NZ590377A - Oxazolopyrimidines as edg-1 receptor agonists - Google Patents

Info

Publication number

NZ590377A

NZ590377A NZ590377A NZ59037709A NZ590377A NZ 590377 A NZ590377 A NZ 590377A NZ 590377 A NZ590377 A NZ 590377A NZ 59037709 A NZ59037709 A NZ 59037709A NZ 590377 A NZ590377 A NZ 590377A

Authority

NZ

New Zealand

Prior art keywords

alkyl

chosen

ring

membered

phenyl

Prior art date

2008-07-15

Links

• Espacenet
• Global Dossier
• Discuss

• BRIOKNPDCPJCOD-UHFFFAOYSA-N [1,3]oxazolo[5,4-d]pyrimidine Chemical class N1=CN=C2OC=NC2=C1 BRIOKNPDCPJCOD-UHFFFAOYSA-N 0.000 title abstract description 21
• 102100025750 Sphingosine 1-phosphate receptor 1 Human genes 0.000 title description 46
• 101000693265 Homo sapiens Sphingosine 1-phosphate receptor 1 Proteins 0.000 title description 45
• 239000000018 receptor agonist Substances 0.000 title description 5
• 229940044601 receptor agonist Drugs 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 356
• 239000000203 mixture Substances 0.000 claims abstract description 86
• 150000003839 salts Chemical class 0.000 claims abstract description 72
• 239000012453 solvate Substances 0.000 claims abstract description 40
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 36
• 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 11
• 206010019280 Heart failures Diseases 0.000 claims abstract description 11
• 208000035475 disorder Diseases 0.000 claims abstract description 11
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 10
• 208000017169 kidney disease Diseases 0.000 claims abstract description 10
• 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims abstract description 9
• 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 9
• 201000011510 cancer Diseases 0.000 claims abstract description 8
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 8
• 230000008728 vascular permeability Effects 0.000 claims abstract description 8
• 230000005961 cardioprotection Effects 0.000 claims abstract description 7
• 230000006378 damage Effects 0.000 claims abstract description 7
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 7
• 208000023504 respiratory system disease Diseases 0.000 claims abstract description 7
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 6
• 208000029078 coronary artery disease Diseases 0.000 claims abstract description 6
• 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 5
• 206010030113 Oedema Diseases 0.000 claims abstract description 5
• 206010063837 Reperfusion injury Diseases 0.000 claims abstract description 5
• 208000010125 myocardial infarction Diseases 0.000 claims abstract description 5
• 208000027418 Wounds and injury Diseases 0.000 claims abstract description 4
• 230000033115 angiogenesis Effects 0.000 claims abstract description 4
• 230000003511 endothelial effect Effects 0.000 claims abstract description 4
• 208000014674 injury Diseases 0.000 claims abstract description 4
• 208000037803 restenosis Diseases 0.000 claims abstract description 4
• 208000004476 Acute Coronary Syndrome Diseases 0.000 claims abstract description 3
• 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 3
• 208000002249 Diabetes Complications Diseases 0.000 claims abstract description 3
• 208000032781 Diabetic cardiomyopathy Diseases 0.000 claims abstract description 3
• 206010012655 Diabetic complications Diseases 0.000 claims abstract description 3
• 206010048554 Endothelial dysfunction Diseases 0.000 claims abstract description 3
• 206010020772 Hypertension Diseases 0.000 claims abstract description 3
• 201000001068 Prinzmetal angina Diseases 0.000 claims abstract description 3
• 208000017442 Retinal disease Diseases 0.000 claims abstract description 3
• 206010038923 Retinopathy Diseases 0.000 claims abstract description 3
• 206010040047 Sepsis Diseases 0.000 claims abstract description 3
• 208000007718 Stable Angina Diseases 0.000 claims abstract description 3
• 208000006011 Stroke Diseases 0.000 claims abstract description 3
• 208000007536 Thrombosis Diseases 0.000 claims abstract description 3
• 208000007814 Unstable Angina Diseases 0.000 claims abstract description 3
• 208000009325 Variant Angina Pectoris Diseases 0.000 claims abstract description 3
• 230000027746 artery morphogenesis Effects 0.000 claims abstract description 3
• 230000008694 endothelial dysfunction Effects 0.000 claims abstract description 3
• 208000031225 myocardial ischemia Diseases 0.000 claims abstract description 3
• 230000004770 neurodegeneration Effects 0.000 claims abstract description 3
• 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 3
• 230000004862 vasculogenesis Effects 0.000 claims abstract description 3
• 230000029663 wound healing Effects 0.000 claims abstract description 3
• KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 claims abstract 2
• -1 hydroxy, amino Chemical group 0.000 claims description 617
• 125000001424 substituent group Chemical group 0.000 claims description 410
• 229910052736 halogen Inorganic materials 0.000 claims description 211
• 150000002367 halogens Chemical class 0.000 claims description 211
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 208
• 125000004432 carbon atom Chemical group C* 0.000 claims description 179
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 143
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 137
• 125000004043 oxo group Chemical group O=* 0.000 claims description 133
• 125000005842 heteroatom Chemical group 0.000 claims description 128
• 229910052717 sulfur Inorganic materials 0.000 claims description 124
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 122
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 121
• 229910052760 oxygen Inorganic materials 0.000 claims description 113
• 125000000217 alkyl group Chemical group 0.000 claims description 102
• 238000000034 method Methods 0.000 claims description 92
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 87
• 125000002950 monocyclic group Chemical group 0.000 claims description 85
• 229920006395 saturated elastomer Polymers 0.000 claims description 84
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 75
• 125000003118 aryl group Chemical group 0.000 claims description 72
• 125000002619 bicyclic group Chemical group 0.000 claims description 62
• 125000004434 sulfur atom Chemical group 0.000 claims description 62
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 60
• 239000011737 fluorine Substances 0.000 claims description 60
• 229910052731 fluorine Inorganic materials 0.000 claims description 60
• 125000000623 heterocyclic group Chemical group 0.000 claims description 57
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 45
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 44
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 40
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 39
• 239000001257 hydrogen Substances 0.000 claims description 37
• 229910052739 hydrogen Inorganic materials 0.000 claims description 37
• 238000011282 treatment Methods 0.000 claims description 23
• 238000002360 preparation method Methods 0.000 claims description 20
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 17
• 229910052740 iodine Inorganic materials 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 14
• 125000000524 functional group Chemical group 0.000 claims description 14
• 239000002243 precursor Substances 0.000 claims description 14
• 230000008569 process Effects 0.000 claims description 14
• 125000001153 fluoro group Chemical group F* 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 239000000654 additive Substances 0.000 claims description 7
• 210000000056 organ Anatomy 0.000 claims description 6
