AU2011376746B2 - Substituted 2-(chroman-6-yloxy)-thiazoles and their use as pharmaceuticals - Google Patents
Substituted 2-(chroman-6-yloxy)-thiazoles and their use as pharmaceuticals Download PDFInfo
- Publication number
- AU2011376746B2 AU2011376746B2 AU2011376746A AU2011376746A AU2011376746B2 AU 2011376746 B2 AU2011376746 B2 AU 2011376746B2 AU 2011376746 A AU2011376746 A AU 2011376746A AU 2011376746 A AU2011376746 A AU 2011376746A AU 2011376746 B2 AU2011376746 B2 AU 2011376746B2
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- series consisting
- phenyl
- cycloalkyl
- formula
- Prior art date
- 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.)
- Ceased
Links
- 239000003814 drug Substances 0.000 title claims abstract description 19
- XFZODDHRWKDGLV-UHFFFAOYSA-N 2-(3,4-dihydro-2h-chromen-6-yloxy)-1,3-thiazole Chemical class C1=C2CCCOC2=CC=C1OC1=NC=CS1 XFZODDHRWKDGLV-UHFFFAOYSA-N 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 444
- 238000000034 method Methods 0.000 claims abstract description 56
- 238000011282 treatment Methods 0.000 claims abstract description 41
- 206010019280 Heart failures Diseases 0.000 claims abstract description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
- 238000002360 preparation method Methods 0.000 claims abstract description 23
- 206010003119 arrhythmia Diseases 0.000 claims abstract description 17
- 230000008569 process Effects 0.000 claims abstract description 17
- 208000006011 Stroke Diseases 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 102000001794 Sodium-Calcium Exchanger Human genes 0.000 claims abstract description 11
- 108010040240 Sodium-Calcium Exchanger Proteins 0.000 claims abstract description 11
- -1 phenyl- Chemical group 0.000 claims description 335
- 125000001424 substituent group Chemical group 0.000 claims description 254
- 229910052757 nitrogen Inorganic materials 0.000 claims description 140
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 126
- 239000001257 hydrogen Substances 0.000 claims description 124
- 229910052739 hydrogen Inorganic materials 0.000 claims description 124
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 117
- 229910052736 halogen Inorganic materials 0.000 claims description 102
- 150000002367 halogens Chemical class 0.000 claims description 102
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 92
- 239000011737 fluorine Substances 0.000 claims description 88
- 229910052731 fluorine Inorganic materials 0.000 claims description 88
- 125000004432 carbon atom Chemical group C* 0.000 claims description 87
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 86
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 84
- 125000005842 heteroatom Chemical group 0.000 claims description 79
- 150000003839 salts Chemical class 0.000 claims description 76
- 239000000203 mixture Substances 0.000 claims description 75
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 73
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 72
- 125000000623 heterocyclic group Chemical group 0.000 claims description 65
- 229910052717 sulfur Inorganic materials 0.000 claims description 59
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 58
- 229910052760 oxygen Inorganic materials 0.000 claims description 58
- 239000001301 oxygen Substances 0.000 claims description 58
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 55
- 239000011593 sulfur Substances 0.000 claims description 55
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 43
- 229910052799 carbon Inorganic materials 0.000 claims description 38
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 claims description 37
- 125000002950 monocyclic group Chemical group 0.000 claims description 37
- 125000002619 bicyclic group Chemical group 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 125000001153 fluoro group Chemical group F* 0.000 claims description 33
- 229920006395 saturated elastomer Polymers 0.000 claims description 30
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 23
- GGNIKGLUPSHSBV-UHFFFAOYSA-N thiazole-5-carboxamide Chemical compound NC(=O)C1=CN=CS1 GGNIKGLUPSHSBV-UHFFFAOYSA-N 0.000 claims description 21
- XDNQVUAKCAPBIG-UHFFFAOYSA-N 1,3-thiazol-5-ylmethanamine Chemical compound NCC1=CN=CS1 XDNQVUAKCAPBIG-UHFFFAOYSA-N 0.000 claims description 19
- 230000005764 inhibitory process Effects 0.000 claims description 18
- 229910052740 iodine Inorganic materials 0.000 claims description 17
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- UOMASYSEPDZKSQ-UHFFFAOYSA-N 1h-pyrazole-4-sulfonamide Chemical compound NS(=O)(=O)C=1C=NNC=1 UOMASYSEPDZKSQ-UHFFFAOYSA-N 0.000 claims description 10
- JGRWVYLWEXXVPQ-UHFFFAOYSA-N [2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazol-5-yl]methanamine Chemical compound CC1=CC=CC=C1C1OC2=CC=C(OC=3SC(CN)=CN=3)C=C2CC1 JGRWVYLWEXXVPQ-UHFFFAOYSA-N 0.000 claims description 9
- 230000035939 shock Effects 0.000 claims description 9
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical compound NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 206010012289 Dementia Diseases 0.000 claims description 7
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 7
- 201000006370 kidney failure Diseases 0.000 claims description 7
- 208000031225 myocardial ischemia Diseases 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- ZVXKYWHJBYIYNI-UHFFFAOYSA-N 1h-pyrazole-4-carboxamide Chemical compound NC(=O)C=1C=NNC=1 ZVXKYWHJBYIYNI-UHFFFAOYSA-N 0.000 claims description 6
- HYQZOWKBOUKHIQ-UHFFFAOYSA-N n-[[2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazol-5-yl]methyl]-1-pyridin-4-ylmethanamine Chemical compound C=1N=C(OC=2C=C3CCC(OC3=CC=2)C=2C=CC=CC=2)SC=1CNCC1=CC=NC=C1 HYQZOWKBOUKHIQ-UHFFFAOYSA-N 0.000 claims description 6
- UZLPFCIFXVIRKX-IBGZPJMESA-N 2-[[2-[[(2s)-2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carbonyl]amino]ethyl dihydrogen phosphate Chemical compound CC1=CC=CC=C1[C@H]1OC2=CC=C(OC=3SC(=CN=3)C(=O)NCCOP(O)(O)=O)C=C2CC1 UZLPFCIFXVIRKX-IBGZPJMESA-N 0.000 claims description 5
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
- PRYCQPHZDXHIJX-IBGZPJMESA-N n-(2-hydroxyethyl)-2-[[(2s)-2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=CC=C1[C@H]1OC2=CC=C(OC=3SC(=CN=3)C(=O)NCCO)C=C2CC1 PRYCQPHZDXHIJX-IBGZPJMESA-N 0.000 claims description 5
- PRYCQPHZDXHIJX-UHFFFAOYSA-N n-(2-hydroxyethyl)-2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=CC=C1C1OC2=CC=C(OC=3SC(=CN=3)C(=O)NCCO)C=C2CC1 PRYCQPHZDXHIJX-UHFFFAOYSA-N 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- MZLAALXYKJSUIA-UHFFFAOYSA-N 2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-n-propyl-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)NCCC)=CN=C1OC1=CC=C(OC(CC2)C=3C=CC=CC=3)C2=C1 MZLAALXYKJSUIA-UHFFFAOYSA-N 0.000 claims description 4
- SOGGDGZGNUBLCC-UHFFFAOYSA-N 2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-n-propyl-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)NCCC)=CN=C1OC1=CC=C(OC(CC2)C=3C(=CC=CC=3)C)C2=C1 SOGGDGZGNUBLCC-UHFFFAOYSA-N 0.000 claims description 4
