CA2979024C - Fused bicyclic heteroaryl derivatives having activity as phd inhibitors - Google Patents

Info

Publication number

CA2979024C

CA2979024C CA2979024A CA2979024A CA2979024C CA 2979024 C CA2979024 C CA 2979024C CA 2979024 A CA2979024 A CA 2979024A CA 2979024 A CA2979024 A CA 2979024A CA 2979024 C CA2979024 C CA 2979024C

Authority

CA

Canada

Prior art keywords

triazolo

pyridin

benzonitrile

cyano

fluoro

Prior art date

2015-03-18

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
• CIPO
• Discuss

• 230000000694 effects Effects 0.000 title description 8
• 239000003112 inhibitor Substances 0.000 title description 7
• 150000001875 compounds Chemical class 0.000 claims abstract description 255
• 150000003839 salts Chemical class 0.000 claims abstract description 34
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
• 238000011282 treatment Methods 0.000 claims abstract description 15
• 206010019280 Heart failures Diseases 0.000 claims abstract description 12
• 208000010125 myocardial infarction Diseases 0.000 claims abstract description 11
• 208000009304 Acute Kidney Injury Diseases 0.000 claims abstract description 9
• 208000033626 Renal failure acute Diseases 0.000 claims abstract description 9
• 201000011040 acute kidney failure Diseases 0.000 claims abstract description 9
• 206010007556 Cardiac failure acute Diseases 0.000 claims abstract description 8
• 208000020832 chronic kidney disease Diseases 0.000 claims abstract description 8
• 208000030613 peripheral artery disease Diseases 0.000 claims abstract description 8
• 102000004079 Prolyl Hydroxylases Human genes 0.000 claims abstract description 5
• 108010043005 Prolyl Hydroxylases Proteins 0.000 claims abstract description 5
• 229940121649 protein inhibitor Drugs 0.000 claims abstract 2
• 239000012268 protein inhibitor Substances 0.000 claims abstract 2
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 754
• 229910052757 nitrogen Inorganic materials 0.000 claims description 120
• 125000001424 substituent group Chemical group 0.000 claims description 114
• -1 Cl-C6 alkyl Chemical group 0.000 claims description 96
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 92
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 80
• 125000000623 heterocyclic group Chemical group 0.000 claims description 80
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 63
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 61
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 61
• 229910052736 halogen Inorganic materials 0.000 claims description 57
• 150000002367 halogens Chemical group 0.000 claims description 57
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 56
• 125000003118 aryl group Chemical group 0.000 claims description 55
• 229910052739 hydrogen Inorganic materials 0.000 claims description 51
• 125000000217 alkyl group Chemical group 0.000 claims description 50
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 50
• 239000001257 hydrogen Substances 0.000 claims description 48
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 44
• 229910052731 fluorine Inorganic materials 0.000 claims description 41
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 38
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 38
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 37
• 125000004043 oxo group Chemical group O=* 0.000 claims description 37
• 239000011737 fluorine Substances 0.000 claims description 36
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 35
• 125000003545 alkoxy group Chemical group 0.000 claims description 33
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 33
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 32
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 30
• 229910052801 chlorine Inorganic materials 0.000 claims description 28
• 125000001072 heteroaryl group Chemical group 0.000 claims description 27
• 150000002431 hydrogen Chemical group 0.000 claims description 26
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 25
• 239000000460 chlorine Substances 0.000 claims description 25
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 24
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 24
• 229910052760 oxygen Chemical group 0.000 claims description 24
• 239000001301 oxygen Chemical group 0.000 claims description 24
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 18
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
• 125000005842 heteroatom Chemical group 0.000 claims description 17
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 14
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 13
• AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims description 13
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 12
• 239000003085 diluting agent Substances 0.000 claims description 11
• 125000005843 halogen group Chemical group 0.000 claims description 11
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
• 125000003566 oxetanyl group Chemical group 0.000 claims description 11
• 125000005475 oxolanyl group Chemical group 0.000 claims description 11
• 229940124530 sulfonamide Drugs 0.000 claims description 11
• 239000003795 chemical substances by application Substances 0.000 claims description 10
• 125000001188 haloalkyl group Chemical group 0.000 claims description 10
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 9
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 9
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• OQNYMAJNLRQKJB-UHFFFAOYSA-N triazolo[1,5-a]pyridine-7-carboxamide Chemical compound NC(=O)C1=CC=CC2=CN=NN12 OQNYMAJNLRQKJB-UHFFFAOYSA-N 0.000 claims description 8
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
• 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 7
• 239000002671 adjuvant Substances 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 6
• 125000003277 amino group Chemical group 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 229910052702 rhenium Inorganic materials 0.000 claims description 6
• 229910052701 rubidium Inorganic materials 0.000 claims description 6
• 238000002560 therapeutic procedure Methods 0.000 claims description 6
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 5
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 5
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
• 229940124597 therapeutic agent Drugs 0.000 claims description 5
• LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical compound C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 0.000 claims description 5
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
• 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 4
• RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 claims description 4
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 3
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
• NJYYWQHQUOODDL-UHFFFAOYSA-N oxetane-3-carboxamide Chemical compound NC(=O)C1COC1 NJYYWQHQUOODDL-UHFFFAOYSA-N 0.000 claims description 3
• FSDNTQSJGHSJBG-UHFFFAOYSA-N piperidine-4-carbonitrile Chemical compound N#CC1CCNCC1 FSDNTQSJGHSJBG-UHFFFAOYSA-N 0.000 claims description 3
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
• TYXLWIGNDNJNFS-UHFFFAOYSA-N 4-([1,2,4]triazolo[1,5-c]pyrimidin-5-yl)benzonitrile Chemical compound N#CC1=CC=C(C=C1)C1=NC=CC2=NC=NN12 TYXLWIGNDNJNFS-UHFFFAOYSA-N 0.000 claims description 2
• KHGDXQZJKLJOIK-UHFFFAOYSA-N 4-[7-[(2,2,2-trifluoroethylamino)methyl]-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound FC(F)(F)CNCC1=CC2=NC=NN2C(=C1)C1=CC=C(C=C1)C#N KHGDXQZJKLJOIK-UHFFFAOYSA-N 0.000 claims description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 2
• OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims 9
• 229940055764 triaz Drugs 0.000 claims 9
• NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 claims 1
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
• QMHVUOAGWLRDPP-UHFFFAOYSA-N 4-(7-amino-6-fluoro-[1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound NC1=CC=2N(C(=C1F)C1=CC=C(C#N)C=C1)N=CN=2 QMHVUOAGWLRDPP-UHFFFAOYSA-N 0.000 claims 1
• HNUCQKUWOZDYFO-UHFFFAOYSA-N 4-(7-benzylsulfanyl-[1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound N#CC1=CC=C(C=C1)C1=CC(SCC2=CC=CC=C2)=CC2=NC=NN12 HNUCQKUWOZDYFO-UHFFFAOYSA-N 0.000 claims 1
• ULZXKIMTJAMTGW-UHFFFAOYSA-N 4-[7-[(oxolan-3-ylamino)methyl]-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound N#CC1=CC=C(C=C1)C1=CC(CNC2CCOC2)=CC2=NC=NN12 ULZXKIMTJAMTGW-UHFFFAOYSA-N 0.000 claims 1
• QBFUVYJSQOPYSY-UHFFFAOYSA-N 4-[7-[(propan-2-ylamino)methyl]-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound CC(C)NCC1=CC=2N(C(=C1)C1=CC=C(C#N)C=C1)N=CN=2 QBFUVYJSQOPYSY-UHFFFAOYSA-N 0.000 claims 1
• FKAGHRYUKLRFOX-UHFFFAOYSA-N 5-(4-cyanophenyl)-N-(cyclopropylmethyl)-[1,2,4]triazolo[1,5-a]pyridine-7-sulfonamide Chemical compound O=S(=O)(NCC1CC1)C1=CC2=NC=NN2C(=C1)C1=CC=C(C=C1)C#N FKAGHRYUKLRFOX-UHFFFAOYSA-N 0.000 claims 1
• SZXOXIUXMHQIGQ-UHFFFAOYSA-N 5-(4-ethynylphenyl)-[1,2,4]triazolo[1,5-a]pyridine Chemical compound C(#C)C1=CC=C(C=C1)C1=CC=CC=2N1N=CN=2 SZXOXIUXMHQIGQ-UHFFFAOYSA-N 0.000 claims 1
• ZECDLNVIDWWXMH-UHFFFAOYSA-N 6-amino-5-([1,2,4]triazolo[1,5-a]pyridin-5-yl)pyridine-2-carbonitrile Chemical compound NC1=C(C=CC(=N1)C#N)C1=CC=CC2=NC=NN12 ZECDLNVIDWWXMH-UHFFFAOYSA-N 0.000 claims 1
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
• JDQJVFORFISJLJ-UHFFFAOYSA-N N-[5-(4-cyano-2-methylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl]-3,3,3-trifluoropropanamide Chemical compound CC1=C(C=CC(=C1)C#N)C1=CC(NC(=O)CC(F)(F)F)=CC2=NC=NN12 JDQJVFORFISJLJ-UHFFFAOYSA-N 0.000 claims 1
