ES2605039T3 - Compuestos de furopiridina y usos de los mismos - Google Patents
Compuestos de furopiridina y usos de los mismos Download PDFInfo
- Publication number
- ES2605039T3 ES2605039T3 ES11715244.7T ES11715244T ES2605039T3 ES 2605039 T3 ES2605039 T3 ES 2605039T3 ES 11715244 T ES11715244 T ES 11715244T ES 2605039 T3 ES2605039 T3 ES 2605039T3
- Authority
- ES
- Spain
- Prior art keywords
- pyridine
- alkyl
- methylsulfonamido
- furo
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
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- YRTCKZIKGWZNCU-UHFFFAOYSA-N furo[3,2-b]pyridine Chemical class C1=CC=C2OC=CC2=N1 YRTCKZIKGWZNCU-UHFFFAOYSA-N 0.000 title 1
- -1 morpholino, piperidino, piperazino Chemical group 0.000 claims abstract description 280
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 16
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 102
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 102
- 235000005152 nicotinamide Nutrition 0.000 claims description 51
- 239000011570 nicotinamide Substances 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 32
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 19
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 11
- DJAQYMZRMHFAFB-UHFFFAOYSA-N 5-[[5-cyclopropyl-3-(methylcarbamoyl)-2-(4-methylphenyl)furo[2,3-b]pyridin-6-yl]-methylsulfonylamino]pentanoic acid Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(C)=CC=3)OC2=NC(N(CCCCC(O)=O)S(C)(=O)=O)=C1C1CC1 DJAQYMZRMHFAFB-UHFFFAOYSA-N 0.000 claims description 3
- SHXLAOFQWUYTDX-UHFFFAOYSA-N 5-iodo-n-methyl-2-(4-methylphenyl)-6-[methylsulfonyl(4-methylsulfonylbutyl)amino]furo[2,3-b]pyridine-3-carboxamide Chemical compound O1C2=NC(N(CCCCS(C)(=O)=O)S(C)(=O)=O)=C(I)C=C2C(C(=O)NC)=C1C1=CC=C(C)C=C1 SHXLAOFQWUYTDX-UHFFFAOYSA-N 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims 2
- RXANCFTWVPGFRL-UHFFFAOYSA-N 5-cyclopropyl-n-methyl-2-(4-methylphenyl)-6-[methylsulfonyl(3-methylsulfonylpropyl)amino]furo[2,3-b]pyridine-3-carboxamide Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(C)=CC=3)OC2=NC(N(CCCS(C)(=O)=O)S(C)(=O)=O)=C1C1CC1 RXANCFTWVPGFRL-UHFFFAOYSA-N 0.000 claims 1
- IXONLEJUCDYTID-UHFFFAOYSA-N 5-cyclopropyl-n-methyl-2-(4-methylphenyl)-6-[methylsulfonyl(4-methylsulfonylbutyl)amino]furo[2,3-b]pyridine-3-carboxamide Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(C)=CC=3)OC2=NC(N(CCCCS(C)(=O)=O)S(C)(=O)=O)=C1C1CC1 IXONLEJUCDYTID-UHFFFAOYSA-N 0.000 claims 1
- FUTXLNJFFGUFNW-UHFFFAOYSA-N 5-ethyl-6-[3-ethylsulfonylpropyl(methylsulfonyl)amino]-2-(4-fluorophenyl)-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound O1C=2N=C(N(CCCS(=O)(=O)CC)S(C)(=O)=O)C(CC)=CC=2C(C(=O)NC)=C1C1=CC=C(F)C=C1 FUTXLNJFFGUFNW-UHFFFAOYSA-N 0.000 claims 1
- JDQGFJWHBQHPKG-UHFFFAOYSA-N 6-[3-cyclopropylsulfonylpropyl(methylsulfonyl)amino]-5-ethyl-2-(4-fluorophenyl)-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound CCC1=CC=2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC=2N=C1N(S(C)(=O)=O)CCCS(=O)(=O)C1CC1 JDQGFJWHBQHPKG-UHFFFAOYSA-N 0.000 claims 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 1
- 201000003278 cryoglobulinemia Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 1
- 230000028993 immune response Effects 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 claims 1
- 208000019423 liver disease Diseases 0.000 claims 1
- ZYNLVZYDZVXBMV-UHFFFAOYSA-N methyl 5-[[5-cyclopropyl-3-(methylcarbamoyl)-2-(4-methylphenyl)furo[2,3-b]pyridin-6-yl]-methylsulfonylamino]pentanoate Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(C)=CC=3)OC2=NC(N(CCCCC(=O)OC)S(C)(=O)=O)=C1C1CC1 ZYNLVZYDZVXBMV-UHFFFAOYSA-N 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 abstract description 15
