ES2831322T3 - Compuestos de 2-oxo-1,2-dihidropiridin-3,5-dicarboxamida como inhibidores de bromodominios - Google Patents

Info

Publication number

ES2831322T3

ES2831322T3 ES16778310T ES16778310T ES2831322T3 ES 2831322 T3 ES2831322 T3 ES 2831322T3 ES 16778310 T ES16778310 T ES 16778310T ES 16778310 T ES16778310 T ES 16778310T ES 2831322 T3 ES2831322 T3 ES 2831322T3

Authority

ES

Spain

Prior art keywords

oxo

methyl

dihydropyridine

dicarboxamide

benzyl

Prior art date

2015-10-05

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 102000001805 Bromodomains Human genes 0.000 title description 44
• 108050009021 Bromodomains Proteins 0.000 title description 43
• 239000003112 inhibitor Substances 0.000 title description 22
• CTZIPFCPXSEUIP-UHFFFAOYSA-N 2-oxo-1H-pyridine-3,5-dicarboxamide Chemical class O=C1NC=C(C=C1C(=O)N)C(=O)N CTZIPFCPXSEUIP-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 221
• 150000003839 salts Chemical class 0.000 claims abstract description 157
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 79
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 75
• -1 -OCHF2 Chemical group 0.000 claims abstract description 64
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 52
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 41
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 32
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 21
• 125000001424 substituent group Chemical group 0.000 claims abstract description 19
• 125000005843 halogen group Chemical group 0.000 claims abstract description 16
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 16
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 15
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 15
• 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 14
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 13
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 13
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims abstract description 11
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 11
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 11
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 10
• 239000011737 fluorine Substances 0.000 claims abstract description 10
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 9
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
• 239000001301 oxygen Chemical group 0.000 claims abstract description 9
• 229910052717 sulfur Chemical group 0.000 claims abstract description 9
• 239000011593 sulfur Chemical group 0.000 claims abstract description 9
• 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 6
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 5
• 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims abstract description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 42
• 238000011282 treatment Methods 0.000 claims description 37
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 29
• 206010028980 Neoplasm Diseases 0.000 claims description 26
• 201000011510 cancer Diseases 0.000 claims description 23
• 230000001154 acute effect Effects 0.000 claims description 20
• 230000001363 autoimmune Effects 0.000 claims description 13
• 230000001684 chronic effect Effects 0.000 claims description 13
• QEXKCLKKZYLBQP-UHFFFAOYSA-N CCCNC(=O)C1=CN(CC2=CC=CC=C2)C(=O)C(=C1)C(=O)NC Chemical compound CCCNC(=O)C1=CN(CC2=CC=CC=C2)C(=O)C(=C1)C(=O)NC QEXKCLKKZYLBQP-UHFFFAOYSA-N 0.000 claims description 8
• IJHWQSXLORJLJY-UHFFFAOYSA-N CNC(=O)C1=CC(=CN(CC2=CC(C)=CC=C2)C1=O)C(=O)NCCC1=CNN=C1 Chemical compound CNC(=O)C1=CC(=CN(CC2=CC(C)=CC=C2)C1=O)C(=O)NCCC1=CNN=C1 IJHWQSXLORJLJY-UHFFFAOYSA-N 0.000 claims description 8
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• UQWYBQVXLSDHKF-UHFFFAOYSA-N 5-N-ethyl-1-[[3-(2-hydroxyethoxy)phenyl]methyl]-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CCNC(=O)C1=CN(CC2=CC(OCCO)=CC=C2)C(=O)C(=C1)C(=O)NC UQWYBQVXLSDHKF-UHFFFAOYSA-N 0.000 claims description 6
• VTJNNPHFQQYQSQ-UHFFFAOYSA-N 1-benzyl-5-N-butyl-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CCCCNC(=O)C1=CN(CC2=CC=CC=C2)C(=O)C(=C1)C(=O)NC VTJNNPHFQQYQSQ-UHFFFAOYSA-N 0.000 claims description 5
• QGDKBYNQYCEMIC-UHFFFAOYSA-N 1-benzyl-3-N-methyl-2-oxo-5-N-(2-pyridin-2-ylethyl)pyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC1=NC=CC=C1 QGDKBYNQYCEMIC-UHFFFAOYSA-N 0.000 claims description 4
• MFSZAVZIJWFJFW-UHFFFAOYSA-N 5-N-ethyl-3-N-methyl-1-[(3-methylphenyl)methyl]-2-oxopyridine-3,5-dicarboxamide Chemical compound CCNC(=O)C1=CN(CC2=CC(C)=CC=C2)C(=O)C(=C1)C(=O)NC MFSZAVZIJWFJFW-UHFFFAOYSA-N 0.000 claims description 4
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 4
• REMQVVQBQSAYFB-UHFFFAOYSA-N CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC1=CN=CN1 Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC1=CN=CN1 REMQVVQBQSAYFB-UHFFFAOYSA-N 0.000 claims description 4
• WDDWXBIKJCMWSY-UHFFFAOYSA-N CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCCC1=NC=CN1 Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCCC1=NC=CN1 WDDWXBIKJCMWSY-UHFFFAOYSA-N 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• 230000002757 inflammatory effect Effects 0.000 claims description 4
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• SXANHRXGPZULMS-UHFFFAOYSA-N 1-benzyl-3-N-methyl-2-oxo-5-N-(3,3,3-trifluoropropyl)pyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC(F)(F)F SXANHRXGPZULMS-UHFFFAOYSA-N 0.000 claims description 3
• SQUQXKBBDZDFFU-UHFFFAOYSA-N 1-benzyl-3-N-methyl-2-oxo-5-N-[2-(1H-pyrazol-4-yl)ethyl]pyridine-3,5-dicarboxamide Chemical compound CNC(=O)c1cc(cn(Cc2ccccc2)c1=O)C(=O)NCCc1cn[nH]c1 SQUQXKBBDZDFFU-UHFFFAOYSA-N 0.000 claims description 3
• JEQGAHKBIFRHMQ-UHFFFAOYSA-N 1-benzyl-3-N-methyl-5-N-(3-methylbutyl)-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC(C)C JEQGAHKBIFRHMQ-UHFFFAOYSA-N 0.000 claims description 3
• MQKOZRUIYLFGEB-UHFFFAOYSA-N 1-benzyl-3-N-methyl-5-N-[4-(methylamino)-4-oxobutyl]-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)CCCNC(=O)C1=CN(CC2=CC=CC=C2)C(=O)C(=C1)C(=O)NC MQKOZRUIYLFGEB-UHFFFAOYSA-N 0.000 claims description 3
• XFWIXXZNFMSKTP-UHFFFAOYSA-N 1-benzyl-5-N-ethyl-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CCNC(=O)C1=CN(CC2=CC=CC=C2)C(=O)C(=C1)C(=O)NC XFWIXXZNFMSKTP-UHFFFAOYSA-N 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• FWZRBPUVQUGTAC-UHFFFAOYSA-N 1-(1H-indol-4-ylmethyl)-3-N-methyl-2-oxo-5-N-[2-(1H-pyrazol-4-yl)ethyl]pyridine-3,5-dicarboxamide Chemical compound CNC(=O)c1cc(cn(Cc2cccc3[nH]ccc23)c1=O)C(=O)NCCc1cn[nH]c1 FWZRBPUVQUGTAC-UHFFFAOYSA-N 0.000 claims description 2
• DUWSWYMITSIPFJ-UHFFFAOYSA-N 1-[(2-fluoro-3-methylphenyl)methyl]-3-N-methyl-2-oxo-5-N-[2-(1H-pyrazol-4-yl)ethyl]pyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=C(F)C(C)=CC=C2)C1=O)C(=O)NCCC1=CNN=C1 DUWSWYMITSIPFJ-UHFFFAOYSA-N 0.000 claims description 2
• LULWCVIDODKXLB-UHFFFAOYSA-N 1-[(2-fluoro-3-methylphenyl)methyl]-5-N-[2-(1H-imidazol-5-yl)ethyl]-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=C(F)C(C)=CC=C2)C1=O)C(=O)NCCC1=CNC=N1 LULWCVIDODKXLB-UHFFFAOYSA-N 0.000 claims description 2
• YRHZKYRURGBODZ-UHFFFAOYSA-N 1-[(3-cyanophenyl)methyl]-3-N,5-N-dimethyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CN(CC2=CC(=CC=C2)C#N)C(=O)C(=C1)C(=O)NC YRHZKYRURGBODZ-UHFFFAOYSA-N 0.000 claims description 2
• ZGVHEXSCYYPCJW-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-N-methyl-2-oxo-5-N-[2-(1H-pyrazol-4-yl)ethyl]pyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC(OC)=CC=C2)C1=O)C(=O)NCCC1=CNN=C1 ZGVHEXSCYYPCJW-UHFFFAOYSA-N 0.000 claims description 2
• VVYUMAQGZVLGMK-UHFFFAOYSA-N 1-[[3-(2-hydroxyethoxy)phenyl]methyl]-3-N-methyl-2-oxo-5-N-[2-(1H-pyrazol-4-yl)ethyl]pyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC(OCCO)=CC=C2)C1=O)C(=O)NCCC1=CNN=C1 VVYUMAQGZVLGMK-UHFFFAOYSA-N 0.000 claims description 2
• ZUHGYWQWGMWHPJ-UHFFFAOYSA-N 1-[[3-(2-hydroxyethoxy)phenyl]methyl]-5-N-[2-(1H-imidazol-5-yl)ethyl]-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC(OCCO)=CC=C2)C1=O)C(=O)NCCC1=CNC=N1 ZUHGYWQWGMWHPJ-UHFFFAOYSA-N 0.000 claims description 2
• DANLNXYNIAMHCE-UHFFFAOYSA-N 1-benzyl-3-N,5-N-dimethyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CN(CC2=CC=CC=C2)C(=O)C(=C1)C(=O)NC DANLNXYNIAMHCE-UHFFFAOYSA-N 0.000 claims description 2
• REGZAFBKNVQTID-UHFFFAOYSA-N 1-benzyl-3-N-methyl-2-oxo-5-N-(2-pyridin-3-ylethyl)pyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC1=CC=CN=C1 REGZAFBKNVQTID-UHFFFAOYSA-N 0.000 claims description 2
• UFIXPEWDAIVQGG-UHFFFAOYSA-N 1-benzyl-3-N-methyl-2-oxo-5-N-(2-pyridin-4-ylethyl)pyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC1=CC=NC=C1 UFIXPEWDAIVQGG-UHFFFAOYSA-N 0.000 claims description 2
• LXCKAASCJJIWBC-UHFFFAOYSA-N 1-benzyl-3-N-methyl-2-oxo-5-N-[2-(1,3-thiazol-4-yl)ethyl]pyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC1=CSC=N1 LXCKAASCJJIWBC-UHFFFAOYSA-N 0.000 claims description 2
• QKNHGOMHDHQWQZ-UHFFFAOYSA-N 1-benzyl-3-N-methyl-2-oxo-5-N-[2-(1H-pyrazol-5-yl)ethyl]pyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC1=CC=NN1 QKNHGOMHDHQWQZ-UHFFFAOYSA-N 0.000 claims description 2
• AHAQFZBVHBOHFW-UHFFFAOYSA-N 1-benzyl-3-N-methyl-2-oxo-5-N-propan-2-ylpyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NC(C)C AHAQFZBVHBOHFW-UHFFFAOYSA-N 0.000 claims description 2
