MX2011004918A - Isoindoles sustituidos como inhibidores de enzima de escision de proteina precursora de amiloide del sitio beta y sus usos. - Google Patents

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Publication number

MX2011004918A

MX2011004918A MX2011004918A MX2011004918A MX2011004918A MX 2011004918 A MX2011004918 A MX 2011004918A MX 2011004918 A MX2011004918 A MX 2011004918A MX 2011004918 A MX2011004918 A MX 2011004918A MX 2011004918 A MX2011004918 A MX 2011004918A

Authority

MX

Mexico

Prior art keywords

fluoro

isoindol

phenyl

amine

pyrimidin

Prior art date

2008-11-14

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 287
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 116
• 230000007170 pathology Effects 0.000 claims abstract description 41
• 206010012289 Dementia Diseases 0.000 claims abstract description 40
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 35
• 238000011282 treatment Methods 0.000 claims abstract description 33
• 208000010877 cognitive disease Diseases 0.000 claims abstract description 31
• 201000010374 Down Syndrome Diseases 0.000 claims abstract description 19
• 208000035475 disorder Diseases 0.000 claims abstract description 19
• 208000024891 symptom Diseases 0.000 claims abstract description 19
• 208000000044 Amnesia Diseases 0.000 claims abstract description 17
• 206010059245 Angiopathy Diseases 0.000 claims abstract description 17
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims abstract description 17
• 208000026139 Memory disease Diseases 0.000 claims abstract description 17
• 208000018737 Parkinson disease Diseases 0.000 claims abstract description 17
• 206010036631 Presenile dementia Diseases 0.000 claims abstract description 17
• 206010039966 Senile dementia Diseases 0.000 claims abstract description 17
• 230000006735 deficit Effects 0.000 claims abstract description 17
• 230000003412 degenerative effect Effects 0.000 claims abstract description 17
• 230000006984 memory degeneration Effects 0.000 claims abstract description 17
• 208000023060 memory loss Diseases 0.000 claims abstract description 17
• 208000027061 mild cognitive impairment Diseases 0.000 claims abstract description 17
• 230000004770 neurodegeneration Effects 0.000 claims abstract description 17
• 230000002792 vascular Effects 0.000 claims abstract description 17
• 206010008111 Cerebral haemorrhage Diseases 0.000 claims abstract description 16
• 230000002265 prevention Effects 0.000 claims abstract description 14
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims abstract description 14
• 208000028698 Cognitive impairment Diseases 0.000 claims abstract description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
• -1 Ci-6alkyl Chemical group 0.000 claims description 343
• 125000000217 alkyl group Chemical group 0.000 claims description 85
• 125000001072 heteroaryl group Chemical group 0.000 claims description 84
• 125000003118 aryl group Chemical group 0.000 claims description 75
• 150000003839 salts Chemical class 0.000 claims description 59
• 229910052736 halogen Inorganic materials 0.000 claims description 58
• 150000002367 halogens Chemical group 0.000 claims description 58
