HRP20020027A2 - Method of inhibiting amyloid protein aggregation and imaging amyloid deposits using isoindoline derivatives - Google Patents

Info

Publication number

HRP20020027A2

HRP20020027A2 HR20020027A HRP20020027A HRP20020027A2 HR P20020027 A2 HRP20020027 A2 HR P20020027A2 HR 20020027 A HR20020027 A HR 20020027A HR P20020027 A HRP20020027 A HR P20020027A HR P20020027 A2 HRP20020027 A2 HR P20020027A2

Authority

HR

Croatia

Prior art keywords

phenyl

dihydro

isoindol

ylamino

benzoic acid

Prior art date

1999-06-10

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims description 64
• 208000037259 Amyloid Plaque Diseases 0.000 title claims description 37
• 102000009091 Amyloidogenic Proteins Human genes 0.000 title claims description 21
• 108010048112 Amyloidogenic Proteins Proteins 0.000 title claims description 21
• 230000002401 inhibitory effect Effects 0.000 title description 4
• GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical class C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 title description 4
• 238000003384 imaging method Methods 0.000 title description 2
• 230000004845 protein aggregation Effects 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims description 155
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 68
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 40
• -1 -Cl-C6 alkyl Chemical group 0.000 claims description 39
• 238000009825 accumulation Methods 0.000 claims description 19
• 125000001424 substituent group Chemical group 0.000 claims description 18
• 125000005843 halogen group Chemical group 0.000 claims description 16
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
• 208000024827 Alzheimer disease Diseases 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 14
• 239000001257 hydrogen Substances 0.000 claims description 13
• 229910052739 hydrogen Inorganic materials 0.000 claims description 13
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
• 125000004076 pyridyl group Chemical group 0.000 claims description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 230000015572 biosynthetic process Effects 0.000 claims description 7
• 201000010099 disease Diseases 0.000 claims description 7
• 150000003536 tetrazoles Chemical class 0.000 claims description 7
• XFKHBOBNEIMEHT-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 XFKHBOBNEIMEHT-UHFFFAOYSA-N 0.000 claims description 6
• LRCXSOHFBLKEHG-UHFFFAOYSA-N 2-[[2-(3-chlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C=CC=3)C2=C1 LRCXSOHFBLKEHG-UHFFFAOYSA-N 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 238000012800 visualization Methods 0.000 claims description 6
• FXSZZASBADHGKA-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 FXSZZASBADHGKA-UHFFFAOYSA-N 0.000 claims description 5
• FZJDWOROOGHBLR-UHFFFAOYSA-N 2-[[2-(3,4-dimethylphenyl)-1,3-dihydroisoindol-5-yl]amino]-5-nitrobenzoic acid Chemical compound C1=C(C)C(C)=CC=C1N1CC2=CC(NC=3C(=CC(=CC=3)[N+]([O-])=O)C(O)=O)=CC=C2C1 FZJDWOROOGHBLR-UHFFFAOYSA-N 0.000 claims description 5
• JRKYVFZLSWJSJO-UHFFFAOYSA-N 2-[[2-(4-chlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(CN(C2)C=3C=CC(Cl)=CC=3)C2=C1 JRKYVFZLSWJSJO-UHFFFAOYSA-N 0.000 claims description 5
• FNAZZRPUQLJTPE-UHFFFAOYSA-N 2-[[2-[4-chloro-3-(trifluoromethyl)phenyl]-1,3-dihydroisoindol-5-yl]amino]-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(CN(C2)C=3C=C(C(Cl)=CC=3)C(F)(F)F)C2=C1 FNAZZRPUQLJTPE-UHFFFAOYSA-N 0.000 claims description 5
• FHVIQUIKAALIDS-UHFFFAOYSA-N 4-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzene-1,3-dicarboxylic acid Chemical compound OC(=O)C1=CC(C(=O)O)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 FHVIQUIKAALIDS-UHFFFAOYSA-N 0.000 claims description 5
• RBMMCERQHQQZSD-UHFFFAOYSA-N 5-nitro-2-[(2-phenyl-1,3-dihydroisoindol-5-yl)amino]benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(CN(C2)C=3C=CC=CC=3)C2=C1 RBMMCERQHQQZSD-UHFFFAOYSA-N 0.000 claims description 5
• BQJAFSJEGRPGOY-UHFFFAOYSA-N 2-[(2-phenyl-1,3-dihydroisoindol-5-yl)amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=CC=CC=3)C2=C1 BQJAFSJEGRPGOY-UHFFFAOYSA-N 0.000 claims description 4
• WGJRQGZKDNABJW-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-methoxybenzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 WGJRQGZKDNABJW-UHFFFAOYSA-N 0.000 claims description 4
• QQTBARHQDOOMHR-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 QQTBARHQDOOMHR-UHFFFAOYSA-N 0.000 claims description 4
• MRSURJSUHNPYRT-UHFFFAOYSA-N 2-[[2-(3,4-dimethylphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound C1=C(C)C(C)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)C(O)=O)=CC=C2C1 MRSURJSUHNPYRT-UHFFFAOYSA-N 0.000 claims description 4
• OIYCHVXDQBBTFF-UHFFFAOYSA-N 2-[[2-(3-chlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C=CC=3)C2=C1 OIYCHVXDQBBTFF-UHFFFAOYSA-N 0.000 claims description 4
