MX2012003718A - Compuestos de piridina de anillo condensado como moduladores selectivos de subtipo de receptores de esfingosina-1-fosfato-2 (s1p2). - Google Patents
Compuestos de piridina de anillo condensado como moduladores selectivos de subtipo de receptores de esfingosina-1-fosfato-2 (s1p2).Info
- Publication number
- MX2012003718A MX2012003718A MX2012003718A MX2012003718A MX2012003718A MX 2012003718 A MX2012003718 A MX 2012003718A MX 2012003718 A MX2012003718 A MX 2012003718A MX 2012003718 A MX2012003718 A MX 2012003718A MX 2012003718 A MX2012003718 A MX 2012003718A
- Authority
- MX
- Mexico
- Prior art keywords
- isopropyl
- group
- alkyl
- pyrazolo
- dimethyl
- Prior art date
Links
- 150000003222 pyridines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 134
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 201000010099 disease Diseases 0.000 claims abstract description 29
- 208000002193 Pain Diseases 0.000 claims abstract description 10
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 9
- 230000004761 fibrosis Effects 0.000 claims abstract description 9
- 208000027418 Wounds and injury Diseases 0.000 claims abstract description 8
- 206010052428 Wound Diseases 0.000 claims abstract description 7
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 7
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract description 6
- 230000007815 allergy Effects 0.000 claims abstract description 6
- 230000009885 systemic effect Effects 0.000 claims abstract description 6
- 230000006453 vascular barrier function Effects 0.000 claims abstract description 6
- 230000004071 biological effect Effects 0.000 claims abstract description 5
- 241000124008 Mammalia Species 0.000 claims abstract description 4
- 208000022873 Ocular disease Diseases 0.000 claims abstract 2
- -1 methoxy, hydroxyl Chemical group 0.000 claims description 122
- 125000000217 alkyl group Chemical group 0.000 claims description 73
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 50
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 claims description 33
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
- 150000002825 nitriles Chemical class 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000004122 cyclic group Chemical group 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 13
- 239000004202 carbamide Substances 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 208000030533 eye disease Diseases 0.000 claims description 4
- XDQJLXNLJHENBK-UHFFFAOYSA-N 1-(2,6-dichloropyridin-4-yl)-3-[(4-methylquinolin-2-yl)amino]urea Chemical compound N=1C2=CC=CC=C2C(C)=CC=1NNC(=O)NC1=CC(Cl)=NC(Cl)=C1 XDQJLXNLJHENBK-UHFFFAOYSA-N 0.000 claims description 3
- XELXFTLTXOLAHQ-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)-3-[(4,5,8-trimethylquinolin-2-yl)amino]urea Chemical compound N1=C2C(C)=CC=C(C)C2=C(C)C=C1NNC(=O)NC1=CC(Cl)=CC(Cl)=C1 XELXFTLTXOLAHQ-UHFFFAOYSA-N 0.000 claims description 3
- NQMYDNLQQJWODH-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)-3-[(5,8-dimethyl-4-propan-2-ylquinolin-2-yl)amino]urea Chemical compound N=1C2=C(C)C=CC(C)=C2C(C(C)C)=CC=1NNC(=O)NC1=CC(Cl)=CC(Cl)=C1 NQMYDNLQQJWODH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- BKWSFLNRRIKSGC-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)-3-[(4,8-dimethylquinolin-2-yl)amino]urea Chemical compound N1=C2C(C)=CC=CC2=C(C)C=C1NNC(=O)NC1=CC(Cl)=CC(Cl)=C1 BKWSFLNRRIKSGC-UHFFFAOYSA-N 0.000 claims description 2
- OWXCWZQVBWXWBH-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)-3-[(4-propan-2-ylquinolin-2-yl)amino]urea Chemical compound N=1C2=CC=CC=C2C(C(C)C)=CC=1NNC(=O)NC1=CC(Cl)=CC(Cl)=C1 OWXCWZQVBWXWBH-UHFFFAOYSA-N 0.000 claims description 2
- 229940122286 Sphingosine 1-phosphate receptor antagonist Drugs 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 3
- 239000003937 drug carrier Substances 0.000 claims 2