- 150000002367 halogens Chemical group 0.000 abstract description 15
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 7
- 125000003282 alkyl amino group Chemical group 0.000 abstract description 6
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 6
- 239000001257 hydrogen Substances 0.000 abstract description 5
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 3
- 125000001153 fluoro group Chemical group F* 0.000 abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 abstract description 3
- 125000001309 chloro group Chemical group Cl* 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 14
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 abstract 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 8
- 125000005842 heteroatom Chemical group 0.000 abstract 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 4
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 abstract 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 2
- 125000004429 atom Chemical group 0.000 abstract 2
- 125000001072 heteroaryl group Chemical group 0.000 abstract 2
- 125000005553 heteroaryloxy group Chemical group 0.000 abstract 2
- 150000002431 hydrogen Chemical class 0.000 abstract 2
- 125000004043 oxo group Chemical group O=* 0.000 abstract 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 abstract 2
- 125000004076 pyridyl group Chemical group 0.000 abstract 2
- 125000001424 substituent group Chemical group 0.000 abstract 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 abstract 1
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 abstract 1
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 abstract 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 abstract 1
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 abstract 1
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 abstract 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 abstract 1
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 abstract 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 abstract 1
- 125000005865 C2-C10alkynyl group Chemical group 0.000 abstract 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract 1
- 102100022626 Glutamate receptor ionotropic, NMDA 2D Human genes 0.000 abstract 1
- 108091008644 NR2D Proteins 0.000 abstract 1
- 125000001589 carboacyl group Chemical group 0.000 abstract 1
- 229910052801 chlorine Inorganic materials 0.000 abstract 1
- 239000000460 chlorine Substances 0.000 abstract 1
- 125000002541 furyl group Chemical group 0.000 abstract 1
- 125000004438 haloalkoxy group Chemical group 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 46
- WRJDMGHOBCKBJC-UHFFFAOYSA-N furo[2,3-b]pyridine-3-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=COC2=N1 WRJDMGHOBCKBJC-UHFFFAOYSA-N 0.000 description 45
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 30
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 28
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 22
- 238000000034 method Methods 0.000 description 21
- 239000000203 mixture Substances 0.000 description 18
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 12
- 150000002500 ions Chemical class 0.000 description 12
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 229910001868 water Inorganic materials 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 239000004530 micro-emulsion Substances 0.000 description 5