• FYNTXIKCFMTBOR-UHFFFAOYSA-N 1-benzyl-3-N-methyl-2-oxo-5-N-pyridazin-4-ylpyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NC1=CN=NC=C1 FYNTXIKCFMTBOR-UHFFFAOYSA-N 0.000 claims description 2
• RIMDTGWDSDEJGW-UHFFFAOYSA-N 1-benzyl-3-N-methyl-5-N-(2-methylpropyl)-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCC(C)C RIMDTGWDSDEJGW-UHFFFAOYSA-N 0.000 claims description 2
• JVHVTBGUMLAESI-UHFFFAOYSA-N 1-benzyl-3-N-methyl-5-N-(2-methylsulfonylethyl)-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCS(C)(=O)=O JVHVTBGUMLAESI-UHFFFAOYSA-N 0.000 claims description 2
• FWQIQTSLUWALKI-UHFFFAOYSA-N 1-benzyl-3-N-methyl-5-N-(3-methylsulfonylpropyl)-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCCS(C)(=O)=O FWQIQTSLUWALKI-UHFFFAOYSA-N 0.000 claims description 2
• GDIQCISRJSUFQR-UHFFFAOYSA-N 1-benzyl-3-N-methyl-5-N-[2-(1,2-oxazol-4-yl)ethyl]-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC1=CON=C1 GDIQCISRJSUFQR-UHFFFAOYSA-N 0.000 claims description 2
• GPPNORSDYVXVGS-UHFFFAOYSA-N 1-benzyl-3-N-methyl-5-N-[2-(1-methylpyrazol-4-yl)ethyl]-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)c1cc(cn(Cc2ccccc2)c1=O)C(=O)NCCc1cnn(C)c1 GPPNORSDYVXVGS-UHFFFAOYSA-N 0.000 claims description 2
• XSUFXEMEOBUCEQ-UHFFFAOYSA-N 1-benzyl-3-N-methyl-5-N-[2-(4-methyl-1,2,4-triazol-3-yl)ethyl]-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)c1cc(cn(Cc2ccccc2)c1=O)C(=O)NCCc1nncn1C XSUFXEMEOBUCEQ-UHFFFAOYSA-N 0.000 claims description 2
• GHQMXKIALCCWIQ-UHFFFAOYSA-N 1-benzyl-3-N-methyl-5-N-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)c1cc(cn(Cc2ccccc2)c1=O)C(=O)NCCc1scnc1C GHQMXKIALCCWIQ-UHFFFAOYSA-N 0.000 claims description 2
• PKSWJRINFNVFHE-UHFFFAOYSA-N 1-benzyl-3-N-methyl-5-N-[3-(methylamino)-3-oxopropyl]-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)CCNC(=O)C1=CN(CC2=CC=CC=C2)C(=O)C(=C1)C(=O)NC PKSWJRINFNVFHE-UHFFFAOYSA-N 0.000 claims description 2
• CRWAKZZBHIGVID-UHFFFAOYSA-N 1-benzyl-5-N-(2-cyanoethyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC#N CRWAKZZBHIGVID-UHFFFAOYSA-N 0.000 claims description 2
• CCJIIOFOFBMUCK-UHFFFAOYSA-N 1-benzyl-5-N-(2-hydroxyethyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCO CCJIIOFOFBMUCK-UHFFFAOYSA-N 0.000 claims description 2
• LTDMXYJCXCTKLZ-UHFFFAOYSA-N 1-benzyl-5-N-(2-methoxyethyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCOC LTDMXYJCXCTKLZ-UHFFFAOYSA-N 0.000 claims description 2
• MVEWQBUZCZGKRP-UHFFFAOYSA-N 1-benzyl-5-N-(2-methoxypropyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCC(C)OC MVEWQBUZCZGKRP-UHFFFAOYSA-N 0.000 claims description 2
• SXWYBTVBONXZDA-UHFFFAOYSA-N 1-benzyl-5-N-(3-cyanopropyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCCC#N SXWYBTVBONXZDA-UHFFFAOYSA-N 0.000 claims description 2
• LZGCBPVDJHVGJZ-UHFFFAOYSA-N 1-benzyl-5-N-(3-hydroxybutyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC(C)O LZGCBPVDJHVGJZ-UHFFFAOYSA-N 0.000 claims description 2
• SPJCTLUAFKRXQY-UHFFFAOYSA-N 1-benzyl-5-N-(3-hydroxypropyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCCO SPJCTLUAFKRXQY-UHFFFAOYSA-N 0.000 claims description 2
• AFWGAMBAZZERNS-UHFFFAOYSA-N 1-benzyl-5-N-(3-methoxypropyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCCOC AFWGAMBAZZERNS-UHFFFAOYSA-N 0.000 claims description 2
• MXQHWXSDTPBJJF-UHFFFAOYSA-N 1-benzyl-5-N-[3-(dimethylamino)butyl]-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCC(C)N(C)C MXQHWXSDTPBJJF-UHFFFAOYSA-N 0.000 claims description 2
• KODXULLKFXZKHH-UHFFFAOYSA-N 1-benzyl-5-N-[3-(dimethylamino)propyl]-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCCN(C)C KODXULLKFXZKHH-UHFFFAOYSA-N 0.000 claims description 2
• FMACSLBHAZPXFU-UHFFFAOYSA-N 5-N-(3-aminopropyl)-1-benzyl-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCCN FMACSLBHAZPXFU-UHFFFAOYSA-N 0.000 claims description 2
• XIFYHEHHBPJHCX-UHFFFAOYSA-N 5-N-[2-(1H-imidazol-5-yl)ethyl]-1-(1H-indol-4-ylmethyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=C3C=CNC3=CC=C2)C1=O)C(=O)NCCC1=CNC=N1 XIFYHEHHBPJHCX-UHFFFAOYSA-N 0.000 claims description 2
• KSAAVHPPBIBSDJ-UHFFFAOYSA-N 5-N-ethyl-1-(1H-indol-4-ylmethyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CCNC(=O)c1cc(C(=O)NC)c(=O)n(Cc2cccc3[nH]ccc23)c1 KSAAVHPPBIBSDJ-UHFFFAOYSA-N 0.000 claims description 2
• JJDJTAIBTQXVRX-UHFFFAOYSA-N 5-N-ethyl-1-[(2-fluoro-3-methylphenyl)methyl]-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CCNC(=O)c1cc(C(=O)NC)c(=O)n(Cc2cccc(C)c2F)c1 JJDJTAIBTQXVRX-UHFFFAOYSA-N 0.000 claims description 2
• PNZQBXHSAADFDL-UHFFFAOYSA-N 5-N-ethyl-1-[(3-methoxyphenyl)methyl]-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CCNC(=O)C1=CN(CC2=CC(OC)=CC=C2)C(=O)C(=C1)C(=O)NC PNZQBXHSAADFDL-UHFFFAOYSA-N 0.000 claims description 2
• DBKCORXXWNVUJC-UHFFFAOYSA-N CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NC1=CN(C)N=C1 Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NC1=CN(C)N=C1 DBKCORXXWNVUJC-UHFFFAOYSA-N 0.000 claims description 2
• IFVGVYHLCFPSDA-UHFFFAOYSA-N CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NC1=NN(C)C=C1 Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NC1=NN(C)C=C1 IFVGVYHLCFPSDA-UHFFFAOYSA-N 0.000 claims description 2
• HRTAVSIQIXZYMT-UHFFFAOYSA-N CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCCC(O)=O Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCCCC(O)=O HRTAVSIQIXZYMT-UHFFFAOYSA-N 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 147
• 235000002639 sodium chloride Nutrition 0.000 description 147
• 239000000203 mixture Substances 0.000 description 116
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
• 239000000243 solution Substances 0.000 description 73
• 239000002904 solvent Substances 0.000 description 65
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
• 235000019439 ethyl acetate Nutrition 0.000 description 61
• 239000007787 solid Substances 0.000 description 60
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 56
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 54
• 239000000047 product Substances 0.000 description 51
• 238000000034 method Methods 0.000 description 47
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 36
• 239000000543 intermediate Substances 0.000 description 34
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 31
• 239000011541 reaction mixture Substances 0.000 description 30
• 239000000725 suspension Substances 0.000 description 29
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
• 201000010099 disease Diseases 0.000 description 27
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 27
• 239000003814 drug Substances 0.000 description 27
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 25
• 238000006243 chemical reaction Methods 0.000 description 25
• 239000006196 drop Substances 0.000 description 25
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
• 239000007821 HATU Substances 0.000 description 23
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 23
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 22
• 102100029895 Bromodomain-containing protein 4 Human genes 0.000 description 22
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
• 108091005625 BRD4 Proteins 0.000 description 21
• 150000001412 amines Chemical class 0.000 description 21
• 238000005160 1H NMR spectroscopy Methods 0.000 description 20
• 125000004429 atom Chemical group 0.000 description 20
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
• 108090000623 proteins and genes Proteins 0.000 description 20
• 239000000843 powder Substances 0.000 description 19
• 239000000377 silicon dioxide Substances 0.000 description 19
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 239000003153 chemical reaction reagent Substances 0.000 description 18
• 230000002209 hydrophobic effect Effects 0.000 description 17
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 17
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
• 239000012044 organic layer Substances 0.000 description 16
• 238000002360 preparation method Methods 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
• 235000018102 proteins Nutrition 0.000 description 15
• 102000004169 proteins and genes Human genes 0.000 description 15
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
• 238000003556 assay Methods 0.000 description 14
• 229940125763 bromodomain inhibitor Drugs 0.000 description 14
• 238000004519 manufacturing process Methods 0.000 description 14
• 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 14
• 239000002253 acid Substances 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 12
• 239000002552 dosage form Substances 0.000 description 12
• 239000012530 fluid Substances 0.000 description 12
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
• JEEHHYLTLPRHGU-UHFFFAOYSA-N 1-benzyl-5-(methylcarbamoyl)-6-oxopyridine-3-carboxylic acid Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(O)=O JEEHHYLTLPRHGU-UHFFFAOYSA-N 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• 239000012267 brine Substances 0.000 description 11
• 238000009472 formulation Methods 0.000 description 11
• 230000004968 inflammatory condition Effects 0.000 description 11