- FPNRZKJVJGUCOW-UHFFFAOYSA-N 1-(2,6-dichloropyridin-4-yl)-3-[(4,8-dimethylquinolin-2-yl)amino]urea Chemical compound N1=C2C(C)=CC=CC2=C(C)C=C1NNC(=O)NC1=CC(Cl)=NC(Cl)=C1 FPNRZKJVJGUCOW-UHFFFAOYSA-N 0.000 claims 1
- MSTNXXMGZNODPF-UHFFFAOYSA-N 1-(2-butoxy-6-chloropyridin-4-yl)-3-[(1,3-dimethyl-7-propan-2-ylpyrazolo[4,3-b]pyridin-5-yl)methyl]urea Chemical compound ClC1=NC(OCCCC)=CC(NC(=O)NCC=2N=C3C(C)=NN(C)C3=C(C(C)C)C=2)=C1 MSTNXXMGZNODPF-UHFFFAOYSA-N 0.000 claims 1
- 239000005557 antagonist Substances 0.000 abstract description 2
- 229940121846 Sphingosine 1-phosphate receptor agonist Drugs 0.000 abstract 1
- 208000019622 heart disease Diseases 0.000 abstract 1
- 238000000034 method Methods 0.000 description 68
- 238000004611 spectroscopical analysis Methods 0.000 description 60
- 238000006243 chemical reaction Methods 0.000 description 49
- 238000005481 NMR spectroscopy Methods 0.000 description 44
- 239000000243 solution Substances 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 34
- 230000015572 biosynthetic process Effects 0.000 description 31
- 238000003786 synthesis reaction Methods 0.000 description 30
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- 238000000746 purification Methods 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 18
- 125000003118 aryl group Chemical group 0.000 description 17
- 239000000543 intermediate Substances 0.000 description 17
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 16
- 229910001868 water Inorganic materials 0.000 description 16
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 12
- 238000011065 in-situ storage Methods 0.000 description 12
- 239000012267 brine Substances 0.000 description 11
- 235000013877 carbamide Nutrition 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- XEFUJGURFLOFAN-UHFFFAOYSA-N 1,3-dichloro-5-isocyanatobenzene Chemical compound ClC1=CC(Cl)=CC(N=C=O)=C1 XEFUJGURFLOFAN-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229910019142 PO4 Inorganic materials 0.000 description 9
- 239000012948 isocyanate Substances 0.000 description 9
- 239000010452 phosphate Substances 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 8
- VOWZNBNDMFLQGM-UHFFFAOYSA-N 2,5-dimethylaniline Chemical compound CC1=CC=C(C)C(N)=C1 VOWZNBNDMFLQGM-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 101150041968 CDC13 gene Proteins 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 125000002877 alkyl aryl group Chemical group 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 229940093499 ethyl acetate Drugs 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 150000003408 sphingolipids Chemical class 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- NBJTYLJXUNUKDZ-UHFFFAOYSA-N 2-chloro-6-ethoxy-4-isocyanatopyridine Chemical compound CCOC1=CC(N=C=O)=CC(Cl)=N1 NBJTYLJXUNUKDZ-UHFFFAOYSA-N 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 125000006413 ring segment Chemical group 0.000 description 6
- 229920006395 saturated elastomer Polymers 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
- 239000000126 substance Substances 0.000 description 6
- XLAIIXJCFLQOAH-UHFFFAOYSA-N 2-butoxy-6-chloro-4-isocyanatopyridine Chemical compound CCCCOC1=CC(N=C=O)=CC(Cl)=N1 XLAIIXJCFLQOAH-UHFFFAOYSA-N 0.000 description 5
- NOZLRQOJDHKGOV-UHFFFAOYSA-N 2-chloro-4-isocyanato-6-methoxypyridine Chemical compound COC1=CC(N=C=O)=CC(Cl)=N1 NOZLRQOJDHKGOV-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 229940106189 ceramide Drugs 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000002440 hepatic effect Effects 0.000 description 5
- 150000002513 isocyanates Chemical class 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 150000003410 sphingosines Chemical class 0.000 description 5
- CKYIBQKOKROEHH-UHFFFAOYSA-N (1,3-dimethyl-7-propan-2-ylpyrazolo[4,3-b]pyridin-5-yl)hydrazine Chemical compound CC(C)C1=CC(NN)=NC2=C1N(C)N=C2C CKYIBQKOKROEHH-UHFFFAOYSA-N 0.000 description 4