• VBKIMPRICDWCCI-UHFFFAOYSA-N 2-[[2-(4-chlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=CC(Cl)=CC=3)C2=C1 VBKIMPRICDWCCI-UHFFFAOYSA-N 0.000 claims description 4
• BSQCYNYUKOKHIY-UHFFFAOYSA-N 2-[[2-(4-phenylphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=CC(=CC=3)C=3C=CC=CC=3)C2=C1 BSQCYNYUKOKHIY-UHFFFAOYSA-N 0.000 claims description 4
• DWWFJNMSNWWLKA-UHFFFAOYSA-N 2-[[2-[4-chloro-3-(trifluoromethyl)phenyl]-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(C(Cl)=CC=3)C(F)(F)F)C2=C1 DWWFJNMSNWWLKA-UHFFFAOYSA-N 0.000 claims description 4
• NENLYAQPNATJSU-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical compound C1NCCC2CCCCC21 NENLYAQPNATJSU-UHFFFAOYSA-N 0.000 claims description 3
• FOQONJINQWZZFX-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n-[2-(tetrazol-1-yl)phenyl]-1,3-dihydroisoindol-5-amine Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)N3N=NN=C3)=CC=C2C1 FOQONJINQWZZFX-UHFFFAOYSA-N 0.000 claims description 3
• MWJGUUZYHAANNG-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n-[2-[2-(tetrazol-1-yl)ethenyl]phenyl]-1,3-dihydroisoindol-5-amine Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)C=CN3N=NN=C3)=CC=C2C1 MWJGUUZYHAANNG-UHFFFAOYSA-N 0.000 claims description 3
• RJRUTIJIALFVDJ-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n-[2-[2-(tetrazol-1-yl)ethyl]phenyl]-1,3-dihydroisoindol-5-amine Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)CCN3N=NN=C3)=CC=C2C1 RJRUTIJIALFVDJ-UHFFFAOYSA-N 0.000 claims description 3
• MSZNEOOZAUURPJ-UHFFFAOYSA-N 2-[2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 MSZNEOOZAUURPJ-UHFFFAOYSA-N 0.000 claims description 3
• DNTYFPRHUJSQKN-UHFFFAOYSA-N 2-[[2-(2,3,4-trimethoxyphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound COC1=C(OC)C(OC)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)C(O)=O)=CC=C2C1 DNTYFPRHUJSQKN-UHFFFAOYSA-N 0.000 claims description 3
• LTRBWLOKTXXDDG-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-3,5-dinitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 LTRBWLOKTXXDDG-UHFFFAOYSA-N 0.000 claims description 3
• GDORYTYYLDITSA-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-3-methylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 GDORYTYYLDITSA-UHFFFAOYSA-N 0.000 claims description 3
• HIXHOJHIXHEVQM-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-4-heptoxybenzoic acid Chemical compound CCCCCCCOC1=CC=C(C(O)=O)C(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 HIXHOJHIXHEVQM-UHFFFAOYSA-N 0.000 claims description 3
• BBPCTSBZXGKBOR-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-4-hexoxybenzoic acid Chemical compound CCCCCCOC1=CC=C(C(O)=O)C(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 BBPCTSBZXGKBOR-UHFFFAOYSA-N 0.000 claims description 3
• BSGSZHGXTXQUJB-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-4-methoxy-5-nitrobenzoic acid Chemical compound C1=C([N+]([O-])=O)C(OC)=CC(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1C(O)=O BSGSZHGXTXQUJB-UHFFFAOYSA-N 0.000 claims description 3
• WGQYHEHKIBEMNV-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 WGQYHEHKIBEMNV-UHFFFAOYSA-N 0.000 claims description 3
• IFCCUIOSUQHJOQ-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-4-nonoxybenzoic acid Chemical compound CCCCCCCCCOC1=CC=C(C(O)=O)C(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 IFCCUIOSUQHJOQ-UHFFFAOYSA-N 0.000 claims description 3
• OQRMPYVEPRMHAO-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-4-octoxybenzoic acid Chemical compound CCCCCCCCOC1=CC=C(C(O)=O)C(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 OQRMPYVEPRMHAO-UHFFFAOYSA-N 0.000 claims description 3
• CCTKVKCCGVPFIW-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-4-pentoxybenzoic acid Chemical compound CCCCCOC1=CC=C(C(O)=O)C(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 CCTKVKCCGVPFIW-UHFFFAOYSA-N 0.000 claims description 3
• GGIBLJWETZNRQP-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-4-propan-2-yloxybenzoic acid Chemical compound CC(C)OC1=CC=C(C(O)=O)C(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 GGIBLJWETZNRQP-UHFFFAOYSA-N 0.000 claims description 3
• MIMKPFFFNULZKC-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-4-propoxybenzoic acid Chemical compound CCCOC1=CC=C(C(O)=O)C(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 MIMKPFFFNULZKC-UHFFFAOYSA-N 0.000 claims description 3
• NWGKHGOGMLXRNK-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC(C(F)(F)F)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 NWGKHGOGMLXRNK-UHFFFAOYSA-N 0.000 claims description 3
• FNLUGHQARXCMAS-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-imidazol-1-ylbenzoic acid Chemical compound OC(=O)C1=CC(N2C=NC=C2)=CC=C1NC(C=C1C2)=CC=C1CN2C1=CC=C(Cl)C(Cl)=C1 FNLUGHQARXCMAS-UHFFFAOYSA-N 0.000 claims description 3
• DHQKEEJMPUUVBU-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-methylbenzoic acid Chemical compound OC(=O)C1=CC(C)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 DHQKEEJMPUUVBU-UHFFFAOYSA-N 0.000 claims description 3