- ASOCGOYSMCISKT-UHFFFAOYSA-N 2-[[2-(5-fluoro-2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-n-(2-hydroxyethyl)-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(F)C=C1C1OC2=CC=C(OC=3SC(=CN=3)C(=O)NCCO)C=C2CC1 ASOCGOYSMCISKT-UHFFFAOYSA-N 0.000 claims description 4
- MMPUZLZVNDIMDW-UHFFFAOYSA-N 2-[[2-(5-fluoro-2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-n-propyl-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)NCCC)=CN=C1OC1=CC=C(OC(CC2)C=3C(=CC=C(F)C=3)C)C2=C1 MMPUZLZVNDIMDW-UHFFFAOYSA-N 0.000 claims description 4
- PTGHHGHHFPDNBR-UHFFFAOYSA-N 2-pyrazol-1-ylacetamide Chemical compound NC(=O)CN1C=CC=N1 PTGHHGHHFPDNBR-UHFFFAOYSA-N 0.000 claims description 4
- BZBQWHWPXBPLKE-UHFFFAOYSA-N 4-methyl-2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-n-(1,2-oxazol-5-ylmethyl)-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)NCC=2ON=CC=2)=C(C)N=C1OC(C=C1CC2)=CC=C1OC2C1=CC=CC=C1C BZBQWHWPXBPLKE-UHFFFAOYSA-N 0.000 claims description 4
- PRYCQPHZDXHIJX-LJQANCHMSA-N n-(2-hydroxyethyl)-2-[[(2r)-2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=CC=C1[C@@H]1OC2=CC=C(OC=3SC(=CN=3)C(=O)NCCO)C=C2CC1 PRYCQPHZDXHIJX-LJQANCHMSA-N 0.000 claims description 4
- FMETUUJKGDCDMN-UHFFFAOYSA-N n-(6,7-dihydro-5h-pyrrolo[2,1-c][1,2,4]triazol-3-ylmethyl)-2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazole-5-carboxamide Chemical compound N=1N=C2CCCN2C=1CNC(=O)C(S1)=CN=C1OC(C=C1CC2)=CC=C1OC2C1=CC=CC=C1 FMETUUJKGDCDMN-UHFFFAOYSA-N 0.000 claims description 4
- UZUNANKEQRRTHJ-UHFFFAOYSA-N n-[(2-chloropyridin-4-yl)methyl]-2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazole-5-carboxamide Chemical compound C1=NC(Cl)=CC(CNC(=O)C=2SC(OC=3C=C4CCC(OC4=CC=3)C=3C=CC=CC=3)=NC=2)=C1 UZUNANKEQRRTHJ-UHFFFAOYSA-N 0.000 claims description 4
- CAFJWFVUPVMRNG-UHFFFAOYSA-N n-[[2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazol-5-yl]methyl]-2-(2-oxopyrrolidin-1-yl)acetamide Chemical compound CC1=CC=CC=C1C1OC2=CC=C(OC=3SC(CNC(=O)CN4C(CCC4)=O)=CN=3)C=C2CC1 CAFJWFVUPVMRNG-UHFFFAOYSA-N 0.000 claims description 4
- AWQKGRZAIHILJV-UHFFFAOYSA-N n-cyclopropyl-2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazole-5-carboxamide Chemical compound C=1N=C(OC=2C=C3CCC(OC3=CC=2)C=2C=CC=CC=2)SC=1C(=O)NC1CC1 AWQKGRZAIHILJV-UHFFFAOYSA-N 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- LSJVQKDTVCDSPE-UHFFFAOYSA-N 1h-pyrazole-5-sulfonamide Chemical compound NS(=O)(=O)C=1C=CNN=1 LSJVQKDTVCDSPE-UHFFFAOYSA-N 0.000 claims description 2
- IOZBFTFIPBDPRX-UHFFFAOYSA-N [2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazol-5-yl]methanamine Chemical compound S1C(CN)=CN=C1OC1=CC=C(OC(CC2)C=3C=CC=CC=3)C2=C1 IOZBFTFIPBDPRX-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- SZXRJWBLACXTIR-UHFFFAOYSA-N n-[(1,5-dimethylpyrazol-4-yl)methyl]-2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazole-5-carboxamide Chemical compound C1=NN(C)C(C)=C1CNC(=O)C(S1)=CN=C1OC1=CC=C(OC(CC2)C=3C=CC=CC=3)C2=C1 SZXRJWBLACXTIR-UHFFFAOYSA-N 0.000 claims description 2
- KFMCNOLLOWMPHN-UHFFFAOYSA-N 2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-n-[2-(2-oxoimidazolidin-1-yl)ethyl]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=CC=C1C1OC2=CC=C(OC=3SC(=CN=3)C(=O)NCCN3C(NCC3)=O)C=C2CC1 KFMCNOLLOWMPHN-UHFFFAOYSA-N 0.000 claims 2
- JAMWWGXYGGGMGS-UHFFFAOYSA-N 3-pyrazol-1-ylpropanamide Chemical compound NC(=O)CCN1C=CC=N1 JAMWWGXYGGGMGS-UHFFFAOYSA-N 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 abstract description 14
- 102100035088 Sodium/calcium exchanger 1 Human genes 0.000 abstract description 13
- 108010067207 sodium-calcium exchanger 1 Proteins 0.000 abstract description 12
- 230000006793 arrhythmia Effects 0.000 abstract description 9
- 239000003112 inhibitor Substances 0.000 abstract description 8
- 230000004094 calcium homeostasis Effects 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 72
- 235000002639 sodium chloride Nutrition 0.000 description 64
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000002904 solvent Substances 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 41
- 125000004043 oxo group Chemical group O=* 0.000 description 39
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 35
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
- 239000003480 eluent Substances 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 31
- 239000002253 acid Substances 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 230000002829 reductive effect Effects 0.000 description 27
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 206010007559 Cardiac failure congestive Diseases 0.000 description 18
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 18
- 201000010099 disease Diseases 0.000 description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
- 239000002243 precursor Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 15
- 229910001424 calcium ion Inorganic materials 0.000 description 15
- 125000000524 functional group Chemical group 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 238000003556 assay Methods 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000011575 calcium Substances 0.000 description 12
- 229910052791 calcium Inorganic materials 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 125000004429 atom Chemical group 0.000 description 11
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 11
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 10
- 206010003658 Atrial Fibrillation Diseases 0.000 description 10
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 150000001408 amides Chemical class 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 125000004430 oxygen atom Chemical group O* 0.000 description 10
- 238000007363 ring formation reaction Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 9
- 239000012131 assay buffer Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 239000000975 dye Substances 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 210000002216 heart Anatomy 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 230000002441 reversible effect Effects 0.000 description 9
- 125000004434 sulfur atom Chemical group 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 125000004122 cyclic group Chemical group 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 8
- 239000012047 saturated solution Substances 0.000 description 8
- 229910001415 sodium ion Inorganic materials 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 7
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 239000003638 chemical reducing agent Substances 0.000 description 7
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 7
- 238000001819 mass spectrum Methods 0.000 description 7
- 230000002265 prevention Effects 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229930192474 thiophene Natural products 0.000 description 7
- 230000002861 ventricular Effects 0.000 description 7