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• 239000008346 aqueous phase Substances 0.000 description 10
• 239000002585 base Substances 0.000 description 10
• 239000010410 layer Substances 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 239000012074 organic phase Substances 0.000 description 10
• 229910000027 potassium carbonate Inorganic materials 0.000 description 10
• 230000008569 process Effects 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 9
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 9
• 229910002091 carbon monoxide Inorganic materials 0.000 description 9
• 238000004587 chromatography analysis Methods 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 208000015181 infectious disease Diseases 0.000 description 9
• 239000000178 monomer Substances 0.000 description 9
• 235000011181 potassium carbonates Nutrition 0.000 description 9
• 206010039073 rheumatoid arthritis Diseases 0.000 description 9
• 150000003512 tertiary amines Chemical class 0.000 description 9
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
• 108010033040 Histones Proteins 0.000 description 8
• 208000036142 Viral infection Diseases 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• 239000006185 dispersion Substances 0.000 description 8
• 235000019000 fluorine Nutrition 0.000 description 8
• 208000032839 leukemia Diseases 0.000 description 8
• 235000019198 oils Nutrition 0.000 description 8
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 8
• 229940124597 therapeutic agent Drugs 0.000 description 8
• 230000009385 viral infection Effects 0.000 description 8
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 239000013543 active substance Substances 0.000 description 7
• 239000000443 aerosol Substances 0.000 description 7
• 150000001408 amides Chemical class 0.000 description 7
• 229910052794 bromium Inorganic materials 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 239000000460 chlorine Substances 0.000 description 7
• 229910052801 chlorine Inorganic materials 0.000 description 7
• 238000005859 coupling reaction Methods 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• 235000019253 formic acid Nutrition 0.000 description 7
• 239000000499 gel Substances 0.000 description 7
• 150000007529 inorganic bases Chemical class 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 239000012299 nitrogen atmosphere Substances 0.000 description 7
• 238000012856 packing Methods 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 239000011550 stock solution Substances 0.000 description 7
• 208000011580 syndromic disease Diseases 0.000 description 7
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 7
• 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 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• 102100033641 Bromodomain-containing protein 2 Human genes 0.000 description 6
• 108010077544 Chromatin Proteins 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• 206010040047 Sepsis Diseases 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 125000004432 carbon atom Chemical group C* 0.000 description 6
• 210000003483 chromatin Anatomy 0.000 description 6
• 239000006071 cream Substances 0.000 description 6
• 239000013078 crystal Substances 0.000 description 6
• 238000003818 flash chromatography Methods 0.000 description 6
• IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
• 230000028709 inflammatory response Effects 0.000 description 6
• 239000004615 ingredient Substances 0.000 description 6
• 239000003446 ligand Substances 0.000 description 6
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
• 239000012011 nucleophilic catalyst Substances 0.000 description 6
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 6
• 235000011121 sodium hydroxide Nutrition 0.000 description 6
• 239000012453 solvate Substances 0.000 description 6
• 238000000825 ultraviolet detection Methods 0.000 description 6
• 239000003643 water by type Substances 0.000 description 6
• 241000894006 Bacteria Species 0.000 description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 5
• 241000233866 Fungi Species 0.000 description 5
• 102000006947 Histones Human genes 0.000 description 5
• 101000871850 Homo sapiens Bromodomain-containing protein 2 Proteins 0.000 description 5
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
• 229920002472 Starch Polymers 0.000 description 5
• 241000700605 Viruses Species 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• 239000011230 binding agent Substances 0.000 description 5
• 238000000576 coating method Methods 0.000 description 5
• 238000006073 displacement reaction Methods 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 230000001973 epigenetic effect Effects 0.000 description 5
• IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 239000000796 flavoring agent Substances 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• 230000003993 interaction Effects 0.000 description 5
• 239000000314 lubricant Substances 0.000 description 5
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 238000002156 mixing Methods 0.000 description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 description 5
• 210000000056 organ Anatomy 0.000 description 5
• 244000045947 parasite Species 0.000 description 5
• 239000002245 particle Substances 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• 235000009518 sodium iodide Nutrition 0.000 description 5
• 229910052938 sodium sulfate Inorganic materials 0.000 description 5
• 235000011152 sodium sulphate Nutrition 0.000 description 5
• 239000011877 solvent mixture Substances 0.000 description 5
• 239000007921 spray Substances 0.000 description 5
• 239000008107 starch Substances 0.000 description 5
• 235000019698 starch Nutrition 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• 239000006188 syrup Substances 0.000 description 5
• 235000020357 syrup Nutrition 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• 238000011200 topical administration Methods 0.000 description 5
• 239000003053 toxin Substances 0.000 description 5
• 231100000765 toxin Toxicity 0.000 description 5
• 108700012359 toxins Proteins 0.000 description 5
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
• SDPVKAGJYCRGDD-UHFFFAOYSA-N 1-benzyl-5-bromo-N-methyl-2-oxopyridine-3-carboxamide Chemical compound CNC(=O)C1=CC(Br)=CN(CC2=CC=CC=C2)C1=O SDPVKAGJYCRGDD-UHFFFAOYSA-N 0.000 description 4
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
• 102100033642 Bromodomain-containing protein 3 Human genes 0.000 description 4
• 201000009030 Carcinoma Diseases 0.000 description 4
• 208000024172 Cardiovascular disease Diseases 0.000 description 4
• 206010009944 Colon cancer Diseases 0.000 description 4
• 239000007995 HEPES buffer Substances 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• 206010033645 Pancreatitis Diseases 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 4
• 206010046851 Uveitis Diseases 0.000 description 4
• 206010047115 Vasculitis Diseases 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 4
• 239000011248 coating agent Substances 0.000 description 4
• 239000003086 colorant Substances 0.000 description 4
• 239000006184 cosolvent Substances 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000002425 crystallisation Methods 0.000 description 4
• 230000008025 crystallization Effects 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 230000003176 fibrotic effect Effects 0.000 description 4
• 239000006260 foam Substances 0.000 description 4
• 239000012458 free base Substances 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 150000004677 hydrates Chemical class 0.000 description 4
• 208000028867 ischemia Diseases 0.000 description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
• 230000004048 modification Effects 0.000 description 4
• 238000012986 modification Methods 0.000 description 4
• 125000002757 morpholinyl group Chemical group 0.000 description 4
• 230000035772 mutation Effects 0.000 description 4
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 4
• 238000007911 parenteral administration Methods 0.000 description 4
• 125000004193 piperazinyl group Chemical group 0.000 description 4
• 125000003386 piperidinyl group Chemical group 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 239000003380 propellant Substances 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 239000012312 sodium hydride Substances 0.000 description 4
• 238000001228 spectrum Methods 0.000 description 4
• 239000003981 vehicle Substances 0.000 description 4
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 3
• BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 3
• MUAARLCXQTWPPF-UHFFFAOYSA-N 5-bromo-2-methoxy-n-methylpyridine-3-carboxamide Chemical compound CNC(=O)C1=CC(Br)=CN=C1OC MUAARLCXQTWPPF-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
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• 239000012099 Alexa Fluor family Substances 0.000 description 3
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 3
• 208000026310 Breast neoplasm Diseases 0.000 description 3
• 102100029894 Bromodomain testis-specific protein Human genes 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