• 230000004913 activation Effects 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 3
• 238000004321 preservation Methods 0.000 claims description 3
• 230000000996 additive effect Effects 0.000 claims description 2
• 238000000338 in vitro Methods 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 173
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 104
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
• 229910052796 boron Inorganic materials 0.000 description 89
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 82
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 82
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
• 238000006243 chemical reaction Methods 0.000 description 52
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
• 239000003480 eluent Substances 0.000 description 51
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 45
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
• 239000000243 solution Substances 0.000 description 42
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 41
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
• 229910052799 carbon Inorganic materials 0.000 description 39
• 238000001819 mass spectrum Methods 0.000 description 39
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
• 229910052757 nitrogen Inorganic materials 0.000 description 34
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 28
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 26
• 150000002431 hydrogen Chemical class 0.000 description 25
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 24
• 201000010099 disease Diseases 0.000 description 24
• 238000000752 ionisation method Methods 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 23
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 20
• 238000000132 electrospray ionisation Methods 0.000 description 20
• 125000004076 pyridyl group Chemical group 0.000 description 20
• 239000002904 solvent Substances 0.000 description 20
• 125000004429 atom Chemical group 0.000 description 19
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 16
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
• 238000001816 cooling Methods 0.000 description 16
• 239000012442 inert solvent Substances 0.000 description 16
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 15
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
• 239000002244 precipitate Substances 0.000 description 15
• 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 14
• 239000000556 agonist Substances 0.000 description 14
• 235000019253 formic acid Nutrition 0.000 description 14
• 239000000543 intermediate Substances 0.000 description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 13
• 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 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 12
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 12
• 230000015572 biosynthetic process Effects 0.000 description 12
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 12
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 12
• 238000002953 preparative HPLC Methods 0.000 description 12
• 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 12
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• 229910052938 sodium sulfate Inorganic materials 0.000 description 11
• 235000011152 sodium sulphate Nutrition 0.000 description 11
• 238000003786 synthesis reaction Methods 0.000 description 11
• 125000001544 thienyl group Chemical group 0.000 description 11
• OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-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
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 10
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 10
• 230000000694 effects Effects 0.000 description 10
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 10
• 230000011664 signaling Effects 0.000 description 10
• 238000010898 silica gel chromatography Methods 0.000 description 10
• 210000000130 stem cell Anatomy 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 9
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 9
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
• 150000001408 amides Chemical class 0.000 description 9
• 125000000392 cycloalkenyl group Chemical group 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 8
• 239000004215 Carbon black (E152) Substances 0.000 description 8
• 125000003342 alkenyl group Chemical group 0.000 description 8
• 125000003545 alkoxy group Chemical group 0.000 description 8
• 125000000304 alkynyl group Chemical group 0.000 description 8
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 8
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 8
• 210000002889 endothelial cell Anatomy 0.000 description 8
• 150000002148 esters Chemical class 0.000 description 8
• 125000002541 furyl group Chemical group 0.000 description 8
• 229930195733 hydrocarbon Natural products 0.000 description 8
• 150000002430 hydrocarbons Chemical class 0.000 description 8
• 125000001624 naphthyl group Chemical group 0.000 description 8
• 239000007858 starting material Substances 0.000 description 8
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
• 239000003643 water by type Substances 0.000 description 8
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 7
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
• 230000001270 agonistic effect Effects 0.000 description 7
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 7
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 7
• 239000000460 chlorine Substances 0.000 description 7
• 229910052801 chlorine Inorganic materials 0.000 description 7
• 125000002757 morpholinyl group Chemical group 0.000 description 7
• 125000003386 piperidinyl group Chemical group 0.000 description 7
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 7
• 125000000714 pyrimidinyl group Chemical group 0.000 description 7
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 6
• 150000004703 alkoxides Chemical class 0.000 description 6
• 150000001409 amidines Chemical class 0.000 description 6
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
• 229910052751 metal Inorganic materials 0.000 description 6
• 239000002184 metal Substances 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 6
• DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 6
• 239000011593 sulfur Substances 0.000 description 6
• 125000003831 tetrazolyl group Chemical group 0.000 description 6
• 125000000335 thiazolyl group Chemical group 0.000 description 6
• 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• 230000002792 vascular Effects 0.000 description 6
• 239000008096 xylene Substances 0.000 description 6
• 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 description 5
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 5
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 5
• AMGLMGGMFIGOQY-UHFFFAOYSA-N 2-(5-bromofuran-2-yl)-5-(morpholin-4-ylmethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3OC(Br)=CC=3)=NC=2C(OCCC)=NC=1CN1CCOCC1 AMGLMGGMFIGOQY-UHFFFAOYSA-N 0.000 description 5
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 5
• 230000002378 acidificating effect Effects 0.000 description 5
• 125000003277 amino group Chemical class 0.000 description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
• 229910052794 bromium Inorganic materials 0.000 description 5
• 125000004122 cyclic group Chemical group 0.000 description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 5
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 5
• 239000010410 layer Substances 0.000 description 5
• 229910000000 metal hydroxide Inorganic materials 0.000 description 5