• JTWGLFKZQDCYAG-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-methylsulfonylbenzoic acid Chemical compound OC(=O)C1=CC(S(=O)(=O)C)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 JTWGLFKZQDCYAG-UHFFFAOYSA-N 0.000 claims description 3
• CITGGSGVPJQGRZ-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 CITGGSGVPJQGRZ-UHFFFAOYSA-N 0.000 claims description 3
• JODHFSDMKVAOKX-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-sulfamoylbenzoic acid Chemical compound OC(=O)C1=CC(S(=O)(=O)N)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 JODHFSDMKVAOKX-UHFFFAOYSA-N 0.000 claims description 3
• ROWHPYQESZQYDV-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-6-nitrobenzoic acid Chemical compound C1=CC=C([N+]([O-])=O)C(C(=O)O)=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 ROWHPYQESZQYDV-UHFFFAOYSA-N 0.000 claims description 3
• WMAPYHCOBSMMCF-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzonitrile Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)C#N)=CC=C2C1 WMAPYHCOBSMMCF-UHFFFAOYSA-N 0.000 claims description 3
• PPRGDWBGBVMWKT-UHFFFAOYSA-N 3-[2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 PPRGDWBGBVMWKT-UHFFFAOYSA-N 0.000 claims description 3
• YLYQEWXIBRFDJN-UHFFFAOYSA-N 3-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-2-methylbenzoic acid Chemical compound C1=CC=C(C(O)=O)C(C)=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 YLYQEWXIBRFDJN-UHFFFAOYSA-N 0.000 claims description 3
• CLAVZJAHVSKTPR-UHFFFAOYSA-N 3-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]phthalic acid Chemical compound OC(=O)C1=CC=CC(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1C(O)=O CLAVZJAHVSKTPR-UHFFFAOYSA-N 0.000 claims description 3
• HHOVQFDPVFEVKT-UHFFFAOYSA-N 4-butoxy-2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound CCCCOC1=CC=C(C(O)=O)C(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 HHOVQFDPVFEVKT-UHFFFAOYSA-N 0.000 claims description 3
• WHOFBMDQNAUKKL-UHFFFAOYSA-N 4-decoxy-2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound CCCCCCCCCCOC1=CC=C(C(O)=O)C(NC=2C=C3CN(CC3=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 WHOFBMDQNAUKKL-UHFFFAOYSA-N 0.000 claims description 3
• DOOVUZNOWRIRRM-UHFFFAOYSA-N 4-methoxy-5-nitro-2-[[2-(3,4,5-trimethoxyphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound COC1=C(OC)C(OC)=CC(N2CC3=CC(NC=4C(=CC(=C(OC)C=4)[N+]([O-])=O)C(O)=O)=CC=C3C2)=C1 DOOVUZNOWRIRRM-UHFFFAOYSA-N 0.000 claims description 3
• ZOVYWCIYFWVBIA-UHFFFAOYSA-N 5-nitro-2-[[2-(3,4,5-trimethoxyphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound COC1=C(OC)C(OC)=CC(N2CC3=CC(NC=4C(=CC(=CC=4)[N+]([O-])=O)C(O)=O)=CC=C3C2)=C1 ZOVYWCIYFWVBIA-UHFFFAOYSA-N 0.000 claims description 3
• QASVCUPMASAGIN-UHFFFAOYSA-N 5-nitro-2-[[2-(4-phenylphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(CN(C2)C=3C=CC(=CC=3)C=3C=CC=CC=3)C2=C1 QASVCUPMASAGIN-UHFFFAOYSA-N 0.000 claims description 3
• 239000005711 Benzoic acid Substances 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• ATNXGEJWNDJJNB-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n-[2-(tetrazol-1-ylmethyl)phenyl]-1,3-dihydroisoindol-5-amine Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)CN3N=NN=C3)=CC=C2C1 ATNXGEJWNDJJNB-UHFFFAOYSA-N 0.000 claims description 2
• NOMWEWXJOQYXMZ-UHFFFAOYSA-N 2-[[2-(2,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C(=CC(Cl)=CC=3)Cl)C2=C1 NOMWEWXJOQYXMZ-UHFFFAOYSA-N 0.000 claims description 2
• URLDYVIAHYGQOY-UHFFFAOYSA-N 2-[[2-(2-chlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C(=CC=CC=3)Cl)C2=C1 URLDYVIAHYGQOY-UHFFFAOYSA-N 0.000 claims description 2
• LDKNVEQJXQLOEE-UHFFFAOYSA-N 2-[[2-(3,4,5-trihydroxyphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(O)C(O)=C(O)C=3)C2=C1 LDKNVEQJXQLOEE-UHFFFAOYSA-N 0.000 claims description 2
• LKZFIABZNLFVNY-UHFFFAOYSA-N 2-[[2-(3,4,5-trimethoxyphenyl)-1,3-dihydroisoindol-5-yl]amino]benzonitrile Chemical compound COC1=C(OC)C(OC)=CC(N2CC3=CC(NC=4C(=CC=CC=4)C#N)=CC=C3C2)=C1 LKZFIABZNLFVNY-UHFFFAOYSA-N 0.000 claims description 2
• WNXIPCSWXVTKQF-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 WNXIPCSWXVTKQF-UHFFFAOYSA-N 0.000 claims description 2
• KCBGVQVSHBXDHW-UHFFFAOYSA-N 2-[[2-(3,4-difluorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(F)C(F)=CC=3)C2=C1 KCBGVQVSHBXDHW-UHFFFAOYSA-N 0.000 claims description 2
• YFNFHPMKDLTSDA-UHFFFAOYSA-N 2-[[2-(3,4-dihydroxyphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(O)C(O)=CC=3)C2=C1 YFNFHPMKDLTSDA-UHFFFAOYSA-N 0.000 claims description 2
• LOKLJOAKLURTAZ-UHFFFAOYSA-N 2-[[2-(3,4-dimethoxyphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)C(O)=O)=CC=C2C1 LOKLJOAKLURTAZ-UHFFFAOYSA-N 0.000 claims description 2
• WMSZBBFGSDOCJT-UHFFFAOYSA-N 2-[[2-(3,5-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C=C(Cl)C=3)C2=C1 WMSZBBFGSDOCJT-UHFFFAOYSA-N 0.000 claims description 2
