SA08290097B1 - مركبات بنزوفيوران وبنزوثيوفين جديدة بها استبدال بأريل غير متجانس بالموضع 2 (709) - Google Patents
مركبات بنزوفيوران وبنزوثيوفين جديدة بها استبدال بأريل غير متجانس بالموضع 2 (709) Download PDFInfo
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- SA08290097B1 SA08290097B1 SA8290097A SA08290097A SA08290097B1 SA 08290097 B1 SA08290097 B1 SA 08290097B1 SA 8290097 A SA8290097 A SA 8290097A SA 08290097 A SA08290097 A SA 08290097A SA 08290097 B1 SA08290097 B1 SA 08290097B1
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- Saudi Arabia
- Prior art keywords
- alkyl
- fluoroalkyl
- fluoro
- compound
- compounds
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- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical class C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title abstract description 16
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 225
- 238000000034 method Methods 0.000 claims abstract description 54
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 238000006467 substitution reaction Methods 0.000 claims abstract description 26
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 77
- -1 hydroxy, methoxy Chemical group 0.000 claims description 71
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 64
- 125000004429 atom Chemical group 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 125000001153 fluoro group Chemical group F* 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 22
- 239000000470 constituent Substances 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims description 18
- 125000002947 alkylene group Chemical group 0.000 claims description 17
- 230000002285 radioactive effect Effects 0.000 claims description 16
- 125000001246 bromo group Chemical group Br* 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- IZFOPMSVNDORMZ-UHFFFAOYSA-N hydroxy-5 benzofuranne Natural products OC1=CC=C2OC=CC2=C1 IZFOPMSVNDORMZ-UHFFFAOYSA-N 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 125000000524 functional group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 239000012458 free base Substances 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 5
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
- PQCXZHFSSVHSPI-UHFFFAOYSA-N 2-[5-fluoro-6-(methylamino)pyridin-3-yl]-1-benzofuran-5-ol Chemical compound C1=C(F)C(NC)=NC=C1C1=CC2=CC(O)=CC=C2O1 PQCXZHFSSVHSPI-UHFFFAOYSA-N 0.000 claims description 3
- FXERARHKNULYEN-UHFFFAOYSA-N 2-[6-fluoro-5-(methylamino)pyridin-2-yl]-1-benzofuran-5-ol Chemical compound N1=C(F)C(NC)=CC=C1C1=CC2=CC(O)=CC=C2O1 FXERARHKNULYEN-UHFFFAOYSA-N 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- YOQRASPYXLBVOK-UHFFFAOYSA-N 2-[6-(methylamino)pyridin-3-yl]-1-benzofuran-5-ol Chemical compound C1=NC(NC)=CC=C1C1=CC2=CC(O)=CC=C2O1 YOQRASPYXLBVOK-UHFFFAOYSA-N 0.000 claims description 2
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 2
- 239000000203 mixture Substances 0.000 abstract description 42
- 208000024827 Alzheimer disease Diseases 0.000 abstract description 28
- 238000003384 imaging method Methods 0.000 abstract description 25
- 210000004556 brain Anatomy 0.000 abstract description 24
- 239000002243 precursor Substances 0.000 abstract description 18
- 208000037259 Amyloid Plaque Diseases 0.000 abstract description 14
- 125000001072 heteroaryl group Chemical group 0.000 abstract description 14
- 239000003814 drug Substances 0.000 abstract description 13
- 238000001727 in vivo Methods 0.000 abstract description 10