• 150000004692 metal hydroxides Chemical class 0.000 description 5
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
• 239000012074 organic phase Substances 0.000 description 5
• 125000004430 oxygen atom Chemical group O* 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 238000007363 ring formation reaction Methods 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000029 sodium carbonate Inorganic materials 0.000 description 5
• 239000007787 solid Substances 0.000 description 5
• 150000003512 tertiary amines Chemical class 0.000 description 5
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 4
• DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 4
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 4
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 4
• 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 4
• 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
• DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 4
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
• 102000036530 EDG receptors Human genes 0.000 description 4
• 108091007263 EDG receptors Proteins 0.000 description 4
• 102000015779 HDL Lipoproteins Human genes 0.000 description 4
• 108010010234 HDL Lipoproteins Proteins 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
• 102000003729 Neprilysin Human genes 0.000 description 4
• 108090000028 Neprilysin Proteins 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• LFMFPKKYRXFHHZ-UHFFFAOYSA-N R24 Chemical compound C1=C(Cl)C(C)=CC=C1NC1=NC(N)=C(C=CC=C2)C2=N1 LFMFPKKYRXFHHZ-UHFFFAOYSA-N 0.000 description 4
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
• 125000002393 azetidinyl group Chemical group 0.000 description 4
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 4
• 230000031709 bromination Effects 0.000 description 4
• 238000005893 bromination reaction Methods 0.000 description 4
• 125000001246 bromo group Chemical group Br* 0.000 description 4
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
• 229910000024 caesium carbonate Inorganic materials 0.000 description 4
• 125000002837 carbocyclic group Chemical group 0.000 description 4
• 229950005499 carbon tetrachloride Drugs 0.000 description 4
• 125000002843 carboxylic acid group Chemical group 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 4
• 150000002576 ketones Chemical class 0.000 description 4
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
• 125000006574 non-aromatic ring group Chemical group 0.000 description 4
• 125000000160 oxazolidinyl group Chemical group 0.000 description 4
• 230000003647 oxidation Effects 0.000 description 4
• 238000007254 oxidation reaction Methods 0.000 description 4
• 229910052763 palladium Inorganic materials 0.000 description 4
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
• 230000000144 pharmacologic effect Effects 0.000 description 4
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 4
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
• 239000000047 product Substances 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 150000003457 sulfones Chemical class 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 4
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 4
• 238000002560 therapeutic procedure Methods 0.000 description 4
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 4
• 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 4
• 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 4
• 125000001984 thiazolidinyl group Chemical group 0.000 description 4
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 4
• 238000002054 transplantation Methods 0.000 description 4
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 3
• CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 3
• HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 description 3
• GSLFEOCFQNMHIR-UHFFFAOYSA-N 2-(3-methylphenyl)-5-(1-phenylethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCCC)=NC(C(C)C=3C=CC=CC=3)=NC=2OC=1C1=CC=CC(C)=C1 GSLFEOCFQNMHIR-UHFFFAOYSA-N 0.000 description 3
• YUHPDZWJFMNUJU-UHFFFAOYSA-N 2-(5-bromofuran-2-yl)-5-(bromomethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCCC)=NC(CBr)=NC=2OC=1C1=CC=C(Br)O1 YUHPDZWJFMNUJU-UHFFFAOYSA-N 0.000 description 3
• ORSNWRMVVNLLNI-UHFFFAOYSA-N 2-(furan-2-yl)-5-(morpholin-4-ylmethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3OC=CC=3)=NC=2C(OCCC)=NC=1CN1CCOCC1 ORSNWRMVVNLLNI-UHFFFAOYSA-N 0.000 description 3
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 3
• 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 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 3
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 3
• JWKXJUFSTOOWPO-UHFFFAOYSA-N 5-(bromomethyl)-2-(furan-2-yl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCCC)=NC(CBr)=NC=2OC=1C1=CC=CO1 JWKXJUFSTOOWPO-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 3
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 206010062016 Immunosuppression Diseases 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 238000005481 NMR spectroscopy Methods 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 102000000536 PPAR gamma Human genes 0.000 description 3
• 108010016731 PPAR gamma Proteins 0.000 description 3
• 239000004793 Polystyrene Substances 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
• 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 description 3
• 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 description 3
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
• 238000001994 activation Methods 0.000 description 3
• 239000008186 active pharmaceutical agent Substances 0.000 description 3
• 230000010933 acylation Effects 0.000 description 3
• 238000005917 acylation reaction Methods 0.000 description 3
• 230000006978 adaptation Effects 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 238000005804 alkylation reaction Methods 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 229910021529 ammonia Inorganic materials 0.000 description 3
• 208000006673 asthma Diseases 0.000 description 3
• 125000003725 azepanyl group Chemical group 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• 238000012512 characterization method Methods 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 3
• 229940088679 drug related substance Drugs 0.000 description 3
• 229960000556 fingolimod Drugs 0.000 description 3
• SWZTYAVBMYWFGS-UHFFFAOYSA-N fingolimod hydrochloride Chemical compound Cl.CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 SWZTYAVBMYWFGS-UHFFFAOYSA-N 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• 125000002883 imidazolyl group Chemical group 0.000 description 3
• 230000001506 immunosuppresive effect Effects 0.000 description 3
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
• 150000007529 inorganic bases Chemical class 0.000 description 3
• 230000035800 maturation Effects 0.000 description 3
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 3
• 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 150000002825 nitriles Chemical class 0.000 description 3
• 150000002902 organometallic compounds Chemical class 0.000 description 3
• 125000003566 oxetanyl group Chemical group 0.000 description 3
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 3
• OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 3
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
• 229920002223 polystyrene Polymers 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 230000000069 prophylactic effect Effects 0.000 description 3
• 125000003373 pyrazinyl group Chemical group 0.000 description 3
• 125000002098 pyridazinyl group Chemical group 0.000 description 3
