PT1824855E - Novos derivados de pirrolo[3,2-d]pirimidin-4-ona e sua utilização em terapia - Google Patents

Info

Publication number

PT1824855E

PT1824855E PT05812036T PT05812036T PT1824855E PT 1824855 E PT1824855 E PT 1824855E PT 05812036 T PT05812036 T PT 05812036T PT 05812036 T PT05812036 T PT 05812036T PT 1824855 E PT1824855 E PT 1824855E

Authority

PT

Portugal

Prior art keywords

pyrimidin

thioxo

pyrrolo

tetrahydro

alkoxy

Prior art date

2004-12-06

Links

• Espacenet
• Global Dossier
• Discuss

• 238000002560 therapeutic procedure Methods 0.000 title description 5
• 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 description 160
• 201000006417 multiple sclerosis Diseases 0.000 claims description 79
• 125000003545 alkoxy group Chemical group 0.000 claims description 68
• 150000003839 salts Chemical class 0.000 claims description 46
• 125000000217 alkyl group Chemical group 0.000 claims description 40
• 125000002947 alkylene group Chemical group 0.000 claims description 40
• 229910052760 oxygen Inorganic materials 0.000 claims description 37
• -1 4,5-dimethyl-1H-benzimidazol-2-yl Chemical group 0.000 claims description 33
• 229910052736 halogen Inorganic materials 0.000 claims description 31
• 150000002367 halogens Chemical class 0.000 claims description 30
• 229910052717 sulfur Inorganic materials 0.000 claims description 28
• 238000011282 treatment Methods 0.000 claims description 28
• 125000005842 heteroatom Chemical group 0.000 claims description 27
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
• 238000000034 method Methods 0.000 claims description 26
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 21
• 125000001424 substituent group Chemical group 0.000 claims description 21
• 201000010099 disease Diseases 0.000 claims description 19
• CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 claims description 18
• 125000003118 aryl group Chemical group 0.000 claims description 17
• 238000011321 prophylaxis Methods 0.000 claims description 17
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 16
• 239000003814 drug Substances 0.000 claims description 16
• 229910052757 nitrogen Inorganic materials 0.000 claims description 15
• 229920006395 saturated elastomer Polymers 0.000 claims description 15
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
• 239000001301 oxygen Substances 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 101100295738 Gallus gallus COR3 gene Proteins 0.000 claims description 13
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• 239000001257 hydrogen Substances 0.000 claims description 12
• 229910052739 hydrogen Inorganic materials 0.000 claims description 12
• 201000001320 Atherosclerosis Diseases 0.000 claims description 10
• 102000004190 Enzymes Human genes 0.000 claims description 9
• 108090000790 Enzymes Proteins 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 230000008569 process Effects 0.000 claims description 9
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
• 239000002671 adjuvant Substances 0.000 claims description 8
• 239000004305 biphenyl Substances 0.000 claims description 8
• 235000010290 biphenyl Nutrition 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 8
• 125000001624 naphthyl group Chemical group 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
• 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 7
• 238000002360 preparation method Methods 0.000 claims description 7
• 230000005764 inhibitory process Effects 0.000 claims description 6
• 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 claims description 5
• 125000001072 heteroaryl group Chemical group 0.000 claims description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
• 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
• 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 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
• 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 description 4
• 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 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
• 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
• 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 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
• 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 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
• 208000018737 Parkinson disease Diseases 0.000 claims description 4
• 230000009286 beneficial effect Effects 0.000 claims description 4
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 150000002431 hydrogen Chemical group 0.000 claims description 4
• 125000002950 monocyclic group Chemical group 0.000 claims description 4
• 230000003287 optical effect Effects 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
• 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 3
• 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 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
• 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 3
• 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 3
• 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 3
• 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 3
• YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-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 2
• 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 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
• 101100134927 Gallus gallus COR8 gene Proteins 0.000 claims description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
• 125000003282 alkyl amino group Chemical group 0.000 claims description 2
• 229910052799 carbon Chemical group 0.000 claims description 2
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