• WIOXTBUBGWILPP-UHFFFAOYSA-N N-[5-(4-cyano-3-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl]-2,2-difluorocyclopropane-1-carboxamide Chemical compound FC1=C(C=CC(=C1)C1=CC(NC(=O)C2CC2(F)F)=CC2=NC=NN12)C#N WIOXTBUBGWILPP-UHFFFAOYSA-N 0.000 claims 1
• OFQIHMZPWBHZJH-UHFFFAOYSA-N N-[5-(4-cyano-3-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl]-2-(oxetan-3-yl)acetamide Chemical compound FC1=C(C=CC(=C1)C1=CC(NC(=O)CC2COC2)=CC2=NC=NN12)C#N OFQIHMZPWBHZJH-UHFFFAOYSA-N 0.000 claims 1
• UHZBVANUVKROCY-UHFFFAOYSA-N N-[5-(4-cyano-3-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl]-2-cyclopropylacetamide Chemical compound FC1=C(C=CC(=C1)C1=CC(NC(=O)CC2CC2)=CC2=NC=NN12)C#N UHZBVANUVKROCY-UHFFFAOYSA-N 0.000 claims 1
• RBCCWUJRBHHFSC-UHFFFAOYSA-N N-[5-(4-cyano-3-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl]-3-fluorocyclobutane-1-carboxamide Chemical compound FC1CC(C1)C(=O)NC1=CC2=NC=NN2C(=C1)C1=CC(F)=C(C=C1)C#N RBCCWUJRBHHFSC-UHFFFAOYSA-N 0.000 claims 1
• KIDNTTIYEICQIJ-UHFFFAOYSA-N N-[5-(4-cyano-3-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl]cyclopropanecarboxamide Chemical compound FC1=C(C=CC(=C1)C1=CC(NC(=O)C2CC2)=CC2=NC=NN12)C#N KIDNTTIYEICQIJ-UHFFFAOYSA-N 0.000 claims 1
• FBDODZQVKOVCDF-UHFFFAOYSA-N OC1=CC2=NC=NN2C(=C1)C1=CC=C(C=C1)C#N Chemical compound OC1=CC2=NC=NN2C(=C1)C1=CC=C(C=C1)C#N FBDODZQVKOVCDF-UHFFFAOYSA-N 0.000 claims 1
• 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims 1
• GXHAENUAJYZNOA-UHFFFAOYSA-N oxolane-2-carboxamide Chemical compound NC(=O)C1CCCO1 GXHAENUAJYZNOA-UHFFFAOYSA-N 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 47
• 239000000203 mixture Substances 0.000 abstract description 39
• 238000002360 preparation method Methods 0.000 abstract description 11
• 230000008569 process Effects 0.000 abstract description 8
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 369
• 238000005481 NMR spectroscopy Methods 0.000 description 194
• 239000000543 intermediate Substances 0.000 description 156
• 238000006243 chemical reaction Methods 0.000 description 131
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 125
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 121
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 113
• 238000005160 1H NMR spectroscopy Methods 0.000 description 101
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 98
• 239000012071 phase Substances 0.000 description 95
• 239000000243 solution Substances 0.000 description 83
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 80
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
• 150000001412 amines Chemical class 0.000 description 65
• 239000002253 acid Substances 0.000 description 63
• 239000011541 reaction mixture Substances 0.000 description 52
• 239000000377 silicon dioxide Substances 0.000 description 51
• 238000003818 flash chromatography Methods 0.000 description 48
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 47
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 44
• 238000002953 preparative HPLC Methods 0.000 description 40
• 150000003857 carboxamides Chemical class 0.000 description 39
• 239000000725 suspension Substances 0.000 description 39
• 239000012074 organic phase Substances 0.000 description 36
• 230000002441 reversible effect Effects 0.000 description 34
• 150000004820 halides Chemical class 0.000 description 33
• 229910021529 ammonia Inorganic materials 0.000 description 32
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 32
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
• 235000002639 sodium chloride Nutrition 0.000 description 30
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 26
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
• 239000012267 brine Substances 0.000 description 25
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 24
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 23
• CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 22
• FTRKHVUBTUHSQK-UHFFFAOYSA-N 5-bromo-[1,2,4]triazolo[1,5-a]pyridine Chemical compound BrC1=CC=CC2=NC=NN12 FTRKHVUBTUHSQK-UHFFFAOYSA-N 0.000 description 22
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 22
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
• 150000001408 amides Chemical class 0.000 description 21
• 239000012043 crude product Substances 0.000 description 21
• WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 21
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 21
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 18
• 229910052681 coesite Inorganic materials 0.000 description 18
• 229910052906 cristobalite Inorganic materials 0.000 description 18
• 229910052682 stishovite Inorganic materials 0.000 description 18
• 229910052905 tridymite Inorganic materials 0.000 description 18
• GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 17
• 239000003153 chemical reaction reagent Substances 0.000 description 17
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 16
• 229910000024 caesium carbonate Inorganic materials 0.000 description 16
• 208000035475 disorder Diseases 0.000 description 16
• 239000007787 solid Substances 0.000 description 16
• 206010021143 Hypoxia Diseases 0.000 description 15
• 235000012239 silicon dioxide Nutrition 0.000 description 15
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
• 206010028980 Neoplasm Diseases 0.000 description 14
• 230000007954 hypoxia Effects 0.000 description 14
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
• 235000017557 sodium bicarbonate Nutrition 0.000 description 14
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 13
• 208000008589 Obesity Diseases 0.000 description 13
• 235000020824 obesity Nutrition 0.000 description 13
• 238000000746 purification Methods 0.000 description 13
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 12
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 12
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• 229910000029 sodium carbonate Inorganic materials 0.000 description 11
• 235000017550 sodium carbonate Nutrition 0.000 description 11
• 239000002904 solvent Substances 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 10
• 125000001207 fluorophenyl group Chemical group 0.000 description 10
• 239000002244 precipitate Substances 0.000 description 10
• 239000003643 water by type Substances 0.000 description 10
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
• 229910052786 argon Inorganic materials 0.000 description 9
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
• 235000015320 potassium carbonate Nutrition 0.000 description 9
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 9
• DECWLXUOZUMPBF-UHFFFAOYSA-N (4-cyano-3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C(F)=C1 DECWLXUOZUMPBF-UHFFFAOYSA-N 0.000 description 8
• 101150041968 CDC13 gene Proteins 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
• 125000002393 azetidinyl group Chemical group 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
• 239000012299 nitrogen atmosphere Substances 0.000 description 8
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 8
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 8
• 230000003595 spectral effect Effects 0.000 description 8
• RGCVYEOTYJCNOS-UHFFFAOYSA-N (4-cyano-2-methylphenyl)boronic acid Chemical compound CC1=CC(C#N)=CC=C1B(O)O RGCVYEOTYJCNOS-UHFFFAOYSA-N 0.000 description 7
• NWPNXBQSRGKSJB-UHFFFAOYSA-N 2-methylbenzonitrile Chemical compound CC1=CC=CC=C1C#N NWPNXBQSRGKSJB-UHFFFAOYSA-N 0.000 description 7
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 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 7
• 229910017912 NH2OH Inorganic materials 0.000 description 7
• 239000005864 Sulphur Substances 0.000 description 7
• 150000001502 aryl halides Chemical class 0.000 description 7
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 7
• 230000006378 damage Effects 0.000 description 7
• 235000019253 formic acid Nutrition 0.000 description 7
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
• 235000019341 magnesium sulphate Nutrition 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• HFAUMAIVCYTVQR-UHFFFAOYSA-N (4-cyano-2-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1F HFAUMAIVCYTVQR-UHFFFAOYSA-N 0.000 description 6
• OGXGCIBHOYGYDL-UHFFFAOYSA-N 2-fluoro-4-(6-fluoro-[1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound FC1=C(C=CC(=C1)C1=C(F)C=CC2=NC=NN12)C#N OGXGCIBHOYGYDL-UHFFFAOYSA-N 0.000 description 6
• ZKHPNASIRYLBNH-UHFFFAOYSA-N 4-(7-amino-[1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound NC1=CC2=NC=NN2C(=C1)C1=CC=C(C=C1)C#N ZKHPNASIRYLBNH-UHFFFAOYSA-N 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
• 208000029523 Interstitial Lung disease Diseases 0.000 description 6
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
• 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 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• WMSPXQIQBQAWLL-UHFFFAOYSA-N cyclopropanesulfonamide Chemical compound NS(=O)(=O)C1CC1 WMSPXQIQBQAWLL-UHFFFAOYSA-N 0.000 description 6
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 6
• 206010012601 diabetes mellitus Diseases 0.000 description 6
• YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 6
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 6
• 230000001939 inductive effect Effects 0.000 description 6
• 229910052740 iodine Inorganic materials 0.000 description 6
• 208000017169 kidney disease Diseases 0.000 description 6
• 125000002950 monocyclic group Chemical group 0.000 description 6
• 239000003921 oil Substances 0.000 description 6
• 235000019198 oils Nutrition 0.000 description 6
• 125000003386 piperidinyl group Chemical group 0.000 description 6