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 229940124597 therapeutic agent Drugs 0.000 abstract description 4
- 230000034994 death Effects 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 41
- 235000019439 ethyl acetate Nutrition 0.000 description 32
- 239000000243 solution Substances 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- 239000007787 solid Substances 0.000 description 23
- 125000003118 aryl group Chemical group 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- 229920002472 Starch Polymers 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 20
- 235000019698 starch Nutrition 0.000 description 20
- 239000008107 starch Substances 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 19
- 230000027455 binding Effects 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 17
- 230000014509 gene expression Effects 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 238000011282 treatment Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 201000010099 disease Diseases 0.000 description 14
- 125000006239 protecting group Chemical group 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 238000001514 detection method Methods 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
- 206010002022 amyloidosis Diseases 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 9
- 238000002600 positron emission tomography Methods 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- XLIQZZGLIJLKTF-UHFFFAOYSA-N (5-methoxy-1-benzofuran-2-yl)boronic acid Chemical compound COC1=CC=C2OC(B(O)O)=CC2=C1 XLIQZZGLIJLKTF-UHFFFAOYSA-N 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 7
- 230000029936 alkylation Effects 0.000 description 7
- 238000005804 alkylation reaction Methods 0.000 description 7
- 150000001907 coumarones Chemical class 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 238000002603 single-photon emission computed tomography Methods 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- 229910052722 tritium Inorganic materials 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 201000010374 Down Syndrome Diseases 0.000 description 6
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 238000004611 spectroscopical analysis Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 239000011593 sulfur Substances 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 239000003643 water by type Substances 0.000 description 6
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 5
- 206010012289 Dementia Diseases 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 206010044688 Trisomy 21 Diseases 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000007853 buffer solution Substances 0.000 description 5
- 150000003857 carboxamides Chemical class 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 125000002346 iodo group Chemical group I* 0.000 description 5
- 238000002372 labelling Methods 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 125000005466 alkylenyl group Chemical group 0.000 description 4
- 230000003941 amyloidogenesis Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
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- 229910052794 bromium Inorganic materials 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
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- 238000004128 high performance liquid chromatography Methods 0.000 description 4
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- 230000000269 nucleophilic effect Effects 0.000 description 4
- 239000005416 organic matter Substances 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