- OCDFIQXUCLQQHY-UHFFFAOYSA-N 2,6-dichloro-4-isocyanatopyridine Chemical compound ClC1=CC(N=C=O)=CC(Cl)=N1 OCDFIQXUCLQQHY-UHFFFAOYSA-N 0.000 description 4
- XHNLFKSZKDDRAN-UHFFFAOYSA-N 2-butyl-6-chloro-4-isocyanatopyridine Chemical compound CCCCC1=CC(N=C=O)=CC(Cl)=N1 XHNLFKSZKDDRAN-UHFFFAOYSA-N 0.000 description 4
- ZALIPONVJRVICJ-UHFFFAOYSA-N 2-chloro-4-isocyanato-6-propoxypyridine Chemical compound CCCOC1=CC(N=C=O)=CC(Cl)=N1 ZALIPONVJRVICJ-UHFFFAOYSA-N 0.000 description 4
- LVNDSLAQUSCKMO-UHFFFAOYSA-N 2-chloro-4-isocyanato-6-propylpyridine Chemical compound CCCC1=CC(N=C=O)=CC(Cl)=N1 LVNDSLAQUSCKMO-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 208000009299 Benign Mucous Membrane Pemphigoid Diseases 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000015779 HDL Lipoproteins Human genes 0.000 description 4
- 108010010234 HDL Lipoproteins Proteins 0.000 description 4
- 206010019668 Hepatic fibrosis Diseases 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 208000012192 Mucous membrane pemphigoid Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 206010034277 Pemphigoid Diseases 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 230000000747 cardiac effect Effects 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 201000010002 cicatricial pemphigoid Diseases 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 210000000795 conjunctiva Anatomy 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 208000005069 pulmonary fibrosis Diseases 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 210000001760 tenon capsule Anatomy 0.000 description 4
- IDGTZROMJOZLQC-UHFFFAOYSA-N (4,8-dimethylquinolin-2-yl)hydrazine Chemical compound C1=C(NN)N=C2C(C)=CC=CC2=C1C IDGTZROMJOZLQC-UHFFFAOYSA-N 0.000 description 3
- HCUFLBADRLGFLY-UHFFFAOYSA-N 2,2-dimethyl-n-[3-(2-methylpropanoyl)pyridin-2-yl]propanamide Chemical compound CC(C)C(=O)C1=CC=CN=C1NC(=O)C(C)(C)C HCUFLBADRLGFLY-UHFFFAOYSA-N 0.000 description 3
- BHHNTRYUSNABMR-UHFFFAOYSA-N 2-chloro-5,8-dimethyl-4-propan-2-ylquinoline Chemical compound C1=CC(C)=C2C(C(C)C)=CC(Cl)=NC2=C1C BHHNTRYUSNABMR-UHFFFAOYSA-N 0.000 description 3
- QWHJJSSPZDHELV-UHFFFAOYSA-N 2-ethoxy-4-isocyanatopyridine Chemical compound CCOC1=CC(N=C=O)=CC=N1 QWHJJSSPZDHELV-UHFFFAOYSA-N 0.000 description 3
- LZZGOJRKOYMVQF-UHFFFAOYSA-N 5,8-dimethyl-4-propan-2-yl-1h-quinolin-2-one Chemical compound C1=CC(C)=C2C(C(C)C)=CC(O)=NC2=C1C LZZGOJRKOYMVQF-UHFFFAOYSA-N 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 108091006027 G proteins Proteins 0.000 description 3
- 102000030782 GTP binding Human genes 0.000 description 3
- 108091000058 GTP-Binding Proteins 0.000 description 3
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 206010064930 age-related macular degeneration Diseases 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 210000004087 cornea Anatomy 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- VEAPZASDDPNKQI-UHFFFAOYSA-N n-(2,5-dimethylphenyl)-4-methyl-3-oxopentanamide Chemical compound CC(C)C(=O)CC(=O)NC1=CC(C)=CC=C1C VEAPZASDDPNKQI-UHFFFAOYSA-N 0.000 description 3
- VSQIBTHKSDKEPR-UHFFFAOYSA-N n-(3-acetylpyridin-2-yl)-2,2-dimethylpropanamide Chemical compound CC(=O)C1=CC=CN=C1NC(=O)C(C)(C)C VSQIBTHKSDKEPR-UHFFFAOYSA-N 0.000 description 3
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- 150000003568 thioethers Chemical class 0.000 description 3
- 150000003672 ureas Chemical class 0.000 description 3
- VNLQITMIHSSLFQ-UHFFFAOYSA-N (1,3,7-trimethylpyrazolo[4,3-b]pyridin-5-yl)methanamine Chemical compound C1=C(CN)N=C2C(C)=NN(C)C2=C1C VNLQITMIHSSLFQ-UHFFFAOYSA-N 0.000 description 2
- ZQDGYDHQDFEARD-UHFFFAOYSA-N (1,3-dimethyl-7-propan-2-ylpyrazolo[4,3-b]pyridin-5-yl)methanamine Chemical compound CC(C)C1=CC(CN)=NC2=C1N(C)N=C2C ZQDGYDHQDFEARD-UHFFFAOYSA-N 0.000 description 2