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 44
• 125000000623 heterocyclic group Chemical group 0.000 claims description 38
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
• 125000003545 alkoxy group Chemical group 0.000 claims description 32
• 125000004076 pyridyl group Chemical group 0.000 claims description 31
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 29
• 229910052739 hydrogen Inorganic materials 0.000 claims description 27
• 239000001257 hydrogen Substances 0.000 claims description 27
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 25
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 24
• 125000004452 carbocyclyl group Chemical group 0.000 claims description 21
• 239000003814 drug Substances 0.000 claims description 21
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 20
• 125000004429 atom Chemical group 0.000 claims description 17
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 16
• 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 16
• 125000001188 haloalkyl group Chemical group 0.000 claims description 14
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 10
• 150000001412 amines Chemical class 0.000 claims description 8
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 8
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
• 239000012458 free base Substances 0.000 claims description 7
• 125000005843 halogen group Chemical group 0.000 claims description 7
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims description 5
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• 239000004480 active ingredient Substances 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical group COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• HNKSCDQWGAJNMX-UHFFFAOYSA-N 7-fluoro-3-(4-fluoro-3-pyrimidin-5-ylphenyl)-3-pyridin-4-ylisoindol-1-amine Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(C(F)=CC=1)C=1C=NC=NC=1)C1=CC=NC=C1 HNKSCDQWGAJNMX-UHFFFAOYSA-N 0.000 claims description 3
• FURYISBFUICYBU-UHFFFAOYSA-N 7-fluoro-3-[4-fluoro-3-(4-methoxypyridin-2-yl)phenyl]-3-pyrimidin-5-ylisoindol-1-amine Chemical compound COC1=CC=NC(C=2C(=CC=C(C=2)C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=NC=NC=2)F)=C1 FURYISBFUICYBU-UHFFFAOYSA-N 0.000 claims description 3
• UDQUVXUVXUGJFO-QHCPKHFHSA-N (3s)-7-fluoro-3-(4-fluoro-3-pyrimidin-5-ylphenyl)-3-[2-(trifluoromethyl)pyridin-4-yl]isoindol-1-amine Chemical compound C1([C@@]2(N=C(C3=C(F)C=CC=C32)N)C=2C=C(C(F)=CC=2)C=2C=NC=NC=2)=CC=NC(C(F)(F)F)=C1 UDQUVXUVXUGJFO-QHCPKHFHSA-N 0.000 claims description 2
• PXITVWWTDHUDOP-UHFFFAOYSA-N 2-[3-[3-amino-4-fluoro-1-(2-methoxypyridin-4-yl)isoindol-1-yl]phenyl]pyridine-4-carbonitrile Chemical compound C1=NC(OC)=CC(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(C=CC=2)C=2N=CC=C(C=2)C#N)=C1 PXITVWWTDHUDOP-UHFFFAOYSA-N 0.000 claims description 2
• IRZCDBOHKLZNFD-UHFFFAOYSA-N 2-[5-[3-amino-4-fluoro-1-(3-pyrimidin-5-ylphenyl)isoindol-1-yl]-2-methoxy-3-methylphenyl]acetonitrile Chemical compound C1=C(CC#N)C(OC)=C(C)C=C1C1(C=2C=C(C=CC=2)C=2C=NC=NC=2)C(C=CC=C2F)=C2C(N)=N1 IRZCDBOHKLZNFD-UHFFFAOYSA-N 0.000 claims description 2