- 239000003643 water by type Substances 0.000 description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 125000006413 ring segment Chemical group 0.000 description 6
- 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 6
- BKZOUCVNTCLNFF-IGXZVFLKSA-N (2s)-2-[(2r,3r,4s,5r,6s)-2-hydroxy-6-[(1s)-1-[(2s,5r,7s,8r,9s)-2-[(2r,5s)-5-[(2r,3s,4r,5r)-5-[(2s,3s,4s,5r,6s)-6-hydroxy-4-methoxy-3,5,6-trimethyloxan-2-yl]-4-methoxy-3-methyloxolan-2-yl]-5-methyloxolan-2-yl]-7-methoxy-2,8-dimethyl-1,10-dioxaspiro[4.5]dec Chemical compound O([C@@H]1[C@@H]2O[C@H]([C@@H](C)[C@H]2OC)[C@@]2(C)O[C@H](CC2)[C@@]2(C)O[C@]3(O[C@@H]([C@H](C)[C@@H](OC)C3)[C@@H](C)[C@@H]3[C@@H]([C@H](OC)[C@@H](C)[C@](O)([C@H](C)C(O)=O)O3)C)CC2)[C@](C)(O)[C@H](C)[C@@H](OC)[C@@H]1C BKZOUCVNTCLNFF-IGXZVFLKSA-N 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- BKZOUCVNTCLNFF-UHFFFAOYSA-N Lonomycin Natural products COC1C(C)C(C2(C)OC(CC2)C2(C)OC3(OC(C(C)C(OC)C3)C(C)C3C(C(OC)C(C)C(O)(C(C)C(O)=O)O3)C)CC2)OC1C1OC(C)(O)C(C)C(OC)C1C BKZOUCVNTCLNFF-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 230000002349 favourable effect Effects 0.000 description 5
- ZWCXYZRRTRDGQE-SORVKSEFSA-N gramicidina Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 ZWCXYZRRTRDGQE-SORVKSEFSA-N 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 238000011321 prophylaxis Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 4
- KNIKACRZOFTUTI-UHFFFAOYSA-N 2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxylic acid Chemical compound CC1=CC=CC=C1C1OC2=CC=C(OC=3SC(=CN=3)C(O)=O)C=C2CC1 KNIKACRZOFTUTI-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 235000005513 chalcones Nutrition 0.000 description 4
- 150000001793 charged compounds Chemical class 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 230000010412 perfusion Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000006268 reductive amination reaction Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 125000000547 substituted alkyl group Chemical group 0.000 description 4
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 4
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
- 229940124549 vasodilator Drugs 0.000 description 4
- 239000003071 vasodilator agent Substances 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 3
- KRQGXYTUMWTZNV-UHFFFAOYSA-N 1,3,5-trimethyl-n-[[2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazol-5-yl]methyl]pyrazole-4-sulfonamide Chemical compound CC1=NN(C)C(C)=C1S(=O)(=O)NCC(S1)=CN=C1OC1=CC=C(OC(CC2)C=3C=CC=CC=3)C2=C1 KRQGXYTUMWTZNV-UHFFFAOYSA-N 0.000 description 3
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- RKFMMWQRSFZZJS-UHFFFAOYSA-N 2-(5-fluoropyridin-3-yl)-6-hydroxy-2,3-dihydrochromen-4-one Chemical compound C1C(=O)C2=CC(O)=CC=C2OC1C1=CN=CC(F)=C1 RKFMMWQRSFZZJS-UHFFFAOYSA-N 0.000 description 3
- HXCOHOUHHMGGCC-UHFFFAOYSA-N 2-(6-methoxy-3,4-dihydro-2h-chromen-2-yl)pyrazine Chemical compound C1CC2=CC(OC)=CC=C2OC1C1=CN=CC=N1 HXCOHOUHHMGGCC-UHFFFAOYSA-N 0.000 description 3
- HDFCUPVSKRDDDT-UHFFFAOYSA-N 2-pyrazin-2-yl-3,4-dihydro-2h-chromen-6-ol Chemical compound C1CC2=CC(O)=CC=C2OC1C1=CN=CC=N1 HDFCUPVSKRDDDT-UHFFFAOYSA-N 0.000 description 3
- QQOXACXHTODPND-UHFFFAOYSA-N 3-(5-bromo-2-fluorophenyl)-1-(2-methylphenyl)propan-1-one Chemical compound CC1=CC=CC=C1C(=O)CCC1=CC(Br)=CC=C1F QQOXACXHTODPND-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- HGWUUOXXAIISDB-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane Chemical compound C1NCC2CC21 HGWUUOXXAIISDB-UHFFFAOYSA-N 0.000 description 3
- MSTDXOZUKAQDRL-UHFFFAOYSA-N 4-Chromanone Chemical compound C1=CC=C2C(=O)CCOC2=C1 MSTDXOZUKAQDRL-UHFFFAOYSA-N 0.000 description 3
- JEXXMOUFDWFSDW-UHFFFAOYSA-N 6-bromo-2-(2-methylphenyl)-2,3-dihydrochromen-4-one Chemical compound CC1=CC=CC=C1C1OC2=CC=C(Br)C=C2C(=O)C1 JEXXMOUFDWFSDW-UHFFFAOYSA-N 0.000 description 3
- OTAARGGKYFQSQB-UHFFFAOYSA-N 6-bromo-2-(2-methylphenyl)-3,4-dihydro-2h-chromen-4-ol Chemical compound CC1=CC=CC=C1C1OC2=CC=C(Br)C=C2C(O)C1 OTAARGGKYFQSQB-UHFFFAOYSA-N 0.000 description 3
- SVMCGQPLCJVTIJ-UHFFFAOYSA-N 6-bromo-2-(2-methylphenyl)-3,4-dihydro-2h-chromene Chemical compound CC1=CC=CC=C1C1OC2=CC=C(Br)C=C2CC1 SVMCGQPLCJVTIJ-UHFFFAOYSA-N 0.000 description 3
- BFRVCQPRUJFVFU-UHFFFAOYSA-N 6-methoxy-3,4-dihydrochromen-2-one Chemical compound O1C(=O)CCC2=CC(OC)=CC=C21 BFRVCQPRUJFVFU-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 208000003037 Diastolic Heart Failure Diseases 0.000 description 3
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- GWDWOYOLCITJIT-TXEPZDRESA-L [Na+].[Na+].Cc1ccccc1[C@@H]1CCc2cc(Oc3ncc(s3)C(=O)NCCOP([O-])([O-])=O)ccc2O1 Chemical compound [Na+].[Na+].Cc1ccccc1[C@@H]1CCc2cc(Oc3ncc(s3)C(=O)NCCOP([O-])([O-])=O)ccc2O1 GWDWOYOLCITJIT-TXEPZDRESA-L 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 230000002763 arrhythmic effect Effects 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical class B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 3
- 230000009460 calcium influx Effects 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 125000002843 carboxylic acid group Chemical group 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- GZCJJOLJSBCUNR-UHFFFAOYSA-N chroman-6-ol Chemical class O1CCCC2=CC(O)=CC=C21 GZCJJOLJSBCUNR-UHFFFAOYSA-N 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000002999 depolarising effect Effects 0.000 description 3
- SNUPKJMLBRTMTI-XIFFEERXSA-N dibenzyl 2-[[2-[[(2s)-2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carbonyl]amino]ethyl phosphate Chemical compound CC1=CC=CC=C1[C@H]1OC2=CC=C(OC=3SC(=CN=3)C(=O)NCCOP(=O)(OCC=3C=CC=CC=3)OCC=3C=CC=CC=3)C=C2CC1 SNUPKJMLBRTMTI-XIFFEERXSA-N 0.000 description 3
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000000004 hemodynamic effect Effects 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229940124975 inotropic drug Drugs 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 229910003002 lithium salt Inorganic materials 0.000 description 3
- 159000000002 lithium salts Chemical class 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229910052987 metal hydride Inorganic materials 0.000 description 3
- 150000004681 metal hydrides Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000004965 peroxy acids Chemical class 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000001536 pro-arrhythmogenic effect Effects 0.000 description 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- VZTBPOKOZKRZNU-INIZCTEOSA-N (1s)-3-(5-bromo-2-fluorophenyl)-1-(2-methylphenyl)propan-1-ol Chemical compound CC1=CC=CC=C1[C@@H](O)CCC1=CC(Br)=CC=C1F VZTBPOKOZKRZNU-INIZCTEOSA-N 0.000 description 2
- SVMCGQPLCJVTIJ-INIZCTEOSA-N (2s)-6-bromo-2-(2-methylphenyl)-3,4-dihydro-2h-chromene Chemical compound CC1=CC=CC=C1[C@H]1OC2=CC=C(Br)C=C2CC1 SVMCGQPLCJVTIJ-INIZCTEOSA-N 0.000 description 2
- USVVENVKYJZFMW-ONEGZZNKSA-N (e)-carboxyiminocarbamic acid Chemical class OC(=O)\N=N\C(O)=O USVVENVKYJZFMW-ONEGZZNKSA-N 0.000 description 2