- HNBDRPTVWVGKBR-UHFFFAOYSA-N n-pentanoic acid methyl ester Natural products CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- BHIZVZJETFVJMJ-UHFFFAOYSA-N 2-hydroxypropyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(C)O BHIZVZJETFVJMJ-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 4
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 3
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 229940095102 methyl benzoate Drugs 0.000 description 3
- UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 3
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 2
- YDBXHEIUYJHTCZ-UHFFFAOYSA-N 6-[3-cyanopropyl(methylsulfonyl)amino]-2-(4-fluorophenyl)-5-iodo-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound O1C2=NC(N(CCCC#N)S(C)(=O)=O)=C(I)C=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 YDBXHEIUYJHTCZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 239000007821 HATU Substances 0.000 description 2
- 208000005176 Hepatitis C Diseases 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
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 2
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 2
- 229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 description 2
- 150000001336 alkenes Chemical group 0.000 description 2
- 238000010976 amide bond formation reaction Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- 125000004470 heterocyclooxy group Chemical group 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000026045 iodination Effects 0.000 description 2
- 238000006192 iodination reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 2
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000008389 polyethoxylated castor oil Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- DSQRAYCAIWKYLW-IEBWSBKVSA-N (1r,2s)-2-[2-[[5-cyclopropyl-3-(methylcarbamoyl)-2-(4-methylphenyl)furo[2,3-b]pyridin-6-yl]-methylsulfonylamino]ethyl]cyclopropane-1-carboxylic acid Chemical compound C1CC1C=1C=C2C(C(=O)NC)=C(C=3C=CC(C)=CC=3)OC2=NC=1N(S(C)(=O)=O)CC[C@@H]1C[C@H]1C(O)=O DSQRAYCAIWKYLW-IEBWSBKVSA-N 0.000 description 1
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- XGLCQRWSPFJJKY-UHFFFAOYSA-N 5-ethyl-2-(4-fluorophenyl)-n-methyl-6-[methyl(methylsulfonyl)amino]furo[2,3-b]pyridine-3-carboxamide Chemical compound O1C=2N=C(N(C)S(C)(=O)=O)C(CC)=CC=2C(C(=O)NC)=C1C1=CC=C(F)C=C1 XGLCQRWSPFJJKY-UHFFFAOYSA-N 0.000 description 1
- ZUDVLKFTAPRGMR-UHFFFAOYSA-N 6-[(3-carbamoylphenyl)methyl-methylsulfonylamino]-2-(4-fluorophenyl)-5-iodo-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound IC=1C=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=NC=1N(S(C)(=O)=O)CC1=CC=CC(C(N)=O)=C1 ZUDVLKFTAPRGMR-UHFFFAOYSA-N 0.000 description 1
- JVRBCXLZCQNNLO-UHFFFAOYSA-N 6-[2-(2-cyanophenoxy)ethyl-methylsulfonylamino]-5-ethyl-2-(4-fluorophenyl)-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound CCC1=CC=2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC=2N=C1N(S(C)(=O)=O)CCOC1=CC=CC=C1C#N JVRBCXLZCQNNLO-UHFFFAOYSA-N 0.000 description 1
- WJCYSYXWZONRNC-UHFFFAOYSA-N 6-[2-(3,4-dimethoxyphenyl)ethyl-methylsulfonylamino]-5-ethyl-2-(4-fluorophenyl)-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound CCC1=CC=2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC=2N=C1N(S(C)(=O)=O)CCC1=CC=C(OC)C(OC)=C1 WJCYSYXWZONRNC-UHFFFAOYSA-N 0.000 description 1
- MSAFLZBJVRHXNX-UHFFFAOYSA-N 6-[3,4-dihydroxybutyl(methylsulfonyl)amino]-2-(4-fluorophenyl)-5-iodo-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound O1C2=NC(N(CCC(O)CO)S(C)(=O)=O)=C(I)C=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 MSAFLZBJVRHXNX-UHFFFAOYSA-N 0.000 description 1