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• 229910000104 sodium hydride Inorganic materials 0.000 description 6
• 229910052938 sodium sulfate Inorganic materials 0.000 description 6
• 235000011152 sodium sulphate Nutrition 0.000 description 6
• KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 6
• 229910000080 stannane Inorganic materials 0.000 description 6
• 208000011580 syndromic disease Diseases 0.000 description 6
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 6
• 238000005406 washing Methods 0.000 description 6
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 5
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 5
• NFJCCSONEBUNGR-UHFFFAOYSA-N 5-bromo-6-methylpyridine-2-carbonitrile Chemical compound CC1=NC(C#N)=CC=C1Br NFJCCSONEBUNGR-UHFFFAOYSA-N 0.000 description 5
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 5
• 239000007821 HATU Substances 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
• 230000004075 alteration Effects 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 230000001684 chronic effect Effects 0.000 description 5
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 5
• 238000001514 detection method Methods 0.000 description 5
• 238000011068 loading method Methods 0.000 description 5
• 239000002480 mineral oil Substances 0.000 description 5
• 235000010446 mineral oil Nutrition 0.000 description 5
• DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 5
• 239000002798 polar solvent Substances 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 5
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 5
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 4
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
• KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 4
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 4
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
• 208000019693 Lung disease Diseases 0.000 description 4
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
• 239000007832 Na2SO4 Substances 0.000 description 4
• 229910021120 PdC12 Inorganic materials 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 125000003342 alkenyl group Chemical group 0.000 description 4
• 125000000304 alkynyl group Chemical group 0.000 description 4
• 208000011775 arteriosclerosis disease Diseases 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• 150000007942 carboxylates Chemical class 0.000 description 4
• 125000004802 cyanophenyl group Chemical group 0.000 description 4
• IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 4
• 230000001965 increasing effect Effects 0.000 description 4
• 230000000302 ischemic effect Effects 0.000 description 4
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 4
• 238000001819 mass spectrum Methods 0.000 description 4
• MYBUXYUDDLFCPJ-UHFFFAOYSA-N methyl 2-amino-6-chloropyridine-4-carboxylate Chemical compound COC(=O)C1=CC(N)=NC(Cl)=C1 MYBUXYUDDLFCPJ-UHFFFAOYSA-N 0.000 description 4
• 125000002757 morpholinyl group Chemical group 0.000 description 4
• 239000012044 organic layer Substances 0.000 description 4
• 239000003960 organic solvent Substances 0.000 description 4
• KTHZBRAXOLUNBN-UHFFFAOYSA-N oxetan-3-ylmethanamine Chemical compound NCC1COC1 KTHZBRAXOLUNBN-UHFFFAOYSA-N 0.000 description 4
• LHKLURCDZIVDBX-UHFFFAOYSA-N oxolane-2-carboxamide Chemical compound O1C(CCC1)C(=O)N.O1C(CCC1)C(=O)N LHKLURCDZIVDBX-UHFFFAOYSA-N 0.000 description 4
• 230000002093 peripheral effect Effects 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 125000004193 piperazinyl group Chemical group 0.000 description 4
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 239000000523 sample Substances 0.000 description 4
• 239000012312 sodium hydride Substances 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• 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 4
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 3
• OVRWUZYZECPJOB-UHFFFAOYSA-N 2,2-difluoroethanamine Chemical compound NCC(F)F OVRWUZYZECPJOB-UHFFFAOYSA-N 0.000 description 3
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 3
• MZBSJLAGBUNNLH-UHFFFAOYSA-N 3,3,3-trifluoropropanamide Chemical compound NC(=O)CC(F)(F)F MZBSJLAGBUNNLH-UHFFFAOYSA-N 0.000 description 3
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 3
• CDYYDUXNFWPTTE-UHFFFAOYSA-N 4-(7-chloro-[1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound ClC1=CC2=NC=NN2C(=C1)C1=CC=C(C=C1)C#N CDYYDUXNFWPTTE-UHFFFAOYSA-N 0.000 description 3
• PWISOHRBGSJIPW-UHFFFAOYSA-N 4-bromo-2-fluoro-3-methylbenzonitrile Chemical compound CC1=C(Br)C=CC(C#N)=C1F PWISOHRBGSJIPW-UHFFFAOYSA-N 0.000 description 3
• AVBKISZUVMWQIA-UHFFFAOYSA-N 4-bromo-2-fluoro-5-methylbenzonitrile Chemical compound CC1=CC(C#N)=C(F)C=C1Br AVBKISZUVMWQIA-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 208000035473 Communicable disease Diseases 0.000 description 3
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 3
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 3
• 208000002705 Glucose Intolerance Diseases 0.000 description 3
• 206010056997 Impaired fasting glucose Diseases 0.000 description 3
• 239000012448 Lithium borohydride Substances 0.000 description 3
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
• 206010035664 Pneumonia Diseases 0.000 description 3
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 239000007900 aqueous suspension Substances 0.000 description 3
• UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 3
• 239000004305 biphenyl Substances 0.000 description 3
• 229910052796 boron Inorganic materials 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 230000002490 cerebral effect Effects 0.000 description 3
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 3
• 125000000068 chlorophenyl group Chemical group 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• 125000004122 cyclic group Chemical group 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 238000000132 electrospray ionisation Methods 0.000 description 3
• 230000002757 inflammatory effect Effects 0.000 description 3
• 239000011630 iodine Substances 0.000 description 3
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
• TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 3
• 229960004592 isopropanol Drugs 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 201000006370 kidney failure Diseases 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
• HYVVJDQGXFXBRZ-UHFFFAOYSA-N metam Chemical compound CNC(S)=S HYVVJDQGXFXBRZ-UHFFFAOYSA-N 0.000 description 3
• XWPMDBMALJQXBS-UHFFFAOYSA-N methyl 5-chloro-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate Chemical compound COC(=O)C1=CC2=NC=NN2C(Cl)=C1 XWPMDBMALJQXBS-UHFFFAOYSA-N 0.000 description 3
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 125000000160 oxazolidinyl group Chemical group 0.000 description 3
• 125000004430 oxygen atom Chemical group O* 0.000 description 3
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
• DJDBLBBSUAQYAA-UHFFFAOYSA-N piperazine-1-carbonitrile Chemical compound N#CN1CCNCC1 DJDBLBBSUAQYAA-UHFFFAOYSA-N 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 235000011056 potassium acetate Nutrition 0.000 description 3
• 229910000160 potassium phosphate Inorganic materials 0.000 description 3
• 235000011009 potassium phosphates Nutrition 0.000 description 3
• 201000009104 prediabetes syndrome Diseases 0.000 description 3
• 150000003141 primary amines Chemical class 0.000 description 3
• 238000011321 prophylaxis Methods 0.000 description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• 238000012216 screening Methods 0.000 description 3
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
• 238000001356 surgical procedure Methods 0.000 description 3
• HLDRVUMVAJNBDD-UHFFFAOYSA-N tert-butyl N-(5-chloro-[1,2,4]triazolo[1,5-a]pyridin-7-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC2=NC=NN2C(Cl)=C1 HLDRVUMVAJNBDD-UHFFFAOYSA-N 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• 125000003944 tolyl group Chemical group 0.000 description 3
• AQWOIRBQLOOZGX-UHFFFAOYSA-N triazolo[1,5-a]pyridine Chemical compound C1=CC=CC2=CN=NN21 AQWOIRBQLOOZGX-UHFFFAOYSA-N 0.000 description 3
• YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical class BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 description 3
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
• UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 2
• GKPHNZYMLJPYJJ-UHFFFAOYSA-N 2,3-difluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1F GKPHNZYMLJPYJJ-UHFFFAOYSA-N 0.000 description 2
• YAXSIJLRAOURJK-UHFFFAOYSA-N 2,6-dichloro-3-fluoropyridine Chemical compound FC1=CC=C(Cl)N=C1Cl YAXSIJLRAOURJK-UHFFFAOYSA-N 0.000 description 2
• WWTWZEXZURTRAX-UHFFFAOYSA-N 2,6-difluoro-4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound FC1=CC(=CC(F)=C1C#N)C1=CC=CC2=NC=NN12 WWTWZEXZURTRAX-UHFFFAOYSA-N 0.000 description 2
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-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
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
• NWNWBLRKHOVSEL-UHFFFAOYSA-N 2-chloro-3-fluoropyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(Cl)=C1F NWNWBLRKHOVSEL-UHFFFAOYSA-N 0.000 description 2
• MHHKFALIEJDOHF-UHFFFAOYSA-N 2-chloro-4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound ClC1=C(C=CC(=C1)C1=CC=CC2=NC=NN12)C#N MHHKFALIEJDOHF-UHFFFAOYSA-N 0.000 description 2
• CUZZZFBECBOGRY-UHFFFAOYSA-N 2-fluoro-4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound FC1=C(C=CC(=C1)C1=CC=CC2=NC=NN12)C#N CUZZZFBECBOGRY-UHFFFAOYSA-N 0.000 description 2