• 208000007514 Herpes zoster Diseases 0.000 description 3
• 101000794028 Homo sapiens Bromodomain testis-specific protein Proteins 0.000 description 3
• 101000871851 Homo sapiens Bromodomain-containing protein 3 Proteins 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
• 208000001344 Macular Edema Diseases 0.000 description 3
• 208000008770 Multiple Hamartoma Syndrome Diseases 0.000 description 3
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 3
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
• 238000005481 NMR spectroscopy Methods 0.000 description 3
• 239000007832 Na2SO4 Substances 0.000 description 3
• 108010047956 Nucleosomes Proteins 0.000 description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 description 3
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 3
• 206010063837 Reperfusion injury Diseases 0.000 description 3
• 206010040070 Septic Shock Diseases 0.000 description 3
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 238000005804 alkylation reaction Methods 0.000 description 3
• 239000003125 aqueous solvent Substances 0.000 description 3
• 125000003725 azepanyl group Chemical group 0.000 description 3
• 125000002393 azetidinyl group Chemical group 0.000 description 3
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
• 125000002619 bicyclic group Chemical group 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• UJXHNEOAOAQONV-UHFFFAOYSA-N butyl 5-(methylcarbamoyl)-6-oxo-1H-pyridine-3-carboxylate Chemical compound CCCCOC(=O)C1=CNC(=O)C(=C1)C(=O)NC UJXHNEOAOAQONV-UHFFFAOYSA-N 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 238000005810 carbonylation reaction Methods 0.000 description 3
• 229910052681 coesite Inorganic materials 0.000 description 3
• 229910052906 cristobalite Inorganic materials 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• MQIKJSYMMJWAMP-UHFFFAOYSA-N dicobalt octacarbonyl Chemical group [Co+2].[Co+2].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-] MQIKJSYMMJWAMP-UHFFFAOYSA-N 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 238000004090 dissolution Methods 0.000 description 3
• 230000004064 dysfunction Effects 0.000 description 3
• 238000010828 elution Methods 0.000 description 3
• PLKCUDOXIGGRFX-UHFFFAOYSA-N ethyl 1-benzyl-5-(methylcarbamoyl)-6-oxopyridine-3-carboxylate Chemical compound C(C1=CC=CC=C1)N1C=C(C=C(C1=O)C(NC)=O)C(=O)OCC PLKCUDOXIGGRFX-UHFFFAOYSA-N 0.000 description 3
• 238000011049 filling Methods 0.000 description 3
• 235000019634 flavors Nutrition 0.000 description 3
• 235000003599 food sweetener Nutrition 0.000 description 3
• 230000006870 function Effects 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 239000003349 gelling agent Substances 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 208000012947 ischemia reperfusion injury Diseases 0.000 description 3
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• MLLZFISOVHOVGC-UHFFFAOYSA-N methyl 1-(4-methylphenyl)sulfonylindole-4-carboxylate Chemical compound C1=CC=2C(C(=O)OC)=CC=CC=2N1S(=O)(=O)C1=CC=C(C)C=C1 MLLZFISOVHOVGC-UHFFFAOYSA-N 0.000 description 3
• IOPDGNZGGDJYEJ-UHFFFAOYSA-N methyl 1-[(3-methoxyphenyl)methyl]-5-(methylcarbamoyl)-6-oxopyridine-3-carboxylate Chemical compound COC=1C=C(CN2C=C(C=C(C2=O)C(NC)=O)C(=O)OC)C=CC=1 IOPDGNZGGDJYEJ-UHFFFAOYSA-N 0.000 description 3
• OUXYCGIFGUZJIX-UHFFFAOYSA-N methyl 5-(methylcarbamoyl)-6-oxo-1H-pyridine-3-carboxylate Chemical compound CNC(=O)C1=CC(=CNC1=O)C(=O)OC OUXYCGIFGUZJIX-UHFFFAOYSA-N 0.000 description 3
• 229920000609 methyl cellulose Polymers 0.000 description 3
• 239000001923 methylcellulose Substances 0.000 description 3
• 235000010981 methylcellulose Nutrition 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• 201000006417 multiple sclerosis Diseases 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 210000001623 nucleosome Anatomy 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• 239000002674 ointment Substances 0.000 description 3
• 201000008482 osteoarthritis Diseases 0.000 description 3
• 229920000642 polymer Polymers 0.000 description 3
• 238000000634 powder X-ray diffraction Methods 0.000 description 3
• 239000002244 precipitate Substances 0.000 description 3
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• 235000012239 silicon dioxide Nutrition 0.000 description 3
• 239000001632 sodium acetate Substances 0.000 description 3
• 235000017281 sodium acetate Nutrition 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 235000017550 sodium carbonate Nutrition 0.000 description 3
• 229910052682 stishovite Inorganic materials 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 239000004094 surface-active agent Substances 0.000 description 3
• 239000003765 sweetening agent Substances 0.000 description 3
• 238000004809 thin layer chromatography Methods 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• 238000013518 transcription Methods 0.000 description 3
• 230000035897 transcription Effects 0.000 description 3
• 230000009466 transformation Effects 0.000 description 3
• 229910052905 tridymite Inorganic materials 0.000 description 3
• 229910052721 tungsten Inorganic materials 0.000 description 3
• 239000001993 wax Substances 0.000 description 3
• QCTVRJWIYRJYJO-UHFFFAOYSA-N (2,4,6-trichlorophenyl) 1-benzyl-5-(methylcarbamoyl)-6-oxopyridine-3-carboxylate Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)OC1=C(Cl)C=C(Cl)C=C1Cl QCTVRJWIYRJYJO-UHFFFAOYSA-N 0.000 description 2
• YSUDXADDVAYVNS-UHFFFAOYSA-N (2,4,6-trichlorophenyl) formate Chemical compound ClC1=CC(Cl)=C(OC=O)C(Cl)=C1 YSUDXADDVAYVNS-UHFFFAOYSA-N 0.000 description 2
• KNKUUGCKVUAOEH-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-5-(methylcarbamoyl)-6-oxopyridine-3-carboxylic acid Chemical compound CNC(=O)C1=CC(=CN(CC2=CC(OC)=CC=C2)C1=O)C(O)=O KNKUUGCKVUAOEH-UHFFFAOYSA-N 0.000 description 2
• PQTPOGOLJDALOP-UHFFFAOYSA-N 1-[[3-(2-hydroxyethoxy)phenyl]methyl]-5-(methylcarbamoyl)-6-oxopyridine-3-carboxylic acid Chemical compound CNC(=O)C1=CC(=CN(CC2=CC(OCCO)=CC=C2)C1=O)C(O)=O PQTPOGOLJDALOP-UHFFFAOYSA-N 0.000 description 2
• FUIJRCNCJHRODM-UHFFFAOYSA-N 2-(1h-pyrazol-4-yl)ethanamine Chemical compound NCCC=1C=NNC=1 FUIJRCNCJHRODM-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
• NGZVNONVXYLYQW-UHFFFAOYSA-N 3,3,3-trifluoropropan-1-amine Chemical compound NCCC(F)(F)F NGZVNONVXYLYQW-UHFFFAOYSA-N 0.000 description 2
• COYHVQPVRWPGEZ-UHFFFAOYSA-N 4-(bromomethyl)-1-(4-methylphenyl)sulfonylindole Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=CC=CC(CBr)=C2C=C1 COYHVQPVRWPGEZ-UHFFFAOYSA-N 0.000 description 2
• MBODLWSNPCNWQC-UHFFFAOYSA-N 5-(methylcarbamoyl)-1-[(3-methylphenyl)methyl]-6-oxopyridine-3-carboxylic acid Chemical compound CNC(=O)C1=CC(=CN(CC2=CC(C)=CC=C2)C1=O)C(O)=O MBODLWSNPCNWQC-UHFFFAOYSA-N 0.000 description 2
• XTJBGMIQYVTYQG-UHFFFAOYSA-N 5-bromo-2-methoxypyridine-3-carbonyl chloride Chemical compound COC1=NC=C(Br)C=C1C(Cl)=O XTJBGMIQYVTYQG-UHFFFAOYSA-N 0.000 description 2
• VUVUVNZRUGEAHB-CYBMUJFWSA-N 7-(3,5-dimethyl-4-isoxazolyl)-8-methoxy-1-[(1R)-1-(2-pyridinyl)ethyl]-3H-imidazo[4,5-c]quinolin-2-one Chemical compound C1([C@@H](C)N2C3=C4C=C(C(=CC4=NC=C3NC2=O)C2=C(ON=C2C)C)OC)=CC=CC=N1 VUVUVNZRUGEAHB-CYBMUJFWSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
• 208000009304 Acute Kidney Injury Diseases 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
• 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
• 229910015845 BBr3 Inorganic materials 0.000 description 2
• 208000020084 Bone disease Diseases 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 108091052242 Bromo- and Extra-Terminal domain (BET) family Proteins 0.000 description 2
• 208000011691 Burkitt lymphomas Diseases 0.000 description 2
• OYQHSTROLYJMFV-UHFFFAOYSA-N CNC(=O)C1=CC(=CN(CC2=CC(OCCO)=CC=C2)C1=O)C(=O)OC Chemical compound CNC(=O)C1=CC(=CN(CC2=CC(OCCO)=CC=C2)C1=O)C(=O)OC OYQHSTROLYJMFV-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• 206010008342 Cervix carcinoma Diseases 0.000 description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
• 206010009900 Colitis ulcerative Diseases 0.000 description 2
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
• 201000002847 Cowden syndrome Diseases 0.000 description 2
• 208000011231 Crohn disease Diseases 0.000 description 2
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
• 108020004414 DNA Proteins 0.000 description 2
• 201000004624 Dermatitis Diseases 0.000 description 2
• 208000003556 Dry Eye Syndromes Diseases 0.000 description 2
• 206010013774 Dry eye Diseases 0.000 description 2
• 208000037487 Endotoxemia Diseases 0.000 description 2
• 241000588724 Escherichia coli Species 0.000 description 2
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
• 241000400611 Eucalyptus deanei Species 0.000 description 2
• 229910052693 Europium Inorganic materials 0.000 description 2
• 201000005569 Gout Diseases 0.000 description 2
• 208000032843 Hemorrhage Diseases 0.000 description 2
• 208000009889 Herpes Simplex Diseases 0.000 description 2
• 102100039869 Histone H2B type F-S Human genes 0.000 description 2
• 101001035372 Homo sapiens Histone H2B type F-S Proteins 0.000 description 2