• UMGQQBVXOXJEID-UHFFFAOYSA-N 2-[[2-(3-bromophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(Br)C=CC=3)C2=C1 UMGQQBVXOXJEID-UHFFFAOYSA-N 0.000 claims description 2
• WKDJNSFBRHWVLR-UHFFFAOYSA-N 2-[[2-(3-fluoro-4-methylphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound C1=C(F)C(C)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)C(O)=O)=CC=C2C1 WKDJNSFBRHWVLR-UHFFFAOYSA-N 0.000 claims description 2
• MKBFFASMJZSIDK-UHFFFAOYSA-N 2-[[2-(3-fluorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(CN(C2)C=3C=C(F)C=CC=3)C2=C1 MKBFFASMJZSIDK-UHFFFAOYSA-N 0.000 claims description 2
• BCHXIIPZTMSMTK-UHFFFAOYSA-N 2-[[2-(3-methoxyphenyl)-1,3-dihydroisoindol-5-yl]amino]-5-nitrobenzoic acid Chemical compound COC1=CC=CC(N2CC3=CC(NC=4C(=CC(=CC=4)[N+]([O-])=O)C(O)=O)=CC=C3C2)=C1 BCHXIIPZTMSMTK-UHFFFAOYSA-N 0.000 claims description 2
• ZQFPGWHDXLUDRD-UHFFFAOYSA-N 2-[[2-(3-methoxyphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound COC1=CC=CC(N2CC3=CC(NC=4C(=CC=CC=4)C(O)=O)=CC=C3C2)=C1 ZQFPGWHDXLUDRD-UHFFFAOYSA-N 0.000 claims description 2
• ITGUXPNFPRHFIX-UHFFFAOYSA-N 2-[[2-[3-(dibutylamino)phenyl]-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound CCCCN(CCCC)C1=CC=CC(N2CC3=CC(NC=4C(=CC=CC=4)C(O)=O)=CC=C3C2)=C1 ITGUXPNFPRHFIX-UHFFFAOYSA-N 0.000 claims description 2
• UQEWGDMSBRLSKR-UHFFFAOYSA-N 2-[[2-[4-(dibutylamino)phenyl]-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound C1=CC(N(CCCC)CCCC)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)C(O)=O)=CC=C2C1 UQEWGDMSBRLSKR-UHFFFAOYSA-N 0.000 claims description 2
• ZUTWRCRXZRQXRW-SFTDATJTSA-N 2-[[2-[4-[(4as,8ar)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]phenyl]-1,3-dihydroisoindol-5-yl]amino]-3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1NC1=CC=C(CN(C2)C=3C=CC(=CC=3)N3C[C@@H]4CCCC[C@H]4CC3)C2=C1 ZUTWRCRXZRQXRW-SFTDATJTSA-N 0.000 claims description 2
• ZSXCGOLYKFSALB-VXKWHMMOSA-N 2-[[2-[4-[(4as,8ar)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]phenyl]-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=CC(=CC=3)N3C[C@@H]4CCCC[C@H]4CC3)C2=C1 ZSXCGOLYKFSALB-VXKWHMMOSA-N 0.000 claims description 2
• CNIDJALRQMLOBR-UHFFFAOYSA-N 2-[[2-[4-fluoro-3-(trifluoromethyl)phenyl]-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(C(F)=CC=3)C(F)(F)F)C2=C1 CNIDJALRQMLOBR-UHFFFAOYSA-N 0.000 claims description 2
• GFDRPLKLIRGDDM-UHFFFAOYSA-N 2-[[2-[4-methyl-3-(trifluoromethyl)phenyl]-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound C1=C(C(F)(F)F)C(C)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)C(O)=O)=CC=C2C1 GFDRPLKLIRGDDM-UHFFFAOYSA-N 0.000 claims description 2
• XYQDWLBCORFLSH-UHFFFAOYSA-N 4-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 XYQDWLBCORFLSH-UHFFFAOYSA-N 0.000 claims description 2
• BYTPUKTUTDXQDL-UHFFFAOYSA-N 5-(dibutylamino)-2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(N(CCCC)CCCC)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 BYTPUKTUTDXQDL-UHFFFAOYSA-N 0.000 claims description 2
• NBEHMEUUWMEJPM-UHFFFAOYSA-N 5-amino-2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(N)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 NBEHMEUUWMEJPM-UHFFFAOYSA-N 0.000 claims description 2
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
• 239000003814 drug Substances 0.000 claims 3
• 229940079593 drug Drugs 0.000 claims 3
• 238000004519 manufacturing process Methods 0.000 claims 3
• 238000002483 medication Methods 0.000 claims 3
• 125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 238000002360 preparation method Methods 0.000 description 43
• 238000002844 melting Methods 0.000 description 42
• 230000008018 melting Effects 0.000 description 42
• 238000004458 analytical method Methods 0.000 description 40
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
• 239000007787 solid Substances 0.000 description 35
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• 239000000243 solution Substances 0.000 description 31
• 239000000047 product Substances 0.000 description 29
• 238000003556 assay Methods 0.000 description 28
• 239000000203 mixture Substances 0.000 description 27
• 229910001868 water Inorganic materials 0.000 description 26
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 21
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
• 210000001519 tissue Anatomy 0.000 description 15
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 12
• 108010064397 amyloid beta-protein (1-40) Proteins 0.000 description 11
• 238000012360 testing method Methods 0.000 description 11
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
• 239000002904 solvent Substances 0.000 description 10
• MMVIDXVHQANYAE-UHFFFAOYSA-N 5-nitro-2-benzofuran-1,3-dione Chemical compound [O-][N+](=O)C1=CC=C2C(=O)OC(=O)C2=C1 MMVIDXVHQANYAE-UHFFFAOYSA-N 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
• 229910000564 Raney nickel Inorganic materials 0.000 description 8
