MX2008015718A - Nuevos benzoxazoles sustituidos con heteroarilo. - Google Patents
Nuevos benzoxazoles sustituidos con heteroarilo.Info
- Publication number
- MX2008015718A MX2008015718A MX2008015718A MX2008015718A MX2008015718A MX 2008015718 A MX2008015718 A MX 2008015718A MX 2008015718 A MX2008015718 A MX 2008015718A MX 2008015718 A MX2008015718 A MX 2008015718A MX 2008015718 A MX2008015718 A MX 2008015718A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- fluoroalkyl
- methoxy
- alkylene
- alkoxy
- Prior art date
Links
- 125000001072 heteroaryl group Chemical group 0.000 title abstract description 18
- 150000000183 1,3-benzoxazoles Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 270
- 238000000034 method Methods 0.000 claims abstract description 73
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 34
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 208000037259 Amyloid Plaque Diseases 0.000 claims abstract description 33
- 238000001727 in vivo Methods 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 15
- 230000008569 process Effects 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 213
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 194
- -1 bromo, iodo Chemical group 0.000 claims description 107
- 125000002947 alkylene group Chemical group 0.000 claims description 99
- 125000003545 alkoxy group Chemical group 0.000 claims description 67
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 57
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 51
- 229910052794 bromium Inorganic materials 0.000 claims description 49
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 48
- 125000004429 atom Chemical group 0.000 claims description 47
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims description 40
- 230000027455 binding Effects 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052731 fluorine Inorganic materials 0.000 claims description 34
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 239000011737 fluorine Substances 0.000 claims description 31
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
- 238000002360 preparation method Methods 0.000 claims description 28
- 230000015572 biosynthetic process Effects 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 239000002243 precursor Substances 0.000 claims description 25
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
- 125000001153 fluoro group Chemical group F* 0.000 claims description 17
- 239000012453 solvate Substances 0.000 claims description 17
- 239000011135 tin Substances 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 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 13
- 238000001514 detection method Methods 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 12
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 11
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 9
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 9
- 239000012458 free base Substances 0.000 claims description 9
- 238000011503 in vivo imaging Methods 0.000 claims description 9
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 9
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 claims description 8
- 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 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 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
- 238000002595 magnetic resonance imaging Methods 0.000 claims description 7
- 238000004611 spectroscopical analysis Methods 0.000 claims description 7
- 201000010374 Down Syndrome Diseases 0.000 claims description 6
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 6
- 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
- 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
- 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 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
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 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 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- 108700028369 Alleles Proteins 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 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 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
- 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 4
- 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 4
- 101100054666 Streptomyces halstedii sch3 gene Proteins 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
- GEOVEUCEIQCBKH-UHFFFAOYSA-N hypoiodous acid Chemical group IO GEOVEUCEIQCBKH-UHFFFAOYSA-N 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
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000000565 sulfonamide group Chemical group 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 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
- 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 3
- 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 3
- 125000004791 2-fluoroethoxy group Chemical group FCCO* 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
