BR112017004140B1 - Agente de imagemamento, seu uso e compostos - Google Patents

Info

Publication number

BR112017004140B1

BR112017004140B1 BR112017004140-5A BR112017004140A BR112017004140B1 BR 112017004140 B1 BR112017004140 B1 BR 112017004140B1 BR 112017004140 A BR112017004140 A BR 112017004140A BR 112017004140 B1 BR112017004140 B1 BR 112017004140B1

Authority

BR

Brazil

Prior art keywords

imidazo

pyridine

carbonitrile

methoxy

methylamino

Prior art date

2014-08-29

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 97
• 239000012216 imaging agent Substances 0.000 title claims abstract description 41
• 150000003839 salts Chemical class 0.000 claims abstract description 29
• -1 -C(O)O- C1-6 alkyl Chemical group 0.000 claims description 150
• 125000000217 alkyl group Chemical group 0.000 claims description 109
• 125000001072 heteroaryl group Chemical group 0.000 claims description 71
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 42
• 108090000623 proteins and genes Proteins 0.000 claims description 32
• 102000004169 proteins and genes Human genes 0.000 claims description 32
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
• 238000002600 positron emission tomography Methods 0.000 claims description 28
• 229910052757 nitrogen Inorganic materials 0.000 claims description 27
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 26
• 125000001424 substituent group Chemical group 0.000 claims description 25
• 125000004432 carbon atom Chemical group C* 0.000 claims description 24
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 239000001257 hydrogen Substances 0.000 claims description 20
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
• 208000023105 Huntington disease Diseases 0.000 claims description 17
• 210000004556 brain Anatomy 0.000 claims description 17
• 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 16
• KIYOXVPZRXLLDR-UHFFFAOYSA-N imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound C1=C(C#N)C=CN2C=CN=C21 KIYOXVPZRXLLDR-UHFFFAOYSA-N 0.000 claims description 15
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
• 238000003384 imaging method Methods 0.000 claims description 14
• 210000004227 basal ganglia Anatomy 0.000 claims description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
• 208000037273 Pathologic Processes Diseases 0.000 claims description 12
• 230000009054 pathological process Effects 0.000 claims description 12
• 238000002595 magnetic resonance imaging Methods 0.000 claims description 11
• 238000012879 PET imaging Methods 0.000 claims description 9
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Chemical group C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
• 208000024827 Alzheimer disease Diseases 0.000 claims description 7
• 229910052731 fluorine Inorganic materials 0.000 claims description 7
• 230000004770 neurodegeneration Effects 0.000 claims description 7
• RVYYSUMYBRASNN-UHFFFAOYSA-N CN(CCOC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C=1)C Chemical compound CN(CCOC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C=1)C RVYYSUMYBRASNN-UHFFFAOYSA-N 0.000 claims description 6
• XOAVMCHKAMGNEK-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OC)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OC)=CC=C2O1 XOAVMCHKAMGNEK-UHFFFAOYSA-N 0.000 claims description 6
• NNDKOIGQUJSQOM-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCC3=CC=CN=C3)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCC3=CC=CN=C3)=CC=C2O1 NNDKOIGQUJSQOM-UHFFFAOYSA-N 0.000 claims description 6
• WNYMMHJVRNYABS-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(COCC2=CC=CN=C2)C=C1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(COCC2=CC=CN=C2)C=C1 WNYMMHJVRNYABS-UHFFFAOYSA-N 0.000 claims description 6
• ZHXPGZQNJIWLDI-UHFFFAOYSA-N COC1=CC=C2OC(=CC2=C1)C1=C(N(C)C)N2C=CC(=CC2=N1)C#N Chemical compound COC1=CC=C2OC(=CC2=C1)C1=C(N(C)C)N2C=CC(=CC2=N1)C#N ZHXPGZQNJIWLDI-UHFFFAOYSA-N 0.000 claims description 6