• 238000006243 chemical reaction Methods 0.000 description 8
• 125000000217 alkyl group Chemical group 0.000 description 7
• 150000001408 amides Chemical class 0.000 description 7
• 239000012131 assay buffer Substances 0.000 description 7
• 238000001514 detection method Methods 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• NSTREUWFTAOOKS-UHFFFAOYSA-N 2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1F NSTREUWFTAOOKS-UHFFFAOYSA-N 0.000 description 6
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 6
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
• 229910000024 caesium carbonate Inorganic materials 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 108090000765 processed proteins & peptides Proteins 0.000 description 6
• 239000000523 sample Substances 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 5
• 208000003808 Amyloid Neuropathies Diseases 0.000 description 5
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
• 229910052782 aluminium Inorganic materials 0.000 description 5
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• FQKSWDPMOKHWNA-UHFFFAOYSA-N bis(4-methylphenyl)-(1-naphthalen-1-ylnaphthalen-2-yl)phosphane Chemical group C1=CC(C)=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1)C1=CC=C(C)C=C1 FQKSWDPMOKHWNA-UHFFFAOYSA-N 0.000 description 5
• 238000000576 coating method Methods 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 239000012280 lithium aluminium hydride Substances 0.000 description 5
• 238000002595 magnetic resonance imaging Methods 0.000 description 5
• 229920001223 polyethylene glycol Polymers 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• OQTDBFDIWWCIBK-UHFFFAOYSA-N 2-(2,3,4-trimethoxyphenyl)-1,3-dihydroisoindol-5-amine Chemical compound COC1=C(OC)C(OC)=CC=C1N1CC2=CC(N)=CC=C2C1 OQTDBFDIWWCIBK-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 229910010084 LiAlH4 Inorganic materials 0.000 description 4
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 206010002022 amyloidosis Diseases 0.000 description 4
• 239000004202 carbamide Substances 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 239000003795 chemical substances by application Substances 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 235000019441 ethanol Nutrition 0.000 description 4
• 235000019439 ethyl acetate Nutrition 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 230000012010 growth Effects 0.000 description 4
• 229910052740 iodine Inorganic materials 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 150000004702 methyl esters Chemical class 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 108090000623 proteins and genes Proteins 0.000 description 4
• SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• JADVWWSKYZXRGX-UHFFFAOYSA-M thioflavine T Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C1=[N+](C)C2=CC=C(C)C=C2S1 JADVWWSKYZXRGX-UHFFFAOYSA-M 0.000 description 4
• 239000000080 wetting agent Substances 0.000 description 4
• CETVOLZSGATHCY-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-amine Chemical compound C1C2=CC(N)=CC=C2CN1C1=CC=C(Cl)C(Cl)=C1 CETVOLZSGATHCY-UHFFFAOYSA-N 0.000 description 3
• LPPLHNABJPJASC-UHFFFAOYSA-N 2-(3-chlorophenyl)-1,3-dihydroisoindol-5-amine Chemical compound C1C2=CC(N)=CC=C2CN1C1=CC=CC(Cl)=C1 LPPLHNABJPJASC-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 241000699660 Mus musculus Species 0.000 description 3
• 241000699670 Mus sp. Species 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
• IOPQYDKQISFMJI-UHFFFAOYSA-N [1-[2-bis(4-methylphenyl)phosphanylnaphthalen-1-yl]naphthalen-2-yl]-bis(4-methylphenyl)phosphane Chemical compound C1=CC(C)=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC(C)=CC=1)C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 IOPQYDKQISFMJI-UHFFFAOYSA-N 0.000 description 3
• 238000010521 absorption reaction Methods 0.000 description 3
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• 239000003995 emulsifying agent Substances 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 239000011888 foil Substances 0.000 description 3
• 235000011187 glycerol Nutrition 0.000 description 3
• 238000005462 in vivo assay Methods 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 239000008363 phosphate buffer Substances 0.000 description 3
• 239000006187 pill Substances 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 239000007909 solid dosage form Substances 0.000 description 3
• 210000000952 spleen Anatomy 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 230000009885 systemic effect Effects 0.000 description 3
• 238000011830 transgenic mouse model Methods 0.000 description 3
• 229910052727 yttrium Inorganic materials 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• QQVLFGAXKABTQS-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-5-nitroisoindole-1,3-dione Chemical compound O=C1C2=CC([N+](=O)[O-])=CC=C2C(=O)N1C1=CC=C(Cl)C(Cl)=C1 QQVLFGAXKABTQS-UHFFFAOYSA-N 0.000 description 2