• 125000002252 acyl group Chemical group 0.000 claims 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 111
• 239000000203 mixture Substances 0.000 description 83
• 238000005481 NMR spectroscopy Methods 0.000 description 66
• 102000003896 Myeloperoxidases Human genes 0.000 description 56
• 108090000235 Myeloperoxidases Proteins 0.000 description 56
• 239000007787 solid Substances 0.000 description 48
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
• 239000002904 solvent Substances 0.000 description 30
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 27
• 239000011541 reaction mixture Substances 0.000 description 27
• 238000006243 chemical reaction Methods 0.000 description 26
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
• 239000000243 solution Substances 0.000 description 25
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 238000007429 general method Methods 0.000 description 20
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 20
• 239000012043 crude product Substances 0.000 description 19
• 238000003818 flash chromatography Methods 0.000 description 19
• 239000000047 product Substances 0.000 description 19
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 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
• 238000005160 1H NMR spectroscopy Methods 0.000 description 16
• BDTDECDAHYOJRO-UHFFFAOYSA-N ethyl n-(sulfanylidenemethylidene)carbamate Chemical group CCOC(=O)N=C=S BDTDECDAHYOJRO-UHFFFAOYSA-N 0.000 description 16
• 238000000746 purification Methods 0.000 description 15
• 238000002953 preparative HPLC Methods 0.000 description 14
• 229910021529 ammonia Inorganic materials 0.000 description 13
• SPNDLEQTZLQLTA-UHFFFAOYSA-N ethyl 3-amino-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC=CC=1N SPNDLEQTZLQLTA-UHFFFAOYSA-N 0.000 description 13
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• 230000004048 modification Effects 0.000 description 11
• 238000012986 modification Methods 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 230000003143 atherosclerotic effect Effects 0.000 description 10
• 230000003902 lesion Effects 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
• 229940088598 enzyme Drugs 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 239000003112 inhibitor Substances 0.000 description 9
• 239000012044 organic layer Substances 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
• 230000000694 effects Effects 0.000 description 8
• 239000000543 intermediate Substances 0.000 description 8
• 229910004809 Na2 SO4 Inorganic materials 0.000 description 7
• 208000035475 disorder Diseases 0.000 description 7
• 210000002540 macrophage Anatomy 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
• 108091005804 Peptidases Proteins 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
• 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
• 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
• 239000000706 filtrate Substances 0.000 description 6
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
• 235000019341 magnesium sulphate Nutrition 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
• 239000003643 water by type Substances 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• 102000035195 Peptidases Human genes 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• 230000006378 damage Effects 0.000 description 5
• QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 5
• 230000007935 neutral effect Effects 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• MFBSDWRZRAMFAA-UHFFFAOYSA-N 3-amino-1h-pyrrole-2-carboxylic acid Chemical compound NC=1C=CNC=1C(O)=O MFBSDWRZRAMFAA-UHFFFAOYSA-N 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
• 206010016654 Fibrosis Diseases 0.000 description 4
• 241000282414 Homo sapiens Species 0.000 description 4
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
• 102000007330 LDL Lipoproteins Human genes 0.000 description 4
• 108010007622 LDL Lipoproteins Proteins 0.000 description 4
• 102100038609 Lactoperoxidase Human genes 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• 208000005764 Peripheral Arterial Disease Diseases 0.000 description 4
• 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 150000001299 aldehydes Chemical class 0.000 description 4
• 208000006673 asthma Diseases 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 230000002526 effect on cardiovascular system Effects 0.000 description 4
• 230000004761 fibrosis Effects 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 208000010125 myocardial infarction Diseases 0.000 description 4
• 239000012299 nitrogen atmosphere Substances 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• 230000003647 oxidation Effects 0.000 description 4
• 238000007254 oxidation reaction Methods 0.000 description 4
• 210000000680 phagosome Anatomy 0.000 description 4
• 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 4
• 150000003254 radicals Chemical class 0.000 description 4
• 208000023504 respiratory system disease Diseases 0.000 description 4
• 206010039083 rhinitis Diseases 0.000 description 4
• JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 4
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
• FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 description 3
• HHIYJPQUMUPZIZ-UHFFFAOYSA-N 2-ethoxy-2-methylpropanal Chemical compound CCOC(C)(C)C=O HHIYJPQUMUPZIZ-UHFFFAOYSA-N 0.000 description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
• 201000003883 Cystic fibrosis Diseases 0.000 description 3
• 102000015779 HDL Lipoproteins Human genes 0.000 description 3
• 108010010234 HDL Lipoproteins Proteins 0.000 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 description 3