- 108010060159 Apolipoprotein E4 Proteins 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 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
- 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 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 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
- 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 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
- 125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 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 2
- 238000002560 therapeutic procedure Methods 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
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims 2
- 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 1
- 101100483630 Arabidopsis thaliana UCH3 gene Proteins 0.000 claims 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 29
- 210000004556 brain Anatomy 0.000 abstract description 26
- 238000003384 imaging method Methods 0.000 abstract description 9
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical class C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 6
- 238000003745 diagnosis Methods 0.000 abstract description 4
- 229940124597 therapeutic agent Drugs 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 238000005481 NMR spectroscopy Methods 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- 239000007787 solid Substances 0.000 description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- 239000002904 solvent Substances 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 26
- 125000003118 aryl group Chemical group 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 25
- 239000000543 intermediate Substances 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 22
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
- 125000006239 protecting group Chemical group 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 238000002600 positron emission tomography Methods 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 125000000623 heterocyclic group Chemical group 0.000 description 11
- 150000002431 hydrogen Chemical group 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 238000004007 reversed phase HPLC Methods 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
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- 238000000338 in vitro Methods 0.000 description 10
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- 229910052763 palladium Inorganic materials 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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 9
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 9
- 206010002022 amyloidosis Diseases 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
- 239000002287 radioligand Substances 0.000 description 8
- 238000002603 single-photon emission computed tomography Methods 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 7
- 238000005804 alkylation reaction Methods 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- 230000009466 transformation Effects 0.000 description 7
- 229910052722 tritium Inorganic materials 0.000 description 7
- 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 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
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- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 1
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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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- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
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- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 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)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Psychiatry (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 (2)
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| US81493606P | 2006-06-19 | 2006-06-19 | |
| PCT/SE2007/000591 WO2007149030A1 (en) | 2006-06-19 | 2007-06-18 | Novel heteroaryl substituted benzoxazoles |
Publications (1)
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|---|---|
| MX2008015718A true MX2008015718A (es) | 2008-12-19 |
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| MX2008015718A MX2008015718A (es) | 2006-06-19 | 2007-06-18 | Nuevos benzoxazoles sustituidos con heteroarilo. |
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| EP (1) | EP2035418A1 (enExample) |
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| CN (1) | CN101506201B (enExample) |
| AR (1) | AR061515A1 (enExample) |
| AU (1) | AU2007261786A1 (enExample) |
| CA (1) | CA2655084A1 (enExample) |
| CL (1) | CL2007001784A1 (enExample) |
| IL (1) | IL195669A0 (enExample) |
| MX (1) | MX2008015718A (enExample) |
| NO (1) | NO20090201L (enExample) |
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| UY (1) | UY30419A1 (enExample) |
| 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 |