- WRXAXSSQNMKMGM-UHFFFAOYSA-N (4,5,8-trimethylquinolin-2-yl)hydrazine Chemical compound C1=C(NN)N=C2C(C)=CC=C(C)C2=C1C WRXAXSSQNMKMGM-UHFFFAOYSA-N 0.000 description 2
- FLDYBLAUDDQRAB-UHFFFAOYSA-N (4-methylquinolin-2-yl)hydrazine Chemical compound C1=CC=C2C(C)=CC(NN)=NC2=C1 FLDYBLAUDDQRAB-UHFFFAOYSA-N 0.000 description 2
- AOLBVTJOLSDWRW-UHFFFAOYSA-N (5,8-dimethyl-4-propan-2-ylquinolin-2-yl)hydrazine Chemical compound C1=CC(C)=C2C(C(C)C)=CC(NN)=NC2=C1C AOLBVTJOLSDWRW-UHFFFAOYSA-N 0.000 description 2
- IMIMBIWNJBKPKL-UHFFFAOYSA-N 1-(2-chloro-6-propylpyridin-4-yl)-3-[(1,3-dimethyl-7-propan-2-ylpyrazolo[4,3-b]pyridin-5-yl)methyl]urea Chemical compound ClC1=NC(CCC)=CC(NC(=O)NCC=2N=C3C(C)=NN(C)C3=C(C(C)C)C=2)=C1 IMIMBIWNJBKPKL-UHFFFAOYSA-N 0.000 description 2
- SLSYWOOCUCXZIX-UHFFFAOYSA-N 1-(3-fluoro-4-propan-2-ylpyridin-2-yl)ethanone Chemical compound CC(C)C1=CC=NC(C(C)=O)=C1F SLSYWOOCUCXZIX-UHFFFAOYSA-N 0.000 description 2
- WRGQSWVCFNIUNZ-GDCKJWNLSA-N 1-oleoyl-sn-glycerol 3-phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)(O)=O WRGQSWVCFNIUNZ-GDCKJWNLSA-N 0.000 description 2
- CGSPVYCZBDFPHJ-UHFFFAOYSA-N 2,2-dimethyl-n-pyridin-2-ylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC=CC=N1 CGSPVYCZBDFPHJ-UHFFFAOYSA-N 0.000 description 2
- JNJKMILXZXZFDW-UHFFFAOYSA-N 2-(3-fluoropyridin-4-yl)propan-2-ol Chemical compound CC(C)(O)C1=CC=NC=C1F JNJKMILXZXZFDW-UHFFFAOYSA-N 0.000 description 2
- IPWYXJMZXVIHSF-UHFFFAOYSA-N 2-chloro-4,5,8-trimethylquinoline Chemical compound C1=C(Cl)N=C2C(C)=CC=C(C)C2=C1C IPWYXJMZXVIHSF-UHFFFAOYSA-N 0.000 description 2
- PFEIMKNQOIFKSW-UHFFFAOYSA-N 2-chloro-4-methylquinoline Chemical compound C1=CC=C2C(C)=CC(Cl)=NC2=C1 PFEIMKNQOIFKSW-UHFFFAOYSA-N 0.000 description 2
- UWWPWCFKWFIWCD-UHFFFAOYSA-N 2-chloro-4-propan-2-yl-1,8-naphthyridine Chemical compound C1=CC=C2C(C(C)C)=CC(Cl)=NC2=N1 UWWPWCFKWFIWCD-UHFFFAOYSA-N 0.000 description 2
- NJKNPEHTSYWZJZ-UHFFFAOYSA-N 2-chloro-4-propan-2-ylquinoline Chemical compound C1=CC=C2C(C(C)C)=CC(Cl)=NC2=C1 NJKNPEHTSYWZJZ-UHFFFAOYSA-N 0.000 description 2
- GKRZKWYQQJJGCZ-UHFFFAOYSA-N 3-fluoro-4-propan-2-ylpyridine Chemical compound CC(C)C1=CC=NC=C1F GKRZKWYQQJJGCZ-UHFFFAOYSA-N 0.000 description 2
- CELKOWQJPVJKIL-UHFFFAOYSA-N 3-fluoropyridine Chemical compound FC1=CC=CN=C1 CELKOWQJPVJKIL-UHFFFAOYSA-N 0.000 description 2
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 2
- ADHRFDCBLJVNFO-UHFFFAOYSA-N 4-methyl-3-oxo-n-phenylpentanamide Chemical compound CC(C)C(=O)CC(=O)NC1=CC=CC=C1 ADHRFDCBLJVNFO-UHFFFAOYSA-N 0.000 description 2
- SNSCXWREOANVGM-UHFFFAOYSA-N 4-propan-2-yl-1h-quinolin-2-one Chemical compound C1=CC=C2C(C(C)C)=CC(=O)NC2=C1 SNSCXWREOANVGM-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 208000008069 Geographic Atrophy Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 229910017852 NH2NH2 Inorganic materials 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 2
- 206010038934 Retinopathy proliferative Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 150000001783 ceramides Chemical class 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 2
- XCLDSQRVMMXWMS-UHFFFAOYSA-N ethyl 4-methyl-3-oxopentanoate Chemical compound CCOC(=O)CC(=O)C(C)C XCLDSQRVMMXWMS-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical class OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 2
- RYPZJWMUMBWFHP-UHFFFAOYSA-N n-(2,5-dimethylphenyl)-3-oxobutanamide Chemical compound CC(=O)CC(=O)NC1=CC(C)=CC=C1C RYPZJWMUMBWFHP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
- XECUAQMMBPDLGM-UHFFFAOYSA-N (3-methylquinolin-2-yl)hydrazine Chemical compound C1=CC=C2N=C(NN)C(C)=CC2=C1 XECUAQMMBPDLGM-UHFFFAOYSA-N 0.000 description 1
- OFDZKBFTLZFTIK-UHFFFAOYSA-N (4-propan-2-yl-1,8-naphthyridin-2-yl)hydrazine Chemical compound C1=CC=C2C(C(C)C)=CC(NN)=NC2=N1 OFDZKBFTLZFTIK-UHFFFAOYSA-N 0.000 description 1