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 3
• 125000000168 pyrrolyl group Chemical group 0.000 description 3
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 238000006722 reduction reaction Methods 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 239000012047 saturated solution Substances 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 230000006641 stabilisation Effects 0.000 description 3
• 238000011105 stabilization Methods 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 3
• 125000004569 thiomorpholin-2-yl group Chemical group N1CC(SCC1)* 0.000 description 3
• 125000004570 thiomorpholin-3-yl group Chemical group N1C(CSCC1)* 0.000 description 3
• ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 3
• 125000001425 triazolyl group Chemical group 0.000 description 3
• 125000006531 (C2-C5) alkyl group Chemical group 0.000 description 2
• 125000006528 (C2-C6) alkyl group Chemical group 0.000 description 2
• 125000006709 (C5-C7) cycloalkenyl group Chemical group 0.000 description 2
• 125000006705 (C5-C7) cycloalkyl group Chemical group 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
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-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
• UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
• UIDMUONFCJEREF-UHFFFAOYSA-N 1-amino-3-[4-[5-[(4-chlorophenyl)methyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]propan-2-ol Chemical compound N=1C=2OC(C=3C=C(C)C(OCC(O)CN)=C(C)C=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 UIDMUONFCJEREF-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• 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 2
• NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 2
• FPKGXSLCPJJJLN-UHFFFAOYSA-N 2-(2-chloro-5-fluorophenyl)-5-methyl-6h-[1,3]oxazolo[5,4-d]pyrimidin-7-one Chemical compound N=1C=2C(=O)NC(C)=NC=2OC=1C1=CC(F)=CC=C1Cl FPKGXSLCPJJJLN-UHFFFAOYSA-N 0.000 description 2
• PNVCBXGNBRXHGW-UHFFFAOYSA-N 2-(3-methylphenyl)-5-(1-phenylethenyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCCC)=NC(C(=C)C=3C=CC=CC=3)=NC=2OC=1C1=CC=CC(C)=C1 PNVCBXGNBRXHGW-UHFFFAOYSA-N 0.000 description 2
• RBRNJSIHQGFEAD-UHFFFAOYSA-N 2-(3-methylphenyl)-5-methylsulfanyl-6h-[1,3]oxazolo[5,4-d]pyrimidin-7-one Chemical compound O1C2=NC(SC)=NC(O)=C2N=C1C1=CC=CC(C)=C1 RBRNJSIHQGFEAD-UHFFFAOYSA-N 0.000 description 2
• CEKMCAMNLCSWOB-UHFFFAOYSA-N 2-(3-methylphenyl)-5-methylsulfanyl-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCCC)=NC(SC)=NC=2OC=1C1=CC=CC(C)=C1 CEKMCAMNLCSWOB-UHFFFAOYSA-N 0.000 description 2
• RFJVXQHIWMVORS-UHFFFAOYSA-N 2-(3-methylphenyl)-5-methylsulfonyl-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCCC)=NC(S(C)(=O)=O)=NC=2OC=1C1=CC=CC(C)=C1 RFJVXQHIWMVORS-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 2
• XMPTYKFIBAQIFM-UHFFFAOYSA-N 3-[4-[5-[(4-chlorophenyl)methyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]propane-1,2-diol Chemical compound N=1C=2OC(C=3C=C(C)C(OCC(O)CO)=C(C)C=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 XMPTYKFIBAQIFM-UHFFFAOYSA-N 0.000 description 2
• NTNQXMJNHOKTBP-UHFFFAOYSA-N 3-[5-(morpholin-4-ylmethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]phenol Chemical compound N=1C=2OC(C=3C=C(O)C=CC=3)=NC=2C(OCCC)=NC=1CN1CCOCC1 NTNQXMJNHOKTBP-UHFFFAOYSA-N 0.000 description 2
• SHOHBUQMJDEFKY-UHFFFAOYSA-N 3-[5-[(4-chlorophenyl)methyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]aniline Chemical compound N=1C=2OC(C=3C=C(N)C=CC=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 SHOHBUQMJDEFKY-UHFFFAOYSA-N 0.000 description 2
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
• SVJSWNBLTMVPML-UHFFFAOYSA-N 5-[(3,4-dichlorophenyl)methyl]-2-(3-methylphenyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C=C(C)C=CC=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C(Cl)=C1 SVJSWNBLTMVPML-UHFFFAOYSA-N 0.000 description 2
• VLEQDECWHNMDIG-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2-(3-fluorophenyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C=C(F)C=CC=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 VLEQDECWHNMDIG-UHFFFAOYSA-N 0.000 description 2
• RACNSXKLEPQMCH-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2-methylsulfanyl-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(SC)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 RACNSXKLEPQMCH-UHFFFAOYSA-N 0.000 description 2
• BPRNIEXWOJQNEI-UHFFFAOYSA-N 5-amino-2-[(4-chlorophenyl)methyl]-4-hydroxy-1h-pyrimidin-6-one Chemical compound N1=C(O)C(N)=C(O)N=C1CC1=CC=C(Cl)C=C1 BPRNIEXWOJQNEI-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 2
• 206010007559 Cardiac failure congestive Diseases 0.000 description 2
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• 229940123583 Factor Xa inhibitor Drugs 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 238000006751 Mitsunobu reaction Methods 0.000 description 2
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
• 208000005764 Peripheral Arterial Disease Diseases 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
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 206010043087 Tachyphylaxis Diseases 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 2
• JINBYESILADKFW-UHFFFAOYSA-N aminomalonic acid Chemical compound OC(=O)C(N)C(O)=O JINBYESILADKFW-UHFFFAOYSA-N 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• 150000001450 anions Chemical class 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 125000004320 azepan-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 2
• 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 description 2
• 125000005604 azodicarboxylate group Chemical group 0.000 description 2
• BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 2
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 2
• 150000001733 carboxylic acid esters Chemical class 0.000 description 2
• 230000000747 cardiac effect Effects 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 150000001793 charged compounds Chemical class 0.000 description 2
• 229910052802 copper Inorganic materials 0.000 description 2
• 239000010949 copper Substances 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 239000000824 cytostatic agent Substances 0.000 description 2
• 125000004652 decahydroisoquinolinyl group Chemical group C1(NCCC2CCCCC12)* 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000006735 deficit Effects 0.000 description 2
• 238000000586 desensitisation Methods 0.000 description 2
• MOYGMFZPSDGVCP-UHFFFAOYSA-N diethyl 2-[(2-chloro-5-fluorobenzoyl)amino]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)NC(=O)C1=CC(F)=CC=C1Cl MOYGMFZPSDGVCP-UHFFFAOYSA-N 0.000 description 2
• WQXAAPPRKIYAGJ-UHFFFAOYSA-N diethyl 2-[(3-fluorobenzoyl)amino]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)NC(=O)C1=CC=CC(F)=C1 WQXAAPPRKIYAGJ-UHFFFAOYSA-N 0.000 description 2
• YDXOJUPKERMBON-UHFFFAOYSA-N diethyl 2-[(3-methylbenzoyl)amino]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)NC(=O)C1=CC=CC(C)=C1 YDXOJUPKERMBON-UHFFFAOYSA-N 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 239000006274 endogenous ligand Substances 0.000 description 2
• 239000003623 enhancer Substances 0.000 description 2
• 238000006266 etherification reaction Methods 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 230000002349 favourable effect Effects 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 150000004820 halides Chemical class 0.000 description 2
• 150000002366 halogen compounds Chemical class 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 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 2
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