• 241000725303 Human immunodeficiency virus Species 0.000 description 2
• 241000701806 Human papillomavirus Species 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• 208000035150 Hypercholesterolemia Diseases 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• 208000008839 Kidney Neoplasms Diseases 0.000 description 2
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 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
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• 206010025415 Macular oedema Diseases 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• 208000003445 Mouth Neoplasms Diseases 0.000 description 2
• 208000034578 Multiple myelomas Diseases 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
• 244000018764 Nyssa sylvatica Species 0.000 description 2
• 235000003339 Nyssa sylvatica Nutrition 0.000 description 2
• 206010030113 Oedema Diseases 0.000 description 2
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
• 206010033128 Ovarian cancer Diseases 0.000 description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 206010033647 Pancreatitis acute Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 206010038389 Renal cancer Diseases 0.000 description 2
• 208000033626 Renal failure acute Diseases 0.000 description 2
• 206010038910 Retinitis Diseases 0.000 description 2
• 206010041067 Small cell lung cancer Diseases 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• 210000001744 T-lymphocyte Anatomy 0.000 description 2
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
• 201000006704 Ulcerative Colitis Diseases 0.000 description 2
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
• RSTLWAHATMQENR-UHFFFAOYSA-N [1-(4-methylphenyl)sulfonylindol-4-yl]methanol Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=CC=CC(CO)=C2C=C1 RSTLWAHATMQENR-UHFFFAOYSA-N 0.000 description 2
• VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 201000011040 acute kidney failure Diseases 0.000 description 2
• 206010069351 acute lung injury Diseases 0.000 description 2
• 201000003229 acute pancreatitis Diseases 0.000 description 2
• 239000004479 aerosol dispenser Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 235000004279 alanine Nutrition 0.000 description 2
• 125000006242 amine protecting group Chemical group 0.000 description 2
• 229940024606 amino acid Drugs 0.000 description 2
• 235000001014 amino acid Nutrition 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 2
• 239000001099 ammonium carbonate Substances 0.000 description 2
• 235000011114 ammonium hydroxide Nutrition 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 235000006708 antioxidants Nutrition 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 206010003230 arteritis Diseases 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• 208000006673 asthma Diseases 0.000 description 2
• 235000012216 bentonite Nutrition 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 229910052796 boron Inorganic materials 0.000 description 2
• 238000005893 bromination reaction Methods 0.000 description 2
• 239000006172 buffering agent Substances 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
• 235000013539 calcium stearate Nutrition 0.000 description 2
• 239000008116 calcium stearate Substances 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 229950008138 carmellose Drugs 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000022131 cell cycle Effects 0.000 description 2
• 230000002490 cerebral effect Effects 0.000 description 2
• 201000010881 cervical cancer Diseases 0.000 description 2
• 239000012320 chlorinating reagent Substances 0.000 description 2
• 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 2
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 238000005056 compaction Methods 0.000 description 2
• 238000007906 compression Methods 0.000 description 2
• 230000006835 compression Effects 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 230000000694 effects Effects 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 201000004101 esophageal cancer Diseases 0.000 description 2
• LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 2
• 239000005038 ethylene vinyl acetate Substances 0.000 description 2
• OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 230000007717 exclusion Effects 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 230000002496 gastric effect Effects 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 238000005469 granulation Methods 0.000 description 2
• 230000003179 granulation Effects 0.000 description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid group Chemical group C(CCCCC)(=O)O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 238000010348 incorporation Methods 0.000 description 2
• 208000027866 inflammatory disease Diseases 0.000 description 2
• 208000037903 inflammatory enteropathy Diseases 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 201000010982 kidney cancer Diseases 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 229960001375 lactose Drugs 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 208000014018 liver neoplasm Diseases 0.000 description 2
• 239000006210 lotion Substances 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 201000005202 lung cancer Diseases 0.000 description 2
• 208000020816 lung neoplasm Diseases 0.000 description 2
• 208000002780 macular degeneration Diseases 0.000 description 2
• 201000010230 macular retinal edema Diseases 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 238000001819 mass spectrum Methods 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• RTLIBDFFZPGHEA-UHFFFAOYSA-N methyl 1-[(3-hydroxyphenyl)methyl]-5-(methylcarbamoyl)-6-oxopyridine-3-carboxylate Chemical compound OC=1C=C(CN2C=C(C=C(C2=O)C(NC)=O)C(=O)OC)C=CC=1 RTLIBDFFZPGHEA-UHFFFAOYSA-N 0.000 description 2
• RVQKGAXDNWQUHD-UHFFFAOYSA-N methyl 1-benzyl-5-bromo-2-oxopyridine-3-carboxylate Chemical compound COC(=O)C1=CC(Br)=CN(CC2=CC=CC=C2)C1=O RVQKGAXDNWQUHD-UHFFFAOYSA-N 0.000 description 2
• 238000012544 monitoring process Methods 0.000 description 2
• 208000010125 myocardial infarction Diseases 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 201000008383 nephritis Diseases 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• 239000006072 paste Substances 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 230000002980 postoperative effect Effects 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• 230000007420 reactivation Effects 0.000 description 2
• 208000023504 respiratory system disease Diseases 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• 208000004644 retinal vein occlusion Diseases 0.000 description 2
• 230000036303 septic shock Effects 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 208000000587 small cell lung carcinoma Diseases 0.000 description 2
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 238000012799 strong cation exchange Methods 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 230000002103 transcriptional effect Effects 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
• RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
• PQMFVUNERGGBPG-UHFFFAOYSA-N (6-bromopyridin-2-yl)hydrazine Chemical compound NNC1=CC=CC(Br)=N1 PQMFVUNERGGBPG-UHFFFAOYSA-N 0.000 description 1
• YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
• LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical class C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 1
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• GHDARRYKLITDCL-UHFFFAOYSA-N 1-(1H-indol-4-ylmethyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical class CNC(=O)c1cc(cn(Cc2cccc3[nH]ccc23)c1=O)C(N)=O GHDARRYKLITDCL-UHFFFAOYSA-N 0.000 description 1
• RDIIDBQLVSISPR-UHFFFAOYSA-N 1-(1H-indol-4-ylmethyl)-5-(methylcarbamoyl)-6-oxopyridine-3-carboxylic acid Chemical compound CNC(=O)C1=CC(=CN(CC2=C3C=CNC3=CC=C2)C1=O)C(O)=O RDIIDBQLVSISPR-UHFFFAOYSA-N 0.000 description 1
• DCGWFNZSJBIAKE-UHFFFAOYSA-N 1-(bromomethyl)-2-fluoro-3-methylbenzene Chemical compound CC1=CC=CC(CBr)=C1F DCGWFNZSJBIAKE-UHFFFAOYSA-N 0.000 description 1
• ZKSOJQDNSNJIQW-UHFFFAOYSA-N 1-(bromomethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CBr)=C1 ZKSOJQDNSNJIQW-UHFFFAOYSA-N 0.000 description 1
• FWLWTILKTABGKQ-UHFFFAOYSA-N 1-(bromomethyl)-3-methylbenzene Chemical compound CC1=CC=CC(CBr)=C1 FWLWTILKTABGKQ-UHFFFAOYSA-N 0.000 description 1
• CFKJMSNVYUDNJL-UHFFFAOYSA-N 1-[(2-fluoro-3-methylphenyl)methyl]-5-(methylcarbamoyl)-6-oxopyridine-3-carboxylic acid Chemical compound CNC(=O)C1=CC(=CN(CC2=C(F)C(C)=CC=C2)C1=O)C(O)=O CFKJMSNVYUDNJL-UHFFFAOYSA-N 0.000 description 1
• GLENKJWLAOXLTM-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical class COC=1C=C(CN2C(C(=CC(=C2)C(=O)N)C(=O)NC)=O)C=CC=1 GLENKJWLAOXLTM-UHFFFAOYSA-N 0.000 description 1
• PRKBXCNAGJXCSJ-UHFFFAOYSA-N 1-[[3-(2-hydroxyethoxy)phenyl]methyl]-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical class OCCOC=1C=C(CN2C(C(=CC(=C2)C(=O)N)C(=O)NC)=O)C=CC=1 PRKBXCNAGJXCSJ-UHFFFAOYSA-N 0.000 description 1
• NCOLECXBVJEWBY-UHFFFAOYSA-N 1-benzyl-5-N-(2-hydroxypropyl)-3-N-methyl-2-oxopyridine-3,5-dicarboxamide Chemical compound CNC(=O)C1=CC(=CN(CC2=CC=CC=C2)C1=O)C(=O)NCC(C)O NCOLECXBVJEWBY-UHFFFAOYSA-N 0.000 description 1