• 108010036012 Iodide peroxidase Proteins 0.000 description 3
• 108010023244 Lactoperoxidase Proteins 0.000 description 3
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 3
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 3
• 208000006011 Stroke Diseases 0.000 description 3
• 102000014267 Thyroid peroxidases Human genes 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 239000012131 assay buffer Substances 0.000 description 3
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
• 235000012000 cholesterol Nutrition 0.000 description 3
• 208000029078 coronary artery disease Diseases 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 208000015181 infectious disease Diseases 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 239000002198 insoluble material Substances 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• 229940057428 lactoperoxidase Drugs 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 210000004072 lung Anatomy 0.000 description 3
• 210000003622 mature neutrocyte Anatomy 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 208000000638 myeloperoxidase deficiency Diseases 0.000 description 3
• 239000002245 particle Substances 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 3
• 238000001953 recrystallisation Methods 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 238000010561 standard procedure Methods 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 238000004809 thin layer chromatography Methods 0.000 description 3
• 238000010626 work up procedure Methods 0.000 description 3
• VVLAGYGCPZFAQX-UHFFFAOYSA-N (6-ethoxypyridin-2-yl)methanol Chemical compound CCOC1=CC=CC(CO)=N1 VVLAGYGCPZFAQX-UHFFFAOYSA-N 0.000 description 2
• 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 description 2
• GPTVQTPMFOLLOA-UHFFFAOYSA-N 1-chloro-2-ethoxyethane Chemical compound CCOCCCl GPTVQTPMFOLLOA-UHFFFAOYSA-N 0.000 description 2
• ADZUEEUKBYCSEY-UHFFFAOYSA-N 1h-indole-5-carbaldehyde Chemical compound O=CC1=CC=C2NC=CC2=C1 ADZUEEUKBYCSEY-UHFFFAOYSA-N 0.000 description 2
• IXWOUPGDGMCKGT-UHFFFAOYSA-N 2,3-dihydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1O IXWOUPGDGMCKGT-UHFFFAOYSA-N 0.000 description 2
• LWRSYTXEQUUTKW-UHFFFAOYSA-N 2,4-dimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1 LWRSYTXEQUUTKW-UHFFFAOYSA-N 0.000 description 2
• XSLFPIYQVRIRCC-UHFFFAOYSA-N 2-(2-methoxyethoxy)-3-propoxybenzaldehyde Chemical compound CCCOC1=CC=CC(C=O)=C1OCCOC XSLFPIYQVRIRCC-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
• ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 2
• HSCUZOQCNBPBST-UHFFFAOYSA-N 2-methoxy-2-methylpropanal Chemical compound COC(C)(C)C=O HSCUZOQCNBPBST-UHFFFAOYSA-N 0.000 description 2
• AQSRRZGQRFFFGS-UHFFFAOYSA-N 2-methylpyridin-3-ol Chemical compound CC1=NC=CC=C1O AQSRRZGQRFFFGS-UHFFFAOYSA-N 0.000 description 2
• UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 2
• SMIAPSTUMAQLFS-UHFFFAOYSA-N 3-(2-ethoxyethoxy)-2-methylpyridine Chemical compound CCOCCOC1=CC=CN=C1C SMIAPSTUMAQLFS-UHFFFAOYSA-N 0.000 description 2
• NBQHHQKLSQOZOF-UHFFFAOYSA-N 3-(2-ethoxyethoxy)pyridine-2-carbaldehyde Chemical compound CCOCCOC1=CC=CN=C1C=O NBQHHQKLSQOZOF-UHFFFAOYSA-N 0.000 description 2
• ACWBBAGYTKWBCD-ZETCQYMHSA-N 3-chloro-L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(Cl)=C1 ACWBBAGYTKWBCD-ZETCQYMHSA-N 0.000 description 2
• AVCGGTCZENZBLN-UHFFFAOYSA-N 3-hydroxy-2-(2-methoxyethoxy)benzaldehyde Chemical compound COCCOC1=C(O)C=CC=C1C=O AVCGGTCZENZBLN-UHFFFAOYSA-N 0.000 description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
• LCVUEIXVCGCYPP-UHFFFAOYSA-N 6-chloro-1h-benzimidazole-2-carbaldehyde Chemical compound ClC1=CC=C2N=C(C=O)NC2=C1 LCVUEIXVCGCYPP-UHFFFAOYSA-N 0.000 description 2
• WRWZDKXPVBFYLO-UHFFFAOYSA-N 6-ethoxypyridine-2-carbaldehyde Chemical compound CCOC1=CC=CC(C=O)=N1 WRWZDKXPVBFYLO-UHFFFAOYSA-N 0.000 description 2
• PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical class C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 description 2
• 208000004476 Acute Coronary Syndrome Diseases 0.000 description 2
• 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 239000005695 Ammonium acetate Substances 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
• TWXBSRWSBFPZJY-UHFFFAOYSA-N C(C)OC(=O)C=1NC=CC1NCC1CCN(CC1)C(=O)O Chemical compound C(C)OC(=O)C=1NC=CC1NCC1CCN(CC1)C(=O)O TWXBSRWSBFPZJY-UHFFFAOYSA-N 0.000 description 2
• OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical class ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 2
• 206010011224 Cough Diseases 0.000 description 2
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
• 208000016192 Demyelinating disease Diseases 0.000 description 2
• 206010012305 Demyelination Diseases 0.000 description 2
• 206010014561 Emphysema Diseases 0.000 description 2
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
• 206010057249 Phagocytosis Diseases 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 206010000891 acute myocardial infarction Diseases 0.000 description 2
• 239000000556 agonist Substances 0.000 description 2
• 235000001014 amino acid Nutrition 0.000 description 2
• 235000019257 ammonium acetate Nutrition 0.000 description 2
• 229940043376 ammonium acetate Drugs 0.000 description 2
• 230000007214 atherothrombosis Effects 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• 206010006451 bronchitis Diseases 0.000 description 2
• 244000309464 bull Species 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 125000001589 carboacyl group Chemical group 0.000 description 2
• 208000026106 cerebrovascular disease Diseases 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