- FNJFUYZZASEULX-UHFFFAOYSA-N (4-propan-2-ylquinolin-2-yl)hydrazine Chemical compound C1=CC=C2C(C(C)C)=CC(NN)=NC2=C1 FNJFUYZZASEULX-UHFFFAOYSA-N 0.000 description 1
- DVTCUDPIYVUMJB-UHFFFAOYSA-N 1,3-dimethyl-7-propan-2-ylpyrazolo[4,3-b]pyridine Chemical compound CC(C)C1=CC=NC2=C1N(C)N=C2C DVTCUDPIYVUMJB-UHFFFAOYSA-N 0.000 description 1
- LMABTFWHIPWRPC-UHFFFAOYSA-N 1-(2,6-dichloropyridin-4-yl)-3-[(1,3-dimethyl-7-propan-2-ylpyrazolo[4,3-b]pyridin-5-yl)methyl]urea Chemical compound N=1C=2C(C)=NN(C)C=2C(C(C)C)=CC=1CNC(=O)NC1=CC(Cl)=NC(Cl)=C1 LMABTFWHIPWRPC-UHFFFAOYSA-N 0.000 description 1
- VBJHQEDFVPOUBY-UHFFFAOYSA-N 1-(2-chloro-6-methoxypyridin-4-yl)-3-[(1,3-dimethyl-7-propan-2-ylpyrazolo[4,3-b]pyridin-5-yl)methyl]urea Chemical compound ClC1=NC(OC)=CC(NC(=O)NCC=2N=C3C(C)=NN(C)C3=C(C(C)C)C=2)=C1 VBJHQEDFVPOUBY-UHFFFAOYSA-N 0.000 description 1
- PTRPWZRYRPWCAX-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)-3-[(1,3,7-trimethylpyrazolo[4,3-b]pyridin-5-yl)methyl]urea Chemical compound N1=C2C(C)=NN(C)C2=C(C)C=C1CNC(=O)NC1=CC(Cl)=CC(Cl)=C1 PTRPWZRYRPWCAX-UHFFFAOYSA-N 0.000 description 1
- NINGJRZBJRFQBJ-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)-3-[(1,3-dimethyl-7-propan-2-ylpyrazolo[4,3-b]pyridin-5-yl)methyl]urea Chemical compound N=1C=2C(C)=NN(C)C=2C(C(C)C)=CC=1CNC(=O)NC1=CC(Cl)=CC(Cl)=C1 NINGJRZBJRFQBJ-UHFFFAOYSA-N 0.000 description 1
- OHKRXLXZZHSWJD-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)-3-[(4-propan-2-yl-1,8-naphthyridin-2-yl)amino]urea Chemical compound N=1C2=NC=CC=C2C(C(C)C)=CC=1NNC(=O)NC1=CC(Cl)=CC(Cl)=C1 OHKRXLXZZHSWJD-UHFFFAOYSA-N 0.000 description 1
- BXSULSOCJNTUJS-YTBMLWRQSA-N 1-(3-O-sulfo-beta-D-galactosyl)sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO[C@@H]1O[C@H](CO)[C@H](O)[C@H](OS(O)(=O)=O)[C@H]1O BXSULSOCJNTUJS-YTBMLWRQSA-N 0.000 description 1
- OHZNSGRDILOLBK-UHFFFAOYSA-N 1-(3-fluoro-4-propan-2-ylpyridin-2-yl)ethanol Chemical compound CC(C)C1=CC=NC(C(C)O)=C1F OHZNSGRDILOLBK-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- SQSYNRCXIZHKAI-UHFFFAOYSA-N 2,6-dichloroisonicotinic acid Chemical compound OC(=O)C1=CC(Cl)=NC(Cl)=C1 SQSYNRCXIZHKAI-UHFFFAOYSA-N 0.000 description 1
- BNYBPNNCZIYMQR-UHFFFAOYSA-N 2-butyl-6-chloropyridine-4-carboxylic acid Chemical compound CCCCC1=CC(C(O)=O)=CC(Cl)=N1 BNYBPNNCZIYMQR-UHFFFAOYSA-N 0.000 description 1
- UAKXMKQZURGJKF-UHFFFAOYSA-N 2-chloro-4,8-dimethylquinoline Chemical compound C1=C(Cl)N=C2C(C)=CC=CC2=C1C UAKXMKQZURGJKF-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- QWUGOXHPDJPRLE-UHFFFAOYSA-N 4,5,8-trimethyl-1h-quinolin-2-one Chemical compound CC1=CC(=O)NC2=C1C(C)=CC=C2C QWUGOXHPDJPRLE-UHFFFAOYSA-N 0.000 description 1
- ZDRVLAOYDGQLFI-UHFFFAOYSA-N 4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol;hydrochloride Chemical compound Cl.C1=CC(O)=CC=C1NC1=NC(C=2C=CC(Cl)=CC=2)=CS1 ZDRVLAOYDGQLFI-UHFFFAOYSA-N 0.000 description 1
- ZYOMICXXLAKTLG-UHFFFAOYSA-N 4-isocyanato-2,6-bis(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC(N=C=O)=CC(C(F)(F)F)=N1 ZYOMICXXLAKTLG-UHFFFAOYSA-N 0.000 description 1
- IGGZHDMWZNFDBQ-UHFFFAOYSA-N 4-isocyanatopyridine Chemical class O=C=NC1=CC=NC=C1 IGGZHDMWZNFDBQ-UHFFFAOYSA-N 0.000 description 1
- UYGZBDXIEDQOTH-UHFFFAOYSA-N 4-methyl-1h-1,8-naphthyridin-2-one Chemical compound C1=CC=C2C(C)=CC(=O)NC2=N1 UYGZBDXIEDQOTH-UHFFFAOYSA-N 0.000 description 1
- WVJNHTAZDQXNBW-UHFFFAOYSA-N 4-propan-2-yl-1h-1,8-naphthyridin-2-one Chemical compound C1=CC=C2C(C(C)C)=CC(=O)NC2=N1 WVJNHTAZDQXNBW-UHFFFAOYSA-N 0.000 description 1
- XCRCMXKLPILHJL-UHFFFAOYSA-N 5-butyl-2-chloropyridine-4-carboxylic acid Chemical compound CCCCC1=CN=C(Cl)C=C1C(O)=O XCRCMXKLPILHJL-UHFFFAOYSA-N 0.000 description 1
- USJZVJJLQHBDCM-UHFFFAOYSA-N 5-chloro-1,3-dimethyl-7-propan-2-ylpyrazolo[4,3-b]pyridine Chemical compound CC(C)C1=CC(Cl)=NC2=C1N(C)N=C2C USJZVJJLQHBDCM-UHFFFAOYSA-N 0.000 description 1