• QTHLBLQVGADVQB-UHFFFAOYSA-N 3-(2-cyclopropylpyridin-4-yl)-7-fluoro-3-(3-pyrazin-2-ylphenyl)isoindol-1-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(N=CC=1)C1CC1)C(C=1)=CC=CC=1C1=CN=CC=N1 QTHLBLQVGADVQB-UHFFFAOYSA-N 0.000 claims description 2
• HLZIYZMSCOXBTI-UHFFFAOYSA-N 3-(2-cyclopropylpyridin-4-yl)-7-fluoro-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(C=CC=1)C=1C=NC=NC=1)C(C=1)=CC=NC=1C1CC1 HLZIYZMSCOXBTI-UHFFFAOYSA-N 0.000 claims description 2
• LDZVCIKKJQWJSC-UHFFFAOYSA-N 3-(3,4-difluoro-5-methoxyphenyl)-7-fluoro-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound FC1=C(F)C(OC)=CC(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(C=CC=2)C=2C=NC=NC=2)=C1 LDZVCIKKJQWJSC-UHFFFAOYSA-N 0.000 claims description 2
• YCGBLIMDVQUJHP-UHFFFAOYSA-N 3-[2-(difluoromethyl)-6-methylpyridin-4-yl]-7-fluoro-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound FC(F)C1=NC(C)=CC(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(C=CC=2)C=2C=NC=NC=2)=C1 YCGBLIMDVQUJHP-UHFFFAOYSA-N 0.000 claims description 2
• MRXBCEQZNKUUIP-UHFFFAOYSA-N 3-[2-(difluoromethyl)pyridin-4-yl]-7-fluoro-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(N=CC=1)C(F)F)C(C=1)=CC=CC=1C1=CN=CN=C1 MRXBCEQZNKUUIP-UHFFFAOYSA-N 0.000 claims description 2
• ABQKMSJSHIBKEW-UHFFFAOYSA-N 5-[3-[3-amino-4-fluoro-1-(2-methoxypyridin-4-yl)isoindol-1-yl]phenyl]pyridine-3-carbonitrile Chemical compound C1=NC(OC)=CC(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(C=CC=2)C=2C=C(C=NC=2)C#N)=C1 ABQKMSJSHIBKEW-UHFFFAOYSA-N 0.000 claims description 2
• IBKUXOABAPJTJV-UHFFFAOYSA-N 5-[3-[3-amino-4-fluoro-1-(2-methylpyridin-4-yl)isoindol-1-yl]-4-fluorophenyl]pyridine-3-carbonitrile Chemical compound C1=NC(C)=CC(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C(=CC=C(C=2)C=2C=C(C=NC=2)C#N)F)=C1 IBKUXOABAPJTJV-UHFFFAOYSA-N 0.000 claims description 2
• IXJQLRGQVCIKGQ-UHFFFAOYSA-N 5-[3-[3-amino-4-fluoro-1-[2-(trifluoromethyl)pyridin-4-yl]isoindol-1-yl]-4-fluorophenyl]pyridine-3-carbonitrile Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C(=CC=C(C=1)C=1C=C(C=NC=1)C#N)F)C1=CC=NC(C(F)(F)F)=C1 IXJQLRGQVCIKGQ-UHFFFAOYSA-N 0.000 claims description 2
• JOAINBRZFKXAKE-UHFFFAOYSA-N 5-[3-amino-4-fluoro-1-(3-pyrimidin-5-ylphenyl)isoindol-1-yl]-2-methoxybenzonitrile Chemical compound C1=C(C#N)C(OC)=CC=C1C1(C=2C=C(C=CC=2)C=2C=NC=NC=2)C(C=CC=C2F)=C2C(N)=N1 JOAINBRZFKXAKE-UHFFFAOYSA-N 0.000 claims description 2
• BQQVKWIMNRWXPB-UHFFFAOYSA-N 5-[5-(3-amino-4-fluoro-1-pyridin-4-ylisoindol-1-yl)-2-fluorophenyl]pyridine-3-carbonitrile Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(C(F)=CC=1)C=1C=C(C=NC=1)C#N)C1=CC=NC=C1 BQQVKWIMNRWXPB-UHFFFAOYSA-N 0.000 claims description 2
• ZLJNYOGNQBCSPZ-UHFFFAOYSA-N 5-[5-[3-amino-4-fluoro-1-[2-(trifluoromethyl)pyridin-4-yl]isoindol-1-yl]-2-fluorophenyl]pyridine-3-carbonitrile Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(C(F)=CC=1)C=1C=C(C=NC=1)C#N)C1=CC=NC(C(F)(F)F)=C1 ZLJNYOGNQBCSPZ-UHFFFAOYSA-N 0.000 claims description 2
• SZNCXZSQMMXATG-UHFFFAOYSA-N 5-chloro-7-fluoro-3-(2-methylpyridin-4-yl)-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound C1=NC(C)=CC(C2(C3=C(C(=CC(Cl)=C3)F)C(N)=N2)C=2C=C(C=CC=2)C=2C=NC=NC=2)=C1 SZNCXZSQMMXATG-UHFFFAOYSA-N 0.000 claims description 2