• 238000010494 dissociation reaction Methods 0.000 description 2
• 230000005593 dissociations Effects 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• ZCIJGNNSPNVZOF-UHFFFAOYSA-N ethyl 3-(1h-benzimidazol-2-ylmethylamino)-1h-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC=2NC3=CC=CC=C3N=2)=C1C(=O)OCC ZCIJGNNSPNVZOF-UHFFFAOYSA-N 0.000 description 2
• MSZGHEOLSPDTNU-UHFFFAOYSA-N ethyl 3-(butylamino)-1h-pyrrole-2-carboxylate Chemical compound CCCCNC=1C=CNC=1C(=O)OCC MSZGHEOLSPDTNU-UHFFFAOYSA-N 0.000 description 2
• WZEZMSFHSCKUEE-UHFFFAOYSA-N ethyl 3-[(6-chloro-1h-benzimidazol-2-yl)methylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC=2NC3=CC=C(Cl)C=C3N=2)=C1C(=O)OCC WZEZMSFHSCKUEE-UHFFFAOYSA-N 0.000 description 2
• GHRPLRWXAMUAMW-UHFFFAOYSA-N ethyl 3-[(6-ethoxypyridin-2-yl)methylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC=2N=C(OCC)C=CC=2)=C1C(=O)OCC GHRPLRWXAMUAMW-UHFFFAOYSA-N 0.000 description 2
• FWHLGQGYNLVAHH-UHFFFAOYSA-N ethyl 3-[[2-(2-methoxyethoxy)-3-propoxyphenyl]methylamino]-1h-pyrrole-2-carboxylate Chemical compound CCCOC1=CC=CC(CNC2=C(NC=C2)C(=O)OCC)=C1OCCOC FWHLGQGYNLVAHH-UHFFFAOYSA-N 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 230000001434 glomerular Effects 0.000 description 2
• 210000000224 granular leucocyte Anatomy 0.000 description 2
• 150000003278 haem Chemical class 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
• JGJLWPGRMCADHB-UHFFFAOYSA-N hypobromite Inorganic materials Br[O-] JGJLWPGRMCADHB-UHFFFAOYSA-N 0.000 description 2
• OLNJUISKUQQNIM-UHFFFAOYSA-N indole-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CNC2=C1 OLNJUISKUQQNIM-UHFFFAOYSA-N 0.000 description 2
• CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
• 230000008595 infiltration Effects 0.000 description 2
• 238000001764 infiltration Methods 0.000 description 2
• 208000027866 inflammatory disease Diseases 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 239000013067 intermediate product Substances 0.000 description 2
• 150000002540 isothiocyanates Chemical class 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 201000005202 lung cancer Diseases 0.000 description 2
• 208000020816 lung neoplasm Diseases 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 238000001819 mass spectrum Methods 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 244000005700 microbiome Species 0.000 description 2
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
• 210000001539 phagocyte Anatomy 0.000 description 2
• 230000008782 phagocytosis Effects 0.000 description 2
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
• 235000018102 proteins Nutrition 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• 230000003595 spectral effect Effects 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
• HTHYFTJHGNIXJA-UHFFFAOYSA-N tert-butyl 3-[[(2-ethoxycarbonyl-1h-pyrrol-3-yl)amino]methyl]piperidine-1-carboxylate Chemical compound N1C=CC(NCC2CN(CCC2)C(=O)OC(C)(C)C)=C1C(=O)OCC HTHYFTJHGNIXJA-UHFFFAOYSA-N 0.000 description 2
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 230000000451 tissue damage Effects 0.000 description 2
• 231100000827 tissue damage Toxicity 0.000 description 2
• 208000019553 vascular disease Diseases 0.000 description 2
• 210000005166 vasculature Anatomy 0.000 description 2
• GIANIJCPTPUNBA-QMMMGPOBSA-N (2s)-3-(4-hydroxyphenyl)-2-nitramidopropanoic acid Chemical compound [O-][N+](=O)N[C@H](C(=O)O)CC1=CC=C(O)C=C1 GIANIJCPTPUNBA-QMMMGPOBSA-N 0.000 description 1
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
• METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
• KZDFOVZPOBSHDH-UHFFFAOYSA-N 1,1-diethoxy-2-methylpropane Chemical compound CCOC(C(C)C)OCC KZDFOVZPOBSHDH-UHFFFAOYSA-N 0.000 description 1
• HRQWOJUAAUOMRO-UHFFFAOYSA-N 1,2,3,4a-tetrahydropyrrolo[3,2-d]pyrimidin-4-one Chemical compound N1CNC(C2C1=CC=N2)=O HRQWOJUAAUOMRO-UHFFFAOYSA-N 0.000 description 1
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
• PXMJPPWEWLOMTC-UHFFFAOYSA-N 1-[(4,5-dimethyl-1H-benzimidazol-2-yl)methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one ethyl 3-[(4,5-dimethyl-1H-benzimidazol-2-yl)methylamino]-1H-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC=2NC3=CC=C(C)C(C)=C3N=2)=C1C(=O)OCC.N=1C2=C(C)C(C)=CC=C2NC=1CN(C(NC1=O)=S)C2=C1NC=C2 PXMJPPWEWLOMTC-UHFFFAOYSA-N 0.000 description 1
• FQQJBTSGMSHOCC-UHFFFAOYSA-N 1-[2-[tert-butyl(dimethyl)silyl]oxy-2-(4-methoxyphenyl)ethyl]-2-sulfanylidene-5h-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1C(O[Si](C)(C)C(C)(C)C)CN1C(=S)NC(=O)C2=C1C=CN2 FQQJBTSGMSHOCC-UHFFFAOYSA-N 0.000 description 1
• XTIGGAHUZJWQMD-UHFFFAOYSA-N 1-chloro-2-methoxyethane Chemical compound COCCCl XTIGGAHUZJWQMD-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• DQOSJWYZDQIMGM-UHFFFAOYSA-N 1H-benzimidazole-2-carbaldehyde Chemical compound C1=CC=C2NC(C=O)=NC2=C1 DQOSJWYZDQIMGM-UHFFFAOYSA-N 0.000 description 1
• XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
• ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical compound O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 1
• VSPBWOAEHQDXRD-UHFFFAOYSA-N 1h-indole-6-carbaldehyde Chemical compound O=CC1=CC=C2C=CNC2=C1 VSPBWOAEHQDXRD-UHFFFAOYSA-N 0.000 description 1
• DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
• QLSWIGRIBOSFMV-UHFFFAOYSA-N 1h-pyrrol-2-amine Chemical compound NC1=CC=CN1 QLSWIGRIBOSFMV-UHFFFAOYSA-N 0.000 description 1
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
• SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
• XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 1
• PIYRJJZQHJFIDJ-UHFFFAOYSA-N 2-[tert-butyl(dimethyl)silyl]oxy-2-(4-methoxyphenyl)acetaldehyde Chemical compound COC1=CC=C(C(O[Si](C)(C)C(C)(C)C)C=O)C=C1 PIYRJJZQHJFIDJ-UHFFFAOYSA-N 0.000 description 1