- DRLIUTKRVAANPG-UHFFFAOYSA-N 6-[3-(2-cyanophenoxy)propyl-methylsulfonylamino]-5-ethyl-2-(4-fluorophenyl)-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound CCC1=CC=2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC=2N=C1N(S(C)(=O)=O)CCCOC1=CC=CC=C1C#N DRLIUTKRVAANPG-UHFFFAOYSA-N 0.000 description 1
- BFOYDNICIAFTNH-UHFFFAOYSA-N 6-[3-tert-butylsulfonylpropyl(methylsulfonyl)amino]-5-ethyl-2-(4-fluorophenyl)-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound O1C=2N=C(N(CCCS(=O)(=O)C(C)(C)C)S(C)(=O)=O)C(CC)=CC=2C(C(=O)NC)=C1C1=CC=C(F)C=C1 BFOYDNICIAFTNH-UHFFFAOYSA-N 0.000 description 1
- UXEASTSSSNCHKB-UHFFFAOYSA-N 6-[4-(2-cyanophenoxy)butyl-methylsulfonylamino]-5-ethyl-2-(4-fluorophenyl)-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound CCC1=CC=2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC=2N=C1N(S(C)(=O)=O)CCCCOC1=CC=CC=C1C#N UXEASTSSSNCHKB-UHFFFAOYSA-N 0.000 description 1
- ROEVRLMHXNUAEU-UHFFFAOYSA-N 6-[4-aminobutyl(methylsulfonyl)amino]-2-(4-fluorophenyl)-5-iodo-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound O1C2=NC(N(CCCCN)S(C)(=O)=O)=C(I)C=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 ROEVRLMHXNUAEU-UHFFFAOYSA-N 0.000 description 1
- PGAATQQKJJNIKQ-UHFFFAOYSA-N 6-[4-bromobutyl(methylsulfonyl)amino]-5-ethyl-2-(4-fluorophenyl)-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound O1C=2N=C(N(CCCCBr)S(C)(=O)=O)C(CC)=CC=2C(C(=O)NC)=C1C1=CC=C(F)C=C1 PGAATQQKJJNIKQ-UHFFFAOYSA-N 0.000 description 1
- AGXNMBKAFSFPEQ-UHFFFAOYSA-N 6-[[5-cyclopropyl-2-(4-ethylphenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-6-yl]-methylsulfonylamino]hexanoic acid Chemical compound C1=CC(CC)=CC=C1C1=C(C(=O)NC)C2=CC(C3CC3)=C(N(CCCCCC(O)=O)S(C)(=O)=O)N=C2O1 AGXNMBKAFSFPEQ-UHFFFAOYSA-N 0.000 description 1
- VUMDFSHQKKODCG-UHFFFAOYSA-N 6-[[5-cyclopropyl-3-(methylcarbamoyl)-2-(4-methylphenyl)furo[2,3-b]pyridin-6-yl]-methylsulfonylamino]-3-hydroxy-2,2-dimethylhexanoic acid Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(C)=CC=3)OC2=NC(N(CCCC(O)C(C)(C)C(O)=O)S(C)(=O)=O)=C1C1CC1 VUMDFSHQKKODCG-UHFFFAOYSA-N 0.000 description 1
- LOHQLFYMIWMKAW-UHFFFAOYSA-N 6-[but-3-enyl(methylsulfonyl)amino]-2-(4-fluorophenyl)-5-iodo-n-methylfuro[2,3-b]pyridine-3-carboxamide Chemical compound O1C2=NC(N(CCC=C)S(C)(=O)=O)=C(I)C=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 LOHQLFYMIWMKAW-UHFFFAOYSA-N 0.000 description 1
- XMTYYRQMGIKRRN-UHFFFAOYSA-N 8-(4-fluorophenyl)-n,5-dimethyl-1-methylsulfonyl-3,5-dihydro-2h-furo[3,4]pyrido[3,5-b][1,4]oxazepine-7-carboxamide Chemical compound O1C2=NC=3N(S(C)(=O)=O)CCOC(C)C=3C=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 XMTYYRQMGIKRRN-UHFFFAOYSA-N 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
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- 238000007341 Heck reaction Methods 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
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- WJXODLFKRQCFGH-UHFFFAOYSA-N N-methyl-3H-indene-1-carboxamide Chemical compound CNC(=O)C1=CCC2=CC=CC=C12 WJXODLFKRQCFGH-UHFFFAOYSA-N 0.000 description 1
- ZYVXHFWBYUDDBM-UHFFFAOYSA-N N-methylnicotinamide Chemical compound CNC(=O)C1=CC=CN=C1 ZYVXHFWBYUDDBM-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000005865 alkene metathesis reaction Methods 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 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
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000005518 carboxamido group Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 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