- ADKDJHASTPQGEO-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[b]pyrrole Chemical compound C1CNC2CCCC21 ADKDJHASTPQGEO-UHFFFAOYSA-N 0.000 description 2
- UZHVXJZEHGSWQV-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrole Chemical compound C1NCC2CCCC21 UZHVXJZEHGSWQV-UHFFFAOYSA-N 0.000 description 2
- YETODIXQMRZKEG-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropyrrolo[2,3-c]pyrrole Chemical compound C1NCC2NCCC21 YETODIXQMRZKEG-UHFFFAOYSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 2
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 2
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 2
- PDELQDSYLBLPQO-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-indole Chemical compound C1CCCC2NCCC21 PDELQDSYLBLPQO-UHFFFAOYSA-N 0.000 description 2
- WYZZNMWIWHRXRM-UHFFFAOYSA-N 2,8-diazaspiro[4.5]decane Chemical compound C1NCCC21CCNCC2 WYZZNMWIWHRXRM-UHFFFAOYSA-N 0.000 description 2
- SGLTYXRTDQXURA-UHFFFAOYSA-N 2,9-diazaspiro[4.5]decane Chemical compound C1NCCC21CNCCC2 SGLTYXRTDQXURA-UHFFFAOYSA-N 0.000 description 2
- MBEKIFZARFVPRG-UHFFFAOYSA-N 2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-ol Chemical compound CC1=CC=CC=C1C1OC2=CC=C(O)C=C2CC1 MBEKIFZARFVPRG-UHFFFAOYSA-N 0.000 description 2
- RKVXQNWRROZHED-UHFFFAOYSA-N 2-(3-hydroxy-3-pyrazin-2-ylpropyl)-4-methoxyphenol Chemical compound COC1=CC=C(O)C(CCC(O)C=2N=CC=NC=2)=C1 RKVXQNWRROZHED-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- RIAMOHSKNNHLFU-UHFFFAOYSA-N 2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carbonitrile Chemical compound CC1=CC=CC=C1C1OC2=CC=C(OC=3SC(=CN=3)C#N)C=C2CC1 RIAMOHSKNNHLFU-UHFFFAOYSA-N 0.000 description 2
- NINJAJLCZUYDGV-UHFFFAOYSA-N 2-azaspiro[4.4]nonane Chemical compound C1CCCC21CNCC2 NINJAJLCZUYDGV-UHFFFAOYSA-N 0.000 description 2
- KLEYVGWAORGTIT-UHFFFAOYSA-N 2-chlorothiazole Chemical class ClC1=NC=CS1 KLEYVGWAORGTIT-UHFFFAOYSA-N 0.000 description 2
- LICHZOBEUWVYSY-UHFFFAOYSA-N 3-azabicyclo[3.2.2]nonane Chemical compound C1CC2CCC1CNC2 LICHZOBEUWVYSY-UHFFFAOYSA-N 0.000 description 2
- OAKURXIZZOAYBC-UHFFFAOYSA-N 3-oxopropanoic acid Chemical compound OC(=O)CC=O OAKURXIZZOAYBC-UHFFFAOYSA-N 0.000 description 2
- HTMGQIXFZMZZKD-UHFFFAOYSA-N 5,6,7,8-tetrahydroisoquinoline Chemical compound N1=CC=C2CCCCC2=C1 HTMGQIXFZMZZKD-UHFFFAOYSA-N 0.000 description 2
- YQDGQEKUTLYWJU-UHFFFAOYSA-N 5,6,7,8-tetrahydroquinoline Chemical compound C1=CC=C2CCCCC2=N1 YQDGQEKUTLYWJU-UHFFFAOYSA-N 0.000 description 2
- BXJLDMLOORQIQH-UHFFFAOYSA-N 6,7-dihydro-5h-[1,3]thiazolo[3,2-a]pyrimidine Chemical compound C1CCN=C2SC=CN21 BXJLDMLOORQIQH-UHFFFAOYSA-N 0.000 description 2
- BRXYDRIZVHRXCQ-UHFFFAOYSA-N 6,7-dihydro-5h-pyrrolo[2,1-c][1,2,4]triazole Chemical compound N1=CN2CCCC2=N1 BRXYDRIZVHRXCQ-UHFFFAOYSA-N 0.000 description 2
- ATVSBKCAPGVZNW-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-2h-chromen-2-ol Chemical compound O1C(O)CCC2=CC(OC)=CC=C21 ATVSBKCAPGVZNW-UHFFFAOYSA-N 0.000 description 2
- SNZSSCZJMVIOCR-UHFFFAOYSA-N 7-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCC1N2 SNZSSCZJMVIOCR-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- 238000006751 Mitsunobu reaction Methods 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 238000012191 PBX calcium assay kit Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 2
- AYSYSOQSKKDJJY-UHFFFAOYSA-N [1,2,4]triazolo[4,3-a]pyridine Chemical compound C1=CC=CN2C=NN=C21 AYSYSOQSKKDJJY-UHFFFAOYSA-N 0.000 description 2
- QOMNQGZXFYNBNG-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-difluoro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(F)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(F)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O QOMNQGZXFYNBNG-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000003416 antiarrhythmic agent Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000003725 azepanyl group Chemical group 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 229940097320 beta blocking agent Drugs 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 2
- 206010007625 cardiogenic shock Diseases 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 150000002366 halogen compounds Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 150000002440 hydroxy compounds Chemical class 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 2
- UFBBWLWUIISIPW-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole Chemical compound C1=CSC2=NC=CN21 UFBBWLWUIISIPW-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 2
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 2
- 238000000752 ionisation method Methods 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- 150000002596 lactones Chemical group 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- ODKCVHFYOIHBNB-UHFFFAOYSA-M lithium;2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxylate Chemical compound [Li+].CC1=CC=CC=C1C1OC2=CC=C(OC=3SC(=CN=3)C([O-])=O)C=C2CC1 ODKCVHFYOIHBNB-UHFFFAOYSA-M 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
- 230000007257 malfunction Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000006263 metalation reaction Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- OHBFSBSPOWZEIB-UHFFFAOYSA-N methyl 2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxylate Chemical compound S1C(C(=O)OC)=CN=C1OC1=CC=C(OC(CC2)C=3C(=CC=CC=3)C)C2=C1 OHBFSBSPOWZEIB-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000002560 nitrile group Chemical group 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 150000002900 organolithium compounds Chemical class 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 2
- 150000003014 phosphoric acid esters Chemical class 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 229920001992 poloxamer 407 Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 230000009090 positive inotropic effect Effects 0.000 description 2
- 239000011698 potassium fluoride Substances 0.000 description 2
- 235000003270 potassium fluoride Nutrition 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 230000036454 renin-angiotensin system Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- LCZVKKUAUWQDPX-UHFFFAOYSA-N tert-butyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl]amino]acetate Chemical compound CC(=O)OC1=CC=CC=C1CN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1=CC=CC=C1OC(C)=O LCZVKKUAUWQDPX-UHFFFAOYSA-N 0.000 description 2
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 2
- 150000003536 tetrazoles Chemical class 0.000 description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- FKTXDTWDCPTPHK-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical group FC(F)(F)[C](F)C(F)(F)F FKTXDTWDCPTPHK-UHFFFAOYSA-N 0.000 description 1
- FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
- 125000006002 1,1-difluoroethyl group Chemical group 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- FCDRINPELRTVHD-UHFFFAOYSA-N 1,2-oxazole Chemical compound C=1C=NOC=1.C=1C=NOC=1 FCDRINPELRTVHD-UHFFFAOYSA-N 0.000 description 1