• QNFKYGPHEFUOOI-UHFFFAOYSA-N 2-formylpiperidine-1-carboxylic acid Chemical compound OC(=O)N1CCCCC1C=O QNFKYGPHEFUOOI-UHFFFAOYSA-N 0.000 description 1
• CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
• VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 1
• HCGFUIQPSOCUHI-UHFFFAOYSA-N 2-propan-2-yloxyethanol Chemical compound CC(C)OCCO HCGFUIQPSOCUHI-UHFFFAOYSA-N 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• UWDNBEDVERNIFP-UHFFFAOYSA-N 3-[(2,4-dimethoxyphenyl)methylamino]-1H-pyrrole-2-carboxylic acid Chemical compound COC1=C(CNC2=C(NC=C2)C(=O)O)C=CC(=C1)OC UWDNBEDVERNIFP-UHFFFAOYSA-N 0.000 description 1
• CQMNPNGQEXVVGO-UHFFFAOYSA-N 3-[[2-[tert-butyl(dimethyl)silyl]oxy-2-(4-methoxyphenyl)ethyl]amino]-1H-pyrrole-2-carboxylic acid Chemical compound [Si](C)(C)(C(C)(C)C)OC(CNC1=C(NC=C1)C(=O)O)C1=CC=C(C=C1)OC CQMNPNGQEXVVGO-UHFFFAOYSA-N 0.000 description 1
• PVFKBMLJRQDMSE-UHFFFAOYSA-N 3-amino-1h-pyrrole-2-carbaldehyde Chemical compound NC=1C=CNC=1C=O PVFKBMLJRQDMSE-UHFFFAOYSA-N 0.000 description 1
• QXNVCYJXFQPEKQ-UHFFFAOYSA-N 3-chloropyridine-2-carbaldehyde Chemical compound ClC1=CC=CN=C1C=O QXNVCYJXFQPEKQ-UHFFFAOYSA-N 0.000 description 1
• WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 1
• 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
• KRUPFSGDOXDDHU-UHFFFAOYSA-N 4,5-dimethyl-1h-benzimidazole-2-carbaldehyde Chemical compound CC1=CC=C2NC(C=O)=NC2=C1C KRUPFSGDOXDDHU-UHFFFAOYSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• VPTONMHDLLMOOV-UHFFFAOYSA-N 4-[3-[4-(2-methylimidazol-1-yl)phenyl]sulfanylphenyl]oxane-4-carboxamide Chemical compound CC1=NC=CN1C(C=C1)=CC=C1SC1=CC=CC(C2(CCOCC2)C(N)=O)=C1 VPTONMHDLLMOOV-UHFFFAOYSA-N 0.000 description 1
• MQLADKMVHOOVET-HXPMCKFVSA-N 5-[4-[(2s,4r)-4-hydroxy-2-methyloxan-4-yl]thiophen-2-yl]sulfanyl-1-methyl-3h-indol-2-one Chemical compound C1CO[C@@H](C)C[C@@]1(O)C1=CSC(SC=2C=C3CC(=O)N(C)C3=CC=2)=C1 MQLADKMVHOOVET-HXPMCKFVSA-N 0.000 description 1
• ZFWBIHAXMSSQOO-UHFFFAOYSA-N 5-chloro-1h-indole-2-carbaldehyde Chemical compound ClC1=CC=C2NC(C=O)=CC2=C1 ZFWBIHAXMSSQOO-UHFFFAOYSA-N 0.000 description 1
• YUAJKGBLPVLADK-UHFFFAOYSA-N 5-fluoro-1h-indole-3-carbaldehyde Chemical compound FC1=CC=C2NC=C(C=O)C2=C1 YUAJKGBLPVLADK-UHFFFAOYSA-N 0.000 description 1
• 239000003406 5-lipoxygenase-activating protein inhibitor Substances 0.000 description 1
• RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
• BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
• VRCWSYYXUCKEED-UHFFFAOYSA-N 6-Hydroxypicolinic acid Chemical compound OC(=O)C1=CC=CC(=O)N1 VRCWSYYXUCKEED-UHFFFAOYSA-N 0.000 description 1
• FKYXIGUDCJRHRB-UHFFFAOYSA-N 6-ethoxypyridine-2-carboxylic acid Chemical compound CCOC1=CC=CC(C(O)=O)=N1 FKYXIGUDCJRHRB-UHFFFAOYSA-N 0.000 description 1
• KRZYMTAWRSVBPH-UHFFFAOYSA-N 6-oxo-1h-pyridine-2-carbaldehyde Chemical compound OC1=CC=CC(C=O)=N1 KRZYMTAWRSVBPH-UHFFFAOYSA-N 0.000 description 1
• 101150092476 ABCA1 gene Proteins 0.000 description 1
• 239000005541 ACE inhibitor Substances 0.000 description 1
• 102000055510 ATP Binding Cassette Transporter 1 Human genes 0.000 description 1
• 108700005241 ATP Binding Cassette Transporter 1 Proteins 0.000 description 1
• 208000020053 Abnormal inflammatory response Diseases 0.000 description 1
• 208000035939 Alveolitis allergic Diseases 0.000 description 1
• KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
• 206010002388 Angina unstable Diseases 0.000 description 1
• 102000007592 Apolipoproteins Human genes 0.000 description 1
• 108010071619 Apolipoproteins Proteins 0.000 description 1
• 201000002909 Aspergillosis Diseases 0.000 description 1
• 208000036641 Aspergillus infections Diseases 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 206010003557 Asthma exercise induced Diseases 0.000 description 1
• 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
• 102100038495 Bile acid receptor Human genes 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 239000002083 C09CA01 - Losartan Substances 0.000 description 1
• 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
• 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
• 101150041968 CDC13 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229940127291 Calcium channel antagonist Drugs 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 description 1
• 206010007134 Candida infections Diseases 0.000 description 1
• 108010078791 Carrier Proteins Proteins 0.000 description 1
• 102000016938 Catalase Human genes 0.000 description 1
• 108010053835 Catalase Proteins 0.000 description 1
• JPNWZSPUHBHTEV-UHFFFAOYSA-N ClN1C(N(C=2N(C(N(C(C1=2)=O)C#N)=O)Cl)Cl)=O Chemical compound ClN1C(N(C=2N(C(N(C(C1=2)=O)C#N)=O)Cl)Cl)=O JPNWZSPUHBHTEV-UHFFFAOYSA-N 0.000 description 1
• 206010010774 Constipation Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000711573 Coronaviridae Species 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 108010061435 Enalapril Proteins 0.000 description 1
• 206010048554 Endothelial dysfunction Diseases 0.000 description 1
• 108010092408 Eosinophil Peroxidase Proteins 0.000 description 1
• 102100028471 Eosinophil peroxidase Human genes 0.000 description 1
• 206010065563 Eosinophilic bronchitis Diseases 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical class C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• PAEYAKGINDQUCT-UHFFFAOYSA-N Ethyl 2-pyrrolecarboxylate Chemical compound CCOC(=O)C1=CC=CN1 PAEYAKGINDQUCT-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• 208000004657 Exercise-Induced Asthma Diseases 0.000 description 1
• 229940123583 Factor Xa inhibitor Drugs 0.000 description 1