- PKRRNTJIHGOMRC-UHFFFAOYSA-N 1-benzofuran-2-ylboronic acid Chemical compound C1=CC=C2OC(B(O)O)=CC2=C1 PKRRNTJIHGOMRC-UHFFFAOYSA-N 0.000 description 3
- MYNQXTDIPMCJCR-UHFFFAOYSA-N 2-[2-fluoro-6-(methylamino)pyridin-3-yl]-1-benzofuran-5-ol Chemical compound FC1=NC(NC)=CC=C1C1=CC2=CC(O)=CC=C2O1 MYNQXTDIPMCJCR-UHFFFAOYSA-N 0.000 description 3
- SRCVFXDEGZMJDT-UHFFFAOYSA-N 2-fluoro-6-(5-methoxy-1-benzofuran-2-yl)pyridin-3-amine Chemical compound C=1C2=CC(OC)=CC=C2OC=1C1=CC=C(N)C(F)=N1 SRCVFXDEGZMJDT-UHFFFAOYSA-N 0.000 description 3
- QLXASFJHUCKEHU-UHFFFAOYSA-N 5-bromo-3-fluoropyridin-2-amine Chemical compound NC1=NC=C(Br)C=C1F QLXASFJHUCKEHU-UHFFFAOYSA-N 0.000 description 3
- SJXWFNBZBXZDCL-UHFFFAOYSA-N 5-bromo-6-fluoropyridin-2-amine Chemical compound NC1=CC=C(Br)C(F)=N1 SJXWFNBZBXZDCL-UHFFFAOYSA-N 0.000 description 3
- IPWPEOLXILHOLV-UHFFFAOYSA-N 5-bromopyridine-2-carboxamide Chemical compound NC(=O)C1=CC=C(Br)C=N1 IPWPEOLXILHOLV-UHFFFAOYSA-N 0.000 description 3
- QYJIKULJTMICLA-UHFFFAOYSA-N 6-bromo-2-fluoropyridin-3-amine Chemical compound NC1=CC=C(Br)N=C1F QYJIKULJTMICLA-UHFFFAOYSA-N 0.000 description 3
- NXKHCMJNTQJOCQ-UHFFFAOYSA-N 6-fluoro-5-(5-methoxy-1-benzofuran-2-yl)pyridin-2-amine Chemical compound C=1C2=CC(OC)=CC=C2OC=1C1=CC=C(N)N=C1F NXKHCMJNTQJOCQ-UHFFFAOYSA-N 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 3
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- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
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- 101100208721 Mus musculus Usp5 gene Proteins 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
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- 125000004849 alkoxymethyl group Chemical group 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
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- 238000001819 mass spectrum Methods 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 229960003966 nicotinamide Drugs 0.000 description 3
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- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US89314907P | 2007-03-06 | 2007-03-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SA08290097B1 true SA08290097B1 (ar) | 2011-10-29 |
Family
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Family Applications (1)
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| SA8290097A SA08290097B1 (ar) | 2007-03-06 | 2008-03-04 | مركبات بنزوفيوران وبنزوثيوفين جديدة بها استبدال بأريل غير متجانس بالموضع 2 (709) |
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| EP (1) | EP2132201B1 (enExample) |
| JP (1) | JP5631009B2 (enExample) |
| KR (1) | KR101530392B1 (enExample) |
| CN (2) | CN102617556A (enExample) |
| AR (1) | AR065599A1 (enExample) |
| AU (1) | AU2008221668B2 (enExample) |
| BR (1) | BRPI0808503B8 (enExample) |
| CA (1) | CA2680157C (enExample) |
| CL (1) | CL2008000645A1 (enExample) |
| CO (1) | CO6220965A2 (enExample) |
| EC (1) | ECSP099641A (enExample) |
| ES (1) | ES2615381T3 (enExample) |
| IL (1) | IL200524A0 (enExample) |
| MX (1) | MX2009009469A (enExample) |
| MY (1) | MY147347A (enExample) |
| NZ (1) | NZ579157A (enExample) |
| PE (1) | PE20090164A1 (enExample) |
| SA (1) | SA08290097B1 (enExample) |
| TW (1) | TW200901998A (enExample) |
| UA (1) | UA98481C2 (enExample) |
| UY (1) | UY30951A1 (enExample) |
| WO (1) | WO2008108730A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200901998A (en) * | 2007-03-06 | 2009-01-16 | Astrazeneca Ab | Novel 2-heteroaryl substituted benzothiophenes and benzofuranes |
| US8530483B2 (en) | 2008-05-30 | 2013-09-10 | Merck Sharp & Dohme Corp. | Substituted azabenzoxazoles |
| DK2308877T3 (da) | 2008-08-05 | 2014-04-22 | Daiichi Sankyo Co Ltd | Imidazopyridin-2-on-derivater |
| US8193363B2 (en) * | 2008-08-29 | 2012-06-05 | Astrazeneca Ab | Compounds suitable as precursors to compounds that are useful for imaging amyloid deposits |
| KR101123178B1 (ko) * | 2009-04-09 | 2012-06-13 | (주)에스메디 | 2-아릴벤조싸이오펜 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 퇴행성 뇌질환의 진단 또는 치료용 약학적 조성물 |
| WO2011059080A1 (ja) * | 2009-11-16 | 2011-05-19 | 第一三共株式会社 | 同位体置換されたジアミン誘導体 |
| EP2388255A1 (en) * | 2010-05-11 | 2011-11-23 | Ikerchem, S.L. | Polysubstituted benzofurans and medicinal applications thereof |
| JP5825608B2 (ja) * | 2010-08-06 | 2015-12-02 | 国立大学法人京都大学 | ピリジルベンゾフラン誘導体 |
| KR20200118005A (ko) * | 2018-02-05 | 2020-10-14 | 위니베르시떼 드 스트라스부르 | 통증 치료용 화합물 및 조성물 |
| EP4010328A1 (en) * | 2019-08-06 | 2022-06-15 | Domain Therapeutics | 5-heteroaryl-pyridin-2-amine confounds as neuropeptide ff receptor antagonists |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU523040B2 (en) | 1978-05-15 | 1982-07-08 | Kanebo Limited | Calcium -antagonistic composition |
| GB8305245D0 (en) | 1983-02-25 | 1983-03-30 | Fujisawa Pharmaceutical Co | Imidazo-heterocyclic compounds |
| CA2034309C (en) | 1990-01-22 | 1997-04-01 | Takashi Iwaki | Mesomorphic compound, liquid crystal composition containing same, liquid crystal device using same and display apparatus |
| JPH09507071A (ja) * | 1993-12-21 | 1997-07-15 | イーライ・リリー・アンド・カンパニー | アミロイド原性ペプチドに関連した状態を治療又は予防する方法 |
| US5518713A (en) | 1995-02-13 | 1996-05-21 | 3V Inc. | Benzoxazole derivatives, the use thereof as sunscreens and cosmetic compositions containing them |
| JPH11116476A (ja) | 1997-10-16 | 1999-04-27 | Sankyo Co Ltd | 縮合複素環化合物 |
| RU2324686C2 (ru) | 2000-08-24 | 2008-05-20 | Юнивесити Оф Питсбэг | ПРОИЗВОДНЫЕ ТИОФЛАВИНА, СВЯЗЫВАЮЩИЕ АМИЛОИД, СПОСОБ ОБНАРУЖЕНИЯ in vivo ОТЛОЖЕНИЙ АМИЛОИДА И СПОСОБ РАСПОЗНАВАНИЯ БОЛЕЗНИ АЛЬЦГЕЙМЕРА |
| WO2002051821A1 (en) | 2000-12-22 | 2002-07-04 | Astrazeneca Ab | Therapeutic compounds |
| JP2004520347A (ja) * | 2001-01-15 | 2004-07-08 | グラクソ グループ リミテッド | Ｌｄｌ−受容体発現のインデューサーとしてのアリールピペリジンおよびピペラジン誘導体 |
| JP4307001B2 (ja) * | 2001-03-14 | 2009-08-05 | キヤノン株式会社 | 金属配位化合物、電界発光素子及び表示装置 |
| US6596731B2 (en) | 2001-03-27 | 2003-07-22 | Hoffmann-La Roche Inc. | Substituted imidazo[1,2-A] pyridine derivatives |
| CA2444214A1 (en) | 2001-04-23 | 2002-10-31 | The Trustees Of The University Of Pennsylvania | Amyloid plaque aggregation inhibitors and diagnostic imaging agents |
| WO2003045929A1 (en) | 2001-11-26 | 2003-06-05 | Takeda Chemical Industries, Ltd. | Bicyclic derivative, process for producing the same, and use |
| GB0130305D0 (en) * | 2001-12-19 | 2002-02-06 | Amersham Plc | Compounds for imaging alzheimers disease |
| WO2003106439A1 (ja) | 2002-06-12 | 2003-12-24 | 株式会社ビーエフ研究所 | アミロイド蓄積性疾患の画像診断プローブ化合物、老人斑／びまん性老人斑染色用化合物、ならびにアミロイド蓄積性疾患の治療薬 |
| TW200401194A (en) | 2002-07-11 | 2004-01-16 | Advanced Micro Devices Inc | Method and apparatus for determining a processor state without interrupting processor operation |
| CA2494139A1 (en) * | 2002-08-02 | 2004-02-12 | Genesoft Pharmaceuticals, Inc. | Biaryl compounds having anti-infective activity |
| JP2004250411A (ja) | 2003-02-21 | 2004-09-09 | Bf Kenkyusho:Kk | アミロイドβ蓄積性疾患の診断プローブおよび治療用化合物 |
| CA2438032C (en) | 2003-03-14 | 2013-05-07 | University Of Pittsburgh | Benzothiazole derivative compounds, compositions and uses |