• MEZXIRVFTDTRHP-UHFFFAOYSA-N COC1=CC=C2OC(=CC2=C1)C1=C(NCCN(C)C)N2C=CC(=CC2=N1)C#N Chemical compound COC1=CC=C2OC(=CC2=C1)C1=C(NCCN(C)C)N2C=CC(=CC2=N1)C#N MEZXIRVFTDTRHP-UHFFFAOYSA-N 0.000 claims description 6
• 108050004784 Huntingtin Proteins 0.000 claims description 6
• KZMRYMBBISTXTB-UHFFFAOYSA-N NC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCCF)=CC=C2O1 Chemical compound NC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCCF)=CC=C2O1 KZMRYMBBISTXTB-UHFFFAOYSA-N 0.000 claims description 6
• SYARCGGAUZTGOC-UHFFFAOYSA-N S1C=2N(C(=C1)COC1=CC=C(C=C1)C=1N=C3N(C=CC(=C3)C#N)C=1NC)CCN=2 Chemical compound S1C=2N(C(=C1)COC1=CC=C(C=C1)C=1N=C3N(C=CC(=C3)C#N)C=1NC)CCN=2 SYARCGGAUZTGOC-UHFFFAOYSA-N 0.000 claims description 6
• 229910052794 bromium Inorganic materials 0.000 claims description 6
• 239000003795 chemical substances by application Substances 0.000 claims description 6
• 239000011737 fluorine Substances 0.000 claims description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
• ZWJAOVYQCAOPFB-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCCF)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OCCF)=CC=C2O1 ZWJAOVYQCAOPFB-UHFFFAOYSA-N 0.000 claims description 5
• MUZWIMCDZKOJJW-UHFFFAOYSA-N COC1=CC=C2OC(=CC2=C1)C1=CN2C=CC(=CC2=N1)C#N Chemical compound COC1=CC=C2OC(=CC2=C1)C1=CN2C=CC(=CC2=N1)C#N MUZWIMCDZKOJJW-UHFFFAOYSA-N 0.000 claims description 5
• OXJOULXWVUPSAD-UHFFFAOYSA-N COC=1C=CC(=NC=1)CNC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC Chemical compound COC=1C=CC(=NC=1)CNC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC OXJOULXWVUPSAD-UHFFFAOYSA-N 0.000 claims description 5
• VLBSNOKHTBGVSK-UHFFFAOYSA-N COC=1C=CC2=C(N(C(=N2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C)C=1 Chemical compound COC=1C=CC2=C(N(C(=N2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C)C=1 VLBSNOKHTBGVSK-UHFFFAOYSA-N 0.000 claims description 5
• QALUACFZNKUXBZ-UHFFFAOYSA-N COC=1N=CC(=NC=1)COC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC Chemical compound COC=1N=CC(=NC=1)COC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC QALUACFZNKUXBZ-UHFFFAOYSA-N 0.000 claims description 5
• 125000005133 alkynyloxy group Chemical group 0.000 claims description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
• 150000002431 hydrogen Chemical group 0.000 claims description 5
• 239000000178 monomer Substances 0.000 claims description 5
• ZPMWXDOTBGBOJU-UHFFFAOYSA-N 2-(5-bromo-1-benzofuran-2-yl)-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound BrC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C=1 ZPMWXDOTBGBOJU-UHFFFAOYSA-N 0.000 claims description 4
• MPRMRYWPRROMHA-UHFFFAOYSA-N 2-(5-methoxy-1-methylbenzimidazol-2-yl)-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound COC1=CC2=C(N(C(=N2)C=2N=C3N(C=CC(=C3)C#N)C=2NC)C)C=C1 MPRMRYWPRROMHA-UHFFFAOYSA-N 0.000 claims description 4
• PYKSYJJOIRRNGO-VMPITWQZSA-N 2-[(E)-2-(4-methoxyphenyl)ethenyl]-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound COC1=CC=C(C=C1)/C=C/C=1N=C2N(C=CC(=C2)C#N)C=1NC PYKSYJJOIRRNGO-VMPITWQZSA-N 0.000 claims description 4
• XAWNDICSNACTDK-UHFFFAOYSA-N 3-(methylamino)-2-[3-(pyridin-3-ylmethoxymethyl)phenyl]imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC(=CC=C1)COCC=1C=NC=CC=1 XAWNDICSNACTDK-UHFFFAOYSA-N 0.000 claims description 4
• VTOJVPBRAFYQFG-UHFFFAOYSA-N C(#N)C1=CC=2N(C=C1)C(=C(N=2)C1=CC=2CN(CCC=2O1)C(=O)OC(C)(C)C)NC Chemical compound C(#N)C1=CC=2N(C=C1)C(=C(N=2)C1=CC=2CN(CCC=2O1)C(=O)OC(C)(C)C)NC VTOJVPBRAFYQFG-UHFFFAOYSA-N 0.000 claims description 4
• SJLUGUZBAJMBQF-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC(OCC2=CC=CN=C2)=CC=C1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC(OCC2=CC=CN=C2)=CC=C1 SJLUGUZBAJMBQF-UHFFFAOYSA-N 0.000 claims description 4
• RBKJEYGQBCKLGM-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(F)=CC=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(F)=CC=C2O1 RBKJEYGQBCKLGM-UHFFFAOYSA-N 0.000 claims description 4
• NPCDZMJJDWIPMB-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC=C(OC)C=C2O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC=C(OC)C=C2O1 NPCDZMJJDWIPMB-UHFFFAOYSA-N 0.000 claims description 4