• 208000027445 Farmer Lung Diseases 0.000 description 1
• 206010017533 Fungal infection Diseases 0.000 description 1
• 108700024827 HOC1 Proteins 0.000 description 1
• 101001099464 Homo sapiens Lactoperoxidase Proteins 0.000 description 1
• 101001099460 Homo sapiens Myeloperoxidase Proteins 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
• 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
• 102100021711 Ileal sodium/bile acid cotransporter Human genes 0.000 description 1
• 101710156096 Ileal sodium/bile acid cotransporter Proteins 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 229940122355 Insulin sensitizer Drugs 0.000 description 1
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• 102100022118 Leukotriene A-4 hydrolase Human genes 0.000 description 1
• 102000004895 Lipoproteins Human genes 0.000 description 1
• 108090001030 Lipoproteins Proteins 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
• 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• IRLWJILLXJGJTD-UHFFFAOYSA-N Muraglitazar Chemical compound C1=CC(OC)=CC=C1OC(=O)N(CC(O)=O)CC(C=C1)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 IRLWJILLXJGJTD-UHFFFAOYSA-N 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• 108010083674 Myelin Proteins Proteins 0.000 description 1
• 102000006386 Myelin Proteins Human genes 0.000 description 1
• 229940122159 Myeloperoxidase inhibitor Drugs 0.000 description 1
• 108010002998 NADPH Oxidases Proteins 0.000 description 1
• 102000004722 NADPH Oxidases Human genes 0.000 description 1
• XEQCCHQDRJPUNM-UHFFFAOYSA-N NC1=C(NC=C1)C(=O)OC Chemical compound NC1=C(NC=C1)C(=O)OC XEQCCHQDRJPUNM-UHFFFAOYSA-N 0.000 description 1
• CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• 208000027771 Obstructive airways disease Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 102000003992 Peroxidases Human genes 0.000 description 1
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
• 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 1
• 208000037581 Persistent Infection Diseases 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
• 206010036774 Proctitis Diseases 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 241000725643 Respiratory syncytial virus Species 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 206010039094 Rhinitis perennial Diseases 0.000 description 1
• 208000036284 Rhinitis seasonal Diseases 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• 101100178273 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HOC1 gene Proteins 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
• 229910000831 Steel Inorganic materials 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 208000007814 Unstable Angina Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 229940020697 accolate Drugs 0.000 description 1
• 239000008351 acetate buffer Substances 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• 201000010105 allergic rhinitis Diseases 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229960000528 amlodipine Drugs 0.000 description 1
• ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
• 230000000954 anitussive effect Effects 0.000 description 1
• 239000004004 anti-anginal agent Substances 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 230000000118 anti-neoplastic effect Effects 0.000 description 1
• 229940124345 antianginal agent Drugs 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940127219 anticoagulant drug Drugs 0.000 description 1
• 229940030600 antihypertensive agent Drugs 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 229960002274 atenolol Drugs 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 238000011888 autopsy Methods 0.000 description 1
• 230000003376 axonal effect Effects 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
• 239000002876 beta blocker Substances 0.000 description 1
• 229940097320 beta blocking agent Drugs 0.000 description 1
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000000480 calcium channel blocker Substances 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• 229960000932 candesartan Drugs 0.000 description 1
• 201000003984 candidiasis Diseases 0.000 description 1
• FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
• 229960000830 captopril Drugs 0.000 description 1
• 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 230000001906 cholesterol absorption Effects 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 208000013116 chronic cough Diseases 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 230000006020 chronic inflammation Effects 0.000 description 1
• 201000009151 chronic rhinitis Diseases 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 238000006880 cross-coupling reaction Methods 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007123 defense Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 239000008367 deionised water Substances 0.000 description 1
• 229910021641 deionized water Inorganic materials 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 230000001687 destabilization Effects 0.000 description 1
• 230000001066 destructive effect Effects 0.000 description 1
• 229960005215 dichloroacetic acid Drugs 0.000 description 1
• 229960001259 diclofenac Drugs 0.000 description 1
• DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
• HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
• 229960004166 diltiazem Drugs 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• 238000007323 disproportionation reaction Methods 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000000428 dust Substances 0.000 description 1