- MIIQJAUWHSUTIT-UHFFFAOYSA-N 1,2-oxazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=NO1 MIIQJAUWHSUTIT-UHFFFAOYSA-N 0.000 description 1
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 1
- UGBLVKBJELNFPS-UHFFFAOYSA-N 1,2-thiazole Chemical compound C=1C=NSC=1.C=1C=NSC=1 UGBLVKBJELNFPS-UHFFFAOYSA-N 0.000 description 1
- CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- QLSAMUCENQZGHN-UHFFFAOYSA-N 1,3,5-trimethylpyrazole-4-sulfonyl chloride Chemical compound CC1=NN(C)C(C)=C1S(Cl)(=O)=O QLSAMUCENQZGHN-UHFFFAOYSA-N 0.000 description 1
- 125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- ZBOWKDHBOFMERX-UHFFFAOYSA-N 1,3-diazepane Chemical compound C1CCNCNC1 ZBOWKDHBOFMERX-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 1
- GCBNIIKPVIHBGR-UHFFFAOYSA-N 1,3-oxazole Chemical compound C1=COC=N1.C1=COC=N1 GCBNIIKPVIHBGR-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- HIZVCIIORGCREW-UHFFFAOYSA-N 1,4-dioxene Chemical compound C1COC=CO1 HIZVCIIORGCREW-UHFFFAOYSA-N 0.000 description 1
- ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical compound C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- CYEIKICLANOPQG-UHFFFAOYSA-N 1-(1,5-dimethylpyrazol-3-yl)-n-[[2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazol-5-yl]methyl]methanamine Chemical compound CN1C(C)=CC(CNCC=2SC(OC=3C=C4CCC(OC4=CC=3)C=3C=CC=CC=3)=NC=2)=N1 CYEIKICLANOPQG-UHFFFAOYSA-N 0.000 description 1
- HQCCNFFIOWYINW-UHFFFAOYSA-N 1-(5-bromo-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(Br)=CC=C1O HQCCNFFIOWYINW-UHFFFAOYSA-N 0.000 description 1
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 1
- VUQVGKNLSOSINI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1.C1=CC=C2SC=CC2=C1 VUQVGKNLSOSINI-UHFFFAOYSA-N 0.000 description 1
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 1
- 125000006420 1-fluorocyclopropyl group Chemical group [H]C1([H])C([H])([H])C1(F)* 0.000 description 1
- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 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
- HYZJCKYKOHLVJF-SFIIULIVSA-N 1H-benzimidazole Chemical group C1=CC=C2N[11CH]=NC2=C1 HYZJCKYKOHLVJF-SFIIULIVSA-N 0.000 description 1
- WLDWSGZHNBANIO-UHFFFAOYSA-N 2',5'-Dihydroxyacetophenone Chemical compound CC(=O)C1=CC(O)=CC=C1O WLDWSGZHNBANIO-UHFFFAOYSA-N 0.000 description 1
- ODSNARDHJFFSRH-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-isoindole Chemical compound C1CCCC2CNCC21 ODSNARDHJFFSRH-UHFFFAOYSA-N 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
- DDVRNOMZDQTUNS-UHFFFAOYSA-N 2,7-diazaspiro[4.4]nonane Chemical compound C1NCCC11CNCC1 DDVRNOMZDQTUNS-UHFFFAOYSA-N 0.000 description 1
- KICXFFZPWFJWFL-UHFFFAOYSA-N 2-(3,4-dihydro-2h-chromen-6-yloxy)-3h-1,3-thiazole-2-carboxylic acid Chemical class C=1C=C2OCCCC2=CC=1OC1(C(=O)O)NC=CS1 KICXFFZPWFJWFL-UHFFFAOYSA-N 0.000 description 1
- VBISRQJCUZZJSN-UHFFFAOYSA-N 2-(3,5-dimethylpyrazol-1-yl)-n-[[2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazol-5-yl]methyl]ethanamine Chemical compound N1=C(C)C=C(C)N1CCNCC(S1)=CN=C1OC1=CC=C(OC(CC2)C=3C=CC=CC=3)C2=C1 VBISRQJCUZZJSN-UHFFFAOYSA-N 0.000 description 1
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- QAPDJGYXOHEMME-UHFFFAOYSA-N 2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazole-5-carbaldehyde Chemical compound S1C(C=O)=CN=C1OC1=CC=C(OC(CC2)C=3C=CC=CC=3)C2=C1 QAPDJGYXOHEMME-UHFFFAOYSA-N 0.000 description 1
- 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 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- ZOTXVQNMZSVEIC-UHFFFAOYSA-N 2-[[2-(2,5-difluorophenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxylic acid;2-[[2-(5-fluoro-2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxylic acid Chemical compound CC1=CC=C(F)C=C1C1OC2=CC=C(OC=3SC(=CN=3)C(O)=O)C=C2CC1.S1C(C(=O)O)=CN=C1OC1=CC=C(OC(CC2)C=3C(=CC=C(F)C=3)F)C2=C1 ZOTXVQNMZSVEIC-UHFFFAOYSA-N 0.000 description 1
- OGCJYKIDIOEHMP-UHFFFAOYSA-N 2-[[2-(2-methylphenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxamide Chemical class CC1=CC=CC=C1C1OC2=CC=C(OC=3SC(=CN=3)C(N)=O)C=C2CC1 OGCJYKIDIOEHMP-UHFFFAOYSA-N 0.000 description 1
- NTVBAAMPVRQZPJ-UHFFFAOYSA-N 2-[[2-(3-fluorophenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carbonitrile;methyl 2-[[2-(3-fluorophenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxylate Chemical compound FC1=CC=CC(C2OC3=CC=C(OC=4SC(=CN=4)C#N)C=C3CC2)=C1.S1C(C(=O)OC)=CN=C1OC1=CC=C(OC(CC2)C=3C=C(F)C=CC=3)C2=C1 NTVBAAMPVRQZPJ-UHFFFAOYSA-N 0.000 description 1
- NYWDDUORRXPBQC-UHFFFAOYSA-N 2-[[2-(3-fluorophenyl)-3,4-dihydro-2h-chromen-6-yl]oxy]-1,3-thiazole-5-carboxylic acid;2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-4-(trifluoromethyl)-1,3-thiazole-5-carboxylic acid Chemical compound S1C(C(=O)O)=CN=C1OC1=CC=C(OC(CC2)C=3C=C(F)C=CC=3)C2=C1.FC(F)(F)C1=C(C(=O)O)SC(OC=2C=C3CCC(OC3=CC=2)C=2C=CC=CC=2)=N1 NYWDDUORRXPBQC-UHFFFAOYSA-N 0.000 description 1
- SFCOKGCNIPSUQF-UHFFFAOYSA-N 2-azaspiro[4.5]decane Chemical compound C1NCCC21CCCCC2 SFCOKGCNIPSUQF-UHFFFAOYSA-N 0.000 description 1
- UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 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
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- MGSHXMOLUWTMGP-UHFFFAOYSA-N 3'-carboxy-alpha-chromanol Chemical class C1=CC=C2C(O)CCOC2=C1 MGSHXMOLUWTMGP-UHFFFAOYSA-N 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- YBBLSBDJIKMXNQ-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzothiazine Chemical compound C1=CC=C2NCCSC2=C1 YBBLSBDJIKMXNQ-UHFFFAOYSA-N 0.000 description 1
- YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical compound C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 description 1
- WPWNEKFMGCWNPR-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromene Chemical compound C1=CC=C2CCCSC2=C1 WPWNEKFMGCWNPR-UHFFFAOYSA-N 0.000 description 1
- VMUXSMXIQBNMGZ-UHFFFAOYSA-N 3,4-dihydrocoumarin Chemical compound C1=CC=C2OC(=O)CCC2=C1 VMUXSMXIQBNMGZ-UHFFFAOYSA-N 0.000 description 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZLXSSLJXCUISKG-UHFFFAOYSA-N 4-bromo-2-(bromomethyl)-1-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1CBr ZLXSSLJXCUISKG-UHFFFAOYSA-N 0.000 description 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 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
- FEPXZFGQVDIXMZ-UHFFFAOYSA-N 5-fluoropyridine-3-carbaldehyde Chemical compound FC1=CN=CC(C=O)=C1 FEPXZFGQVDIXMZ-UHFFFAOYSA-N 0.000 description 1
- QOPRWBRNMPANKN-UHFFFAOYSA-N 5-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2C(=O)CCC2=C1 QOPRWBRNMPANKN-UHFFFAOYSA-N 0.000 description 1
- HXFLZWAZSSPLCO-UHFFFAOYSA-N 6,6-dimethylbicyclo[3.1.1]heptyl Chemical group C1[C-]2C([CH2+])([CH2-])[C+]1CCC2 HXFLZWAZSSPLCO-UHFFFAOYSA-N 0.000 description 1
- RUOWWYMRQXMGMH-UHFFFAOYSA-N 6-hydroxy-2-pyridin-3-yl-2,3-dihydrochromen-4-one Chemical compound C1C(=O)C2=CC(O)=CC=C2OC1C1=CC=CN=C1 RUOWWYMRQXMGMH-UHFFFAOYSA-N 0.000 description 1