• AJYCMRRMPQDPSD-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(Br)O1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(Br)O1 AJYCMRRMPQDPSD-UHFFFAOYSA-N 0.000 claims description 4
• MPQVZUNLXDYAKW-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(C=C1)C#N Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(C=C1)C#N MPQVZUNLXDYAKW-UHFFFAOYSA-N 0.000 claims description 4
• PQAVQXOXMMLDCR-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(C=C1)C1=CN=CC=N1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(C=C1)C1=CN=CC=N1 PQAVQXOXMMLDCR-UHFFFAOYSA-N 0.000 claims description 4
• MLMXEQIOYTVWIA-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(OCC2=CC=CN=C2)C=C1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C(OCC2=CC=CN=C2)C=C1 MLMXEQIOYTVWIA-UHFFFAOYSA-N 0.000 claims description 4
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• XTZNLAAKBBAFNN-UHFFFAOYSA-N CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C2OCCOC2=C1 Chemical compound CNC1=C(N=C2C=C(C=CN12)C#N)C1=CC=C2OCCOC2=C1 XTZNLAAKBBAFNN-UHFFFAOYSA-N 0.000 claims description 4
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• POEHWOYCAHVSBZ-UHFFFAOYSA-N CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC(=CC=C1)C1=NC=CN=C1 Chemical compound CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC(=CC=C1)C1=NC=CN=C1 POEHWOYCAHVSBZ-UHFFFAOYSA-N 0.000 claims description 4
• LYLXYCVZZZHIKK-UHFFFAOYSA-N CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC=C(C=C1)OCC#C Chemical compound CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC=C(C=C1)OCC#C LYLXYCVZZZHIKK-UHFFFAOYSA-N 0.000 claims description 4
• KYYQKHITWXMMTA-UHFFFAOYSA-N COC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC Chemical compound COC1=CC=C(C=C1)C=1N=C2N(C=CC(=C2)C#N)C=1NC KYYQKHITWXMMTA-UHFFFAOYSA-N 0.000 claims description 4
• JOGISKJJUIXZLP-UHFFFAOYSA-N COC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NCCOC)C=1 Chemical compound COC=1C=CC2=C(C=C(O2)C=2N=C3N(C=CC(=C3)C#N)C=2NCCOC)C=1 JOGISKJJUIXZLP-UHFFFAOYSA-N 0.000 claims description 4
• RPLRRHYMJPUMAU-UHFFFAOYSA-N COC=1N=CC(=NC=1)COC=1C=C(C=CC=1)C=1N=C2N(C=CC(=C2)C#N)C=1NC Chemical compound COC=1N=CC(=NC=1)COC=1C=C(C=CC=1)C=1N=C2N(C=CC(=C2)C#N)C=1NC RPLRRHYMJPUMAU-UHFFFAOYSA-N 0.000 claims description 4
• RJPMFPORUSDNOA-UHFFFAOYSA-N COCC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OC)=CC=C2O1 Chemical compound COCC1=C(N=C2C=C(C=CN12)C#N)C1=CC2=CC(OC)=CC=C2O1 RJPMFPORUSDNOA-UHFFFAOYSA-N 0.000 claims description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
• GECCHUDLYZTUMC-UHFFFAOYSA-N FC1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)O)NC Chemical compound FC1=CC=2N(C=C1)C(=C(N=2)C=1OC2=C(C=1)C=C(C=C2)O)NC GECCHUDLYZTUMC-UHFFFAOYSA-N 0.000 claims description 4
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• 102000016252 Huntingtin Human genes 0.000 claims description 4
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• 239000000460 chlorine Substances 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 4
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• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 3
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 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
• 238000013170 computed tomography imaging Methods 0.000 claims description 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 12
• 125000001475 halogen functional group Chemical group 0.000 claims 8
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 3
• VJFJMCSJLDRDRR-UHFFFAOYSA-N 2-[5-[(5-methoxypyrazin-2-yl)methoxy]pyridin-2-yl]-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound COC=1N=CC(=NC=1)COC=1C=CC(=NC=1)C=1N=C2N(C=CC(=C2)C#N)C=1NC VJFJMCSJLDRDRR-UHFFFAOYSA-N 0.000 claims 2
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• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
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• 238000000034 method Methods 0.000 abstract description 163
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