• HTNBFLTXQKEDBA-UHFFFAOYSA-N 2-fluoro-4-[7-(oxolan-2-ylmethoxy)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound FC1=C(C=CC(=C1)C1=CC(OCC2CCCO2)=CC2=NC=NN12)C#N HTNBFLTXQKEDBA-UHFFFAOYSA-N 0.000 description 2
• OVLYPFVIMFTQMP-UHFFFAOYSA-N 2-fluoro-4-[7-(oxolan-3-ylmethoxy)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound FC1=C(C=CC(=C1)C1=CC(OCC2CCOC2)=CC2=NC=NN12)C#N OVLYPFVIMFTQMP-UHFFFAOYSA-N 0.000 description 2
• LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 2
• YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 2
• HBNUXWFTHWHLHL-UHFFFAOYSA-N 3-amino-4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound NC1=C(C=CC(=C1)C#N)C1=CC=CC2=NC=NN12 HBNUXWFTHWHLHL-UHFFFAOYSA-N 0.000 description 2
• URBXKEHMAICHMQ-UHFFFAOYSA-N 3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound CC1=C(C=CC(=C1)C#N)C1=CC=CC2=NC=NN12 URBXKEHMAICHMQ-UHFFFAOYSA-N 0.000 description 2
• JHNLZOVBAQWGQU-UHFFFAOYSA-N 380814_sial Chemical compound CS(O)(=O)=O.O=P(=O)OP(=O)=O JHNLZOVBAQWGQU-UHFFFAOYSA-N 0.000 description 2
• AGJMDETXSYICGZ-UHFFFAOYSA-N 4,6-dichloropyridin-2-amine Chemical compound NC1=CC(Cl)=CC(Cl)=N1 AGJMDETXSYICGZ-UHFFFAOYSA-N 0.000 description 2
• UPFXRFBLFJLCNO-UHFFFAOYSA-N 4-(6-amino-3-fluoropyridin-2-yl)benzonitrile Chemical compound NC1=CC=C(C(=N1)C1=CC=C(C#N)C=C1)F UPFXRFBLFJLCNO-UHFFFAOYSA-N 0.000 description 2
• BRELHWHYDASUDA-UHFFFAOYSA-N 4-(6-chloro-3-fluoropyridin-2-yl)benzonitrile Chemical compound ClC1=CC=C(C(=N1)C1=CC=C(C#N)C=C1)F BRELHWHYDASUDA-UHFFFAOYSA-N 0.000 description 2
• ZEMUMFOIIYWVQZ-UHFFFAOYSA-N 4-[7-(benzylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound N#CC1=CC=C(C=C1)C1=CC(NCC2=CC=CC=C2)=CC2=NC=NN12 ZEMUMFOIIYWVQZ-UHFFFAOYSA-N 0.000 description 2
• JCSJIJVKUYLANF-UHFFFAOYSA-N 4-[7-(cyclopropylmethoxy)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound N#CC1=CC=C(C=C1)C1=CC(OCC2CC2)=CC2=NC=NN12 JCSJIJVKUYLANF-UHFFFAOYSA-N 0.000 description 2
• ROJZYGFAQBIEGG-UHFFFAOYSA-N 4-[7-(ethylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound CCNC1=CC2=NC=NN2C(=C1)C1=CC=C(C=C1)C#N ROJZYGFAQBIEGG-UHFFFAOYSA-N 0.000 description 2
• LRMUGJVHRUVMHP-UHFFFAOYSA-N 4-bromo-3,5-difluorobenzonitrile Chemical compound FC1=CC(C#N)=CC(F)=C1Br LRMUGJVHRUVMHP-UHFFFAOYSA-N 0.000 description 2
• RIEQOYPBMKFGPN-UHFFFAOYSA-N 5,7-dichloro-[1,2,4]triazolo[1,5-a]pyridine Chemical compound ClC1=CC2=NC=NN2C(Cl)=C1 RIEQOYPBMKFGPN-UHFFFAOYSA-N 0.000 description 2
• LQKFTGMXROMIGG-UHFFFAOYSA-N 5,7-dichloro-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound N1=C(Cl)C=C(Cl)N2N=CN=C21 LQKFTGMXROMIGG-UHFFFAOYSA-N 0.000 description 2
• PGPARSKOVPYPPP-UHFFFAOYSA-N 5-([1,2,4]triazolo[1,5-a]pyridin-5-yl)pyrazine-2-carbonitrile Chemical compound N=1C=NN2C=1C=CC=C2C=1N=CC(=NC=1)C#N PGPARSKOVPYPPP-UHFFFAOYSA-N 0.000 description 2
• QOMVEWRHNWLNQR-UHFFFAOYSA-N 5-([1,2,4]triazolo[1,5-a]pyridin-5-yl)pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=C(C=N1)C1=CC=CC2=NC=NN12 QOMVEWRHNWLNQR-UHFFFAOYSA-N 0.000 description 2
• RXAUIZRIEYYSPU-UHFFFAOYSA-N 5-bromo-4,6-dimethyl-1-oxidopyrimidin-1-ium Chemical compound BrC=1C(=NC=[N+](C=1C)[O-])C RXAUIZRIEYYSPU-UHFFFAOYSA-N 0.000 description 2
• WDMWXYZJJVYMHE-UHFFFAOYSA-N 5-bromo-4,6-dimethylpyrimidine Chemical compound CC1=NC=NC(C)=C1Br WDMWXYZJJVYMHE-UHFFFAOYSA-N 0.000 description 2
• SHDFCVPKNYRBTP-UHFFFAOYSA-N 5-chloro-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylic acid Chemical compound OC(=O)C1=CC2=NC=NN2C(Cl)=C1 SHDFCVPKNYRBTP-UHFFFAOYSA-N 0.000 description 2
• YJTXQLYMECWULH-UHFFFAOYSA-N 5-fluoropyridin-2-amine Chemical compound NC1=CC=C(F)C=N1 YJTXQLYMECWULH-UHFFFAOYSA-N 0.000 description 2
• CXRXKDSDRWLKTK-UHFFFAOYSA-N 6-bromo-[1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=C(Br)C=CC2=NC=NN21 CXRXKDSDRWLKTK-UHFFFAOYSA-N 0.000 description 2
• KPZRCZMNXPBHEH-UHFFFAOYSA-N 6-chloro-5-methylpyridin-2-amine Chemical compound CC1=CC=C(N)N=C1Cl KPZRCZMNXPBHEH-UHFFFAOYSA-N 0.000 description 2
• ARBLELSFPPCKQO-UHFFFAOYSA-N 6-fluoro-5-iodo-[1,2,4]triazolo[1,5-a]pyridine Chemical compound FC1=C(I)N2N=CN=C2C=C1 ARBLELSFPPCKQO-UHFFFAOYSA-N 0.000 description 2
• CMRMDXQHVKMVBY-UHFFFAOYSA-N 6-fluoro-[1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=C(F)C=CC2=NC=NN21 CMRMDXQHVKMVBY-UHFFFAOYSA-N 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 239000005695 Ammonium acetate Substances 0.000 description 2
• 208000000575 Arteriosclerosis Obliterans Diseases 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 2
• 208000020084 Bone disease Diseases 0.000 description 2
• 208000014644 Brain disease Diseases 0.000 description 2
• 206010048962 Brain oedema Diseases 0.000 description 2
• 101100352919 Caenorhabditis elegans ppm-2 gene Proteins 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 206010007559 Cardiac failure congestive Diseases 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 102100037249 Egl nine homolog 1 Human genes 0.000 description 2
• 101710111663 Egl nine homolog 1 Proteins 0.000 description 2
• 206010016654 Fibrosis Diseases 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 206010020772 Hypertension Diseases 0.000 description 2
• 239000005909 Kieselgur Substances 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
• 206010025323 Lymphomas Diseases 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 208000003926 Myelitis Diseases 0.000 description 2
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
• 208000028389 Nerve injury Diseases 0.000 description 2
• 101100028920 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cfp gene Proteins 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 2
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
• 206010035226 Plasma cell myeloma Diseases 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 102100037248 Prolyl hydroxylase EGLN2 Human genes 0.000 description 2
• 101710170760 Prolyl hydroxylase EGLN2 Proteins 0.000 description 2
• 206010060862 Prostate cancer Diseases 0.000 description 2
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
• 208000010378 Pulmonary Embolism Diseases 0.000 description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
• 206010063837 Reperfusion injury Diseases 0.000 description 2
• 208000017442 Retinal disease Diseases 0.000 description 2
• 206010038923 Retinopathy Diseases 0.000 description 2
• 206010040047 Sepsis Diseases 0.000 description 2
• 206010040070 Septic Shock Diseases 0.000 description 2
• 208000019802 Sexually transmitted disease Diseases 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 208000007536 Thrombosis Diseases 0.000 description 2
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• RLCWLXLOTSWZPK-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyridin-5-amine Chemical compound NC1=CC=CC2=NC=NN12 RLCWLXLOTSWZPK-UHFFFAOYSA-N 0.000 description 2
• DACWQSNZECJJGG-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=CC=CN2N=CN=C21 DACWQSNZECJJGG-UHFFFAOYSA-N 0.000 description 2
• SRNKZYRMFBGSGE-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CN=C21 SRNKZYRMFBGSGE-UHFFFAOYSA-N 0.000 description 2
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
• 239000012346 acetyl chloride Substances 0.000 description 2
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• 235000019257 ammonium acetate Nutrition 0.000 description 2
• 229940043376 ammonium acetate Drugs 0.000 description 2
• 208000007502 anemia Diseases 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 2
• 125000003725 azepanyl group Chemical group 0.000 description 2
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 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
• 125000002619 bicyclic group Chemical group 0.000 description 2
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• 210000000988 bone and bone Anatomy 0.000 description 2
• 208000006752 brain edema Diseases 0.000 description 2
• 201000011510 cancer Diseases 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 150000001718 carbodiimides Chemical class 0.000 description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 238000005341 cation exchange Methods 0.000 description 2
• 206010008118 cerebral infarction Diseases 0.000 description 2
• 208000026106 cerebrovascular disease Diseases 0.000 description 2
• 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 239000013058 crude material Substances 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 2
• 125000006317 cyclopropyl amino group Chemical group 0.000 description 2
• WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 2
• 201000003146 cystitis Diseases 0.000 description 2
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• QGBQGMHXBSLYLZ-UHFFFAOYSA-N ditert-butyl-(1-naphthalen-1-ylnaphthalen-2-yl)phosphane Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3P(C(C)(C)C)C(C)(C)C)=CC=CC2=C1 QGBQGMHXBSLYLZ-UHFFFAOYSA-N 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• ZFTAEJJVVQTXKD-UHFFFAOYSA-N ethyl 2-amino-6-chloropyridine-4-carboxylate Chemical compound CCOC(=O)C1=CC(N)=NC(Cl)=C1 ZFTAEJJVVQTXKD-UHFFFAOYSA-N 0.000 description 2
• JDHAGHSWXVCJQA-UHFFFAOYSA-N ethyl 5-chloro-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate Chemical compound CCOC(=O)C1=CC2=NC=NN2C(Cl)=C1 JDHAGHSWXVCJQA-UHFFFAOYSA-N 0.000 description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 239000012065 filter cake Substances 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 230000002496 gastric effect Effects 0.000 description 2
• 125000005456 glyceride group Chemical group 0.000 description 2
• 208000014951 hematologic disease Diseases 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
• JHBZAAACZVPPRQ-UHFFFAOYSA-L lithium;magnesium;2,2,6,6-tetramethylpiperidin-1-ide;dichloride Chemical compound [Li+].[Cl-].[Cl-].CC1(C)CCCC(C)(C)N1[Mg+] JHBZAAACZVPPRQ-UHFFFAOYSA-L 0.000 description 2
• 208000019423 liver disease Diseases 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 235000011090 malic acid Nutrition 0.000 description 2
• 230000003211 malignant effect Effects 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• 208000030159 metabolic disease Diseases 0.000 description 2
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
• ZVEGSWOSYWFZOR-UHFFFAOYSA-N methyl 2-chloro-3-fluoropyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(Cl)=C1F ZVEGSWOSYWFZOR-UHFFFAOYSA-N 0.000 description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 201000000050 myeloid neoplasm Diseases 0.000 description 2
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 230000008764 nerve damage Effects 0.000 description 2
• 238000004172 nitrogen cycle Methods 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 230000008816 organ damage Effects 0.000 description 2
• 201000008482 osteoarthritis Diseases 0.000 description 2
• 201000008968 osteosarcoma Diseases 0.000 description 2
• MKWDBRVVGMHOAQ-UHFFFAOYSA-N oxetane-2-carboxamide Chemical compound NC(=O)C1CCO1 MKWDBRVVGMHOAQ-UHFFFAOYSA-N 0.000 description 2
• DUXPFRRFZLRICX-UHFFFAOYSA-N oxolane-3-carboxamide Chemical compound NC(=O)C1CCOC1 DUXPFRRFZLRICX-UHFFFAOYSA-N 0.000 description 2
• 239000005022 packaging material Substances 0.000 description 2
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
• 208000028591 pheochromocytoma Diseases 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
• 239000004810 polytetrafluoroethylene Substances 0.000 description 2
• 235000011181 potassium carbonates Nutrition 0.000 description 2
• 239000000843 powder Substances 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
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 210000000664 rectum Anatomy 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• 208000013223 septicemia Diseases 0.000 description 2
• 201000000849 skin cancer Diseases 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 238000012799 strong cation exchange Methods 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 229910021653 sulphate ion Inorganic materials 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 2
• DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
• 150000003573 thiols Chemical class 0.000 description 2
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• REDSKZBUUUQMSK-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC REDSKZBUUUQMSK-UHFFFAOYSA-N 0.000 description 2
• PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 2
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
• ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-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
• 125000004417 unsaturated alkyl group Chemical group 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 201000002282 venous insufficiency Diseases 0.000 description 2
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
• UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
• MSCQYLAIRMCGGF-UHFFFAOYSA-N (2-chloro-4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1Cl MSCQYLAIRMCGGF-UHFFFAOYSA-N 0.000 description 1
• KZEDPVFJLQLDIZ-UHFFFAOYSA-N (5-diphenylphosphanyl-9,9-dimethylxanthen-4-yl)-diphenylphosphane 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.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 KZEDPVFJLQLDIZ-UHFFFAOYSA-N 0.000 description 1
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• GPCDGGKVBPVZCT-UHFFFAOYSA-N 1,1-difluorocyclopropane Chemical compound FC1(F)CC1 GPCDGGKVBPVZCT-UHFFFAOYSA-N 0.000 description 1
• QAVIPYUSPQRVKA-UHFFFAOYSA-N 1,2-diazaspiro[3.3]heptane Chemical compound C1CCC21NNC2 QAVIPYUSPQRVKA-UHFFFAOYSA-N 0.000 description 1
• 125000005960 1,4-diazepanyl group Chemical group 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
• 125000000196 1,4-pentadienyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])=C([H])[H] 0.000 description 1
• HHEKNWQXFVOUNJ-UHFFFAOYSA-N 1-(2-aminoethyl)pyrrolidin-2-one Chemical compound NCCN1CCCC1=O HHEKNWQXFVOUNJ-UHFFFAOYSA-N 0.000 description 1
• WDQFELCEOPFLCZ-UHFFFAOYSA-N 1-(2-hydroxyethyl)pyrrolidin-2-one Chemical compound OCCN1CCCC1=O WDQFELCEOPFLCZ-UHFFFAOYSA-N 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
• 125000006039 1-hexenyl group Chemical group 0.000 description 1
• 125000004486 1-methylpiperidin-3-yl group Chemical group CN1CC(CCC1)* 0.000 description 1
• PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• 125000006023 1-pentenyl group Chemical group 0.000 description 1
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
• GXBDCPYXMVITMR-UHFFFAOYSA-N 1h-[1,2,4]triazolo[1,5-a]pyrimidin-7-one Chemical compound O=C1C=CN=C2N=CNN12 GXBDCPYXMVITMR-UHFFFAOYSA-N 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• KMLMOVWSQPHQME-UHFFFAOYSA-N 2,2-difluorocyclopropane-1-carboxylic acid Chemical compound OC(=O)C1CC1(F)F KMLMOVWSQPHQME-UHFFFAOYSA-N 0.000 description 1
• PAQNXWWTZCDJGC-UHFFFAOYSA-N 2,3-difluoro-4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound FC1=C(C=CC(=C1F)C1=CC=CC2=NC=NN12)C#N PAQNXWWTZCDJGC-UHFFFAOYSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• WKJOQYHMXRVQDK-UHFFFAOYSA-N 2-(dimethylamino)acetamide Chemical compound CN(C)CC(N)=O WKJOQYHMXRVQDK-UHFFFAOYSA-N 0.000 description 1
• WGFCNCNTGOFBBF-UHFFFAOYSA-N 2-bromopyrazine Chemical compound BrC1=CN=CC=N1 WGFCNCNTGOFBBF-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• JBSLANHIBKBQGE-UHFFFAOYSA-N 2-cyclopropylacetamide Chemical compound NC(=O)CC1CC1 JBSLANHIBKBQGE-UHFFFAOYSA-N 0.000 description 1
• DYYNCYBQURWPHG-UHFFFAOYSA-N 2-fluoro-3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound CC1=C(C=CC(C#N)=C1F)C1=CC=CC2=NC=NN12 DYYNCYBQURWPHG-UHFFFAOYSA-N 0.000 description 1
• UWZQEPNPYYQBNV-UHFFFAOYSA-N 2-fluoro-4-(6-methyl-[1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound CC1=C(N2N=CN=C2C=C1)C1=CC(F)=C(C=C1)C#N UWZQEPNPYYQBNV-UHFFFAOYSA-N 0.000 description 1
• QUDUUEZTWYVOCS-UHFFFAOYSA-N 2-fluorobenzonitrile;hydrochloride Chemical compound Cl.FC1=CC=CC=C1C#N QUDUUEZTWYVOCS-UHFFFAOYSA-N 0.000 description 1
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
• VWOHQDZHCQQGLW-UHFFFAOYSA-N 2-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound CC1=C(C=CC(=C1)C1=CC=CC2=NC=NN12)C#N VWOHQDZHCQQGLW-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• FZIIBDOXPQOKBP-UHFFFAOYSA-N 2-methyloxetane Chemical compound CC1CCO1 FZIIBDOXPQOKBP-UHFFFAOYSA-N 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• YDHIMEXEGOCNHU-UHFFFAOYSA-N 2-pyridin-3-ylacetamide Chemical compound NC(=O)CC1=CC=CN=C1 YDHIMEXEGOCNHU-UHFFFAOYSA-N 0.000 description 1
• NAHHNSMHYCLMON-UHFFFAOYSA-N 2-pyridin-3-ylethanamine Chemical compound NCCC1=CC=CN=C1 NAHHNSMHYCLMON-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• YFUPQNBWHXCVAW-UHFFFAOYSA-N 3,5-difluoro-4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1C1=CC=CC=2N1N=CN=2)F YFUPQNBWHXCVAW-UHFFFAOYSA-N 0.000 description 1
• PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
• WBUOVKBZJOIOAE-UHFFFAOYSA-N 3-chlorobenzonitrile Chemical compound ClC1=CC=CC(C#N)=C1 WBUOVKBZJOIOAE-UHFFFAOYSA-N 0.000 description 1
• JCKPMHQVYXQULF-UHFFFAOYSA-N 3-fluoro-4-(6-fluoro-[1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound FC1=C(C=CC(=C1)C#N)C1=C(F)C=CC2=NC=NN12 JCKPMHQVYXQULF-UHFFFAOYSA-N 0.000 description 1
• KIMDFRBRYJBQCN-UHFFFAOYSA-N 3-fluoro-4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1C1=CC=CC=2N1N=CN=2 KIMDFRBRYJBQCN-UHFFFAOYSA-N 0.000 description 1
• DYBVVKHTQNXUPV-UHFFFAOYSA-N 3-fluoro-4-[7-(2-methoxyethylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1C1=CC(=CC=2N1N=CN=2)NCCOC DYBVVKHTQNXUPV-UHFFFAOYSA-N 0.000 description 1
• SBAVDTSBJDDFOK-UHFFFAOYSA-N 3-fluoro-5-([1,2,4]triazolo[1,5-a]pyridin-5-yl)pyridine-2-carbonitrile Chemical compound FC=1C(=NC=C(C=1)C1=CC=CC=2N1N=CN=2)C#N SBAVDTSBJDDFOK-UHFFFAOYSA-N 0.000 description 1
• XDPCNPCKDGQBAN-UHFFFAOYSA-N 3-hydroxytetrahydrofuran Chemical compound OC1CCOC1 XDPCNPCKDGQBAN-UHFFFAOYSA-N 0.000 description 1
• 125000004919 3-methyl-2-pentyl group Chemical group CC(C(C)*)CC 0.000 description 1
• UDXCZASRILSJQX-UHFFFAOYSA-N 4-(5-chloro-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)benzonitrile Chemical compound ClC1=NC2=NC=NN2C(=C1)C1=CC=C(C=C1)C#N UDXCZASRILSJQX-UHFFFAOYSA-N 0.000 description 1
• JFPRQLNDBOCDKC-UHFFFAOYSA-N 4-(6-fluoro-[1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound FC1=C(N2N=CN=C2C=C1)C1=CC=C(C=C1)C#N JFPRQLNDBOCDKC-UHFFFAOYSA-N 0.000 description 1
• OAEPDIOJHOTRRM-UHFFFAOYSA-N 4-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound CC1=CC=2N(C(=C1)C1=CC=C(C#N)C=C1)N=CN=2 OAEPDIOJHOTRRM-UHFFFAOYSA-N 0.000 description 1
• DEYMFBHALUHGST-UHFFFAOYSA-N 4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound N#CC1=CC=C(C=C1)C1=CC=CC2=NC=NN12 DEYMFBHALUHGST-UHFFFAOYSA-N 0.000 description 1
• FWLJWTXHHOSGNP-UHFFFAOYSA-N 4-([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)benzonitrile Chemical compound N1=CN=C2N1C(=CC=N2)C1=CC=C(C#N)C=C1 FWLJWTXHHOSGNP-UHFFFAOYSA-N 0.000 description 1
• VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
• RTKLFQXFDKPHSN-BQYQJAHWSA-N 4-[(e)-3-(dimethylamino)prop-2-enoyl]benzonitrile Chemical compound CN(C)\C=C\C(=O)C1=CC=C(C#N)C=C1 RTKLFQXFDKPHSN-BQYQJAHWSA-N 0.000 description 1
• HROMSNWTIDLGSP-UHFFFAOYSA-N 4-[5-(cyclopropylamino)-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]benzonitrile Chemical compound N#CC1=CC=C(C=C1)C1=CC(NC2CC2)=NC2=NC=NN12 HROMSNWTIDLGSP-UHFFFAOYSA-N 0.000 description 1
• PDUUXICHUULHEW-UHFFFAOYSA-N 4-[7-(oxan-4-ylmethylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound N#CC1=CC=C(C=C1)C1=CC(NCC2CCOCC2)=CC2=NC=NN12 PDUUXICHUULHEW-UHFFFAOYSA-N 0.000 description 1
• LXMQJJCMQAWJPY-UHFFFAOYSA-N 4-[7-[(2,2-difluoroethylamino)methyl]-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound FC(F)CNCC1=CC2=NC=NN2C(=C1)C1=CC=C(C=C1)C#N LXMQJJCMQAWJPY-UHFFFAOYSA-N 0.000 description 1
• OESRLBUJEOVQFO-UHFFFAOYSA-N 4-[7-[(2-fluorophenyl)methylamino]-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound FC1=C(CNC2=CC3=NC=NN3C(=C2)C2=CC=C(C=C2)C#N)C=CC=C1 OESRLBUJEOVQFO-UHFFFAOYSA-N 0.000 description 1
• DUKBFVQAMAGALG-UHFFFAOYSA-N 4-[7-[(3-fluorophenyl)methylamino]-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound FC=1C=C(C=CC=1)CNC1=CC=2N(C(=C1)C1=CC=C(C#N)C=C1)N=CN=2 DUKBFVQAMAGALG-UHFFFAOYSA-N 0.000 description 1
• DDBNRFRBPGDKLB-UHFFFAOYSA-N 4-[7-[(4-fluorophenyl)methylamino]-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound FC1=CC=C(C=C1)CNC1=CC=2N(C(=C1)C1=CC=C(C#N)C=C1)N=CN=2 DDBNRFRBPGDKLB-UHFFFAOYSA-N 0.000 description 1
• MRVPHJBVQHRMMO-UHFFFAOYSA-N 4-[7-[(oxetan-3-ylmethylamino)methyl]-[1,2,4]triazolo[1,5-a]pyridin-5-yl]benzonitrile Chemical compound O1CC(C1)CNCC1=CC=2N(C(=C1)C1=CC=C(C#N)C=C1)N=CN=2 MRVPHJBVQHRMMO-UHFFFAOYSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• ITPYJIMXMPQSBK-UHFFFAOYSA-N 4-bromo-2,3-difluorobenzonitrile Chemical compound FC1=C(F)C(C#N)=CC=C1Br ITPYJIMXMPQSBK-UHFFFAOYSA-N 0.000 description 1
• QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
• 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 description 1
• IQRKYLDFWJMPQL-UHFFFAOYSA-N 4-methyl-5-([1,2,4]triazolo[1,5-a]pyridin-5-yl)pyridine-2-carbonitrile Chemical compound CC1=CC(=NC=C1C1=CC=CC=2N1N=CN=2)C#N IQRKYLDFWJMPQL-UHFFFAOYSA-N 0.000 description 1
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
• YUYPQDVCXUWEDQ-UHFFFAOYSA-N 5-([1,2,4]triazolo[1,5-a]pyridin-5-yl)pyridine-2-carbonitrile Chemical compound N#CC1=NC=C(C=C1)C1=CC=CC2=NC=NN12 YUYPQDVCXUWEDQ-UHFFFAOYSA-N 0.000 description 1
• HMURQOFNWZWERT-UHFFFAOYSA-N 5-bromo-3-fluoropyridine-2-carbonitrile Chemical compound FC1=CC(Br)=CN=C1C#N HMURQOFNWZWERT-UHFFFAOYSA-N 0.000 description 1
• JAQLBGDFALXUMV-UHFFFAOYSA-N 5-bromo-4-methylpyridine-2-carbonitrile Chemical compound CC1=CC(C#N)=NC=C1Br JAQLBGDFALXUMV-UHFFFAOYSA-N 0.000 description 1
• NYNMRMWOXDTPKF-UHFFFAOYSA-N 5-bromo-[1,2,4]triazolo[1,5-a]pyridin-6-amine Chemical compound NC1=C(Br)N2N=CN=C2C=C1 NYNMRMWOXDTPKF-UHFFFAOYSA-N 0.000 description 1
• UYJKKDQSZIAPOI-UHFFFAOYSA-N 5-chloro-6-methyl-[1,2,4]triazolo[1,5-a]pyridine Chemical compound CC1=C(Cl)N2N=CN=C2C=C1 UYJKKDQSZIAPOI-UHFFFAOYSA-N 0.000 description 1
• BGEBZHIAGXMEMV-UHFFFAOYSA-N 5-methoxypsoralen Chemical compound O1C(=O)C=CC2=C1C=C1OC=CC1=C2OC BGEBZHIAGXMEMV-UHFFFAOYSA-N 0.000 description 1
• BIAJHALBGBFEPB-UHFFFAOYSA-N 5-piperazin-1-yl-[1,2,4]triazolo[1,5-a]pyridine Chemical compound C1CN(CCN1)C1=CC=CC2=NC=NN12 BIAJHALBGBFEPB-UHFFFAOYSA-N 0.000 description 1
• HENICZDKXPFILD-UHFFFAOYSA-N 6-([1,2,4]triazolo[1,5-a]pyridin-5-yl)pyridazine-3-carbonitrile Chemical compound N=1C=NN2C=1C=CC=C2C1=CC=C(N=N1)C#N HENICZDKXPFILD-UHFFFAOYSA-N 0.000 description 1
• KFOGCVZDTSAKDZ-UHFFFAOYSA-N 6-([1,2,4]triazolo[1,5-a]pyridin-5-yl)pyridine-3-carbonitrile Chemical compound N=1C=NN2C=1C=CC=C2C1=CC=C(C=N1)C#N KFOGCVZDTSAKDZ-UHFFFAOYSA-N 0.000 description 1
• VTCJIPLHTZNBOP-UHFFFAOYSA-N 6-methyl-5-([1,2,4]triazolo[1,5-a]pyridin-5-yl)pyridine-2-carbonitrile Chemical compound CC1=C(C=CC(=N1)C#N)C1=CC=CC2=NC=NN12 VTCJIPLHTZNBOP-UHFFFAOYSA-N 0.000 description 1
• LLQWUYRNYQZFHK-UHFFFAOYSA-N 7-chloro-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound ClC1=CC=NC2=NC=NN12 LLQWUYRNYQZFHK-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 239000005541 ACE inhibitor Substances 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 1
• 208000004611 Abdominal Obesity Diseases 0.000 description 1
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 208000026872 Addison Disease Diseases 0.000 description 1
• 208000003200 Adenoma Diseases 0.000 description 1
• 206010001233 Adenoma benign Diseases 0.000 description 1
• 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 208000031091 Amnestic disease Diseases 0.000 description 1
• 206010002198 Anaphylactic reaction Diseases 0.000 description 1
• 206010002329 Aneurysm Diseases 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 102000008873 Angiotensin II receptor Human genes 0.000 description 1
• 108050000824 Angiotensin II receptor Proteins 0.000 description 1
• 206010002869 Anxiety symptoms Diseases 0.000 description 1
• 200000000007 Arterial disease Diseases 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 239000005485 Azilsartan Substances 0.000 description 1
• 206010004053 Bacterial toxaemia Diseases 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 208000010392 Bone Fractures Diseases 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• 206010006448 Bronchiolitis Diseases 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• 239000002083 C09CA01 - Losartan Substances 0.000 description 1
• 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
• 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
• 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
• 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
• COTNUBDHGSIOTA-LHHVLQQYSA-N CO.[2H]OC([2H])([2H])[2H] Chemical compound CO.[2H]OC([2H])([2H])[2H] COTNUBDHGSIOTA-LHHVLQQYSA-N 0.000 description 1
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
• 206010006895 Cachexia Diseases 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 206010054936 Cardiac cirrhosis Diseases 0.000 description 1
• 206010007558 Cardiac failure chronic Diseases 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 208000031229 Cardiomyopathies Diseases 0.000 description 1
• 101000613598 Carica papaya Caricain Proteins 0.000 description 1
• 241000206601 Carnobacterium mobile Species 0.000 description 1
• 208000002177 Cataract Diseases 0.000 description 1
• 206010065941 Central obesity Diseases 0.000 description 1
• 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
• 206010008263 Cervical dysplasia Diseases 0.000 description 1
• 208000013725 Chronic Kidney Disease-Mineral and Bone disease Diseases 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• NIYCABGPIXWHNG-OZLKFZLXSA-M Cl(=O)(=O)(=O)[O-].Cl\C(=C/C=[N+](C)C)\C1=CC=C(C=C1)C#N Chemical compound Cl(=O)(=O)(=O)[O-].Cl\C(=C/C=[N+](C)C)\C1=CC=C(C=C1)C#N NIYCABGPIXWHNG-OZLKFZLXSA-M 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 206010010582 Congenital osteodystrophy Diseases 0.000 description 1
• 206010010741 Conjunctivitis Diseases 0.000 description 1
• 208000016998 Conn syndrome Diseases 0.000 description 1
• 201000006306 Cor pulmonale Diseases 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 208000014311 Cushing syndrome Diseases 0.000 description 1
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
• 241000701022 Cytomegalovirus Species 0.000 description 1
• 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 1
• 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 1
• 206010051055 Deep vein thrombosis Diseases 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 208000002249 Diabetes Complications Diseases 0.000 description 1
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
• 208000002230 Diabetic coma Diseases 0.000 description 1
• 206010012655 Diabetic complications Diseases 0.000 description 1
• 206010012665 Diabetic gangrene Diseases 0.000 description 1
• 208000007652 Dysostoses Diseases 0.000 description 1
• 201000001324 Dysostosis Diseases 0.000 description 1
• 239000004150 EU approved colour Substances 0.000 description 1
• 208000032274 Encephalopathy Diseases 0.000 description 1
• 208000017701 Endocrine disease Diseases 0.000 description 1
• 201000009273 Endometriosis Diseases 0.000 description 1
• 206010048554 Endothelial dysfunction Diseases 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• 206010057671 Female sexual dysfunction Diseases 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 208000007882 Gastritis Diseases 0.000 description 1
• 208000010412 Glaucoma Diseases 0.000 description 1
• 208000032612 Glial tumor Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• 208000023661 Haematological disease Diseases 0.000 description 1
• 208000031071 Hamman-Rich Syndrome Diseases 0.000 description 1
• 206010019196 Head injury Diseases 0.000 description 1
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
• 206010056328 Hepatic ischaemia Diseases 0.000 description 1
• 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 208000037147 Hypercalcaemia Diseases 0.000 description 1
• 208000035150 Hypercholesterolemia Diseases 0.000 description 1
• 208000031226 Hyperlipidaemia Diseases 0.000 description 1
• 206010020710 Hyperphagia Diseases 0.000 description 1
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
• 206010052341 Impaired insulin secretion Diseases 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 102000004877 Insulin Human genes 0.000 description 1
• 108090001061 Insulin Proteins 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 208000002260 Keloid Diseases 0.000 description 1
• 206010023330 Keloid scar Diseases 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 229910013470 LiC1 Inorganic materials 0.000 description 1
• 206010054805 Macroangiopathy Diseases 0.000 description 1
• 208000016207 Male Genital disease Diseases 0.000 description 1