• HPWHNUKTQGMPDV-UHFFFAOYSA-N 1-benzyl-5-bromo-2-oxopyridine-3-carboxylic acid Chemical compound O=C1C(C(=O)O)=CC(Br)=CN1CC1=CC=CC=C1 HPWHNUKTQGMPDV-UHFFFAOYSA-N 0.000 description 1
• CTTIPOGAOKXCDF-UHFFFAOYSA-N 1-benzyl-5-bromopyridin-2-one Chemical compound C1=C(Br)C=CC(=O)N1CC1=CC=CC=C1 CTTIPOGAOKXCDF-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• LINPIYWFGCPVIE-UHFFFAOYSA-N 2,4,6-trichlorophenol Chemical compound OC1=C(Cl)C=C(Cl)C=C1Cl LINPIYWFGCPVIE-UHFFFAOYSA-N 0.000 description 1
• OZMLUMPWPFZWTP-UHFFFAOYSA-N 2-(tributyl-$l^{5}-phosphanylidene)acetonitrile Chemical compound CCCCP(CCCC)(CCCC)=CC#N OZMLUMPWPFZWTP-UHFFFAOYSA-N 0.000 description 1
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• KHIJAVHPLSAGLB-SNVBAGLBSA-N 2-oxo-1-[(1r)-1-phenylethyl]pyridine-3-carboxylic acid Chemical compound C1([C@@H](C)N2C(C(C(O)=O)=CC=C2)=O)=CC=CC=C1 KHIJAVHPLSAGLB-SNVBAGLBSA-N 0.000 description 1
• XPQIPUZPSLAZDV-UHFFFAOYSA-N 2-pyridylethylamine Chemical compound NCCC1=CC=CC=N1 XPQIPUZPSLAZDV-UHFFFAOYSA-N 0.000 description 1
• ZZVDXRCAGGQFAK-UHFFFAOYSA-N 2h-oxazaphosphinine Chemical class N1OC=CC=P1 ZZVDXRCAGGQFAK-UHFFFAOYSA-N 0.000 description 1
• HQNOODJDSFSURF-UHFFFAOYSA-N 3-(1h-imidazol-2-yl)propan-1-amine Chemical compound NCCCC1=NC=CN1 HQNOODJDSFSURF-UHFFFAOYSA-N 0.000 description 1
• UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-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
• CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
• NAVSCJJGECHRQY-UHFFFAOYSA-N 4-amino-n-methylbutanamide;hydrochloride Chemical compound Cl.CNC(=O)CCCN NAVSCJJGECHRQY-UHFFFAOYSA-N 0.000 description 1
• RTFIYCVULRXCPX-UHFFFAOYSA-N 5-(methylcarbamoyl)-6-oxo-1-(1-phenylethyl)pyridine-3-carboxylic acid Chemical compound CNC(=O)C1=CC(=CN(C1=O)C(C)C1=CC=CC=C1)C(=O)O RTFIYCVULRXCPX-UHFFFAOYSA-N 0.000 description 1
• RTFIYCVULRXCPX-SNVBAGLBSA-N 5-(methylcarbamoyl)-6-oxo-1-[(1R)-1-phenylethyl]pyridine-3-carboxylic acid Chemical compound CNC(=O)C1=CC(=CN([C@H](C)C2=CC=CC=C2)C1=O)C(O)=O RTFIYCVULRXCPX-SNVBAGLBSA-N 0.000 description 1
• CVIVNWSFEOWJFP-GFCCVEGCSA-N 5-N-ethyl-3-N-methyl-2-oxo-1-[(1R)-1-phenylethyl]pyridine-3,5-dicarboxamide Chemical compound CCNC(=O)C1=CN([C@H](C)C2=CC=CC=C2)C(=O)C(=C1)C(=O)NC CVIVNWSFEOWJFP-GFCCVEGCSA-N 0.000 description 1
• PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
• SJLXURQPRRMPIV-UHFFFAOYSA-N 5-bromo-2-methoxypyridine-3-carboxylic acid Chemical compound COC1=NC=C(Br)C=C1C(O)=O SJLXURQPRRMPIV-UHFFFAOYSA-N 0.000 description 1
• YUDFVMQNXBQMLB-UHFFFAOYSA-N 5-bromo-2-oxo-1-(1-phenylethyl)pyridine-3-carboxylic acid Chemical compound CC(c1ccccc1)n1cc(Br)cc(C(O)=O)c1=O YUDFVMQNXBQMLB-UHFFFAOYSA-N 0.000 description 1
• BLHCMGRVFXRYRN-UHFFFAOYSA-N 6-hydroxynicotinic acid Chemical compound OC(=O)C1=CC=C(O)N=C1 BLHCMGRVFXRYRN-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 206010000871 Acute monocytic leukaemia Diseases 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
• 208000026872 Addison Disease Diseases 0.000 description 1
• 208000010370 Adenoviridae Infections Diseases 0.000 description 1
• 241000701386 African swine fever virus Species 0.000 description 1
• 239000012114 Alexa Fluor 647 Substances 0.000 description 1
• 201000004384 Alopecia Diseases 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 206010003658 Atrial Fibrillation Diseases 0.000 description 1
• 108091052240 BRD2 family Proteins 0.000 description 1
• 108091052241 BRD3 family Proteins 0.000 description 1
• 108091052244 BRD4 family Proteins 0.000 description 1
• 108091052243 BRDT family Proteins 0.000 description 1
• 101150034980 BRDT gene Proteins 0.000 description 1
• 201000007815 Bannayan-Riley-Ruvalcaba syndrome Diseases 0.000 description 1
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
• 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 108091005575 Bromodomain-containing proteins Proteins 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• MJZGCNMEFBFKQB-UHFFFAOYSA-N C(=O)([Co])[Co].[Co] Chemical compound C(=O)([Co])[Co].[Co] MJZGCNMEFBFKQB-UHFFFAOYSA-N 0.000 description 1
• AIAMCBJGQPITOS-UHFFFAOYSA-N CCNC(C(C=C1/C(/NC)=[O]/C)=CN(Cc2cc(C)ccc2)C1=O)=O Chemical compound CCNC(C(C=C1/C(/NC)=[O]/C)=CN(Cc2cc(C)ccc2)C1=O)=O AIAMCBJGQPITOS-UHFFFAOYSA-N 0.000 description 1
• XSPGPZSPGRBKKU-CQSZACIVSA-N CNC(=O)C1=CC(=CN([C@H](C)C2=CC=CC=C2)C1=O)C(=O)NCCC1=CNN=C1 Chemical compound CNC(=O)C1=CC(=CN([C@H](C)C2=CC=CC=C2)C1=O)C(=O)NCCC1=CNN=C1 XSPGPZSPGRBKKU-CQSZACIVSA-N 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• 208000031229 Cardiomyopathies Diseases 0.000 description 1
• 201000006082 Chickenpox Diseases 0.000 description 1
• 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
• 208000002691 Choroiditis Diseases 0.000 description 1
• 208000000668 Chronic Pancreatitis Diseases 0.000 description 1
• 208000002330 Congenital Heart Defects Diseases 0.000 description 1
• 241000711573 Coronaviridae Species 0.000 description 1
• 208000012609 Cowden disease Diseases 0.000 description 1
• 206010058202 Cystoid macular oedema Diseases 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
• 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
• 206010012688 Diabetic retinal oedema Diseases 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 239000001692 EU approved anti-caking agent Substances 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 206010014967 Ependymoma Diseases 0.000 description 1
• 208000001351 Epiretinal Membrane Diseases 0.000 description 1
• 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
• 208000036566 Erythroleukaemia Diseases 0.000 description 1
• OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
• KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• 206010061172 Gastrointestinal injury Diseases 0.000 description 1
• 241000206672 Gelidium Species 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• 102220471907 Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1_Y66A_mutation Human genes 0.000 description 1
• 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 208000037357 HIV infectious disease Diseases 0.000 description 1
• 208000013875 Heart injury Diseases 0.000 description 1
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 206010062767 Hypophysitis Diseases 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 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 1
• 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 description 1
• 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 description 1
• 206010023125 Jarisch-Herxheimer reaction Diseases 0.000 description 1
• 208000011200 Kawasaki disease Diseases 0.000 description 1
• 206010023330 Keloid scar Diseases 0.000 description 1
• 208000009319 Keratoconjunctivitis Sicca Diseases 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• 239000004395 L-leucine Substances 0.000 description 1
• 235000019454 L-leucine Nutrition 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 208000022010 Lhermitte-Duclos disease Diseases 0.000 description 1
• 206010061523 Lip and/or oral cavity cancer Diseases 0.000 description 1
• 208000017170 Lipid metabolism disease Diseases 0.000 description 1
• 206010067125 Liver injury Diseases 0.000 description 1
• 208000000185 Localized scleroderma Diseases 0.000 description 1
• 208000005777 Lupus Nephritis Diseases 0.000 description 1
• 208000031471 Macular fibrosis Diseases 0.000 description 1
• 208000035719 Maculopathy Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 208000001940 Massive Hepatic Necrosis Diseases 0.000 description 1
• 208000000172 Medulloblastoma Diseases 0.000 description 1
• 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 description 1
• 201000009906 Meningitis Diseases 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 208000029725 Metabolic bone disease Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 1
• 206010027982 Morphoea Diseases 0.000 description 1
• 229920000715 Mucilage Polymers 0.000 description 1
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
• 208000003926 Myelitis Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• 208000009525 Myocarditis Diseases 0.000 description 1
• 201000002481 Myositis Diseases 0.000 description 1
• DTERQYGMUDWYAZ-ZETCQYMHSA-N N(6)-acetyl-L-lysine Chemical compound CC(=O)NCCCC[C@H]([NH3+])C([O-])=O DTERQYGMUDWYAZ-ZETCQYMHSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
• 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 208000003435 Optic Neuritis Diseases 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 206010049088 Osteopenia Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 102220466393 PRA1 family protein 2_Y73A_mutation Human genes 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 206010033649 Pancreatitis chronic Diseases 0.000 description 1
• 208000009608 Papillomavirus Infections Diseases 0.000 description 1
• 208000004788 Pars Planitis Diseases 0.000 description 1
• 208000031481 Pathologic Constriction Diseases 0.000 description 1
• 208000007452 Plasmacytoma Diseases 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• 206010035742 Pneumonitis Diseases 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 206010036346 Posterior capsule opacification Diseases 0.000 description 1