• VHTMYWKRQDERJA-UHFFFAOYSA-N 5-chloro-7-fluoro-3-(3-pyrimidin-5-ylphenyl)-3-[2-(trifluoromethyl)pyridin-4-yl]isoindol-1-amine Chemical compound C12=CC(Cl)=CC(F)=C2C(N)=NC1(C=1C=C(N=CC=1)C(F)(F)F)C(C=1)=CC=CC=1C1=CN=CN=C1 VHTMYWKRQDERJA-UHFFFAOYSA-N 0.000 claims description 2
• JPPFOTMIISPHLL-UHFFFAOYSA-N 7-fluoro-3-(2-fluoro-5-pyrimidin-5-ylphenyl)-3-[2-(trifluoromethyl)pyridin-4-yl]isoindol-1-amine Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C(=CC=C(C=1)C=1C=NC=NC=1)F)C1=CC=NC(C(F)(F)F)=C1 JPPFOTMIISPHLL-UHFFFAOYSA-N 0.000 claims description 2
• OJAQXSAISVSZNQ-UHFFFAOYSA-N 7-fluoro-3-(2-methoxypyridin-4-yl)-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound C1=NC(OC)=CC(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(C=CC=2)C=2C=NC=NC=2)=C1 OJAQXSAISVSZNQ-UHFFFAOYSA-N 0.000 claims description 2
• BFFLVDCVWYROAY-UHFFFAOYSA-N 7-fluoro-3-(3-fluoro-4-methoxy-5-methylphenyl)-3-(2-pyrimidin-5-ylpyridin-4-yl)isoindol-1-amine Chemical compound C1=C(F)C(OC)=C(C)C=C1C1(C=2C=C(N=CC=2)C=2C=NC=NC=2)C(C=CC=C2F)=C2C(N)=N1 BFFLVDCVWYROAY-UHFFFAOYSA-N 0.000 claims description 2
• UDQUVXUVXUGJFO-UHFFFAOYSA-N 7-fluoro-3-(4-fluoro-3-pyrimidin-5-ylphenyl)-3-[2-(trifluoromethyl)pyridin-4-yl]isoindol-1-amine Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(C(F)=CC=1)C=1C=NC=NC=1)C1=CC=NC(C(F)(F)F)=C1 UDQUVXUVXUGJFO-UHFFFAOYSA-N 0.000 claims description 2
• SMSWJWMOZMPDKT-UHFFFAOYSA-N 7-fluoro-3-(4-methoxyphenyl)-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound C1=CC(OC)=CC=C1C1(C=2C=C(C=CC=2)C=2C=NC=NC=2)C(C=CC=C2F)=C2C(N)=N1 SMSWJWMOZMPDKT-UHFFFAOYSA-N 0.000 claims description 2
• HLWMPHXAKRXVIS-UHFFFAOYSA-N 7-fluoro-3-[3-(5-fluoropyridin-3-yl)phenyl]-3-pyridin-4-ylisoindol-1-amine Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(C=CC=1)C=1C=C(F)C=NC=1)C1=CC=NC=C1 HLWMPHXAKRXVIS-UHFFFAOYSA-N 0.000 claims description 2
• JTYGZAPMRYLRCN-UHFFFAOYSA-N 7-fluoro-3-pyridin-4-yl-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(C=CC=1)C=1C=NC=NC=1)C1=CC=NC=C1 JTYGZAPMRYLRCN-UHFFFAOYSA-N 0.000 claims description 2
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
• JTYGZAPMRYLRCN-HSZRJFAPSA-N (3s)-7-fluoro-3-pyridin-4-yl-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound C1([C@@]2(N=C(C3=C(F)C=CC=C32)N)C=2C=C(C=CC=2)C=2C=NC=NC=2)=CC=NC=C1 JTYGZAPMRYLRCN-HSZRJFAPSA-N 0.000 claims 1
• CJEIMBHNYRNICW-UHFFFAOYSA-N 3-(2,6-dimethylpyrimidin-4-yl)-7-fluoro-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound CC1=NC(C)=CC(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(C=CC=2)C=2C=NC=NC=2)=N1 CJEIMBHNYRNICW-UHFFFAOYSA-N 0.000 claims 1
• GKEMYVAIQCCEOA-UHFFFAOYSA-N 3-[2-(difluoromethyl)pyridin-4-yl]-7-fluoro-3-(2-pyrimidin-5-ylpyridin-4-yl)isoindol-1-amine Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(N=CC=1)C=1C=NC=NC=1)C1=CC=NC(C(F)F)=C1 GKEMYVAIQCCEOA-UHFFFAOYSA-N 0.000 claims 1
• YFSROEJZFCNGBG-UHFFFAOYSA-N 5-[3-amino-4-fluoro-1-(3-pyrimidin-5-ylphenyl)isoindol-1-yl]-2-methoxy-3-methylbenzonitrile Chemical compound C1=C(C#N)C(OC)=C(C)C=C1C1(C=2C=C(C=CC=2)C=2C=NC=NC=2)C(C=CC=C2F)=C2C(N)=N1 YFSROEJZFCNGBG-UHFFFAOYSA-N 0.000 claims 1
• VUZSNSMEUFXECY-UHFFFAOYSA-N 7-fluoro-3-(2-methoxypyridin-4-yl)-3-(3-pyrazin-2-ylphenyl)isoindol-1-amine Chemical compound C1=NC(OC)=CC(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(C=CC=2)C=2N=CC=NC=2)=C1 VUZSNSMEUFXECY-UHFFFAOYSA-N 0.000 claims 1