| JP2011524864A (ja) * | 2008-05-30 | 2011-09-08 | メルク・シャープ・エンド・ドーム・コーポレイション | 新規な置換されたアザベンゾオキサゾール |
| US20110212031A1 (en) * | 2008-10-31 | 2011-09-01 | Cyrille Sur | Novel substituted azabenzoxazoles |
| US8779149B2 (en) | 2010-08-23 | 2014-07-15 | Syntrix Biosystems, Inc. | Aminopyridine- and aminopyrimidinecarboxamides as CXCR2 modulators |
| JP5937102B2 (ja) * | 2010-12-14 | 2016-06-22 | エレクトロフォレティクス リミテッド | カゼインキナーゼ１デルタ（ｃｋ１デルタ）阻害剤 |
| 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 |
| WO2017031239A1 (en) * | 2015-08-18 | 2017-02-23 | The Regents Of The University Of California | Nitroxide containing amyloid binding agents for imaging and therapeutic uses |
| 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 |
| EP4097092A1 (en) * | 2020-01-28 | 2022-12-07 | Protego Biopharma, Inc. | Compounds, compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding |
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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 |
| 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 |
| EP2264018B1 (en) | 2000-08-24 | 2015-02-11 | University of Pittsburgh - Of the Commonwealth System of Higher Education | Thioflavin derivatives for use in the diagnosis of Alzheimer's disease |
| US7045539B2 (en) | 2000-12-22 | 2006-05-16 | Astrazeneca Ab | Therapeutic benzoxazole compounds |
| US6596731B2 (en) | 2001-03-27 | 2003-07-22 | Hoffmann-La Roche Inc. | Substituted imidazo[1,2-A] pyridine derivatives |
| ES2274973T3 (es) | 2001-04-23 | 2007-06-01 | The Trustees Of The University Of Pennsylvania | Inhibidores de la agregacion de placas amiloides y agentes de obtencion de imagenes diagnosticas. |
| US7622479B2 (en) * | 2001-11-26 | 2009-11-24 | Takeda Pharmaceutical Company Limited | Bicyclic derivative, its production and use |
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| TW200401194A (en) | 2002-07-11 | 2004-01-16 | Advanced Micro Devices Inc | Method and apparatus for determining a processor state without interrupting processor operation |
| AU2003258022A1 (en) | 2002-08-02 | 2004-02-23 | 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 |
| JPWO2004087641A1 (ja) | 2003-03-31 | 2006-06-29 | 第一製薬株式会社 | ヒドラゾン誘導体 |
| PL1636217T3 (pl) | 2003-05-13 | 2009-02-27 | Hoffmann La Roche | 1-Imidazobenzotiazole jako ligandy receptora adenozynowego |
| DK1771208T3 (da) | 2004-07-02 | 2013-09-02 | Univ Pittsburgh | Anvendelse af thioflavin radiomarkerede derivater i amyloid billeddannelse til vurdering af anti-amyloide terapier |
| GB0420722D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| WO2006125324A1 (en) | 2005-05-27 | 2006-11-30 | Queen's University At Kingston | Treatment of protein folding disorders |
| 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 |
| ES2379987T3 (es) | 2005-10-11 | 2012-05-07 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Compuestos de benzofurano marcados isotópicamente como radiotrazadores para proteínas amiloidógenas |
| WO2007063946A1 (ja) | 2005-11-30 | 2007-06-07 | Fujifilm Ri Pharma Co., Ltd. | アミロイドの凝集及び／又は沈着に起因する疾患の診断薬及び治療薬 |
| TW201018678A (en) | 2006-01-27 | 2010-05-16 | Astrazeneca Ab | Novel heteroaryl substituted benzothiazoles |
| AU2007213451B2 (en) * | 2006-02-10 | 2013-02-07 | Summit (Oxford) Limited | Treatment of Duchenne muscular dystrophy |
| WO2008118122A2 (en) * | 2006-05-08 | 2008-10-02 | Molecular Neuroimaging, Llc | Compounds and amyloid probes thereof for therapeutic and imaging uses |
| CN101641354A (zh) | 2007-01-22 | 2010-02-03 | 阿斯利康(瑞典)有限公司 | 杂芳基取代的新咪唑并[1，2-a]吡啶衍生物 |
-
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 AU AU2007261786A patent/AU2007261786A1/en not_active Abandoned
- 2007-06-18 CL CL2007001784A patent/CL2007001784A1/es unknown
- 2007-06-18 MX MX2008015718A patent/MX2008015718A/es not_active Application Discontinuation
- 2007-06-18 EP EP07748254A patent/EP2035418A1/en not_active Withdrawn
- 2007-06-18 WO PCT/SE2007/000591 patent/WO2007149030A1/en not_active Ceased
- 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 CA CA002655084A patent/CA2655084A1/en not_active Abandoned
- 2007-06-18 UY UY30419A patent/UY30419A1/es not_active Application Discontinuation
- 2007-06-18 KR KR1020097000992A patent/KR20090021224A/ko not_active Withdrawn
- 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 |
|---|---|
| AR061515A1 (es) | 2008-09-03 |
| CN101506201B (zh) | 2012-03-14 |
| UY30419A1 (es) | 2008-01-31 |
| TW200813035A (en) | 2008-03-16 |
| JP2009541309A (ja) | 2009-11-26 |
| AU2007261786A1 (en) | 2007-12-27 |
| NO20090201L (no) | 2009-01-13 |
| IL195669A0 (en) | 2009-09-01 |
| CA2655084A1 (en) | 2007-12-27 |
| EP2035418A1 (en) | 2009-03-18 |
| US7670591B2 (en) | 2010-03-02 |
| CN101506201A (zh) | 2009-08-12 |
| KR20090021224A (ko) | 2009-02-27 |
| JP5548842B2 (ja) | 2014-07-16 |
| CL2007001784A1 (es) | 2008-01-18 |
| WO2007149030A8 (en) | 2008-02-28 |
| ZA200810163B (en) | 2010-05-26 |
| WO2007149030A1 (en) | 2007-12-27 |
| US20080027051A1 (en) | 2008-01-31 |
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