• XFLQIRAKKLNXRQ-UUWRZZSWSA-N elobixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)NCC(O)=O)C=3C=CC=CC=3)C=C2S(=O)(=O)CC(CCCC)(CCCC)CN1C1=CC=CC=C1 XFLQIRAKKLNXRQ-UUWRZZSWSA-N 0.000 description 1
• GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
• 229960000873 enalapril Drugs 0.000 description 1
• 230000008694 endothelial dysfunction Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• ZIWYNSORYRPEBU-UHFFFAOYSA-N ethyl 3-(1h-imidazol-2-ylmethylamino)-1h-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC=2NC=CN=2)=C1C(=O)OCC ZIWYNSORYRPEBU-UHFFFAOYSA-N 0.000 description 1
• AHNORAYOCSZZDW-UHFFFAOYSA-N ethyl 3-(1h-indol-3-ylmethylamino)-1h-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC=2C3=CC=CC=C3NC=2)=C1C(=O)OCC AHNORAYOCSZZDW-UHFFFAOYSA-N 0.000 description 1
• KRLVTTCDZBTLOA-UHFFFAOYSA-N ethyl 3-(2-methylpropylamino)-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC=CC=1NCC(C)C KRLVTTCDZBTLOA-UHFFFAOYSA-N 0.000 description 1
• PFLOOZKAKDVXMY-UHFFFAOYSA-N ethyl 3-(2-propan-2-yloxyethylamino)-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC=CC=1NCCOC(C)C PFLOOZKAKDVXMY-UHFFFAOYSA-N 0.000 description 1
• SAVRXDRPYRIZMB-UHFFFAOYSA-N ethyl 3-[(2,4-dimethoxyphenyl)methylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC=2C(=CC(OC)=CC=2)OC)=C1C(=O)OCC SAVRXDRPYRIZMB-UHFFFAOYSA-N 0.000 description 1
• CRNIDRULOKNBMG-UHFFFAOYSA-N ethyl 3-[(2-ethoxy-2-methylpropyl)amino]-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC=CC=1NCC(C)(C)OCC CRNIDRULOKNBMG-UHFFFAOYSA-N 0.000 description 1
• ZPNAWUUFMZALEA-UHFFFAOYSA-N ethyl 3-[(2-methoxyphenyl)methylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC=2C(=CC=CC=2)OC)=C1C(=O)OCC ZPNAWUUFMZALEA-UHFFFAOYSA-N 0.000 description 1
• FDWVYFLKRLBDPB-UHFFFAOYSA-N ethyl 3-[(3-methoxyphenyl)methylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC=2C=C(OC)C=CC=2)=C1C(=O)OCC FDWVYFLKRLBDPB-UHFFFAOYSA-N 0.000 description 1
• WBHWSDFAUBTWBH-UHFFFAOYSA-N ethyl 3-[(6-oxo-1h-pyridin-2-yl)methylamino]-1h-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC=2NC(=O)C=CC=2)=C1C(=O)OCC WBHWSDFAUBTWBH-UHFFFAOYSA-N 0.000 description 1
• CYFBVNOISGURAT-UHFFFAOYSA-N ethyl 3-[[2-[tert-butyl(dimethyl)silyl]oxy-2-(4-methoxyphenyl)ethyl]amino]-1h-pyrrole-2-carboxylate Chemical compound N1C=CC(NCC(O[Si](C)(C)C(C)(C)C)C=2C=CC(OC)=CC=2)=C1C(=O)OCC CYFBVNOISGURAT-UHFFFAOYSA-N 0.000 description 1
• ZSCGLTGRUFNJOM-UHFFFAOYSA-N ethyl 3-amino-4-bromo-1h-pyrrole-2-carboxylate;ethyl 4-bromo-3-(2-methylpropylamino)-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC=C(Br)C=1N.CCOC(=O)C=1NC=C(Br)C=1NCC(C)C ZSCGLTGRUFNJOM-UHFFFAOYSA-N 0.000 description 1
• QYLRWLZUJOZFJT-UHFFFAOYSA-N ethyl 4-bromo-3-(2-methylpropylamino)-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC=C(Br)C=1NCC(C)C QYLRWLZUJOZFJT-UHFFFAOYSA-N 0.000 description 1
• LEKWWVNHYUXVAW-UHFFFAOYSA-N ethyl 6-ethoxypyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC(OCC)=N1 LEKWWVNHYUXVAW-UHFFFAOYSA-N 0.000 description 1
• VXNZUUAINFGPBY-UHFFFAOYSA-N ethyl ethylene Natural products CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
• 230000005713 exacerbation Effects 0.000 description 1
• 208000024695 exercise-induced bronchoconstriction Diseases 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
• OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
• 208000022195 farmer lung disease Diseases 0.000 description 1
• 229960003580 felodipine Drugs 0.000 description 1
• YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
• 229960002297 fenofibrate Drugs 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 229960002390 flurbiprofen Drugs 0.000 description 1
• SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
• 229960003765 fluvastatin Drugs 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 102000051251 human MPO Human genes 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• 230000009610 hypersensitivity Effects 0.000 description 1
• 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
• 230000000642 iatrogenic effect Effects 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 229960000905 indomethacin Drugs 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 239000003999 initiator Substances 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
• 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
• 229960002198 irbesartan Drugs 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 108010072713 leukotriene A4 hydrolase Proteins 0.000 description 1
• 229940065725 leukotriene receptor antagonists for obstructive airway diseases Drugs 0.000 description 1
• 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
• 150000002617 leukotrienes Chemical class 0.000 description 1
• UAWXGRJVZSAUSZ-UHFFFAOYSA-N licofelone Chemical compound OC(=O)CC=1N2CC(C)(C)CC2=C(C=2C=CC=CC=2)C=1C1=CC=C(Cl)C=C1 UAWXGRJVZSAUSZ-UHFFFAOYSA-N 0.000 description 1
• 229950003488 licofelone Drugs 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000006372 lipid accumulation Effects 0.000 description 1
• 230000037356 lipid metabolism Effects 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
• 229960004773 losartan Drugs 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• RXVKSXZEZOODTF-UHFFFAOYSA-N methyl 2-hydroxy-2-(4-methoxyphenyl)acetate Chemical compound COC(=O)C(O)C1=CC=C(OC)C=C1 RXVKSXZEZOODTF-UHFFFAOYSA-N 0.000 description 1
• GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
• 229960002237 metoprolol Drugs 0.000 description 1
• IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
• 230000003641 microbiacidal effect Effects 0.000 description 1
• 210000000274 microglia Anatomy 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 235000016337 monopotassium tartrate Nutrition 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• 229950001135 muraglitazar Drugs 0.000 description 1