• OASJLOBJAWKJLW-UHFFFAOYSA-N 7-fluoro-3-(3-pyrazin-2-ylphenyl)-3-[2-(trifluoromethyl)pyridin-4-yl]isoindol-1-amine Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(N=CC=1)C(F)(F)F)C(C=1)=CC=CC=1C1=CN=CC=N1 OASJLOBJAWKJLW-UHFFFAOYSA-N 0.000 claims 1
• KJPBADHCKFUMIL-UHFFFAOYSA-N 7-fluoro-3-(3-pyrimidin-5-ylphenyl)-3-[2-(trifluoromethyl)pyridin-4-yl]isoindol-1-amine Chemical compound C12=CC=CC(F)=C2C(N)=NC1(C=1C=C(N=CC=1)C(F)(F)F)C(C=1)=CC=CC=1C1=CN=CN=C1 KJPBADHCKFUMIL-UHFFFAOYSA-N 0.000 claims 1
• UZSHWRAUEVAKFN-UHFFFAOYSA-N 7-fluoro-3-(4-fluoro-3-methoxyphenyl)-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound C1=C(F)C(OC)=CC(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(C=CC=2)C=2C=NC=NC=2)=C1 UZSHWRAUEVAKFN-UHFFFAOYSA-N 0.000 claims 1
• LAYVJEWHRVBQSK-UHFFFAOYSA-N 7-fluoro-3-(4-fluoro-3-pyrimidin-5-ylphenyl)-3-(2-methoxypyridin-4-yl)isoindol-1-amine Chemical compound C1=NC(OC)=CC(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(C(F)=CC=2)C=2C=NC=NC=2)=C1 LAYVJEWHRVBQSK-UHFFFAOYSA-N 0.000 claims 1
• AUBWOOMBEPBCKT-UHFFFAOYSA-N 7-fluoro-3-(4-methoxy-3,5-dimethylphenyl)-3-(2-pyrimidin-5-ylpyridin-4-yl)isoindol-1-amine Chemical compound C1=C(C)C(OC)=C(C)C=C1C1(C=2C=C(N=CC=2)C=2C=NC=NC=2)C(C=CC=C2F)=C2C(N)=N1 AUBWOOMBEPBCKT-UHFFFAOYSA-N 0.000 claims 1
• JZSUZGNJXWXUQC-UHFFFAOYSA-N 7-fluoro-3-(4-methoxy-3-pyrimidin-5-ylphenyl)-3-[2-(trifluoromethyl)pyridin-4-yl]isoindol-1-amine Chemical compound COC1=CC=C(C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(N=CC=2)C(F)(F)F)C=C1C1=CN=CN=C1 JZSUZGNJXWXUQC-UHFFFAOYSA-N 0.000 claims 1
• DJUIWDIVXGOXBA-UHFFFAOYSA-N 7-fluoro-3-(5-methoxy-4,6-dimethylpyridin-2-yl)-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound N1=C(C)C(OC)=C(C)C=C1C1(C=2C=C(C=CC=2)C=2C=NC=NC=2)C(C=CC=C2F)=C2C(N)=N1 DJUIWDIVXGOXBA-UHFFFAOYSA-N 0.000 claims 1
• MGWNWXUQKGQHIA-UHFFFAOYSA-N 7-fluoro-3-[2-fluoro-5-(5-methylsulfonylpyridin-3-yl)phenyl]-3-[2-(trifluoromethyl)pyridin-4-yl]isoindol-1-amine Chemical compound CS(=O)(=O)C1=CN=CC(C=2C=C(C(F)=CC=2)C2(C3=C(C(=CC=C3)F)C(N)=N2)C=2C=C(N=CC=2)C(F)(F)F)=C1 MGWNWXUQKGQHIA-UHFFFAOYSA-N 0.000 claims 1
• DCCOJOUQUIVBIQ-UHFFFAOYSA-N 7-fluoro-3-[6-methoxy-5-(trifluoromethyl)pyridin-3-yl]-3-(3-pyrimidin-5-ylphenyl)isoindol-1-amine Chemical compound C1=C(C(F)(F)F)C(OC)=NC=C1C1(C=2C=C(C=CC=2)C=2C=NC=NC=2)C(C=CC=C2F)=C2C(N)=N1 DCCOJOUQUIVBIQ-UHFFFAOYSA-N 0.000 claims 1
• YTBODSVQSOILIJ-UHFFFAOYSA-N N-[5-[7-[2-[4-(2-hydroxypropan-2-yl)piperidin-1-yl]ethoxy]-1,3-dihydro-2-benzofuran-5-yl]-2-methoxypyridin-3-yl]methanesulfonamide Chemical group COc1ncc(cc1NS(C)(=O)=O)-c1cc2COCc2c(OCCN2CCC(CC2)C(C)(C)O)c1 YTBODSVQSOILIJ-UHFFFAOYSA-N 0.000 claims 1
• AKQZEFRALAUBFS-UHFFFAOYSA-N ilamine Natural products COC(C)C(O)(C(=O)OCC1=CCN2CCCC12)C(C)(C)O AKQZEFRALAUBFS-UHFFFAOYSA-N 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 abstract description 21
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• 230000001054 cortical effect Effects 0.000 abstract 1
• 230000007850 degeneration Effects 0.000 abstract 1
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