C=1NC=CC=1[NH3+] MWWQOUGXCWIOSR-UHFFFAOYSA-N 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
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