- FJNJDGVJWCIUFW-UHFFFAOYSA-N 6-propylpyridine Chemical compound CCCC1=C=CC=C[N]1 FJNJDGVJWCIUFW-UHFFFAOYSA-N 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010006811 Bursitis Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000004201 Ceramidases Human genes 0.000 description 1
- 108090000751 Ceramidases Proteins 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- MJINEYZQNHRUAM-UHFFFAOYSA-N ClC1=CC(=CC(Cl)=N1)[N+]#[C-] Chemical compound ClC1=CC(=CC(Cl)=N1)[N+]#[C-] MJINEYZQNHRUAM-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- LNQCUTNLHUQZLR-VNPYQEQNSA-N Iridin Natural products O(C)c1c(O)c2C(=O)C(c3cc(OC)c(OC)c(O)c3)=COc2cc1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 LNQCUTNLHUQZLR-VNPYQEQNSA-N 0.000 description 1
- 208000000501 Lipidoses Diseases 0.000 description 1
- 206010024585 Lipidosis Diseases 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010028391 Musculoskeletal Pain Diseases 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010040047 Sepsis Diseases 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
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 206010043255 Tendonitis Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010069363 Traumatic lung injury Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000000489 anti-atherogenic effect Effects 0.000 description 1
- 230000002300 anti-fibrosis Effects 0.000 description 1
- 230000003510 anti-fibrotic effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000036523 atherogenesis Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000005841 biaryl group Chemical group 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 239000011903 deuterated solvents Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000547 effect on apoptosis Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- XVWFJKVWKCCZME-UHFFFAOYSA-N ethyl 2,4-dioxooctanoate Chemical compound CCCCC(=O)CC(=O)C(=O)OCC XVWFJKVWKCCZME-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000009067 heart development Effects 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 108010047623 iridine Proteins 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- HAWUPFPGLDIOFA-UHFFFAOYSA-N n-methoxy-n,2-dimethylpropanamide Chemical compound CON(C)C(=O)C(C)C HAWUPFPGLDIOFA-UHFFFAOYSA-N 0.000 description 1
- OYVXVLSZQHSNDK-UHFFFAOYSA-N n-methoxy-n-methylacetamide Chemical compound CON(C)C(C)=O OYVXVLSZQHSNDK-UHFFFAOYSA-N 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 108010035597 sphingosine kinase Proteins 0.000 description 1
- JLVSPVFPBBFMBE-HXSWCURESA-O sphingosylphosphocholine acid Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H]([NH3+])COP([O-])(=O)OCC[N+](C)(C)C JLVSPVFPBBFMBE-HXSWCURESA-O 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Oncology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24664209P | 2009-09-29 | 2009-09-29 | |
| PCT/US2010/050486 WO2011041287A1 (en) | 2009-09-29 | 2010-09-28 | Condensed ring pyridine compounds as subtype-selective modulators of sphingosine-1-phosphate-2 (s1p2) receptors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2012003718A true MX2012003718A (es) | 2012-06-28 |
Family
ID=43031503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2012003718A MX2012003718A (es) | 2009-09-29 | 2010-09-28 | Compuestos de piridina de anillo condensado como moduladores selectivos de subtipo de receptores de esfingosina-1-fosfato-2 (s1p2). |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US8507682B2 (enExample) |
| EP (1) | EP2483245A1 (enExample) |
| JP (1) | JP2013506003A (enExample) |
| KR (1) | KR20120087932A (enExample) |
| CN (1) | CN102741232A (enExample) |
| AU (1) | AU2010300791A1 (enExample) |
| BR (1) | BR112012007095A2 (enExample) |
| CA (1) | CA2775587A1 (enExample) |
| IL (1) | IL218843A0 (enExample) |
| MX (1) | MX2012003718A (enExample) |