- LLHFIDJREATKDX-UHFFFAOYSA-N 6-hydroxy-3-methyl-2-phenyl-2,3-dihydrochromen-4-one Chemical compound O1C2=CC=C(O)C=C2C(=O)C(C)C1C1=CC=CC=C1 LLHFIDJREATKDX-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- YEKSGIKCEBEDJZ-UHFFFAOYSA-N BrC=1C=C2C(CC(OC2=CC1)C1=C(C=CC(=C1)F)C)=O.OC=1C=C2C(CC(OC2=CC1)C1=CC=C(C=C1)S(=O)(=O)C)=O.BrC=1C=C2C(CC(OC2=CC1)C1=C(C=CC=C1C)C)=O.FC1=C(C=C(C=C1)F)C1OC2=CC=C(C=C2C(C1)=O)O Chemical compound BrC=1C=C2C(CC(OC2=CC1)C1=C(C=CC(=C1)F)C)=O.OC=1C=C2C(CC(OC2=CC1)C1=CC=C(C=C1)S(=O)(=O)C)=O.BrC=1C=C2C(CC(OC2=CC1)C1=C(C=CC=C1C)C)=O.FC1=C(C=C(C=C1)F)C1OC2=CC=C(C=C2C(C1)=O)O YEKSGIKCEBEDJZ-UHFFFAOYSA-N 0.000 description 1
- NOQJUIIRKJHTLM-SFVHDIHTSA-N BrC=1C=CC(=C(C1)CCC(O)C1=C(C=CC=C1)C)F.BrC=1C=C2CC[C@H](OC2=CC1)C1=C(C=CC=C1)C Chemical compound BrC=1C=CC(=C(C1)CCC(O)C1=C(C=CC=C1)C)F.BrC=1C=C2CC[C@H](OC2=CC1)C1=C(C=CC=C1)C NOQJUIIRKJHTLM-SFVHDIHTSA-N 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- GLZNYAFMTKBPLW-UHFFFAOYSA-N C1(=CC=CC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C#N.COC(=O)C1=C(N=C(S1)OC=1C=C2CCC(OC2=CC1)C1=CC=CC=C1)Cl.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=CC=CC=C1 Chemical compound C1(=CC=CC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C#N.COC(=O)C1=C(N=C(S1)OC=1C=C2CCC(OC2=CC1)C1=CC=CC=C1)Cl.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=CC=CC=C1 GLZNYAFMTKBPLW-UHFFFAOYSA-N 0.000 description 1
- JBCBVHYWKHNJOK-OTJANGPCSA-N CC1=C(C(=CC=C1)C)C1OC2=CC=C(C=C2CC1)O.FC=1C=CC(=C(C1)C1OC2=CC=C(C=C2CC1)O)C.CS(=O)(=O)C1=CC=C(C=C1)C1OC2=CC=C(C=C2CC1)O.C1(=C(C=CC=C1)[C@H]1OC2=CC=C(C=C2CC1)O)C.C(C)C1=C(C=CC=C1)C1OC2=CC=C(C=C2CC1)O Chemical compound CC1=C(C(=CC=C1)C)C1OC2=CC=C(C=C2CC1)O.FC=1C=CC(=C(C1)C1OC2=CC=C(C=C2CC1)O)C.CS(=O)(=O)C1=CC=C(C=C1)C1OC2=CC=C(C=C2CC1)O.C1(=C(C=CC=C1)[C@H]1OC2=CC=C(C=C2CC1)O)C.C(C)C1=C(C=CC=C1)C1OC2=CC=C(C=C2CC1)O JBCBVHYWKHNJOK-OTJANGPCSA-N 0.000 description 1
- YNOPWDJPAKITTH-UHFFFAOYSA-N CC1C(OC2=CC=C(C=C2C1)O)C1=CC=CC=C1.FC1=C(C=CC=C1OC)C1OC2=CC=C(C=C2CC1)O.CC1=C(C=C2CCC(OC2=C1)C1=C(C=CC=C1)C)O.FC=1C=C(C=NC1)C1OC2=CC=C(C=C2CC1)O.S1C=C(C=C1)C1OC2=CC=C(C=C2CC1)O Chemical compound CC1C(OC2=CC=C(C=C2C1)O)C1=CC=CC=C1.FC1=C(C=CC=C1OC)C1OC2=CC=C(C=C2CC1)O.CC1=C(C=C2CCC(OC2=C1)C1=C(C=CC=C1)C)O.FC=1C=C(C=NC1)C1OC2=CC=C(C=C2CC1)O.S1C=C(C=C1)C1OC2=CC=C(C=C2CC1)O YNOPWDJPAKITTH-UHFFFAOYSA-N 0.000 description 1
- SRQUPPZIQBZGIF-UHFFFAOYSA-N CC1C(OC2=CC=C(C=C2C1)OC=1SC(=CN1)C(=O)O)C1=CC=CC=C1.CC1=C(C=C2CCC(OC2=C1)C1=C(C=CC=C1)C)OC=1SC(=CN1)C(=O)O Chemical compound CC1C(OC2=CC=C(C=C2C1)OC=1SC(=CN1)C(=O)O)C1=CC=CC=C1.CC1=C(C=C2CCC(OC2=C1)C1=C(C=CC=C1)C)OC=1SC(=CN1)C(=O)O SRQUPPZIQBZGIF-UHFFFAOYSA-N 0.000 description 1
- WWGLAGWMMGPCAA-UHFFFAOYSA-N CC=1N=C(SC1C(=O)O)OC=1C=C2CCC(OC2=CC1)C1=CC=CC=C1.ClC=1N=C(SC1C(=O)O)OC=1C=C2CCC(OC2=CC1)C1=CC=CC=C1.C1(=CC=CC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O Chemical compound CC=1N=C(SC1C(=O)O)OC=1C=C2CCC(OC2=CC1)C1=CC=CC=C1.ClC=1N=C(SC1C(=O)O)OC=1C=C2CCC(OC2=CC1)C1=CC=CC=C1.C1(=CC=CC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O WWGLAGWMMGPCAA-UHFFFAOYSA-N 0.000 description 1
- HPTTXADHIFVWKM-UHFFFAOYSA-N COC(=O)C1=C(N=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1)C)C.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=CC=C(C=C1)S(=O)(=O)C Chemical compound COC(=O)C1=C(N=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1)C)C.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=CC=C(C=C1)S(=O)(=O)C HPTTXADHIFVWKM-UHFFFAOYSA-N 0.000 description 1
- GFISBJRVXGMFPO-UHFFFAOYSA-N COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC(=C1)F)C.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C=1C=NC=CC1 Chemical compound COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC(=C1)F)C.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C=1C=NC=CC1 GFISBJRVXGMFPO-UHFFFAOYSA-N 0.000 description 1
- VFAMBTHITUVXLQ-UHFFFAOYSA-N COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=CSC=C1.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1)CC Chemical compound COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=CSC=C1.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1)CC VFAMBTHITUVXLQ-UHFFFAOYSA-N 0.000 description 1
- RVBZAJFHNGHFOI-UHFFFAOYSA-N COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C=1C=NC(=CC1)C.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=NC=CN=C1 Chemical compound COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C=1C=NC(=CC1)C.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=NC=CN=C1 RVBZAJFHNGHFOI-UHFFFAOYSA-N 0.000 description 1
- AOEADRPBWOOZJW-UHFFFAOYSA-N COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C=1C=NC(=CC1)Cl.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1C)C Chemical compound COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C=1C=NC(=CC1)Cl.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1C)C AOEADRPBWOOZJW-UHFFFAOYSA-N 0.000 description 1
- QDGRQUXNRSDVMP-UHFFFAOYSA-N COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C=1C=NC=C(C1)F.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC(=C1)F)F Chemical compound COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C=1C=NC=C(C1)F.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC(=C1)F)F QDGRQUXNRSDVMP-UHFFFAOYSA-N 0.000 description 1
- OWEJXMDXLXYMQI-UHFFFAOYSA-N COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1C)C1=C(C=CC=C1)C.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C(=CC=C1)OC)F Chemical compound COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1C)C1=C(C=CC=C1)C.COC(=O)C1=CN=C(S1)OC=1C=C2CCC(OC2=CC1)C1=C(C(=CC=C1)OC)F OWEJXMDXLXYMQI-UHFFFAOYSA-N 0.000 description 1
- KQJNQDVAUABHQB-NRYUZRROSA-N COC(=O)C1=CN=C(S1)OC=1C=C2CC[C@H](OC2=CC1)C1=C(C=CC=C1)C.COC(=O)C=1N=C(SC1)OC=1C=C2CC[C@H](OC2=CC1)C1=CC=CC=C1 Chemical compound COC(=O)C1=CN=C(S1)OC=1C=C2CC[C@H](OC2=CC1)C1=C(C=CC=C1)C.COC(=O)C=1N=C(SC1)OC=1C=C2CC[C@H](OC2=CC1)C1=CC=CC=C1 KQJNQDVAUABHQB-NRYUZRROSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 206010015856 Extrasystoles Diseases 0.000 description 1
- MYUHZAKHNDVCNN-UHFFFAOYSA-N FC1=C(C=C(C=C1)F)C1OC2=CC=C(C=C2CC1)O.CC1=CC=C(C=N1)C1OC2=CC=C(C=C2CC1)O.BrC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1)CC.BrC=1C=C2CCC(OC2=CC1)C1=CC(=CC=C1)OC(C)C.FC=1C=C(C=CC1)C1OC2=CC=C(C=C2CC1)O Chemical compound FC1=C(C=C(C=C1)F)C1OC2=CC=C(C=C2CC1)O.CC1=CC=C(C=N1)C1OC2=CC=C(C=C2CC1)O.BrC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1)CC.BrC=1C=C2CCC(OC2=CC1)C1=CC(=CC=C1)OC(C)C.FC=1C=C(C=CC1)C1OC2=CC=C(C=C2CC1)O MYUHZAKHNDVCNN-UHFFFAOYSA-N 0.000 description 1
- OYMDHGSJKIKAPS-UHFFFAOYSA-N FC1=C(C=CC=C1OC)C1OC2=CC=C(C=C2C(C1)=O)O.OC=1C=C2C(C(C(OC2=CC1)C1=CC=CC=C1)C)=O.OC=1C=C2C(CC(OC2=CC1)C=1C=NC(=CC1)C)=O.ClC1=CC=C(C=N1)C1OC2=CC=C(C=C2C(C1)=O)O Chemical compound FC1=C(C=CC=C1OC)C1OC2=CC=C(C=C2C(C1)=O)O.OC=1C=C2C(C(C(OC2=CC1)C1=CC=CC=C1)C)=O.OC=1C=C2C(CC(OC2=CC1)C=1C=NC(=CC1)C)=O.ClC1=CC=C(C=N1)C1OC2=CC=C(C=C2C(C1)=O)O OYMDHGSJKIKAPS-UHFFFAOYSA-N 0.000 description 1