• 125000002632 imidazolidinyl group Chemical group 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 208000028867 ischemia Diseases 0.000 description 2
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 2
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 229910052744 lithium Inorganic materials 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
• 229910052987 metal hydride Inorganic materials 0.000 description 2
• 150000004681 metal hydrides Chemical class 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 238000010172 mouse model Methods 0.000 description 2
• VIRQIWZNGIBACK-UHFFFAOYSA-N n-(4-hydroxy-2-methylsulfanyl-6-oxo-1h-pyrimidin-5-yl)-3-methylbenzamide Chemical compound OC1=NC(SC)=NC(O)=C1NC(=O)C1=CC=CC(C)=C1 VIRQIWZNGIBACK-UHFFFAOYSA-N 0.000 description 2
• MDTDADVJSNWEOB-UHFFFAOYSA-N n-(6-hydroxy-4-oxo-2-sulfanylidene-1h-pyrimidin-5-yl)-3-methylbenzamide Chemical compound CC1=CC=CC(C(=O)NC=2C(=NC(S)=NC=2O)O)=C1 MDTDADVJSNWEOB-UHFFFAOYSA-N 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 239000007922 nasal spray Substances 0.000 description 2
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
• 150000007524 organic acids 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
• 125000004288 oxazolidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC1([H])* 0.000 description 2
• 125000004322 oxepan-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 125000003551 oxepanyl group Chemical group 0.000 description 2
• 125000004274 oxetan-2-yl group Chemical group [H]C1([H])OC([H])(*)C1([H])[H] 0.000 description 2
• 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 description 2
• 150000002941 palladium compounds Chemical class 0.000 description 2
• QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 2
• 150000004965 peroxy acids Chemical class 0.000 description 2
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 229960004063 propylene glycol Drugs 0.000 description 2
• 230000004224 protection Effects 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
• 230000008439 repair process Effects 0.000 description 2
• ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• RNVYQYLELCKWAN-UHFFFAOYSA-N solketal Chemical compound CC1(C)OCC(CO)O1 RNVYQYLELCKWAN-UHFFFAOYSA-N 0.000 description 2
• 108010035597 sphingosine kinase Proteins 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• 230000006103 sulfonylation Effects 0.000 description 2
• 238000005694 sulfonylation reaction Methods 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• 230000008685 targeting Effects 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000004300 thiazolidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])SC1([H])* 0.000 description 2
• 125000004275 thietan-2-yl group Chemical group [H]C1([H])SC([H])(*)C1([H])[H] 0.000 description 2
• 125000006300 thietan-3-yl group Chemical group [H]C1([H])SC([H])([H])C1([H])* 0.000 description 2
• 125000002053 thietanyl group Chemical group 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 2
• 229910000404 tripotassium phosphate Inorganic materials 0.000 description 2
• 235000019798 tripotassium phosphate Nutrition 0.000 description 2
• DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 2
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
• 210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
• 210000005166 vasculature Anatomy 0.000 description 2
• YCTDREDEOBUKJL-QFIPXVFZSA-N (2s)-1-[2-[4-[5-[(4-chlorophenyl)methyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]acetyl]pyrrolidine-2-carboxylic acid Chemical compound N=1C=2OC(C=3C=C(C)C(OCC(=O)N4[C@@H](CCC4)C(O)=O)=C(C)C=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 YCTDREDEOBUKJL-QFIPXVFZSA-N 0.000 description 1
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 1
• 125000006532 (C3-C5) alkyl group Chemical group 0.000 description 1
• 125000006704 (C5-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
• 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
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
• HTJMXYRLEDBSLT-UHFFFAOYSA-N 1,2,4,5-tetrazine Chemical compound C1=NN=CN=N1 HTJMXYRLEDBSLT-UHFFFAOYSA-N 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
• 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 1
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
• MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 1
• JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 1
• JUYWDXUELATAOI-UHFFFAOYSA-N 1,3-oxazepine Chemical compound O1C=CC=CN=C1 JUYWDXUELATAOI-UHFFFAOYSA-N 0.000 description 1
• JBCFJMYPJJWIRG-UHFFFAOYSA-N 1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC=N1 JBCFJMYPJJWIRG-UHFFFAOYSA-N 0.000 description 1
• SIMIXFVGSWZJJV-UHFFFAOYSA-N 1,3-thiazepine Chemical compound S1C=CC=CN=C1 SIMIXFVGSWZJJV-UHFFFAOYSA-N 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
• HPARLNRMYDSBNO-UHFFFAOYSA-N 1,4-benzodioxine Chemical compound C1=CC=C2OC=COC2=C1 HPARLNRMYDSBNO-UHFFFAOYSA-N 0.000 description 1
• AKAIWNDBVZJOAJ-UHFFFAOYSA-N 1,4-dithiine Chemical compound S1C=CSC=C1 AKAIWNDBVZJOAJ-UHFFFAOYSA-N 0.000 description 1
• WXLCDTBTIVJDCE-UHFFFAOYSA-N 1,4-oxazepine Chemical compound O1C=CC=NC=C1 WXLCDTBTIVJDCE-UHFFFAOYSA-N 0.000 description 1
• QPPOMEOQNLTFRU-UHFFFAOYSA-N 1,4-thiazepine Chemical compound S1C=CC=NC=C1 QPPOMEOQNLTFRU-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
• YMLGGPGIMOBQOH-UHFFFAOYSA-N 1-[4-[5-[(4-chlorophenyl)methyl]-7-ethoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]-3-(diethylamino)propan-2-ol Chemical compound N=1C=2OC(C=3C=C(C)C(OCC(O)CN(CC)CC)=C(C)C=3)=NC=2C(OCC)=NC=1CC1=CC=C(Cl)C=C1 YMLGGPGIMOBQOH-UHFFFAOYSA-N 0.000 description 1
• WSLWTXWTYJUZIH-UHFFFAOYSA-N 1-[4-[5-[(4-chlorophenyl)methyl]-7-ethoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]-3-morpholin-4-ylpropan-2-ol Chemical compound N=1C=2OC(C=3C=C(C)C(OCC(O)CN4CCOCC4)=C(C)C=3)=NC=2C(OCC)=NC=1CC1=CC=C(Cl)C=C1 WSLWTXWTYJUZIH-UHFFFAOYSA-N 0.000 description 1
• 125000006420 1-fluorocyclopropyl group Chemical group [H]C1([H])C([H])([H])C1(F)* 0.000 description 1
• GQXURJDNDYACGE-UHFFFAOYSA-N 1-hydroxycyclopropane-1-carboxylic acid Chemical compound OC(=O)C1(O)CC1 GQXURJDNDYACGE-UHFFFAOYSA-N 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
• MFJCPDOGFAYSTF-UHFFFAOYSA-N 1H-isochromene Chemical compound C1=CC=C2COC=CC2=C1 MFJCPDOGFAYSTF-UHFFFAOYSA-N 0.000 description 1
• JPPREFOETTUXDK-UHFFFAOYSA-N 1h-1,3-diazepine Chemical compound N1C=CC=CN=C1 JPPREFOETTUXDK-UHFFFAOYSA-N 0.000 description 1
• POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 description 1
• VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 1
• 125000005938 2,3-dihydro-1H-isoindolyl group Chemical group 0.000 description 1
• OZSWAEYPIVJXRX-UHFFFAOYSA-N 2,3-dihydropyrazolyl Chemical group [N]1C=C=C=N1 OZSWAEYPIVJXRX-UHFFFAOYSA-N 0.000 description 1
• ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
• BTXCDYXPJZHLSX-UHFFFAOYSA-N 2-(2-chloro-5-fluorophenyl)-5-(1,4-oxazepan-4-ylmethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C(=CC=C(F)C=3)Cl)=NC=2C(OCCC)=NC=1CN1CCCOCC1 BTXCDYXPJZHLSX-UHFFFAOYSA-N 0.000 description 1
• SXZWHJMSRZMEBU-UHFFFAOYSA-N 2-(2-chloro-5-fluorophenyl)-5-(morpholin-4-ylmethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C(=CC=C(F)C=3)Cl)=NC=2C(OCCC)=NC=1CN1CCOCC1 SXZWHJMSRZMEBU-UHFFFAOYSA-N 0.000 description 1
• QPLPBTIOJHJYLA-UHFFFAOYSA-N 2-(2-chloro-5-fluorophenyl)-5-methyl-6-propyl-[1,3]oxazolo[5,4-d]pyrimidin-7-one Chemical compound N=1C=2C(=O)N(CCC)C(C)=NC=2OC=1C1=CC(F)=CC=C1Cl QPLPBTIOJHJYLA-UHFFFAOYSA-N 0.000 description 1
• ZIFIZVVFJDMKHQ-UHFFFAOYSA-N 2-(2-chloro-5-fluorophenyl)-5-methyl-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCCC)=NC(C)=NC=2OC=1C1=CC(F)=CC=C1Cl ZIFIZVVFJDMKHQ-UHFFFAOYSA-N 0.000 description 1