• BWVIDCNGGRXBHR-UHFFFAOYSA-N 2-(3,4-dimethylphenyl)-1,3-dihydroisoindol-5-amine Chemical compound C1=C(C)C(C)=CC=C1N1CC2=CC(N)=CC=C2C1 BWVIDCNGGRXBHR-UHFFFAOYSA-N 0.000 description 2
• MNANCBZQVVYXHW-UHFFFAOYSA-N 2-(3,4-dimethylphenyl)-5-nitroisoindole-1,3-dione Chemical compound C1=C(C)C(C)=CC=C1N1C(=O)C2=CC([N+]([O-])=O)=CC=C2C1=O MNANCBZQVVYXHW-UHFFFAOYSA-N 0.000 description 2
• QLBOOELISYNLAC-UHFFFAOYSA-N 2-(3-chlorophenyl)-5-nitroisoindole-1,3-dione Chemical compound O=C1C2=CC([N+](=O)[O-])=CC=C2C(=O)N1C1=CC=CC(Cl)=C1 QLBOOELISYNLAC-UHFFFAOYSA-N 0.000 description 2
• ZODTZCZWBWAKJB-UHFFFAOYSA-N 2-(4-chlorophenyl)-1,3-dihydroisoindol-5-amine Chemical compound C1C2=CC(N)=CC=C2CN1C1=CC=C(Cl)C=C1 ZODTZCZWBWAKJB-UHFFFAOYSA-N 0.000 description 2
• PJKKYNOQULHYEC-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-nitroisoindole-1,3-dione Chemical compound O=C1C2=CC([N+](=O)[O-])=CC=C2C(=O)N1C1=CC=C(Cl)C=C1 PJKKYNOQULHYEC-UHFFFAOYSA-N 0.000 description 2
• DFOWPHGHFDEOAO-UHFFFAOYSA-N 2-[4-chloro-3-(trifluoromethyl)phenyl]-5-nitroisoindole-1,3-dione Chemical compound O=C1C2=CC([N+](=O)[O-])=CC=C2C(=O)N1C1=CC=C(Cl)C(C(F)(F)F)=C1 DFOWPHGHFDEOAO-UHFFFAOYSA-N 0.000 description 2
• SPSYMWKHDUJABD-UHFFFAOYSA-N 2h-isoindol-1-amine Chemical compound C1=CC=CC2=C(N)NC=C21 SPSYMWKHDUJABD-UHFFFAOYSA-N 0.000 description 2
• DOLQYFPDPKPQSS-UHFFFAOYSA-N 3,4-dimethylaniline Chemical compound CC1=CC=C(N)C=C1C DOLQYFPDPKPQSS-UHFFFAOYSA-N 0.000 description 2
• HTYXEIGVENOQMI-UHFFFAOYSA-N 5-amino-2-(2,3,4-trimethoxyphenyl)isoindole-1,3-dione Chemical compound COC1=C(OC)C(OC)=CC=C1N1C(=O)C2=CC(N)=CC=C2C1=O HTYXEIGVENOQMI-UHFFFAOYSA-N 0.000 description 2
• CQMWFZXDHTXQKF-UHFFFAOYSA-N 5-amino-2-(3,4-dichlorophenyl)isoindole-1,3-dione Chemical compound O=C1C2=CC(N)=CC=C2C(=O)N1C1=CC=C(Cl)C(Cl)=C1 CQMWFZXDHTXQKF-UHFFFAOYSA-N 0.000 description 2
• OXHUKLPNXVCKLP-UHFFFAOYSA-N 5-amino-2-(3,4-dimethylphenyl)isoindole-1,3-dione Chemical compound C1=C(C)C(C)=CC=C1N1C(=O)C2=CC(N)=CC=C2C1=O OXHUKLPNXVCKLP-UHFFFAOYSA-N 0.000 description 2
• ISFLAAHUBHNNFX-UHFFFAOYSA-N 5-amino-2-(3-chlorophenyl)isoindole-1,3-dione Chemical compound O=C1C2=CC(N)=CC=C2C(=O)N1C1=CC=CC(Cl)=C1 ISFLAAHUBHNNFX-UHFFFAOYSA-N 0.000 description 2
• PVODUYDDMCAUCG-UHFFFAOYSA-N 5-amino-2-(4-chlorophenyl)isoindole-1,3-dione Chemical compound O=C1C2=CC(N)=CC=C2C(=O)N1C1=CC=C(Cl)C=C1 PVODUYDDMCAUCG-UHFFFAOYSA-N 0.000 description 2
• KBABLDYJFIQUHH-UHFFFAOYSA-N 5-amino-2-[4-chloro-3-(trifluoromethyl)phenyl]isoindole-1,3-dione Chemical compound O=C1C2=CC(N)=CC=C2C(=O)N1C1=CC=C(Cl)C(C(F)(F)F)=C1 KBABLDYJFIQUHH-UHFFFAOYSA-N 0.000 description 2
• BNZYEEOIIGOTAI-UHFFFAOYSA-N 5-nitro-2-(2,3,4-trimethoxyphenyl)isoindole-1,3-dione Chemical compound COC1=C(OC)C(OC)=CC=C1N1C(=O)C2=CC([N+]([O-])=O)=CC=C2C1=O BNZYEEOIIGOTAI-UHFFFAOYSA-N 0.000 description 2
• 208000018282 ACys amyloidosis Diseases 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 102000001049 Amyloid Human genes 0.000 description 2
• 108010094108 Amyloid Proteins 0.000 description 2
• 206010002025 Amyloidosis senile Diseases 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 208000014644 Brain disease Diseases 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 206010007509 Cardiac amyloidosis Diseases 0.000 description 2
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 2
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 2
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 201000010374 Down Syndrome Diseases 0.000 description 2
• 238000004435 EPR spectroscopy Methods 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 241000206672 Gelidium Species 0.000 description 2
• 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 description 2
• 229910010082 LiAlH Inorganic materials 0.000 description 2
• 208000037196 Medullary thyroid carcinoma Diseases 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 201000002795 Muckle-Wells syndrome Diseases 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• 208000018737 Parkinson disease Diseases 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• 206010035226 Plasma cell myeloma Diseases 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 239000004743 Polypropylene Substances 0.000 description 2
• 206010037660 Pyrexia Diseases 0.000 description 2
• 239000007868 Raney catalyst Substances 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 230000032683 aging Effects 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 230000001746 atrial effect Effects 0.000 description 2
• 238000011888 autopsy Methods 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 235000012216 bentonite Nutrition 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• 235000010233 benzoic acid Nutrition 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 102000015736 beta 2-Microglobulin Human genes 0.000 description 2