| NZ (1) | NZ599595A (enExample) |
| RU (1) | RU2012114718A (enExample) |
| SG (1) | SG10201406178WA (enExample) |
| WO (1) | WO2011041287A1 (enExample) |
| ZA (1) | ZA201202366B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013148460A1 (en) | 2012-03-26 | 2013-10-03 | Swenson Rolf E | Novel sphingosine 1-phosphate receptor antagonists |
| WO2014158302A1 (en) * | 2013-03-25 | 2014-10-02 | Swenson Rolf Eric | Novel sphingosine 1-phosphate receptor antagonists |
| CA2953208C (en) * | 2014-06-02 | 2022-05-10 | Dalhousie University | Treatment of familial exudative vitreoretinopathy through s1pr2 inhibition |
| US10487082B2 (en) | 2015-06-01 | 2019-11-26 | Dalhousie University | S1PR2 antagonists and uses therefor |
| US10858358B2 (en) | 2015-06-01 | 2020-12-08 | Dalhousie University | S1PR2 antagonists and uses therefor |
| CN107849038A (zh) * | 2015-06-01 | 2018-03-27 | 达尔豪西大学 | S1pr2拮抗剂及其用途 |
| CN107382965A (zh) * | 2017-08-14 | 2017-11-24 | 河南科技大学第附属医院 | 具有抗肿瘤活性的新型s1p‑1受体激动剂药物分子的合成方法 |
| CN113896646B (zh) * | 2020-07-06 | 2023-06-02 | 浙江海森药业股份有限公司 | 一种4-甲基-3-氧代-n-苯基戊酰胺的高效绿色制备方法 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0146810A3 (de) | 1983-12-05 | 1987-05-13 | Solco Basel AG | Verfahren zur Herstellung von Sphingosinderivaten |
| US5110987A (en) | 1988-06-17 | 1992-05-05 | Emory University | Method of preparing sphingosine derivatives |
| ZA902794B (en) | 1989-04-18 | 1991-04-24 | Duphar Int Res | New 3-n substituted carbamoyl-indole derivatives |
| US5294722A (en) | 1992-04-16 | 1994-03-15 | E. R. Squibb & Sons, Inc. | Process for the preparation of imidazoles useful in angiotensin II antagonism |
| US5403851A (en) | 1994-04-05 | 1995-04-04 | Interneuron Pharmaceuticals, Inc. | Substituted tryptamines, phenalkylamines and related compounds |
| JP4001929B2 (ja) | 1997-03-12 | 2007-10-31 | タカラバイオ株式会社 | スフィンゴシン類縁化合物 |
| AU9002298A (en) | 1997-09-11 | 1999-03-29 | Takara Shuzo Co., Ltd. | Sphingosine derivatives and medicinal composition |
| WO2001098301A1 (en) * | 2000-06-20 | 2001-12-27 | Japan Tobacco Inc. | Pyrazolopyridine compounds and use thereof as drugs |
| US20020183762A1 (en) | 2001-06-01 | 2002-12-05 | Ams Research Corporation | Bone anchor inserters and methods |
| WO2003000253A1 (en) | 2001-06-20 | 2003-01-03 | Wyeth | Substituted indole acid derivatives as inhibitors of plasminogen activator inhibitor-1 (pai-1) |
| JPWO2003020313A1 (ja) * | 2001-09-04 | 2004-12-16 | 小野薬品工業株式会社 | スフィンゴシン−１−リン酸受容体調節剤からなる呼吸器疾患治療剤 |
| WO2003051876A1 (en) * | 2001-12-14 | 2003-06-26 | Japan Tobacco Inc. | Pyrazolopyridine derivatives and medicinal use thereof |
| GB0206876D0 (en) * | 2002-03-22 | 2002-05-01 | Merck Sharp & Dohme | Therapeutic agents |
| US7429609B2 (en) | 2002-05-31 | 2008-09-30 | Eisai R & D Management Co., Ltd. | Pyrazole compound and medicinal composition containing the same |
| WO2008154470A1 (en) | 2007-06-08 | 2008-12-18 | University Of Connecticut | Nhibitor of the receptor activity of the s1p2 receptor for inhibiting pathological angiogenesis in the eye |
| WO2009074969A2 (en) * | 2007-12-12 | 2009-06-18 | University Of Lausanne | Sphingosine-1-phosphate, analogs and antagonists for use as medicaments |
-
2010
- 2010-09-28 CA CA2775587A patent/CA2775587A1/en not_active Abandoned
- 2010-09-28 RU RU2012114718/04A patent/RU2012114718A/ru not_active Application Discontinuation
- 2010-09-28 KR KR1020127010718A patent/KR20120087932A/ko not_active Withdrawn
- 2010-09-28 WO PCT/US2010/050486 patent/WO2011041287A1/en not_active Ceased
- 2010-09-28 MX MX2012003718A patent/MX2012003718A/es active IP Right Grant
- 2010-09-28 SG SG10201406178WA patent/SG10201406178WA/en unknown
- 2010-09-28 US US13/498,499 patent/US8507682B2/en not_active Expired - Fee Related
- 2010-09-28 BR BR112012007095A patent/BR112012007095A2/pt not_active IP Right Cessation