• BUOMRAHIKNJNFF-UHFFFAOYSA-N 2-(2-chloropyridin-4-yl)-5-(morpholin-4-ylmethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C=C(Cl)N=CC=3)=NC=2C(OCCC)=NC=1CN1CCOCC1 BUOMRAHIKNJNFF-UHFFFAOYSA-N 0.000 description 1
• FNCDOJPMXOQXKC-UHFFFAOYSA-N 2-(3-fluorophenyl)-5-(morpholin-4-ylmethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C=C(F)C=CC=3)=NC=2C(OCCC)=NC=1CN1CCOCC1 FNCDOJPMXOQXKC-UHFFFAOYSA-N 0.000 description 1
• GLMMXAPYIIAKTR-UHFFFAOYSA-N 2-(3-fluorophenyl)-7-propoxy-5-[[4-(trifluoromethyl)phenyl]methyl]-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C=C(F)C=CC=3)=NC=2C(OCCC)=NC=1CC1=CC=C(C(F)(F)F)C=C1 GLMMXAPYIIAKTR-UHFFFAOYSA-N 0.000 description 1
• RPNNRFZWWKDYED-UHFFFAOYSA-N 2-(3-methoxyphenyl)-5-(morpholin-4-ylmethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C=C(OC)C=CC=3)=NC=2C(OCCC)=NC=1CN1CCOCC1 RPNNRFZWWKDYED-UHFFFAOYSA-N 0.000 description 1
• POORWPHLLDLNDW-UHFFFAOYSA-N 2-(3-methylphenyl)-5-methylsulfanyl-6-propyl-[1,3]oxazolo[5,4-d]pyrimidin-7-one Chemical compound N=1C=2C(=O)N(CCC)C(SC)=NC=2OC=1C1=CC=CC(C)=C1 POORWPHLLDLNDW-UHFFFAOYSA-N 0.000 description 1
• JVWYWIOGQGTDGZ-UHFFFAOYSA-N 2-(4-chlorophenyl)ethanimidamide;hydrochloride Chemical compound Cl.NC(=N)CC1=CC=C(Cl)C=C1 JVWYWIOGQGTDGZ-UHFFFAOYSA-N 0.000 description 1
• XDKZLLQPECDIEW-UHFFFAOYSA-N 2-(5-bromofuran-2-yl)-5-(morpholin-4-ylmethyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C=2OC(C=3OC(Br)=CC=3)=NC=2C(OCCC)=NC=1CN1CCOCC1 XDKZLLQPECDIEW-UHFFFAOYSA-N 0.000 description 1
• QDCSHZWUIFTBJU-UHFFFAOYSA-N 2-(furan-2-yl)-5-methyl-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCCC)=NC(C)=NC=2OC=1C1=CC=CO1 QDCSHZWUIFTBJU-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
• WSCSPQPZFAHGBX-UHFFFAOYSA-N 2-[4-[5-[(4-chlorophenyl)methyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]ethanol Chemical compound N=1C=2OC(C=3C=C(C)C(OCCO)=C(C)C=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 WSCSPQPZFAHGBX-UHFFFAOYSA-N 0.000 description 1
• WBMKSVXJTUETPA-UHFFFAOYSA-N 2-[[2-[4-[5-[(4-chlorophenyl)methyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]acetyl]amino]acetic acid Chemical compound N=1C=2OC(C=3C=C(C)C(OCC(=O)NCC(O)=O)=C(C)C=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 WBMKSVXJTUETPA-UHFFFAOYSA-N 0.000 description 1
• WSSDGZWSPMAECX-UHFFFAOYSA-N 2-azabicyclo[3.1.0]hexane Chemical compound C1CNC2CC21 WSSDGZWSPMAECX-UHFFFAOYSA-N 0.000 description 1
• LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
• OHZFXPPWJWZDKY-UHFFFAOYSA-N 2-chloro-5-fluoro-n-(4-hydroxy-2-methyl-6-oxo-1h-pyrimidin-5-yl)benzamide Chemical compound OC1=NC(C)=NC(O)=C1NC(=O)C1=CC(F)=CC=C1Cl OHZFXPPWJWZDKY-UHFFFAOYSA-N 0.000 description 1
• SGZSJPBASHYOHQ-UHFFFAOYSA-N 2-chloro-5-fluorobenzoyl chloride Chemical compound FC1=CC=C(Cl)C(C(Cl)=O)=C1 SGZSJPBASHYOHQ-UHFFFAOYSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• DIQOUXNTSMWQSA-UHFFFAOYSA-N 2-oxa-5-azabicyclo[2.2.1]heptane Chemical compound C1OC2CNC1C2 DIQOUXNTSMWQSA-UHFFFAOYSA-N 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([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
• 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
• KGWNRZLPXLBMPS-UHFFFAOYSA-N 2h-1,3-oxazine Chemical compound C1OC=CC=N1 KGWNRZLPXLBMPS-UHFFFAOYSA-N 0.000 description 1
• NTYABNDBNKVWOO-UHFFFAOYSA-N 2h-1,3-thiazine Chemical compound C1SC=CC=N1 NTYABNDBNKVWOO-UHFFFAOYSA-N 0.000 description 1
• PVTXJGJDOHYFOX-UHFFFAOYSA-N 2h-1,4-benzoxazine Chemical compound C1=CC=C2N=CCOC2=C1 PVTXJGJDOHYFOX-UHFFFAOYSA-N 0.000 description 1
• YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical compound C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 1
• ZAISDHPZTZIFQF-UHFFFAOYSA-N 2h-1,4-thiazine Chemical compound C1SC=CN=C1 ZAISDHPZTZIFQF-UHFFFAOYSA-N 0.000 description 1
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
• YUNINEFNNVLVHN-UHFFFAOYSA-N 3-[5-[(4-chlorophenyl)methyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]aniline;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C=2OC(C=3C=C(N)C=CC=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 YUNINEFNNVLVHN-UHFFFAOYSA-N 0.000 description 1
• BUIWDHZLIJXXJJ-UHFFFAOYSA-N 3-[[3-[4-[5-[(4-chlorophenyl)methyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]-2-hydroxypropyl]amino]propanoic acid Chemical compound N=1C=2OC(C=3C=C(C)C(OCC(O)CNCCC(O)=O)=C(C)C=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 BUIWDHZLIJXXJJ-UHFFFAOYSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• SYVNVEGIRVXRQH-UHFFFAOYSA-N 3-fluorobenzoyl chloride Chemical compound FC1=CC=CC(C(Cl)=O)=C1 SYVNVEGIRVXRQH-UHFFFAOYSA-N 0.000 description 1
• CELKOWQJPVJKIL-UHFFFAOYSA-N 3-fluoropyridine Chemical compound FC1=CC=CN=C1 CELKOWQJPVJKIL-UHFFFAOYSA-N 0.000 description 1
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
• YHOYYHYBFSYOSQ-UHFFFAOYSA-N 3-methylbenzoyl chloride Chemical compound CC1=CC=CC(C(Cl)=O)=C1 YHOYYHYBFSYOSQ-UHFFFAOYSA-N 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
• XLWSBDFQAJXCQX-UHFFFAOYSA-N 4-(bromomethyl)-1,2-dichlorobenzene Chemical compound ClC1=CC=C(CBr)C=C1Cl XLWSBDFQAJXCQX-UHFFFAOYSA-N 0.000 description 1
• VFGYOMXYUKHRHX-UHFFFAOYSA-N 4-[5-[(4-chlorophenyl)methyl]-7-ethoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2-fluorophenol Chemical compound N=1C=2OC(C=3C=C(F)C(O)=CC=3)=NC=2C(OCC)=NC=1CC1=CC=C(Cl)C=C1 VFGYOMXYUKHRHX-UHFFFAOYSA-N 0.000 description 1
• FCLLJMWRDVDREM-UHFFFAOYSA-N 4-[5-[(4-chlorophenyl)methyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenol Chemical compound N=1C=2OC(C=3C=C(C)C(O)=C(C)C=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 FCLLJMWRDVDREM-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
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
• FSCYPXBTOHREPQ-UHFFFAOYSA-N 4h-1,3-dithiine Chemical compound C1SCC=CS1 FSCYPXBTOHREPQ-UHFFFAOYSA-N 0.000 description 1
• QZIFQBPBYAANRD-UHFFFAOYSA-N 5-(bromomethyl)-2-(2-chloro-5-fluorophenyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCCC)=NC(CBr)=NC=2OC=1C1=CC(F)=CC=C1Cl QZIFQBPBYAANRD-UHFFFAOYSA-N 0.000 description 1
• ZZHLZJBMGORQAX-UHFFFAOYSA-N 5-(bromomethyl)-2-(3-fluorophenyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCCC)=NC(CBr)=NC=2OC=1C1=CC=CC(F)=C1 ZZHLZJBMGORQAX-UHFFFAOYSA-N 0.000 description 1
• DHBPXAFAYWJXOP-UHFFFAOYSA-N 5-(cyclohexylmethyl)-2-(3-methylphenyl)-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C=C(C)C=CC=3)=NC=2C(OCCC)=NC=1CC1CCCCC1 DHBPXAFAYWJXOP-UHFFFAOYSA-N 0.000 description 1
• QYWKDGCPDCTIFZ-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2-(3-fluorophenyl)-6h-[1,3]oxazolo[5,4-d]pyrimidin-7-one Chemical compound FC1=CC=CC(C=2OC3=C(C(NC(CC=4C=CC(Cl)=CC=4)=N3)=O)N=2)=C1 QYWKDGCPDCTIFZ-UHFFFAOYSA-N 0.000 description 1
• WXEDBCOIDAQXFQ-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2-[3,5-dimethyl-4-(oxiran-2-ylmethoxy)phenyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C=C(C)C(OCC4OC4)=C(C)C=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 WXEDBCOIDAQXFQ-UHFFFAOYSA-N 0.000 description 1
• WQMXZHUZMORLEH-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2-[4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-3,5-dimethylphenyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2OC(C=3C=C(C)C(OCC4OC(C)(C)OC4)=C(C)C=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 WQMXZHUZMORLEH-UHFFFAOYSA-N 0.000 description 1
• XBLPHSIQOCZIQV-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2-methylsulfanyl-6h-[1,3]oxazolo[5,4-d]pyrimidin-7-one Chemical compound N1=C2OC(SC)=NC2=C(O)N=C1CC1=CC=C(Cl)C=C1 XBLPHSIQOCZIQV-UHFFFAOYSA-N 0.000 description 1