- 239000012043 crude product Substances 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000005906 dihydroxylation reaction Methods 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 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
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
- CNCMVGXVKBJYNU-UHFFFAOYSA-N methyl oxane-4-carboxylate Chemical compound COC(=O)C1CCOCC1 CNCMVGXVKBJYNU-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-M prolinate Chemical compound [O-]C(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-M 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- NZCRJKRKKOLAOJ-XRCRFVBUSA-N rifaximin Chemical compound OC1=C(C(O)=C2C)C3=C4N=C5C=C(C)C=CN5C4=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O NZCRJKRKKOLAOJ-XRCRFVBUSA-N 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- IMXYQPGLNHQCJH-UHFFFAOYSA-N tert-butyl 4-[2-[[5-ethyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-6-yl]-methylsulfonylamino]ethyl]piperazine-1-carboxylate Chemical compound CCC1=CC=2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC=2N=C1N(S(C)(=O)=O)CCN1CCN(C(=O)OC(C)(C)C)CC1 IMXYQPGLNHQCJH-UHFFFAOYSA-N 0.000 description 1
- QPXXZLUNEOQVJG-UHFFFAOYSA-N tert-butyl 4-[3-[[5-ethyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-6-yl]-methylsulfonylamino]propyl]piperazine-1-carboxylate Chemical compound CCC1=CC=2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC=2N=C1N(S(C)(=O)=O)CCCN1CCN(C(=O)OC(C)(C)C)CC1 QPXXZLUNEOQVJG-UHFFFAOYSA-N 0.000 description 1
- ZUGNLQSMJYBIFS-UHFFFAOYSA-N tert-butyl n-pentylcarbamate Chemical compound CCCCCNC(=O)OC(C)(C)C ZUGNLQSMJYBIFS-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32649110P | 2010-04-21 | 2010-04-21 | |
| US326491P | 2010-04-21 | ||
| PCT/EP2011/056304 WO2011131709A1 (en) | 2010-04-21 | 2011-04-20 | Furopyridine compounds and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2605039T3 true ES2605039T3 (es) | 2017-03-10 |
Family
ID=44010017
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11715244.7T Active ES2605039T3 (es) | 2010-04-21 | 2011-04-20 | Compuestos de furopiridina y usos de los mismos |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US8324239B2 (enExample) |
| EP (1) | EP2560976B9 (enExample) |
| JP (1) | JP5756850B2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| BR112013009789A2 (pt) * | 2010-10-26 | 2016-07-19 | Presidio Pharmaceuticals Inc | inibidores do vírus da hepatite c |
| WO2013163466A1 (en) * | 2012-04-25 | 2013-10-31 | Presidio Pharmaceuticals, Inc. | Inhibitors of hepatitis c virus |
| TWI731854B (zh) | 2015-03-23 | 2021-07-01 | 美商共結晶製藥公司 | Ｃ型肝炎病毒聚合酶之抑制劑 |
| BR112017023821A2 (pt) | 2015-05-06 | 2018-07-31 | Leidos Biomedical Res Inc | moduladores de k-ras |
| BR112019021899A2 (pt) | 2017-04-20 | 2020-08-18 | The Regents Of The University Of California | moduladores de k-ras |
| KR102659322B1 (ko) * | 2017-05-19 | 2024-04-22 | 엔플렉션 테라퓨틱스, 인코포레이티드 | 피부병 치료를 위한 융합된 헤테로방향족-아닐린 화합물 |
| WO2019204449A1 (en) * | 2018-04-18 | 2019-10-24 | Theras, Inc. | K-ras modulators with a vinyl sulfone moiety |
| CN108727309B (zh) * | 2018-06-20 | 2023-04-07 | 天津全和诚科技有限责任公司 | 一种3-氧杂环丁烷羧酸的合成方法 |
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| US8324239B2 (en) | 2012-12-04 |
| AR082453A1 (es) | 2012-12-12 |
| JP2013527842A (ja) | 2013-07-04 |
| JP5756850B2 (ja) | 2015-07-29 |
| EP2560976B9 (en) | 2017-06-07 |
| CN103025738B (zh) | 2015-08-19 |
| CN103025738A (zh) | 2013-04-03 |
| US20120015907A1 (en) | 2012-01-19 |
| EP2560976B1 (en) | 2016-08-24 |
| EP2560976A1 (en) | 2013-02-27 |
| WO2011131709A1 (en) | 2011-10-27 |
| UY33348A (es) | 2011-12-01 |
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