- FEFXQYSCUMRPHN-FWRSRWJCSA-N FC1=C(C=CC=C1OC)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.C1(=C(C=CC=C1)[C@H]1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O)C.C1(=CC=CC=C1)[C@H]1OC2=CC=C(C=C2CC1)OC=1SC=C(N1)C(=O)O Chemical compound FC1=C(C=CC=C1OC)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.C1(=C(C=CC=C1)[C@H]1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O)C.C1(=CC=CC=C1)[C@H]1OC2=CC=C(C=C2CC1)OC=1SC=C(N1)C(=O)O FEFXQYSCUMRPHN-FWRSRWJCSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 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 1
- 239000004166 Lanolin Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000009378 Low Cardiac Output Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- HDMQSEMMPIULPV-NRFANRHFSA-N N-[(1,5-dimethylpyrazol-4-yl)methyl]-2-[[(2S)-2-(3-fluorophenyl)-3,4-dihydro-2H-chromen-6-yl]oxy]-1,3-thiazole-5-carboxamide Chemical compound Cc1c(CNC(=O)c2cnc(Oc3ccc4O[C@@H](CCc4c3)c3cccc(F)c3)s2)cnn1C HDMQSEMMPIULPV-NRFANRHFSA-N 0.000 description 1
- FQQGLNHNGNGZKK-UHFFFAOYSA-N N1=C(C=NC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.ClC1=CC=C(C=N1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.CC1=C(C(=CC=C1)C)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O Chemical compound N1=C(C=NC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.ClC1=CC=C(C=N1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.CC1=C(C(=CC=C1)C)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O FQQGLNHNGNGZKK-UHFFFAOYSA-N 0.000 description 1
- UPRGZTZSGLAZSS-UHFFFAOYSA-N N1=CC(=CC=C1)C1OC2=CC=C(C=C2CC1)O.ClC1=CC=C(C=N1)C1OC2=CC=C(C=C2CC1)O.BrC=1C=C2CCC(OC2=CC1)C1=C(C=CC(=C1)F)C.BrC=1C=C2CCC(OC2=CC1)C1=CC=C(C=C1)S(=O)(=O)C.BrC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1C)C Chemical compound N1=CC(=CC=C1)C1OC2=CC=C(C=C2CC1)O.ClC1=CC=C(C=N1)C1OC2=CC=C(C=C2CC1)O.BrC=1C=C2CCC(OC2=CC1)C1=C(C=CC(=C1)F)C.BrC=1C=C2CCC(OC2=CC1)C1=CC=C(C=C1)S(=O)(=O)C.BrC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1C)C UPRGZTZSGLAZSS-UHFFFAOYSA-N 0.000 description 1
- OBSCOZSYRTWJRP-UHFFFAOYSA-N N1=CC(=CC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.CC=1N=C(SC1C(=O)O)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1)C.CS(=O)(=O)C1=CC=C(C=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O Chemical compound N1=CC(=CC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.CC=1N=C(SC1C(=O)O)OC=1C=C2CCC(OC2=CC1)C1=C(C=CC=C1)C.CS(=O)(=O)C1=CC=C(C=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O OBSCOZSYRTWJRP-UHFFFAOYSA-N 0.000 description 1
- JWAQUYBJSJYUDB-UHFFFAOYSA-N OC=1C=C2C(CC(OC2=CC1)C1=CSC=C1)=O.BrC=1C=C2C(CC(OC2=CC1)C1=C(C=CC=C1)CC)=O.BrC=1C=C2C(CC(OC2=CC1)C1=CC(=CC=C1)OC(C)C)=O.FC=1C=C(C=CC1)C1OC2=CC=C(C=C2C(C1)=O)O Chemical compound OC=1C=C2C(CC(OC2=CC1)C1=CSC=C1)=O.BrC=1C=C2C(CC(OC2=CC1)C1=C(C=CC=C1)CC)=O.BrC=1C=C2C(CC(OC2=CC1)C1=CC(=CC=C1)OC(C)C)=O.FC=1C=C(C=CC1)C1OC2=CC=C(C=C2C(C1)=O)O JWAQUYBJSJYUDB-UHFFFAOYSA-N 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 208000000418 Premature Cardiac Complexes Diseases 0.000 description 1
- LJUSXRJZLPQGSR-UHFFFAOYSA-N S1C=C(C=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.C(C)C1=C(C=CC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.FC=1C=C(C=NC1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O Chemical compound S1C=C(C=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.C(C)C1=C(C=CC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O.FC=1C=C(C=NC1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C(=O)O LJUSXRJZLPQGSR-UHFFFAOYSA-N 0.000 description 1
- 108091006253 SLC8A1 Proteins 0.000 description 1
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 208000008253 Systolic Heart Failure Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
- 208000008131 Ventricular Flutter Diseases 0.000 description 1
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000007098 aminolysis reaction Methods 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000003126 arrythmogenic effect Effects 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 1
- 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- QXNDZONIWRINJR-UHFFFAOYSA-N azocane Chemical compound C1CCCNCCC1 QXNDZONIWRINJR-UHFFFAOYSA-N 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical class [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 230000001964 calcium overload Effects 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 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
- PSEHHVRCDVOTID-VMAIWCPRSA-N chloro-bis[(1r,3r,4s,5r)-4,6,6-trimethyl-3-bicyclo[3.1.1]heptanyl]borane Chemical compound C([C@H]([C@@H]1C)B(Cl)[C@H]2[C@H](C)[C@]3(C[C@@](C2)(C3(C)C)[H])[H])[C@@]2([H])C(C)(C)[C@]1([H])C2 PSEHHVRCDVOTID-VMAIWCPRSA-N 0.000 description 1
- JYWJULGYGOLCGW-UHFFFAOYSA-N chloromethyl chloroformate Chemical compound ClCOC(Cl)=O JYWJULGYGOLCGW-UHFFFAOYSA-N 0.000 description 1
- 238000011208 chromatographic data Methods 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#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
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 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 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000005661 deetherification reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 208000038003 heart failure with preserved ejection fraction Diseases 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- PYGSKMBEVAICCR-UHFFFAOYSA-N hexa-1,5-diene Chemical group C=CCCC=C PYGSKMBEVAICCR-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 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
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000001057 ionotropic effect Effects 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical compound C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- ANYSGBYRTLOUPO-UHFFFAOYSA-N lithium tetramethylpiperidide Chemical compound [Li]N1C(C)(C)CCCC1(C)C ANYSGBYRTLOUPO-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- UPTAJBKRNDZYTA-UHFFFAOYSA-N methyl 2-[(3-methyl-2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazole-5-carboxylate Chemical compound S1C(C(=O)OC)=CN=C1OC1=CC=C(OC(C(C)C2)C=3C=CC=CC=3)C2=C1 UPTAJBKRNDZYTA-UHFFFAOYSA-N 0.000 description 1
- ITGAFIAWKUGNIJ-UHFFFAOYSA-N methyl 2-chloro-1,3-thiazole-5-carboxylate Chemical compound COC(=O)C1=CN=C(Cl)S1 ITGAFIAWKUGNIJ-UHFFFAOYSA-N 0.000 description 1
- JWIUIMDIPDFRDI-UHFFFAOYSA-N methyl 3-(2-methylphenyl)-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1=CC=CC=C1C JWIUIMDIPDFRDI-UHFFFAOYSA-N 0.000 description 1
- PGABNXFKPBEQLK-UHFFFAOYSA-N methyl 4-methyl-2-[(2-phenyl-3,4-dihydro-2H-chromen-6-yl)oxy]-1,3-thiazole-5-carboxylate 2-[(2-phenyl-3,4-dihydro-2H-chromen-6-yl)oxy]-1,3-thiazole-5-carbaldehyde 2-[(2-phenyl-3,4-dihydro-2H-chromen-6-yl)oxy]-4-(trifluoromethyl)-1,3-thiazole-5-carboxylic acid Chemical compound C1(=CC=CC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=C(N1)C(F)(F)F)C(=O)O.C1(=CC=CC=C1)C1OC2=CC=C(C=C2CC1)OC=1SC(=CN1)C=O.COC(=O)C1=C(N=C(S1)OC=1C=C2CCC(OC2=CC1)C1=CC=CC=C1)C PGABNXFKPBEQLK-UHFFFAOYSA-N 0.000 description 1