• OWPMSOGNWYKYBY-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2-sulfanylidene-1,6-dihydro-[1,3]oxazolo[5,4-d]pyrimidin-7-one Chemical compound N=1C=2OC(S)=NC=2C(O)=NC=1CC1=CC=C(Cl)C=C1 OWPMSOGNWYKYBY-UHFFFAOYSA-N 0.000 description 1
• VZXDLEYPIIHXNU-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-7-(cyclopropylmethoxy)-2-(3-methylphenyl)-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound CC1=CC=CC(C=2OC3=NC(CC=4C=CC(Cl)=CC=4)=NC(OCC4CC4)=C3N=2)=C1 VZXDLEYPIIHXNU-UHFFFAOYSA-N 0.000 description 1
• QRDSDKAGXMWBID-UHFFFAOYSA-N 5-azabicyclo[3.1.0]hexane Chemical compound C1CCN2CC21 QRDSDKAGXMWBID-UHFFFAOYSA-N 0.000 description 1
• FEAIFRKKVREQPU-UHFFFAOYSA-N 7-ethoxy-2-(3-fluorophenyl)-5-(1-phenylethyl)-[1,3]oxazolo[5,4-d]pyrimidine Chemical compound N=1C=2C(OCC)=NC(C(C)C=3C=CC=CC=3)=NC=2OC=1C1=CC=CC(F)=C1 FEAIFRKKVREQPU-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 102000007469 Actins Human genes 0.000 description 1
• 108010085238 Actins Proteins 0.000 description 1
• 208000030090 Acute Disease Diseases 0.000 description 1
• 208000009304 Acute Kidney Injury Diseases 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 102000000905 Cadherin Human genes 0.000 description 1
• 108050007957 Cadherin Proteins 0.000 description 1
• 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
• 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
• 208000017667 Chronic Disease Diseases 0.000 description 1
• 239000005749 Copper compound Substances 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 208000003037 Diastolic Heart Failure Diseases 0.000 description 1
• WLTCKEHCTUYJGI-UHFFFAOYSA-N Diethyl aminomalonate Chemical compound CCOC(=O)C(N)C(=O)OCC WLTCKEHCTUYJGI-UHFFFAOYSA-N 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
• FSXCJHULTCISMI-UHFFFAOYSA-N FC(C(=O)O)(F)F.C(CC)OC=1OC=2N=CN=CC2N1 Chemical compound FC(C(=O)O)(F)F.C(CC)OC=1OC=2N=CN=CC2N1 FSXCJHULTCISMI-UHFFFAOYSA-N 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 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 1
• 208000032843 Hemorrhage Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000653759 Homo sapiens Sphingosine 1-phosphate receptor 5 Proteins 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 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
• 239000002841 Lewis acid Substances 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• 102000004317 Lyases Human genes 0.000 description 1
• 108090000856 Lyases Proteins 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 102100031829 Myosin light polypeptide 6 Human genes 0.000 description 1
• 101710101143 Myosin light polypeptide 6 Proteins 0.000 description 1
• 102100031787 Myosin regulatory light polypeptide 9 Human genes 0.000 description 1
• 101710107065 Myosin regulatory light polypeptide 9 Proteins 0.000 description 1
• 108050000637 N-cadherin Proteins 0.000 description 1
• 150000001204 N-oxides Chemical class 0.000 description 1
• 101000881330 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) Dynein heavy chain, cytoplasmic Proteins 0.000 description 1
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 239000004146 Propane-1,2-diol Substances 0.000 description 1
• 206010037423 Pulmonary oedema Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 208000033626 Renal failure acute Diseases 0.000 description 1
• 206010063897 Renal ischaemia Diseases 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• 108020004459 Small interfering RNA Proteins 0.000 description 1
• 208000005392 Spasm Diseases 0.000 description 1
• 101710155454 Sphingosine 1-phosphate receptor 1 Proteins 0.000 description 1
• 102100025749 Sphingosine 1-phosphate receptor 2 Human genes 0.000 description 1
• 101710155462 Sphingosine 1-phosphate receptor 2 Proteins 0.000 description 1
• 102100025747 Sphingosine 1-phosphate receptor 3 Human genes 0.000 description 1
• 101710155457 Sphingosine 1-phosphate receptor 3 Proteins 0.000 description 1
• 102100029803 Sphingosine 1-phosphate receptor 4 Human genes 0.000 description 1
• 101710155458 Sphingosine 1-phosphate receptor 4 Proteins 0.000 description 1
• 102100029802 Sphingosine 1-phosphate receptor 5 Human genes 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 208000008253 Systolic Heart Failure Diseases 0.000 description 1
• 206010042957 Systolic hypertension Diseases 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 208000032594 Vascular Remodeling Diseases 0.000 description 1
• ALMFIOZYDASRRC-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)C=C1 ALMFIOZYDASRRC-UHFFFAOYSA-N 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
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
• ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
• ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 201000011040 acute kidney failure Diseases 0.000 description 1
• 208000012998 acute renal failure Diseases 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 210000002867 adherens junction Anatomy 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 210000004102 animal cell Anatomy 0.000 description 1
• 238000005349 anion exchange Methods 0.000 description 1
• 230000000181 anti-adherent effect Effects 0.000 description 1
• 230000001772 anti-angiogenic effect Effects 0.000 description 1
• 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000012300 argon atmosphere Substances 0.000 description 1
• 150000001543 aryl boronic acids Chemical class 0.000 description 1
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000002238 attenuated effect Effects 0.000 description 1
• QRNWCBFBJCLGLF-UHFFFAOYSA-N azecine Chemical compound C1=CC=CC=NC=CC=C1 QRNWCBFBJCLGLF-UHFFFAOYSA-N 0.000 description 1
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
• LKSPYOVNNMPMIZ-UHFFFAOYSA-N azete Chemical compound C1=CN=C1 LKSPYOVNNMPMIZ-UHFFFAOYSA-N 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
• XXRGLCKZBCIEKO-DLMDZQPMSA-N azocine Chemical compound C/1=C/C=C\N=C/C=C\1 XXRGLCKZBCIEKO-DLMDZQPMSA-N 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• FBOSKQVOIHEWAX-UHFFFAOYSA-N benzothiazine Chemical compound C1=CC=C2N=CCSC2=C1 FBOSKQVOIHEWAX-UHFFFAOYSA-N 0.000 description 1
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 150000003938 benzyl alcohols Chemical class 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 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 1
• 150000001602 bicycloalkyls Chemical group 0.000 description 1
• 239000012472 biological sample Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 150000001718 carbodiimides Chemical class 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
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 125000001721 carboxyacetyl group Chemical group 0.000 description 1
• 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
• 125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 1
• 238000007675 cardiac surgery Methods 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 238000005341 cation exchange Methods 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 238000002659 cell therapy Methods 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
• 238000011208 chromatographic data Methods 0.000 description 1
• QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
• 230000001684 chronic effect Effects 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
• 229940125773 compound 10 Drugs 0.000 description 1
• 150000001879 copper Chemical class 0.000 description 1
• 150000001880 copper compounds Chemical class 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 238000007887 coronary angioplasty Methods 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 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