• 206010057672 Male sexual dysfunction Diseases 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000007054 Medullary Carcinoma Diseases 0.000 description 1
• 201000009906 Meningitis Diseases 0.000 description 1
• 208000017657 Menopausal disease Diseases 0.000 description 1
• 208000029725 Metabolic bone disease Diseases 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• 208000034486 Multi-organ failure Diseases 0.000 description 1
• 208000010718 Multiple Organ Failure Diseases 0.000 description 1
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
• 208000009525 Myocarditis Diseases 0.000 description 1
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
• ZKGNPQKYVKXMGJ-UHFFFAOYSA-N N,N-dimethylacetamide Chemical compound CN(C)C(C)=O.CN(C)C(C)=O ZKGNPQKYVKXMGJ-UHFFFAOYSA-N 0.000 description 1
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 206010029164 Nephrotic syndrome Diseases 0.000 description 1
• 206010029216 Nervousness Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 206010060860 Neurological symptom Diseases 0.000 description 1
• 208000005890 Neuroma Diseases 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• 208000022873 Ocular disease Diseases 0.000 description 1
• 206010030043 Ocular hypertension Diseases 0.000 description 1
• 206010030201 Oesophageal ulcer Diseases 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 206010067472 Organising pneumonia Diseases 0.000 description 1
• 206010031149 Osteitis Diseases 0.000 description 1
• 208000010191 Osteitis Deformans Diseases 0.000 description 1
• 206010049088 Osteopenia Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 description 1
• 208000027067 Paget disease of bone Diseases 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 208000007683 Pediatric Obesity Diseases 0.000 description 1
• 208000006735 Periostitis Diseases 0.000 description 1
• 201000007100 Pharyngitis Diseases 0.000 description 1
• 208000008601 Polycythemia Diseases 0.000 description 1
• 229910052777 Praseodymium Inorganic materials 0.000 description 1
• 102100037247 Prolyl hydroxylase EGLN3 Human genes 0.000 description 1
• 101710170720 Prolyl hydroxylase EGLN3 Proteins 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 208000004186 Pulmonary Heart Disease Diseases 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• 208000003782 Raynaud disease Diseases 0.000 description 1
• 208000012322 Raynaud phenomenon Diseases 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 206010063897 Renal ischaemia Diseases 0.000 description 1
• 206010057190 Respiratory tract infections Diseases 0.000 description 1
• 206010039085 Rhinitis allergic Diseases 0.000 description 1
• 208000027786 Rickettsial infectious disease Diseases 0.000 description 1
• 206010061495 Rickettsiosis Diseases 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 206010048908 Seasonal allergy Diseases 0.000 description 1
• 201000010208 Seminoma Diseases 0.000 description 1
• 201000010001 Silicosis Diseases 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 108020004459 Small interfering RNA Proteins 0.000 description 1
• 206010062255 Soft tissue infection Diseases 0.000 description 1
• 206010041591 Spinal osteoarthritis Diseases 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• 208000007107 Stomach Ulcer Diseases 0.000 description 1
• 206010042674 Swelling Diseases 0.000 description 1
• 201000008736 Systemic mastocytosis Diseases 0.000 description 1
• 208000001871 Tachycardia Diseases 0.000 description 1
• 206010043540 Thromboangiitis obliterans Diseases 0.000 description 1
• 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 1
• 208000013222 Toxemia Diseases 0.000 description 1
• GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 206010046543 Urinary incontinence Diseases 0.000 description 1
• 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
• 208000012931 Urologic disease Diseases 0.000 description 1
• 206010046798 Uterine leiomyoma Diseases 0.000 description 1
• 206010047097 Vascular purpura Diseases 0.000 description 1
• 206010047249 Venous thrombosis Diseases 0.000 description 1
• 208000005946 Xerostomia Diseases 0.000 description 1
• 241000607479 Yersinia pestis Species 0.000 description 1
• AWGQBBWIROVBOB-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyridine-7-carboxamide Chemical compound N=1C=NN2C=1C=C(C=C2)C(=O)N AWGQBBWIROVBOB-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 229940124532 absorption promoter Drugs 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 201000004073 acute interstitial pneumonia Diseases 0.000 description 1
• 206010000891 acute myocardial infarction Diseases 0.000 description 1
• 208000009956 adenocarcinoma Diseases 0.000 description 1
• 230000001919 adrenal effect Effects 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 201000010105 allergic rhinitis Diseases 0.000 description 1
• 102000004305 alpha Adrenergic Receptors Human genes 0.000 description 1
• 108090000861 alpha Adrenergic Receptors Proteins 0.000 description 1
• 208000008445 altitude sickness Diseases 0.000 description 1
• SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 230000006986 amnesia Effects 0.000 description 1
• 230000036783 anaphylactic response Effects 0.000 description 1
• 208000003455 anaphylaxis Diseases 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 208000028922 artery disease Diseases 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 150000001499 aryl bromides Chemical class 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 239000005441 aurora Substances 0.000 description 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
• XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 1
• 238000010533 azeotropic distillation Methods 0.000 description 1
• KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 description 1
• 229960002731 azilsartan Drugs 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 210000000270 basal cell Anatomy 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 239000012455 biphasic mixture Substances 0.000 description 1
• 208000016738 bone Paget disease Diseases 0.000 description 1
• 208000018339 bone inflammation disease Diseases 0.000 description 1
• 125000005620 boronic acid group Chemical class 0.000 description 1
• 210000000621 bronchi Anatomy 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229960000932 candesartan Drugs 0.000 description 1
• SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 235000011089 carbon dioxide Nutrition 0.000 description 1
• 229960004424 carbon dioxide Drugs 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000009134 cell regulation Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 208000013677 cerebrovascular dementia Diseases 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• KWTSZCJMWHGPOS-UHFFFAOYSA-M chloro(trimethyl)stannane Chemical compound C[Sn](C)(C)Cl KWTSZCJMWHGPOS-UHFFFAOYSA-M 0.000 description 1
• 201000001883 cholelithiasis Diseases 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
• 201000002816 chronic venous insufficiency Diseases 0.000 description 1
• 230000007882 cirrhosis Effects 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 208000018631 connective tissue disease Diseases 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 238000007887 coronary angioplasty Methods 0.000 description 1
• 201000009805 cryptogenic organizing pneumonia Diseases 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
• 108010011222 cyclo(Arg-Pro) Proteins 0.000 description 1
• MFNYBOWJWGPXFM-UHFFFAOYSA-N cyclobutanecarboxamide Chemical compound NC(=O)C1CCC1 MFNYBOWJWGPXFM-UHFFFAOYSA-N 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 201000009803 desquamative interstitial pneumonia Diseases 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 208000033679 diabetic kidney disease Diseases 0.000 description 1
• 238000002059 diagnostic imaging Methods 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 150000004985 diamines Chemical class 0.000 description 1
• ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
• 125000004188 dichlorophenyl group Chemical group 0.000 description 1
• 125000006001 difluoroethyl group Chemical group 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 230000001079 digestive effect Effects 0.000 description 1
• JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
• 229960001760 dimethyl sulfoxide Drugs 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
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
• 239000002934 diuretic Substances 0.000 description 1
• 229940030606 diuretics Drugs 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 206010013663 drug dependence Diseases 0.000 description 1
• 206010013781 dry mouth Diseases 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000008694 endothelial dysfunction Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• 230000010437 erythropoiesis Effects 0.000 description 1
• 208000028299 esophageal disease Diseases 0.000 description 1
• 208000019064 esophageal ulcer Diseases 0.000 description 1
• 101150014588 ethA gene Proteins 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 210000000232 gallbladder Anatomy 0.000 description 1
• 201000008361 ganglioneuroma Diseases 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 201000005917 gastric ulcer Diseases 0.000 description 1