- 2010-09-28 NZ NZ599595A patent/NZ599595A/en not_active IP Right Cessation
- 2010-09-28 JP JP2012532230A patent/JP2013506003A/ja active Pending
- 2010-09-28 CN CN2010800492699A patent/CN102741232A/zh active Pending
- 2010-09-28 EP EP10763267A patent/EP2483245A1/en not_active Withdrawn
- 2010-09-28 AU AU2010300791A patent/AU2010300791A1/en not_active Abandoned
-
2012
- 2012-03-26 IL IL218843A patent/IL218843A0/en unknown
- 2012-04-02 ZA ZA2012/02366A patent/ZA201202366B/en unknown
-
2013
- 2013-06-27 US US13/929,451 patent/US8703797B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20120208840A1 (en) | 2012-08-16 |
| CA2775587A1 (en) | 2011-04-07 |
| US8703797B2 (en) | 2014-04-22 |
| SG10201406178WA (en) | 2014-11-27 |
| EP2483245A1 (en) | 2012-08-08 |
| IL218843A0 (en) | 2012-06-28 |
| ZA201202366B (en) | 2012-12-27 |
| US8507682B2 (en) | 2013-08-13 |
| RU2012114718A (ru) | 2013-11-10 |
| WO2011041287A1 (en) | 2011-04-07 |
| CN102741232A (zh) | 2012-10-17 |
| KR20120087932A (ko) | 2012-08-07 |
| JP2013506003A (ja) | 2013-02-21 |
| NZ599595A (en) | 2014-03-28 |
| US20130296361A1 (en) | 2013-11-07 |
| AU2010300791A1 (en) | 2012-04-19 |
| BR112012007095A2 (pt) | 2016-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8703797B2 (en) | Condensed ring pyridine compounds as subtype-selective modulators of sphingosine-1-phosphate-2 (S1P2) receptors | |
| AU2013371146B2 (en) | 2,3-dihydro-isoindole-1-on derivative as BTK kinase suppressant, and pharmaceutical composition including same | |
| RU2193036C2 (ru) | Производные имидазо[1,2-а]пиридина, способы их получения, фармацевтический препарат на их основе, способ ингибирования секреции желудочной кислоты, способ лечения желудочно-кишечных воспалительных заболеваний и способ лечения состояний, в которые вовлечено инфицирование h.pylori | |
| US8536339B2 (en) | AZA-indoles and related compounds having sphingosine-1-phosphate (S1P) receptor antagonist biological activity | |
| DK165249B (da) | Imidazooe4,5-baaquinolin-2-thionderivater samt fremgangsmaade til fremstilling deraf | |
| CA2969597C (en) | 1h-pyrazolo[4,3-c][1,5]naphthyridin-4(5h)-one compounds and their use as pde2 inhibitors | |
| KR20120130294A (ko) | 비시클릭 화합물 및 이중 ｃ―ｓｒｃ／ｊａｋ 억제제로서의 그의 용도 | |
| WO2003057695A1 (en) | 1,6 naphthyridines useful as inhibitors of syk kinase | |
| JP2003511451A (ja) | 二環状イミダゾ−３−イル−アミン誘導体 | |
| AU2007292347A1 (en) | Heteroaromatic compounds having sphingosine-1-phosphate (S1P) receptor agonist and/or antagonist biological activity | |
| JP2014513078A (ja) | パーキンソン病の治療方法及び治療用組成物 | |
| KR20140014104A (ko) | 치환된 이미다조퀴놀린 유도체 | |
| KR20150054833A (ko) | 단백질 키나제 억제제로서의 아미노이소퀴놀린 유도체 | |
| NO811041L (no) | Imidazopyridiner og fremgangsmaate til deres fremstilling | |
| CZ20021243A3 (cs) | Bicyklické deriváty imidazo-3-yl-aminu, substituované na šestičlenném kruhu | |
| JP2008543880A (ja) | ナフチリジン化合物 | |
| JP2002020386A (ja) | ピラゾロピリジン誘導体 | |
| KR101803866B1 (ko) | 동맥경화증 치료에 유용한 콜레스테릴 에스테르-전달 단백질(cetp) 억제제로서 5-벤질아미노메틸-6-아미노피라졸로[3,4-b]피리딘 유도체 | |
| KR100633814B1 (ko) | 안트라닐산 아미드 및 그의 제약상 용도 | |
| JPS62277359A (ja) | ３−ヒドロキシピリジン誘導体 | |
| WO2008030838A2 (en) | Heteroaromatic compounds having sphingosine-1-phosphate (s1p) receptor agonist biological activity | |
| WO2011008475A1 (en) | Optionally substituted 2-(arylmethyl, aryloxy or arylthio) -n- pyridin-2 -yl-aryl acetamide or 2, 2-bis (aryl) -n-pyridin-2-yl acetamide compounds as medicaments for the treatment of eye diseases | |
| EP3459948B1 (en) | Fluorine-containing triazolopyridine, and manufacturing method, pharmaceutical composition, and application thereof | |
| AU2023357817A1 (en) | 8-hydroxyquinoline compound and use thereof | |
| KR20110025751A (ko) | 치료적으로 유용한 치환된 1,7-다이페닐-1,2,3,5,6,7-헥사하이드로피리도[3,2,1-ij]퀴놀린 화합물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Grant or registration |