• 125000006622 cycloheptylmethyl group Chemical group 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• YEDVUDDWJVRKIS-UHFFFAOYSA-N cyclopenta[b]pyrrole Chemical compound C1=C[C]2[N]C=CC2=C1 YEDVUDDWJVRKIS-UHFFFAOYSA-N 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
• 230000001085 cytostatic effect Effects 0.000 description 1
• 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
• 238000005661 deetherification reaction Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 125000004663 dialkyl amino group Chemical group 0.000 description 1
• 235000013681 dietary sucrose Nutrition 0.000 description 1
• GLFVNTDRBTZJIY-UHFFFAOYSA-N diethyl 2-aminopropanedioate;hydron;chloride Chemical compound Cl.CCOC(=O)C(N)C(=O)OCC GLFVNTDRBTZJIY-UHFFFAOYSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 125000005045 dihydroisoquinolinyl group Chemical group C1(NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000005048 dihydroisoxazolyl group Chemical group O1N(CC=C1)* 0.000 description 1
• 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000010595 endothelial cell migration Effects 0.000 description 1
• 230000008753 endothelial function Effects 0.000 description 1
• 210000003038 endothelium Anatomy 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 1
• 125000001033 ether group Chemical group 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 239000000835 fiber Substances 0.000 description 1
• 239000007941 film coated tablet Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 230000009760 functional impairment Effects 0.000 description 1
• 238000007306 functionalization reaction Methods 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
• 239000008103 glucose Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 235000013773 glyceryl triacetate Nutrition 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 230000002140 halogenating effect Effects 0.000 description 1
• 208000038003 heart failure with preserved ejection fraction Diseases 0.000 description 1
• 125000001072 heteroaryl group Chemical group 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical group OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
• 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000010255 intramuscular injection Methods 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
• 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
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 235000019388 lanolin Nutrition 0.000 description 1
• 229940039717 lanolin Drugs 0.000 description 1
• 239000006390 lc 2 Substances 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000005265 lung cell Anatomy 0.000 description 1
• 230000035168 lymphangiogenesis Effects 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• JMZFEHDNIAQMNB-UHFFFAOYSA-N m-aminophenylboronic acid Chemical compound NC1=CC=CC(B(O)O)=C1 JMZFEHDNIAQMNB-UHFFFAOYSA-N 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• BPHQBQAJVFDYRF-UHFFFAOYSA-M magnesium;ethenylbenzene;bromide Chemical compound [Mg+2].[Br-].C=[C-]C1=CC=CC=C1 BPHQBQAJVFDYRF-UHFFFAOYSA-M 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 125000005394 methallyl group Chemical group 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
• NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
• HYICPDIYQCZMCV-UHFFFAOYSA-N n-(4-cyano-1,3-oxazol-5-yl)acetamide Chemical compound CC(=O)NC=1OC=NC=1C#N HYICPDIYQCZMCV-UHFFFAOYSA-N 0.000 description 1
• JRAFGUQVKIZTEK-UHFFFAOYSA-N n-(4-cyano-2-phenyl-1,3-oxazol-5-yl)acetamide Chemical compound N#CC1=C(NC(=O)C)OC(C=2C=CC=CC=2)=N1 JRAFGUQVKIZTEK-UHFFFAOYSA-N 0.000 description 1
• DPZHVNONPCBHMN-UHFFFAOYSA-N n-[2-[(4-chlorophenyl)methyl]-4-hydroxy-6-oxo-1h-pyrimidin-5-yl]-3-fluorobenzamide;hydrochloride Chemical compound Cl.N=1C(O)=C(NC(=O)C=2C=C(F)C=CC=2)C(O)=NC=1CC1=CC=C(Cl)C=C1 DPZHVNONPCBHMN-UHFFFAOYSA-N 0.000 description 1
• FGIYNYKXZNZPIV-UHFFFAOYSA-N n-[3-[4-[5-[(4-chlorophenyl)methyl]-7-propoxy-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]-2-hydroxypropyl]acetamide Chemical compound N=1C=2OC(C=3C=C(C)C(OCC(O)CNC(C)=O)=C(C)C=3)=NC=2C(OCCC)=NC=1CC1=CC=C(Cl)C=C1 FGIYNYKXZNZPIV-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 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
• 150000005054 naphthyridines Chemical class 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
• 150000002829 nitrogen Chemical group 0.000 description 1
• QJGQUHMNIGDVPM-OUBTZVSYSA-N nitrogen-15 Chemical group [15N] QJGQUHMNIGDVPM-OUBTZVSYSA-N 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 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
• 239000002674 ointment Substances 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
• 150000002900 organolithium compounds Chemical class 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 150000002940 palladium Chemical class 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 150000002978 peroxides Chemical class 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
• 230000001766 physiological effect Effects 0.000 description 1
• 125000004193 piperazinyl group Chemical group 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
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 208000007232 portal hypertension Diseases 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 239000000843 powder Substances 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
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
• 208000005333 pulmonary edema Diseases 0.000 description 1
• 208000002815 pulmonary hypertension Diseases 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
• 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 1
• 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 1
• 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000001172 regenerating effect Effects 0.000 description 1
• 230000008521 reorganization Effects 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 125000006413 ring segment Chemical group 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
• 230000036303 septic shock Effects 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• XGRLSUFHELJJAB-JGSYTFBMSA-M sodium;[(2r)-2-hydroxy-3-[(z)-octadec-9-enoyl]oxypropyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)([O-])=O XGRLSUFHELJJAB-JGSYTFBMSA-M 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010561 standard procedure 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
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 229960004793 sucrose Drugs 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
• 125000001174 sulfone group Chemical group 0.000 description 1
• 150000003459 sulfonic acid esters Chemical class 0.000 description 1
• 125000003375 sulfoxide group Chemical group 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 230000001502 supplementing effect Effects 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000006557 surface reaction Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 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
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid 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
• 150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• MKYRMMMSZSVIGD-UHFFFAOYSA-N thieno[3,2-c]pyridine Chemical compound N1=CC=C2SC=CC2=C1 MKYRMMMSZSVIGD-UHFFFAOYSA-N 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 229960002622 triacetin Drugs 0.000 description 1
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
• 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• 239000004246 zinc acetate Substances 0.000 description 1