• 208000003971 Posterior uveitis Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000005585 Poxviridae Infections Diseases 0.000 description 1
• 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
• 208000010378 Pulmonary Embolism Diseases 0.000 description 1
• 206010037423 Pulmonary oedema Diseases 0.000 description 1
• 208000006311 Pyoderma Diseases 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• 238000001237 Raman spectrum Methods 0.000 description 1
• 206010061481 Renal injury Diseases 0.000 description 1
• 206010038848 Retinal detachment Diseases 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• 241000219061 Rheum Species 0.000 description 1
• 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
• 206010061934 Salivary gland cancer Diseases 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 206010039705 Scleritis Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• 102220474279 Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform_Y97A_mutation Human genes 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 206010040628 Sialoadenitis Diseases 0.000 description 1
• 241000700584 Simplexvirus Species 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
• 229910000831 Steel Inorganic materials 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• 239000012505 Superdex™ Substances 0.000 description 1
• 102000004183 Synaptosomal-Associated Protein 25 Human genes 0.000 description 1
• 108010057722 Synaptosomal-Associated Protein 25 Proteins 0.000 description 1
• 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000001106 Takayasu Arteritis Diseases 0.000 description 1
• 208000024313 Testicular Neoplasms Diseases 0.000 description 1
• 206010057644 Testis cancer Diseases 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
• 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
• 206010044248 Toxic shock syndrome Diseases 0.000 description 1
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 206010046980 Varicella Diseases 0.000 description 1
• 241000700647 Variola virus Species 0.000 description 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• 206010047642 Vitiligo Diseases 0.000 description 1
• 208000035307 Vitreous adhesions Diseases 0.000 description 1
• 206010047741 Vulval cancer Diseases 0.000 description 1
• 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
• 208000008383 Wilms tumor Diseases 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
• 230000009102 absorption Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 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
• 229930183665 actinomycin Natural products 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000012042 active reagent Substances 0.000 description 1
• 208000021841 acute erythroid leukemia Diseases 0.000 description 1
• 208000013593 acute megakaryoblastic leukemia Diseases 0.000 description 1
• 208000020700 acute megakaryocytic leukemia Diseases 0.000 description 1
• 208000012998 acute renal failure Diseases 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 238000011166 aliquoting Methods 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 150000001347 alkyl bromides Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
• 150000008052 alkyl sulfonates Chemical class 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 208000002205 allergic conjunctivitis Diseases 0.000 description 1
• 231100000360 alopecia Toxicity 0.000 description 1
• HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 238000005910 aminocarbonylation reaction Methods 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000003432 anti-folate effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 229940044684 anti-microtubule agent Drugs 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940127074 antifolate Drugs 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 229940121357 antivirals Drugs 0.000 description 1
• 208000007474 aortic aneurysm Diseases 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 239000008122 artificial sweetener Substances 0.000 description 1
• 235000021311 artificial sweeteners Nutrition 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 206010069664 atopic keratoconjunctivitis Diseases 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 239000000022 bacteriostatic agent Substances 0.000 description 1
• 238000010945 base-catalyzed hydrolysis reactiony Methods 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• 229940124748 beta 2 agonist Drugs 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 229920013641 bioerodible polymer Polymers 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical class N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 238000007664 blowing Methods 0.000 description 1
• 229910021538 borax Inorganic materials 0.000 description 1
• 239000004327 boric acid Substances 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 208000019748 bullous skin disease Diseases 0.000 description 1
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
• QDHFHIQKOVNCNC-UHFFFAOYSA-M butane-1-sulfonate Chemical compound CCCCS([O-])(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-M 0.000 description 1
• IQBVYZUOXFKSGT-UHFFFAOYSA-N butyl 1-[(2-fluoro-3-methylphenyl)methyl]-5-(methylcarbamoyl)-6-oxopyridine-3-carboxylate Chemical compound C(CCC)OC(=O)C1=CN(C(C(=C1)C(NC)=O)=O)CC1=C(C(=CC=C1)C)F IQBVYZUOXFKSGT-UHFFFAOYSA-N 0.000 description 1
• CSTSPXSZVFXMGS-UHFFFAOYSA-N butyl 5-(methylcarbamoyl)-1-[[1-(4-methylphenyl)sulfonylindol-4-yl]methyl]-6-oxopyridine-3-carboxylate Chemical compound CCCCOC(=O)C1=CN(CC2=C3C=CN(C3=CC=C2)S(=O)(=O)C2=CC=C(C)C=C2)C(=O)C(=C1)C(=O)NC CSTSPXSZVFXMGS-UHFFFAOYSA-N 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 230000009787 cardiac fibrosis Effects 0.000 description 1
• 230000002612 cardiopulmonary effect Effects 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 230000032823 cell division Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 201000005667 central retinal vein occlusion Diseases 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• ARQRPTNYUOLOGH-UHFFFAOYSA-N chcl3 chloroform Chemical compound ClC(Cl)Cl.ClC(Cl)Cl ARQRPTNYUOLOGH-UHFFFAOYSA-N 0.000 description 1
• 239000013522 chelant Substances 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 201000010903 chronic neutrophilic leukemia Diseases 0.000 description 1
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 229910017052 cobalt Inorganic materials 0.000 description 1
• 239000010941 cobalt Substances 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 208000028831 congenital heart disease Diseases 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 208000029078 coronary artery disease Diseases 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 201000003740 cowpox Diseases 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 230000001351 cycling effect Effects 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 239000012649 demethylating agent Substances 0.000 description 1
• 238000010520 demethylation reaction Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 201000011190 diabetic macular edema Diseases 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 238000000113 differential scanning calorimetry Methods 0.000 description 1
• 238000009792 diffusion process Methods 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution 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
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 150000004141 diterpene derivatives Chemical class 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 230000009881 electrostatic interaction Effects 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 206010014599 encephalitis Diseases 0.000 description 1
• 206010014665 endocarditis Diseases 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 210000000981 epithelium Anatomy 0.000 description 1
• 230000003628 erosive effect Effects 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 108091007167 extracellular matrix enzymes Proteins 0.000 description 1
• 102000036444 extracellular matrix enzymes Human genes 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 238000002875 fluorescence polarization Methods 0.000 description 1
• 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 239000004052 folic acid antagonist Substances 0.000 description 1
• 230000003325 follicular Effects 0.000 description 1
• 150000004675 formic acid derivatives Chemical class 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 230000005714 functional activity Effects 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 238000001030 gas--liquid chromatography Methods 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
• 238000001879 gelation Methods 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229940049906 glutamate Drugs 0.000 description 1
• 239000003979 granulating agent Substances 0.000 description 1
• 201000009277 hairy cell leukemia Diseases 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 201000005787 hematologic cancer Diseases 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 150000002391 heterocyclic compounds Chemical class 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