- LNCNRPALSKTJBG-UHFFFAOYSA-N methyl 5-chloro-2-iodobenzoate Chemical compound COC(=O)C1=CC(Cl)=CC=C1I LNCNRPALSKTJBG-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- VVNPLWNCNNGWKX-UHFFFAOYSA-N n-[(1-ethyl-3-methylpyrazol-4-yl)methyl]-1-[2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazol-5-yl]methanamine Chemical compound CC1=NN(CC)C=C1CNCC(S1)=CN=C1OC1=CC=C(OC(CC2)C=3C=CC=CC=3)C2=C1 VVNPLWNCNNGWKX-UHFFFAOYSA-N 0.000 description 1
- ZEMMMDGDBJVBHG-UHFFFAOYSA-N n-[1-(1,5-dimethylpyrazol-4-yl)ethyl]-2-[(2-phenyl-3,4-dihydro-2h-chromen-6-yl)oxy]-1,3-thiazole-5-carboxamide Chemical compound C1=NN(C)C(C)=C1C(C)NC(=O)C(S1)=CN=C1OC(C=C1CC2)=CC=C1OC2C1=CC=CC=C1 ZEMMMDGDBJVBHG-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- LSCYTCMNCWMCQE-UHFFFAOYSA-N n-methylpyridin-4-amine Chemical compound CNC1=CC=NC=C1 LSCYTCMNCWMCQE-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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- UHHKSVZZTYJVEG-UHFFFAOYSA-N oxepane Chemical compound C1CCCOCC1 UHHKSVZZTYJVEG-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 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
- 230000008092 positive effect Effects 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 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
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 229960003081 probenecid Drugs 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- IWOLVLSIZCEOHM-UHFFFAOYSA-M silver;dibenzyl phosphate Chemical compound [Ag+].C=1C=CC=CC=1COP(=O)([O-])OCC1=CC=CC=C1 IWOLVLSIZCEOHM-UHFFFAOYSA-M 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000003457 sulfones Chemical group 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 150000003462 sulfoxides Chemical group 0.000 description 1
- 150000003470 sulfuric acid monoesters Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- JWCVYQRPINPYQJ-UHFFFAOYSA-N thiepane Chemical compound C1CCCSCC1 JWCVYQRPINPYQJ-UHFFFAOYSA-N 0.000 description 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical compound NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- GRWFGVWFFZKLTI-UHFFFAOYSA-N α-pinene Chemical compound CC1=CCC2C(C)(C)C1C2 GRWFGVWFFZKLTI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2011/065712 WO2013037388A1 (fr) | 2011-09-12 | 2011-09-12 | Thiazoles à substitution 2-(chroman-6-yloxy) et leur utilisation comme produits pharmaceutiques |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2011376746A1 AU2011376746A1 (en) | 2014-03-20 |
| AU2011376746B2 true AU2011376746B2 (en) | 2017-06-15 |
Family
ID=44645708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2011376746A Ceased AU2011376746B2 (en) | 2011-09-12 | 2011-09-12 | Substituted 2-(chroman-6-yloxy)-thiazoles and their use as pharmaceuticals |
Country Status (8)
| Country | Link |
|---|---|
| KR (1) | KR101817925B1 (fr) |
| AU (1) | AU2011376746B2 (fr) |
| CA (1) | CA2846347C (fr) |
| IL (1) | IL231096A (fr) |
| MA (1) | MA35814B1 (fr) |
| SG (1) | SG11201400518RA (fr) |
| WO (1) | WO2013037388A1 (fr) |
| ZA (1) | ZA201401335B (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20240057300A (ko) | 2022-10-24 | 2024-05-02 | 고려대학교 산학협력단 | 별아교세포의 미세아교세포 내 칼슘 항상성 조절 용도 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003006452A1 (fr) * | 2001-07-10 | 2003-01-23 | Orion Corporation | Nouveaux composes, lesquels sont des inhibiteurs puissants du mecanisme d'echange na+/ca2+ et qui sont utilises pour le traitement des arythmies |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4168380A (en) | 1978-04-21 | 1979-09-18 | Hoffmann-La Roche Inc. | 7-Methoxy-5-oxo-5H-thiazolo[2,3-b]quinazoline-2-carboxylic acid |
| JPH0967336A (ja) | 1995-09-04 | 1997-03-11 | Kanebo Ltd | 新規なイソチオウレア誘導体 |
| EP0978506B1 (fr) | 1997-03-27 | 2003-01-08 | Taisho Pharmaceutical Co., Ltd | Derives de 2-phenoxyaniline |
| SK4772002A3 (en) | 1999-09-10 | 2002-11-06 | Merck & Co Inc | Tyrosine kinase inhibitors, pharmaceutical composition containing the same and their use |
| AU2001295951A1 (en) | 2000-10-18 | 2002-04-29 | Senju Pharmaceutical Co. Ltd. | Novel 4-benzyloxyphenyl derivative and use thereof |
| WO2004000813A1 (fr) | 2002-06-25 | 2003-12-31 | Yamanouchi Pharmaceutical Co., Ltd. | Derive de phenoxypyridine ou sel de ce derive |
| FI20030030A0 (fi) | 2003-01-09 | 2003-01-09 | Orion Corp | Uusia yhdisteitä |
| JP5092111B2 (ja) | 2007-02-05 | 2012-12-05 | トーアエイヨー株式会社 | ブトキシアニリン誘導体 |
| EP2103939A1 (fr) | 2008-03-20 | 2009-09-23 | sanofi-aventis | Analyse à base de fluorescence pour détecter les composés de modulation de mode inversé (NCX) d'échangeur de sodium/calcium |
| EP2348859B1 (fr) | 2008-10-01 | 2013-12-04 | Merck Sharp & Dohme Corp. | Promédicaments d'inhibiteurs de cetp à base d'oxazolidinone |
-
2011
- 2011-09-12 SG SG11201400518RA patent/SG11201400518RA/en unknown
- 2011-09-12 AU AU2011376746A patent/AU2011376746B2/en not_active Ceased
- 2011-09-12 KR KR1020147009758A patent/KR101817925B1/ko active IP Right Grant
- 2011-09-12 CA CA2846347A patent/CA2846347C/fr not_active Expired - Fee Related
- 2011-09-12 WO PCT/EP2011/065712 patent/WO2013037388A1/fr active Application Filing
-
2014
- 2014-02-21 ZA ZA2014/01335A patent/ZA201401335B/en unknown
- 2014-02-23 IL IL231096A patent/IL231096A/en active IP Right Grant
- 2014-03-12 MA MA36819A patent/MA35814B1/fr unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003006452A1 (fr) * | 2001-07-10 | 2003-01-23 | Orion Corporation | Nouveaux composes, lesquels sont des inhibiteurs puissants du mecanisme d'echange na+/ca2+ et qui sont utilises pour le traitement des arythmies |
Also Published As
| Publication number | Publication date |
|---|---|
| KR101817925B1 (ko) | 2018-01-12 |
| IL231096A0 (en) | 2014-03-31 |
| AU2011376746A1 (en) | 2014-03-20 |
| SG11201400518RA (en) | 2014-04-28 |
| MA35814B1 (fr) | 2014-12-01 |
| CA2846347A1 (fr) | 2013-03-21 |
| CA2846347C (fr) | 2019-05-21 |
| KR20140063807A (ko) | 2014-05-27 |
| ZA201401335B (en) | 2015-08-26 |
| WO2013037388A1 (fr) | 2013-03-21 |
| IL231096A (en) | 2017-07-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20180148440A1 (en) | Substituted 2-(chroman-6-yloxyl)-thiazoles and their use as pharmaceuticals | |
| DK2755970T3 (en) | Substituted 2- (chroman-6-yloxy) -thiazoles and their use as drugs | |
| EP2964623B1 (fr) | Chromane-6-yloxy-cycloalkanes substitués et leur utilisation en tant que produits pharmaceutiques | |
| AU2011376746B2 (en) | Substituted 2-(chroman-6-yloxy)-thiazoles and their use as pharmaceuticals | |
| JP5941637B2 (ja) | 置換２−（クロマン−６−イルオキシ）−チアゾール及び医薬としてのその使用 | |
| OA16755A (en) | Substituted 2-(chroman-6-yloxy)-thiazoles and their use as pharmaceuticals. | |
| NZ622127B2 (en) | Substituted 2-(chroman-6-yloxy)-thiazoles and their use as pharmaceuticals | |
| CN102993195A (zh) | 取代的2-(色满-6-基氧基)噻唑及其作为药物的用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |