AU2007261786A1 - Novel heteroaryl substituted benzoxazoles - Google Patents
Novel heteroaryl substituted benzoxazoles Download PDFInfo
- Publication number
- AU2007261786A1 AU2007261786A1 AU2007261786A AU2007261786A AU2007261786A1 AU 2007261786 A1 AU2007261786 A1 AU 2007261786A1 AU 2007261786 A AU2007261786 A AU 2007261786A AU 2007261786 A AU2007261786 A AU 2007261786A AU 2007261786 A1 AU2007261786 A1 AU 2007261786A1
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- fluoroalkyl
- methoxy
- nhc
- alkoxy
- 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.)
- Abandoned
Links
- 125000001072 heteroaryl group Chemical group 0.000 title description 18
- 150000000183 1,3-benzoxazoles Chemical class 0.000 title description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 296
- 150000001875 compounds Chemical class 0.000 claims description 264
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 222
- -1 bromo, iodo Chemical group 0.000 claims description 109
- 125000003545 alkoxy group Chemical group 0.000 claims description 93
- 238000000034 method Methods 0.000 claims description 66
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 51
- 125000004429 atom Chemical group 0.000 claims description 45
- 230000027455 binding Effects 0.000 claims description 43
- 125000001153 fluoro group Chemical group F* 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 33
- 208000024827 Alzheimer disease Diseases 0.000 claims description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
- 208000037259 Amyloid Plaque Diseases 0.000 claims description 31
- 125000002947 alkylene group Chemical group 0.000 claims description 29
- 239000002243 precursor Substances 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 125000001246 bromo group Chemical group Br* 0.000 claims description 21
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 19
- 238000001727 in vivo Methods 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 238000003384 imaging method Methods 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 239000012453 solvate Substances 0.000 claims description 17
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 16
- 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 15
- 238000011282 treatment Methods 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 238000001514 detection method Methods 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 238000011503 in vivo imaging Methods 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- OKCTZPKXJWOEEN-UHFFFAOYSA-N 5-(6-methoxy-1,3-benzoxazol-2-yl)pyridin-2-amine Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CC=C(N)N=C1 OKCTZPKXJWOEEN-UHFFFAOYSA-N 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- TXFCYCHIDAWSKH-UHFFFAOYSA-N 5-(6-methoxy-1,3-benzoxazol-2-yl)-n-methylpyridin-2-amine Chemical compound C1=NC(NC)=CC=C1C1=NC2=CC=C(OC)C=C2O1 TXFCYCHIDAWSKH-UHFFFAOYSA-N 0.000 claims description 9
- 239000012458 free base Substances 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 125000000524 functional group Chemical group 0.000 claims description 7
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 7
- 238000004611 spectroscopical analysis Methods 0.000 claims description 7
- YGOSXGXSOQDVMZ-UHFFFAOYSA-N 2-(6-bromopyridin-3-yl)-6-methoxy-1,3-benzoxazole Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CC=C(Br)N=C1 YGOSXGXSOQDVMZ-UHFFFAOYSA-N 0.000 claims description 6
- YJLXFCMFMJTMNI-UHFFFAOYSA-N 2-(6-fluoropyridin-3-yl)-6-methoxy-1,3-benzoxazole Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CC=C(F)N=C1 YJLXFCMFMJTMNI-UHFFFAOYSA-N 0.000 claims description 6
- MUNSCAJTQCLVNR-UHFFFAOYSA-N 2-[6-(methylamino)pyridin-3-yl]-1,3-benzoxazol-6-ol Chemical compound C1=NC(NC)=CC=C1C1=NC2=CC=C(O)C=C2O1 MUNSCAJTQCLVNR-UHFFFAOYSA-N 0.000 claims description 6
- OVGMJBWEKPKLLO-UHFFFAOYSA-N 5-(6-methoxy-1,3-benzoxazol-2-yl)-n-methylpyrimidin-2-amine Chemical compound C1=NC(NC)=NC=C1C1=NC2=CC=C(OC)C=C2O1 OVGMJBWEKPKLLO-UHFFFAOYSA-N 0.000 claims description 6
- DECLYJIGPYNKTH-UHFFFAOYSA-N 5-(6-methoxy-1,3-benzoxazol-2-yl)-n-phenylpyrimidin-2-amine Chemical compound O1C2=CC(OC)=CC=C2N=C1C(C=N1)=CN=C1NC1=CC=CC=C1 DECLYJIGPYNKTH-UHFFFAOYSA-N 0.000 claims description 6
- QMZQYCHTMLIPOK-UHFFFAOYSA-N 5-(6-methoxy-1,3-benzoxazol-2-yl)pyrimidin-2-amine Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CN=C(N)N=C1 QMZQYCHTMLIPOK-UHFFFAOYSA-N 0.000 claims description 6
- UDAVSWULZNLITD-UHFFFAOYSA-N 5-(6-methyl-1,3-benzoxazol-2-yl)pyrimidin-2-amine Chemical compound O1C2=CC(C)=CC=C2N=C1C1=CN=C(N)N=C1 UDAVSWULZNLITD-UHFFFAOYSA-N 0.000 claims description 6
- 201000010374 Down Syndrome Diseases 0.000 claims description 6
- 206010044688 Trisomy 21 Diseases 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 238000002595 magnetic resonance imaging Methods 0.000 claims description 6
- OWLGAGALTSVSSS-UHFFFAOYSA-N n-(2-fluoroethyl)-5-(6-methoxy-1,3-benzoxazol-2-yl)pyridin-2-amine Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CC=C(NCCF)N=C1 OWLGAGALTSVSSS-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 5
- MJNSIXWSKLVPSV-UHFFFAOYSA-N 2-(1h-indol-5-yl)-6-methoxy-1,3-benzoxazole Chemical compound C1=C2NC=CC2=CC(C2=NC3=CC=C(C=C3O2)OC)=C1 MJNSIXWSKLVPSV-UHFFFAOYSA-N 0.000 claims description 5
- FSFKUQZDHKZBLL-UHFFFAOYSA-N 2-(5-aminopyridin-2-yl)-1,3-benzoxazol-6-amine Chemical compound N1=CC(N)=CC=C1C1=NC2=CC=C(N)C=C2O1 FSFKUQZDHKZBLL-UHFFFAOYSA-N 0.000 claims description 5
- RVJVDPDTDMWHQD-UHFFFAOYSA-N 2-(5-bromopyridin-2-yl)-6-methoxy-1,3-benzoxazole Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CC=C(Br)C=N1 RVJVDPDTDMWHQD-UHFFFAOYSA-N 0.000 claims description 5
- WHXBBKCQUJHZDF-UHFFFAOYSA-N 2-(5-methylpyridin-2-yl)-1,3-benzoxazole Chemical compound N1=CC(C)=CC=C1C1=NC2=CC=CC=C2O1 WHXBBKCQUJHZDF-UHFFFAOYSA-N 0.000 claims description 5
- IEDOEYOGCKTFEL-UHFFFAOYSA-N 2-(6-aminopyridin-3-yl)-1,3-benzoxazol-6-ol Chemical compound C1=NC(N)=CC=C1C1=NC2=CC=C(O)C=C2O1 IEDOEYOGCKTFEL-UHFFFAOYSA-N 0.000 claims description 5
- IMVSIIKTEDBTKB-UHFFFAOYSA-N 2-[2-(dimethylamino)pyrimidin-5-yl]-1,3-benzoxazol-6-ol Chemical compound C1=NC(N(C)C)=NC=C1C1=NC2=CC=C(O)C=C2O1 IMVSIIKTEDBTKB-UHFFFAOYSA-N 0.000 claims description 5
- RTEOLQIZQATWRQ-UHFFFAOYSA-N 2-[6-(dimethylamino)pyridin-3-yl]-1,3-benzoxazol-5-ol Chemical compound C1=NC(N(C)C)=CC=C1C1=NC2=CC(O)=CC=C2O1 RTEOLQIZQATWRQ-UHFFFAOYSA-N 0.000 claims description 5
- HMECLUHCEMVGIG-UHFFFAOYSA-N 2-[6-(dimethylamino)pyridin-3-yl]-1,3-benzoxazol-6-ol Chemical compound C1=NC(N(C)C)=CC=C1C1=NC2=CC=C(O)C=C2O1 HMECLUHCEMVGIG-UHFFFAOYSA-N 0.000 claims description 5
- ZKTVEWCZBLTWOU-UHFFFAOYSA-N 5-(6-methoxy-1,3-benzoxazol-2-yl)-n,n-dimethylpyridin-2-amine Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CC=C(N(C)C)N=C1 ZKTVEWCZBLTWOU-UHFFFAOYSA-N 0.000 claims description 5
- 108700028369 Alleles Proteins 0.000 claims description 5
- 108010060159 Apolipoprotein E4 Proteins 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- NWQWRLMTZFTONP-UHFFFAOYSA-N 2-(6-fluoro-5-methylpyridin-3-yl)-6-methoxy-1,3-benzoxazole Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CN=C(F)C(C)=C1 NWQWRLMTZFTONP-UHFFFAOYSA-N 0.000 claims description 4
- GCIWQBXSMSCWCO-UHFFFAOYSA-N 2-(6-methoxypyridin-3-yl)-1,3-benzoxazol-6-ol Chemical compound C1=NC(OC)=CC=C1C1=NC2=CC=C(O)C=C2O1 GCIWQBXSMSCWCO-UHFFFAOYSA-N 0.000 claims description 4
- BKRGFNKOVNFDQQ-UHFFFAOYSA-N 5-methyl-2-(6-methylpyridin-3-yl)-1,3-benzoxazole Chemical compound N=1C2=CC(C)=CC=C2OC=1C1=CC=C(C)N=C1 BKRGFNKOVNFDQQ-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 claims description 4
- 208000015756 familial Alzheimer disease Diseases 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- OKYACJPYGTYVQH-UHFFFAOYSA-N n-(2-fluoroethyl)-5-(6-methoxy-1,3-benzoxazol-2-yl)pyrimidin-2-amine Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CN=C(NCCF)N=C1 OKYACJPYGTYVQH-UHFFFAOYSA-N 0.000 claims description 4
- PMYOVKULDGQRPS-UHFFFAOYSA-N n-[5-(6-methoxy-1,3-benzoxazol-2-yl)pyridin-2-yl]-n-methylacetamide Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CC=C(N(C)C(C)=O)N=C1 PMYOVKULDGQRPS-UHFFFAOYSA-N 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- KIIIHCXEONLFSZ-UHFFFAOYSA-N tert-butyl n-[5-(6-methoxy-1,3-benzoxazol-2-yl)pyridin-2-yl]carbamate Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CC=C(NC(=O)OC(C)(C)C)N=C1 KIIIHCXEONLFSZ-UHFFFAOYSA-N 0.000 claims description 4
- BGQJXBYZFGZVTE-UHFFFAOYSA-N tert-butyl n-[5-(6-methoxy-1,3-benzoxazol-2-yl)pyrimidin-2-yl]carbamate Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CN=C(NC(=O)OC(C)(C)C)N=C1 BGQJXBYZFGZVTE-UHFFFAOYSA-N 0.000 claims description 4
- SXNMOAMMLMXNFC-UHFFFAOYSA-N 2-(1-benzofuran-2-yl)-6-methoxy-1,3-benzoxazole Chemical compound C1=CC=C2OC(C3=NC4=CC=C(C=C4O3)OC)=CC2=C1 SXNMOAMMLMXNFC-UHFFFAOYSA-N 0.000 claims description 3
- KLXNFYDOVNTPMI-UHFFFAOYSA-N 2-(5-fluoro-6-methoxypyridin-3-yl)-6-methoxy-1,3-benzoxazole Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CN=C(OC)C(F)=C1 KLXNFYDOVNTPMI-UHFFFAOYSA-N 0.000 claims description 3
- UWHPNURHXXGJAZ-UHFFFAOYSA-N 5-(5-methoxy-1,3-benzoxazol-2-yl)-n,n-dimethylpyridin-2-amine Chemical compound N=1C2=CC(OC)=CC=C2OC=1C1=CC=C(N(C)C)N=C1 UWHPNURHXXGJAZ-UHFFFAOYSA-N 0.000 claims description 3
- KSNMWTQKDUOCMX-UHFFFAOYSA-N 5-[6-[tert-butyl(dimethyl)silyl]oxy-1,3-benzoxazol-2-yl]pyridin-2-amine Chemical compound O1C2=CC(O[Si](C)(C)C(C)(C)C)=CC=C2N=C1C1=CC=C(N)N=C1 KSNMWTQKDUOCMX-UHFFFAOYSA-N 0.000 claims description 3
- PVNIAKNZFUDCCQ-UHFFFAOYSA-N 6-methoxy-2-(6-methoxypyridin-3-yl)-1,3-benzoxazole Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CC=C(OC)N=C1 PVNIAKNZFUDCCQ-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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- SOHOMFMEUMYUGG-UHFFFAOYSA-N tert-butyl 5-methoxy-2-(6-methoxy-1,3-benzoxazol-2-yl)indole-1-carboxylate Chemical compound C1=C(OC)C=C2OC(C=3N(C(=O)OC(C)(C)C)C4=CC=C(C=C4C=3)OC)=NC2=C1 SOHOMFMEUMYUGG-UHFFFAOYSA-N 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 2
- MNCMBBIFTVWHIP-UHFFFAOYSA-N 1-anthracen-9-yl-2,2,2-trifluoroethanone Chemical group C1=CC=C2C(C(=O)C(F)(F)F)=C(C=CC=C3)C3=CC2=C1 MNCMBBIFTVWHIP-UHFFFAOYSA-N 0.000 claims description 2
- BAJBDICKCWWWHL-UHFFFAOYSA-N 2-(6-morpholin-4-ylpyridin-3-yl)-1,3-benzoxazole Chemical compound C1COCCN1C1=CC=C(C=2OC3=CC=CC=C3N=2)C=N1 BAJBDICKCWWWHL-UHFFFAOYSA-N 0.000 claims description 2
- YOADTNNBRKOTAC-UHFFFAOYSA-N 2-[6-(2-fluoroethoxy)pyridin-3-yl]-6-methoxy-1,3-benzoxazole Chemical compound O1C2=CC(OC)=CC=C2N=C1C1=CC=C(OCCF)N=C1 YOADTNNBRKOTAC-UHFFFAOYSA-N 0.000 claims description 2
- WBQUBKGXZVXILO-UHFFFAOYSA-N 2-[6-(2-fluoroethylamino)pyridin-3-yl]-1,3-benzoxazol-6-ol Chemical compound O1C2=CC(O)=CC=C2N=C1C1=CC=C(NCCF)N=C1 WBQUBKGXZVXILO-UHFFFAOYSA-N 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 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
- 239000000470 constituent Substances 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- MZLNLHZXUZRHEC-UHFFFAOYSA-N methyl 2-[2-(dimethylamino)pyrimidin-5-yl]-1,3-benzoxazole-6-carboxylate Chemical compound O1C2=CC(C(=O)OC)=CC=C2N=C1C1=CN=C(N(C)C)N=C1 MZLNLHZXUZRHEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 13
- 101000932768 Conus catus Alpha-conotoxin CIC Proteins 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 32
- 238000005481 NMR spectroscopy Methods 0.000 description 30
- 239000007787 solid Substances 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 27
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- 210000004556 brain Anatomy 0.000 description 26
- 239000000543 intermediate Substances 0.000 description 26
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- 238000006243 chemical reaction Methods 0.000 description 25
- 125000003118 aryl group Chemical group 0.000 description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 22
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000002372 labelling Methods 0.000 description 16
- 230000009466 transformation Effects 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 125000006239 protecting group Chemical group 0.000 description 15
- 239000011734 sodium Substances 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 125000000623 heterocyclic group Chemical group 0.000 description 11
- 150000002431 hydrogen Chemical class 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical class C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
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- 230000015572 biosynthetic process Effects 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 238000002600 positron emission tomography Methods 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 238000004007 reversed phase HPLC Methods 0.000 description 9
- 238000000844 transformation Methods 0.000 description 9
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
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- 206010002022 amyloidosis Diseases 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
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- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
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| US81493606P | 2006-06-19 | 2006-06-19 | |
| US60/814,936 | 2006-06-19 | ||
| PCT/SE2007/000591 WO2007149030A1 (en) | 2006-06-19 | 2007-06-18 | Novel heteroaryl substituted benzoxazoles |
Publications (1)
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| AU2007261786A1 true AU2007261786A1 (en) | 2007-12-27 |
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| AU (1) | AU2007261786A1 (enExample) |
| CA (1) | CA2655084A1 (enExample) |
| CL (1) | CL2007001784A1 (enExample) |
| IL (1) | IL195669A0 (enExample) |
| MX (1) | MX2008015718A (enExample) |
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| WO (1) | WO2007149030A1 (enExample) |
| ZA (1) | ZA200810163B (enExample) |
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| TW201018678A (en) | 2006-01-27 | 2010-05-16 | Astrazeneca Ab | Novel heteroaryl substituted benzothiazoles |
| TW200901998A (en) | 2007-03-06 | 2009-01-16 | Astrazeneca Ab | Novel 2-heteroaryl substituted benzothiophenes and benzofuranes |
| EP2300481B1 (en) * | 2008-05-30 | 2015-09-30 | Merck Sharp & Dohme Corp. | Novel substituted azabenzoxazoles |
| AU2009309027A1 (en) * | 2008-10-31 | 2010-05-06 | Merck Sharp & Dohme Corp. | Novel substituted azabenzoxazoles |
| WO2012027289A1 (en) * | 2010-08-23 | 2012-03-01 | Syntrix Biosystems Inc. | Aminopyridine- and aminopyrimidinecarboxamides as cxcr2 modulators |
| ES2650744T3 (es) * | 2010-12-14 | 2018-01-22 | Electrophoretics Limited | Inhibidores de la caseína quinasa 1 delta (CK1delta) |
| WO2014132919A1 (ja) * | 2013-02-28 | 2014-09-04 | 国立大学法人京都大学 | 診断用組成物 |
| KR101499329B1 (ko) * | 2013-06-17 | 2015-03-06 | 주식회사 대웅제약 | (2-(3,4-다이메톡시페닐)-5-(3-메톡시프로필)벤조퓨란)의결정형 및 이의 제조방법 |
| JP6149684B2 (ja) * | 2013-10-21 | 2017-06-21 | ブラザー工業株式会社 | 携帯端末、画像処理装置、及びプログラム |
| WO2015112048A1 (en) * | 2014-01-24 | 2015-07-30 | Huawei Technologies Co., Ltd. | Method and device for cross-polarization interference suppression |
| CN104059028B (zh) * | 2014-06-06 | 2020-10-16 | 北京智博高科生物技术有限公司 | 与Aβ斑块具有亲和力的含手性侧链取代的氟代2-芳基苯并杂环化合物、其制备方法及应用 |
| KR101709731B1 (ko) * | 2015-05-22 | 2017-02-23 | 한국과학기술연구원 | 벤조옥사졸 또는 벤조티아졸 화합물, 그의 제조, 및 용도 |
| US10324943B2 (en) * | 2015-08-10 | 2019-06-18 | Business Objects Software, Ltd. | Auto-monitoring and adjustment of dynamic data visualizations |
| KR20180052611A (ko) * | 2015-08-18 | 2018-05-18 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 영상화 및 치료 용도를 위한 니트록사이드 함유 아밀로이드 결합 제제 |
| KR101812424B1 (ko) * | 2016-12-28 | 2017-12-27 | 충북대학교 산학협력단 | 2-(2-아미노-5-(1-(피퍼리딘-4-일)-1H-피라졸-3-일)피리딘-3-일)벤조[d]옥사졸-6-올 및 이를 유효성분으로 포함하는 치매의 예방 및 치료용 조성물 |
| WO2021154842A1 (en) * | 2020-01-28 | 2021-08-05 | Protego Biopharma, Inc. | Compounds, compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding |
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| GB8305245D0 (en) | 1983-02-25 | 1983-03-30 | Fujisawa Pharmaceutical Co | Imidazo-heterocyclic compounds |
| JPS6394248A (ja) * | 1986-10-08 | 1988-04-25 | Canon Inc | 電子写真感光体 |
| 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 |
| EP0735821A4 (en) | 1993-12-21 | 1998-04-01 | Lilly Co Eli | METHODS FOR TREATING OR PREVENTING CONDITIONS ASSOCIATED WITH AMYLO DOGEN PEPTIDES |
| 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 |
| BRPI0113470B8 (pt) | 2000-08-24 | 2021-05-25 | Univ Pittsburgh | composto de ligação amilóide, composição farmacêutica e métodos de síntese de composto, de detecção in vivo de depósitos amilóides num indivíduo e em tecido humano ou animal, de quantificação de depósito amilóide em tecido de biópsia ou postmortem e de distinção de um cérebro de doença de alzheimer de um cérebro normal |
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| 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 |
| DE60326735D1 (de) | 2002-08-02 | 2009-04-30 | Genesoft Pharmaceuticals Inc | Biaryl-verbindungen mit antiinfektiver wirkung |
| 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 |
| US20060276433A1 (en) | 2003-03-31 | 2006-12-07 | Keiichi Kawagoe | Hydrazone derivative |
| PL1636217T3 (pl) | 2003-05-13 | 2009-02-27 | Hoffmann La Roche | 1-Imidazobenzotiazole jako ligandy receptora adenozynowego |
| CN101137397A (zh) | 2004-07-02 | 2008-03-05 | 匹兹堡大学高等教育联邦体系 | 淀粉样蛋白成像作为抗淀粉样蛋白疗法的功效的替代标记物 |
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| TW201018678A (en) | 2006-01-27 | 2010-05-16 | Astrazeneca Ab | Novel heteroaryl substituted benzothiazoles |
| NZ570625A (en) * | 2006-02-10 | 2011-10-28 | Biomarin Iga Ltd | Treatment of duchenne muscular dystrophy |
| US7700616B2 (en) * | 2006-05-08 | 2010-04-20 | Molecular Neuroimaging, Llc. | Compounds and amyloid probes thereof for therapeutic and imaging uses |
| KR20090101469A (ko) | 2007-01-22 | 2009-09-28 | 아스트라제네카 아베 | 신규 헤테로아릴 치환된 이미다조〔１，２ａ〕피리딘 유도체 |
-
2007
- 2007-06-08 TW TW096120843A patent/TW200813035A/zh unknown
- 2007-06-14 US US11/763,151 patent/US7670591B2/en not_active Expired - Fee Related
- 2007-06-18 CA CA002655084A patent/CA2655084A1/en not_active Abandoned
- 2007-06-18 WO PCT/SE2007/000591 patent/WO2007149030A1/en not_active Ceased
- 2007-06-18 UY UY30419A patent/UY30419A1/es not_active Application Discontinuation
- 2007-06-18 AU AU2007261786A patent/AU2007261786A1/en not_active Abandoned
- 2007-06-18 KR KR1020097000992A patent/KR20090021224A/ko not_active Withdrawn
- 2007-06-18 EP EP07748254A patent/EP2035418A1/en not_active Withdrawn
- 2007-06-18 MX MX2008015718A patent/MX2008015718A/es not_active Application Discontinuation
- 2007-06-18 JP JP2009516443A patent/JP5548842B2/ja not_active Expired - Fee Related
- 2007-06-18 CN CN2007800308078A patent/CN101506201B/zh not_active Expired - Fee Related
- 2007-06-18 CL CL2007001784A patent/CL2007001784A1/es unknown
- 2007-06-19 AR ARP070102680A patent/AR061515A1/es unknown
-
2008
- 2008-11-28 ZA ZA200810163A patent/ZA200810163B/xx unknown
- 2008-12-02 IL IL195669A patent/IL195669A0/en unknown
-
2009
- 2009-01-13 NO NO20090201A patent/NO20090201L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IL195669A0 (en) | 2009-09-01 |
| NO20090201L (no) | 2009-01-13 |
| CL2007001784A1 (es) | 2008-01-18 |
| US7670591B2 (en) | 2010-03-02 |
| UY30419A1 (es) | 2008-01-31 |
| AR061515A1 (es) | 2008-09-03 |
| ZA200810163B (en) | 2010-05-26 |
| WO2007149030A1 (en) | 2007-12-27 |
| CA2655084A1 (en) | 2007-12-27 |
| CN101506201B (zh) | 2012-03-14 |
| MX2008015718A (es) | 2008-12-19 |
| JP5548842B2 (ja) | 2014-07-16 |
| US20080027051A1 (en) | 2008-01-31 |
| JP2009541309A (ja) | 2009-11-26 |
| KR20090021224A (ko) | 2009-02-27 |
| TW200813035A (en) | 2008-03-16 |
| EP2035418A1 (en) | 2009-03-18 |
| WO2007149030A8 (en) | 2008-02-28 |
| CN101506201A (zh) | 2009-08-12 |
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