• 108010081355 beta 2-Microglobulin Proteins 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 description 2
• 239000008367 deionised water Substances 0.000 description 2
• 229910021641 deionized water Inorganic materials 0.000 description 2
• 238000000502 dialysis Methods 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000001804 emulsifying effect Effects 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 239000003701 inert diluent Substances 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 206010022498 insulinoma Diseases 0.000 description 2
• 210000004153 islets of langerhan Anatomy 0.000 description 2
• 206010023497 kuru Diseases 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• DVRXJAVRVBKYJS-UHFFFAOYSA-N methyl 2-fluoro-4-methoxy-5-nitrobenzoate Chemical compound COC(=O)C1=CC([N+]([O-])=O)=C(OC)C=C1F DVRXJAVRVBKYJS-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 201000000050 myeloid neoplasm Diseases 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 238000010899 nucleation Methods 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 235000019198 oils Nutrition 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 235000008390 olive oil Nutrition 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• 208000021255 pancreatic insulinoma Diseases 0.000 description 2
• 239000008194 pharmaceutical composition Substances 0.000 description 2
• 239000002953 phosphate buffered saline Substances 0.000 description 2
• 230000007505 plaque formation Effects 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 229920001155 polypropylene Polymers 0.000 description 2
• 235000021395 porridge Nutrition 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 230000002285 radioactive effect Effects 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 238000007127 saponification reaction Methods 0.000 description 2
• 208000008864 scrapie Diseases 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• 208000007056 sickle cell anemia Diseases 0.000 description 2
• 229910001961 silver nitrate Inorganic materials 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 239000001488 sodium phosphate Substances 0.000 description 2
• 229910000162 sodium phosphate Inorganic materials 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000011550 stock solution Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
• 239000008215 water for injection Substances 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• 238000009736 wetting Methods 0.000 description 2
• YQYGGOPUTPQHAY-KIQLFZLRSA-N (4S)-4-[[(2S)-2-[[(2S)-2-[2-[6-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[[(4S,7R)-7-[[(2S)-1-[(2S)-6-amino-2-[[(2R)-2-[[(2S)-5-amino-2-[[(2S,3R)-2-[[(2S)-6-amino-2-[[(2S)-4-carboxy-2-hydrazinylbutanoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoyl]amino]propanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-2-methyl-5,6-dioxooctan-4-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-4-amino-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-6-oxohexyl]hydrazinyl]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-4-amino-1-[[(2S)-1-hydroxy-3-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC[C@@H](C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(=O)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1ccccc1)NC(=O)C(CCCCNN[C@@H](Cc1ccccc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C=O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO)[C@H](C)O)C(C)C)[C@H](C)O YQYGGOPUTPQHAY-KIQLFZLRSA-N 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
• 125000006824 (C1-C6) dialkyl amine group Chemical group 0.000 description 1
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical class CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• XRARCMOGDHJTAL-UHFFFAOYSA-N 2,3,4-trimethoxyaniline Chemical compound COC1=CC=C(N)C(OC)=C1OC XRARCMOGDHJTAL-UHFFFAOYSA-N 0.000 description 1
• MWTBPISZBRUNFD-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n-[2-(2h-tetrazol-5-yl)phenyl]-1,3-dihydroisoindol-5-amine Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CC2=CC(NC=3C(=CC=CC=3)C3=NNN=N3)=CC=C2C1 MWTBPISZBRUNFD-UHFFFAOYSA-N 0.000 description 1
• OHGGDIMGQRRMAX-UHFFFAOYSA-N 2-[4-[3-(3,4-dichlorophenyl)propyl]anilino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC(C=C1)=CC=C1CCCC1=CC=C(Cl)C(Cl)=C1 OHGGDIMGQRRMAX-UHFFFAOYSA-N 0.000 description 1
• WWTYXIFFYMTBCI-UHFFFAOYSA-N 2-[4-chloro-3-(trifluoromethyl)phenyl]-1,3-dihydroisoindol-5-amine Chemical compound C1C2=CC(N)=CC=C2CN1C1=CC=C(Cl)C(C(F)(F)F)=C1 WWTYXIFFYMTBCI-UHFFFAOYSA-N 0.000 description 1
• OXQGPRKQYXDCOR-UHFFFAOYSA-N 2-[[2-(3,4-dichlorophenyl)-1,3-dihydroisoindol-5-yl]amino]-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1NC1=CC=C(CN(C2)C=3C=C(Cl)C(Cl)=CC=3)C2=C1 OXQGPRKQYXDCOR-UHFFFAOYSA-N 0.000 description 1