• 201000005298 gastrointestinal allergy Diseases 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 206010061989 glomerulosclerosis Diseases 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 229960005150 glycerol Drugs 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 230000034659 glycolysis Effects 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 201000011066 hemangioma Diseases 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 208000018706 hematopoietic system disease Diseases 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 239000000833 heterodimer Substances 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
• 150000004677 hydrates Chemical class 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 125000001183 hydrocarbyl group Chemical group 0.000 description 1
• 230000000148 hypercalcaemia Effects 0.000 description 1
• 208000030915 hypercalcemia disease Diseases 0.000 description 1
• 230000002727 hyperosmolar Effects 0.000 description 1
• 206010020718 hyperplasia Diseases 0.000 description 1
• 230000002390 hyperplastic effect Effects 0.000 description 1
• 230000001631 hypertensive effect Effects 0.000 description 1
• 201000009939 hypertensive encephalopathy Diseases 0.000 description 1
• 230000002267 hypothalamic effect Effects 0.000 description 1
• 230000001146 hypoxic effect Effects 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 229940125396 insulin Drugs 0.000 description 1
• 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
• 208000028774 intestinal disease Diseases 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000002608 intravascular ultrasound Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229960002198 irbesartan Drugs 0.000 description 1
• YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
• 201000002529 islet cell tumor Diseases 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 210000001117 keloid Anatomy 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 230000032297 kinesis Effects 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 206010023841 laryngeal neoplasm Diseases 0.000 description 1
• 208000001921 latent autoimmune diabetes in adults Diseases 0.000 description 1
• 201000010901 lateral sclerosis Diseases 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 201000010260 leiomyoma Diseases 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 1
• 229910001486 lithium perchlorate Inorganic materials 0.000 description 1
• DBTNVRCCIDISMV-UHFFFAOYSA-L lithium;magnesium;propane;dichloride Chemical compound [Li+].[Mg+2].[Cl-].[Cl-].C[CH-]C DBTNVRCCIDISMV-UHFFFAOYSA-L 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• WLHQHAUOOXYABV-UHFFFAOYSA-N lornoxicam Chemical compound OC=1C=2SC(Cl)=CC=2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 WLHQHAUOOXYABV-UHFFFAOYSA-N 0.000 description 1
• 229960004773 losartan Drugs 0.000 description 1
• KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
• 210000003141 lower extremity Anatomy 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 230000000527 lymphocytic effect Effects 0.000 description 1
• 208000005158 lymphoid interstitial pneumonia Diseases 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 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
• 230000036244 malformation Effects 0.000 description 1
• 210000005075 mammary gland Anatomy 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 208000008585 mastocytosis Diseases 0.000 description 1
• 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 230000003340 mental effect Effects 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• FBBDOOHMGLLEGJ-UHFFFAOYSA-N methane;hydrochloride Chemical compound C.Cl FBBDOOHMGLLEGJ-UHFFFAOYSA-N 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• VNKYTQGIUYNRMY-UHFFFAOYSA-N methoxypropane Chemical compound CCCOC VNKYTQGIUYNRMY-UHFFFAOYSA-N 0.000 description 1
• 208000005264 motor neuron disease Diseases 0.000 description 1
• 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• URHXQSTYLJNJMT-UHFFFAOYSA-N n-methylpyrrolidine-2-carboxamide Chemical compound CNC(=O)C1CCCN1 URHXQSTYLJNJMT-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 210000003739 neck Anatomy 0.000 description 1
• 201000008383 nephritis Diseases 0.000 description 1
• 201000009925 nephrosclerosis Diseases 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 201000004071 non-specific interstitial pneumonia Diseases 0.000 description 1
• VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
• 208000030212 nutrition disease Diseases 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
• 208000005368 osteomalacia Diseases 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• 208000015124 ovarian disease Diseases 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• KHDGSULFSVLOPM-UHFFFAOYSA-N oxane-3-carboxamide Chemical compound NC(=O)C1CCCOC1 KHDGSULFSVLOPM-UHFFFAOYSA-N 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• UWOTZNQZPLAURK-UHFFFAOYSA-N oxetane-3-carboxylic acid Chemical compound OC(=O)C1COC1 UWOTZNQZPLAURK-UHFFFAOYSA-N 0.000 description 1
• 230000010627 oxidative phosphorylation Effects 0.000 description 1
• YNOGYQAEJGADFJ-UHFFFAOYSA-N oxolan-2-ylmethanamine Chemical compound NCC1CCCO1 YNOGYQAEJGADFJ-UHFFFAOYSA-N 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• PHDNDSSMEIRHSI-UHFFFAOYSA-L palladium(2+);prop-2-enylbenzene;dichloride Chemical compound [Pd+]Cl.[Pd+]Cl.C=C[CH-]C1=CC=CC=C1.C=C[CH-]C1=CC=CC=C1 PHDNDSSMEIRHSI-UHFFFAOYSA-L 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
• 208000022102 pancreatic neuroendocrine neoplasm Diseases 0.000 description 1
• 230000000849 parathyroid Effects 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 238000005191 phase separation Methods 0.000 description 1
• DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 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
• 239000010452 phosphate Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
• 201000004338 pollen allergy Diseases 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 208000014081 polyp of colon Diseases 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
• LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
• 229940074439 potassium sodium tartrate Drugs 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• 201000011461 pre-eclampsia Diseases 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 208000013846 primary aldosteronism Diseases 0.000 description 1
• 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
• 229940048914 protamine Drugs 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 208000020016 psychiatric disease Diseases 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 208000002815 pulmonary hypertension Diseases 0.000 description 1
• 201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
• 208000008128 pulmonary tuberculosis Diseases 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 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
• 230000002285 radioactive effect Effects 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 201000006409 renal osteodystrophy Diseases 0.000 description 1
• 239000002461 renin inhibitor Substances 0.000 description 1
• 229940086526 renin-inhibitors Drugs 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 208000023504 respiratory system disease Diseases 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• 208000007442 rickets 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
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 206010039722 scoliosis Diseases 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 201000008261 skin carcinoma Diseases 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 206010040872 skin infection Diseases 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
• QPILZZVXGUNELN-UHFFFAOYSA-M sodium;4-amino-5-hydroxynaphthalene-2,7-disulfonate;hydron Chemical compound [Na+].OS(=O)(=O)C1=CC(O)=C2C(N)=CC(S([O-])(=O)=O)=CC2=C1 QPILZZVXGUNELN-UHFFFAOYSA-M 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 208000005801 spondylosis Diseases 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 239000012607 strong cation exchange resin Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 208000011117 substance-related disease Diseases 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
• 150000005846 sugar alcohols Chemical class 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 230000006794 tachycardia Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 229960005187 telmisartan Drugs 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 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
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 230000008719 thickening Effects 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 230000002537 thrombolytic effect Effects 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 201000010875 transient cerebral ischemia Diseases 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
• 239000013638 trimer Substances 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 230000003827 upregulation Effects 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 208000014001 urinary system disease Diseases 0.000 description 1
• 208000019206 urinary tract infection Diseases 0.000 description 1
• 125000005500 uronium group Chemical group 0.000 description 1
• 208000010579 uterine corpus leiomyoma Diseases 0.000 description 1
• 201000007954 uterine fibroid Diseases 0.000 description 1
• 229940070710 valerate Drugs 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• 229960004699 valsartan Drugs 0.000 description 1
• SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
• 229940124549 vasodilator Drugs 0.000 description 1
• 239000003071 vasodilator agent Substances 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 229950000339 xinafoate Drugs 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1