• 210000005012 myelin Anatomy 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 229960002009 naproxen Drugs 0.000 description 1
• CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
• 201000009240 nasopharyngitis Diseases 0.000 description 1
• 230000001338 necrotic effect Effects 0.000 description 1
• 230000002314 neuroinflammatory effect Effects 0.000 description 1
• 230000003962 neuroinflammatory response Effects 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 150000002826 nitrites Chemical class 0.000 description 1
• 230000009635 nitrosylation Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 230000036542 oxidative stress Effects 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 208000022719 perennial allergic rhinitis Diseases 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 238000001050 pharmacotherapy Methods 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• 239000003428 phospholipase inhibitor Substances 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 229960005095 pioglitazone Drugs 0.000 description 1
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
• 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
• 102000054765 polymorphisms of proteins Human genes 0.000 description 1
• 208000015768 polyposis Diseases 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• KYKNRZGSIGMXFH-ZVGUSBNCSA-M potassium bitartrate Chemical compound [K+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O KYKNRZGSIGMXFH-ZVGUSBNCSA-M 0.000 description 1
• 229940081543 potassium bitartrate Drugs 0.000 description 1
• 239000008057 potassium phosphate buffer Substances 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 229960002965 pravastatin Drugs 0.000 description 1
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
• 238000004237 preparative chromatography Methods 0.000 description 1
• 230000000207 pro-atherogenic effect Effects 0.000 description 1
• FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
• 229960003912 probucol Drugs 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 125000002577 pseudohalo group Chemical group 0.000 description 1
• 230000005180 public health Effects 0.000 description 1
• 210000001147 pulmonary artery Anatomy 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 208000002815 pulmonary hypertension Diseases 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
• JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
• 229960001455 quinapril Drugs 0.000 description 1
• HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
• 229960003401 ramipril Drugs 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 230000000250 revascularization Effects 0.000 description 1
• 230000004141 reverse cholesterol transport Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 229960004586 rosiglitazone Drugs 0.000 description 1
• 229960000672 rosuvastatin Drugs 0.000 description 1
• BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
• 208000033610 salivary peroxidase Diseases 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 208000017022 seasonal allergic rhinitis Diseases 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 238000011894 semi-preparative HPLC Methods 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 208000013223 septicemia Diseases 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 230000000391 smoking effect Effects 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 239000012064 sodium phosphate buffer Substances 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 1
• 229960002370 sotalol Drugs 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 208000020431 spinal cord injury Diseases 0.000 description 1
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 239000010959 steel Substances 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 230000009897 systematic effect Effects 0.000 description 1
• 229960003080 taurine Drugs 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• OJCLHERKFHHUTB-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(CO)C1 OJCLHERKFHHUTB-UHFFFAOYSA-N 0.000 description 1
• CTVHINDANRPFIL-UHFFFAOYSA-N tert-butyl 3-formylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(C=O)C1 CTVHINDANRPFIL-UHFFFAOYSA-N 0.000 description 1
• JYUQEWCJWDGCRX-UHFFFAOYSA-N tert-butyl 4-formylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C=O)CC1 JYUQEWCJWDGCRX-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• 150000003573 thiols Chemical class 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
• 229960004072 thrombin Drugs 0.000 description 1
• PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
• 229960005001 ticlopidine Drugs 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• 201000008827 tuberculosis Diseases 0.000 description 1
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 210000003934 vacuole Anatomy 0.000 description 1
• 238000003828 vacuum filtration Methods 0.000 description 1
• HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
• 230000003156 vasculitic effect Effects 0.000 description 1
• 208000001319 vasomotor rhinitis Diseases 0.000 description 1
• 229960001722 verapamil Drugs 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• ZXIBCJHYVWYIKI-PZJWPPBQSA-N ximelagatran Chemical compound C1([C@@H](NCC(=O)OCC)C(=O)N2[C@@H](CC2)C(=O)NCC=2C=CC(=CC=2)C(\N)=N\O)CCCCC1 ZXIBCJHYVWYIKI-PZJWPPBQSA-N 0.000 description 1
• 229960001522 ximelagatran Drugs 0.000 description 1
• MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical compound C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 description 1
• 229960005332 zileuton Drugs 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1