| CA2521056A1 (en) | 2003-03-31 | 2004-10-14 | Daiichi Pharmaceutical Co., Ltd. | Hydrazone derivative |
| WO2004101558A1 (en) | 2003-05-13 | 2004-11-25 | F. Hoffmann-La Roche Ag | 2-imidazo-benzothiazoles as adenosine receptor ligands |
| EP1644365A2 (en) * | 2003-07-02 | 2006-04-12 | Biofocus Discovery Ltd | Pyrazine and pyridine derivatives as rho kinase inhibitors |
| GB0420722D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| JP2008545663A (ja) | 2005-05-27 | 2008-12-18 | クイーンズ ユニバーシティ アット キングストン | タンパク質フォールディング障害の治療 |
| CN103110635A (zh) * | 2005-07-04 | 2013-05-22 | 海波因特制药有限责任公司 | 组胺h3受体拮抗剂 |
| WO2007033080A2 (en) | 2005-09-12 | 2007-03-22 | Emory University | Alzheimer's disease imaging agents |
| EP1937260A2 (en) | 2005-09-16 | 2008-07-02 | University of Pittsburgh | In-vivo and in-vitro method for detecting amyloid deposits having at least one amyloidogenic protein |
| US8138360B2 (en) | 2005-10-11 | 2012-03-20 | University of Pittsburgh—of the Commonwealth System of Higher Education | Isotopically-labeled benzofuran compounds as imaging agents for amyloidogenic proteins |
| US8022075B2 (en) | 2005-11-30 | 2011-09-20 | Fujifilm Ri Pharma Co., Ltd. | Diagnostic and remedy for disease caused by amyloid aggregation and/or deposition |
| TW201018678A (en) | 2006-01-27 | 2010-05-16 | Astrazeneca Ab | Novel heteroaryl substituted benzothiazoles |
| EP2023919A4 (en) | 2006-05-08 | 2010-12-22 | Molecular Neuroimaging Llc | COMPOUNDS AND AMYLOID PROBES FOR THERAPY AND IMAGING USES |
| TW200813035A (en) | 2006-06-19 | 2008-03-16 | Astrazeneca Ab | Novel heteroaryl substituted benzoxazoles |
| AU2008208091A1 (en) | 2007-01-22 | 2008-07-31 | Astrazeneca Ab | Novel heteroaryl substituted imidazo [1,2 -a] pyridine derivatives |
| TW200901998A (en) * | 2007-03-06 | 2009-01-16 | Astrazeneca Ab | Novel 2-heteroaryl substituted benzothiophenes and benzofuranes |
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2008
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- 2008-03-04 SA SA8290097A patent/SA08290097B1/ar unknown
- 2008-03-05 PE PE2008000429A patent/PE20090164A1/es not_active Application Discontinuation
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- 2008-03-05 MX MX2009009469A patent/MX2009009469A/es active IP Right Grant
- 2008-03-05 KR KR1020097018603A patent/KR101530392B1/ko active Active
- 2008-03-05 NZ NZ579157A patent/NZ579157A/en not_active IP Right Cessation
- 2008-03-05 UY UY30951A patent/UY30951A1/es not_active Application Discontinuation
- 2008-03-05 WO PCT/SE2008/050243 patent/WO2008108730A1/en not_active Ceased
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- 2008-03-05 US US12/042,795 patent/US7772256B2/en active Active
- 2008-03-05 AU AU2008221668A patent/AU2008221668B2/en active Active
- 2008-03-05 MY MYPI20093695A patent/MY147347A/en unknown
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- 2008-03-05 BR BRPI0808503A patent/BRPI0808503B8/pt active IP Right Grant
- 2008-03-05 ES ES08724190.7T patent/ES2615381T3/es active Active
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- 2008-05-03 UA UAA200908596A patent/UA98481C2/ru unknown
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2009
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- 2009-09-07 CO CO09095235A patent/CO6220965A2/es not_active Application Discontinuation
- 2009-09-21 EC EC2009009641A patent/ECSP099641A/es unknown
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