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 230000006195 histone acetylation Effects 0.000 description 1
• 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
• 239000003276 histone deacetylase inhibitor Substances 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• 239000008309 hydrophilic cream Substances 0.000 description 1
• 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
• 208000015210 hypertensive heart disease Diseases 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 239000002955 immunomodulating agent Substances 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 201000004653 inflammatory breast carcinoma Diseases 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 238000002329 infrared spectrum Methods 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 239000003999 initiator Substances 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 230000007794 irritation Effects 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
• BMFVGAAISNGQNM-UHFFFAOYSA-N isopentylamine Chemical compound CC(C)CCN BMFVGAAISNGQNM-UHFFFAOYSA-N 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 208000037806 kidney injury Diseases 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 229960001021 lactose monohydrate Drugs 0.000 description 1
• 229960003136 leucine Drugs 0.000 description 1
• 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
• 230000037356 lipid metabolism Effects 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 201000005296 lung carcinoma Diseases 0.000 description 1
• 201000011649 lymphoblastic lymphoma Diseases 0.000 description 1
• 208000003747 lymphoid leukemia Diseases 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 201000004792 malaria Diseases 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 201000008806 mesenchymal cell neoplasm Diseases 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
• 229940071648 metered dose inhaler Drugs 0.000 description 1
• WEAXQUBYRSEBJD-UHFFFAOYSA-N methyl 1h-indole-4-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1C=CN2 WEAXQUBYRSEBJD-UHFFFAOYSA-N 0.000 description 1
• GJVZWOMUTYNUCE-UHFFFAOYSA-N methyl 2-oxopyran-3-carboxylate Chemical compound COC(=O)C1=CC=COC1=O GJVZWOMUTYNUCE-UHFFFAOYSA-N 0.000 description 1
• KVQGGLZHHFGHPU-UHFFFAOYSA-N methyl 4-aminobutanoate Chemical compound COC(=O)CCCN KVQGGLZHHFGHPU-UHFFFAOYSA-N 0.000 description 1
• DCEPLYOSZFXDOE-UHFFFAOYSA-N methyl 5-(methylcarbamoyl)-1-[(3-methylphenyl)methyl]-6-oxopyridine-3-carboxylate Chemical compound CC=1C=C(CN2C=C(C=C(C2=O)C(NC)=O)C(=O)OC)C=CC=1 DCEPLYOSZFXDOE-UHFFFAOYSA-N 0.000 description 1
• TXZVFXMZHYRSDN-UHFFFAOYSA-N methyl 5-bromo-2-oxo-1h-pyridine-3-carboxylate Chemical compound COC(=O)C1=CC(Br)=CNC1=O TXZVFXMZHYRSDN-UHFFFAOYSA-N 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
• 239000003149 muscarinic antagonist Substances 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 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
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 210000003928 nasal cavity Anatomy 0.000 description 1
• 235000021096 natural sweeteners Nutrition 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 201000002165 neuroretinitis Diseases 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
• 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 150000003891 oxalate salts Chemical class 0.000 description 1
• 125000003431 oxalo group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 239000003002 pH adjusting agent Substances 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 239000011236 particulate material Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 235000019477 peppermint oil Nutrition 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 208000008494 pericarditis Diseases 0.000 description 1
• 208000030613 peripheral artery disease Diseases 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229920000747 poly(lactic acid) Polymers 0.000 description 1
• 201000006292 polyarteritis nodosa Diseases 0.000 description 1
• 229920001610 polycaprolactone Polymers 0.000 description 1
• 239000004632 polycaprolactone Substances 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical class [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 238000003825 pressing Methods 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 230000000861 pro-apoptotic effect Effects 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
• 239000011253 protective coating Substances 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 229940121649 protein inhibitor Drugs 0.000 description 1
• 239000012268 protein inhibitor Substances 0.000 description 1
• 208000005333 pulmonary edema Diseases 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 230000009103 reabsorption Effects 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 108091006082 receptor inhibitors Proteins 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000006894 reductive elimination reaction Methods 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 201000002793 renal fibrosis Diseases 0.000 description 1
• 230000010410 reperfusion Effects 0.000 description 1
• 230000004264 retinal detachment Effects 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• 208000004124 rheumatic heart disease Diseases 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
• 229960001860 salicylate Drugs 0.000 description 1
• 239000012266 salt solution Substances 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 230000036573 scar formation Effects 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 208000010157 sclerosing cholangitis Diseases 0.000 description 1
• 239000000565 sealant Substances 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 208000013223 septicemia Diseases 0.000 description 1
• 238000007493 shaping process Methods 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 208000001050 sialadenitis Diseases 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 239000012748 slip agent Substances 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 235000011083 sodium citrates Nutrition 0.000 description 1
• 239000001540 sodium lactate Substances 0.000 description 1
• 235000011088 sodium lactate Nutrition 0.000 description 1
• 229940005581 sodium lactate Drugs 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 235000011008 sodium phosphates Nutrition 0.000 description 1
• 235000010339 sodium tetraborate Nutrition 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 238000000638 solvent extraction Methods 0.000 description 1
• 239000002594 sorbent Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000010959 steel Substances 0.000 description 1
• 230000036262 stenosis Effects 0.000 description 1
• 208000037804 stenosis Diseases 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 238000009495 sugar coating Methods 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 230000010741 sumoylation Effects 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 150000003892 tartrate salts Chemical class 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
• POHWAQLZBIMPRN-UHFFFAOYSA-N tert-butyl n-(3-aminopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCN POHWAQLZBIMPRN-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 201000003120 testicular cancer Diseases 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 238000002411 thermogravimetry Methods 0.000 description 1
• 229920001187 thermosetting polymer Polymers 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
• 230000009974 thixotropic effect Effects 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 206010043778 thyroiditis Diseases 0.000 description 1
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 229940100611 topical cream Drugs 0.000 description 1
• 229940042130 topical foam Drugs 0.000 description 1
• 229940042129 topical gel Drugs 0.000 description 1
• 229940100615 topical ointment Drugs 0.000 description 1
• 229940041677 topical spray Drugs 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 206010044412 transitional cell carcinoma Diseases 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 150000004654 triazenes Chemical class 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
• MHNHYTDAOYJUEZ-UHFFFAOYSA-N triphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 MHNHYTDAOYJUEZ-UHFFFAOYSA-N 0.000 description 1
• BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 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
• 238000010798 ubiquitination Methods 0.000 description 1
• 238000001195 ultra high performance liquid chromatography Methods 0.000 description 1
• 238000002604 ultrasonography Methods 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 208000018464 vernal keratoconjunctivitis Diseases 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical class C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
• 201000005102 vulva cancer Diseases 0.000 description 1
• 235000012431 wafers Nutrition 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229930195724 β-lactose Natural products 0.000 description 1