• CXRVSOIQRUGHOS-UHFFFAOYSA-N 2-[[2-(3-fluorophenyl)-1,3-dihydroisoindol-5-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C=C(F)C=CC=3)C2=C1 CXRVSOIQRUGHOS-UHFFFAOYSA-N 0.000 description 1
• UVFWYVCDRKRAJH-UHFFFAOYSA-N 2-bromo-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1Br UVFWYVCDRKRAJH-UHFFFAOYSA-N 0.000 description 1
• XRXMNWGCKISMOH-UHFFFAOYSA-N 2-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Br XRXMNWGCKISMOH-UHFFFAOYSA-N 0.000 description 1
• ICXSHFWYCHJILC-UHFFFAOYSA-N 2-fluoro-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1F ICXSHFWYCHJILC-UHFFFAOYSA-N 0.000 description 1
• GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 1
• 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
• SDYWXFYBZPNOFX-UHFFFAOYSA-N 3,4-dichloroaniline Chemical compound NC1=CC=C(Cl)C(Cl)=C1 SDYWXFYBZPNOFX-UHFFFAOYSA-N 0.000 description 1
• PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
• QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
• BGLROEQCXZTUFA-UHFFFAOYSA-N 5-(4-fluorophenyl)-2,3-diphenyl-3,4-dihydropyrazole Chemical compound C1=CC(F)=CC=C1C1=NN(C=2C=CC=CC=2)C(C=2C=CC=CC=2)C1 BGLROEQCXZTUFA-UHFFFAOYSA-N 0.000 description 1
• ASPDJZINBYYZRU-UHFFFAOYSA-N 5-amino-2-chlorobenzotrifluoride Chemical compound NC1=CC=C(Cl)C(C(F)(F)F)=C1 ASPDJZINBYYZRU-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 1
• 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 1
• 206010002023 Amyloidoses Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 238000007125 Buchwald synthesis reaction Methods 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 239000004606 Fillers/Extenders Substances 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000009018 Medullary thyroid cancer Diseases 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 206010028289 Muscle atrophy Diseases 0.000 description 1
• 201000002481 Myositis Diseases 0.000 description 1
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 102100034574 P protein Human genes 0.000 description 1
• 101710181008 P protein Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 101710177166 Phosphoprotein Proteins 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 108700019146 Transgenes Proteins 0.000 description 1
• 238000008083 Urea Assay Methods 0.000 description 1
• 208000010399 Wasting Syndrome Diseases 0.000 description 1
• 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
• 229940022663 acetate Drugs 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000003463 adsorbent Substances 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 108010000737 amyloid enhancing factor Proteins 0.000 description 1
• DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 235000019437 butane-1,3-diol Nutrition 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 238000002591 computed tomography Methods 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 239000002872 contrast media Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 239000003431 cross linking reagent Substances 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 230000002354 daily effect Effects 0.000 description 1
• 238000001804 debridement Methods 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000003412 degenerative effect Effects 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000002996 emotional effect Effects 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 230000003203 everyday effect Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000003885 eye ointment Substances 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000003205 fragrance Substances 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 150000002240 furans Chemical class 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 239000007986 glycine-NaOH buffer Substances 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 210000002837 heart atrium Anatomy 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 210000003000 inclusion body Anatomy 0.000 description 1
• 201000008319 inclusion body myositis Diseases 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• ACJRABDJODWXCK-UHFFFAOYSA-N lithium;[dimethyl(propan-2-yl)silyl]-trimethylsilylazanide Chemical compound [Li+].CC(C)[Si](C)(C)[N-][Si](C)(C)C ACJRABDJODWXCK-UHFFFAOYSA-N 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 231100000863 loss of memory Toxicity 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000003340 mental effect Effects 0.000 description 1
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
• GBTJUXRENCDJFC-UHFFFAOYSA-N methyl 2-[[2-(2,3,4-trimethoxyphenyl)-1,3-dihydroisoindol-5-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC=C1NC1=CC=C(CN(C2)C=3C(=C(OC)C(OC)=CC=3)OC)C2=C1 GBTJUXRENCDJFC-UHFFFAOYSA-N 0.000 description 1
• VSEYYEKRZNRECT-UHFFFAOYSA-N methyl 2-bromo-5-nitrobenzoate Chemical compound COC(=O)C1=CC([N+]([O-])=O)=CC=C1Br VSEYYEKRZNRECT-UHFFFAOYSA-N 0.000 description 1
• SWGQITQOBPXVRC-UHFFFAOYSA-N methyl 2-bromobenzoate Chemical compound COC(=O)C1=CC=CC=C1Br SWGQITQOBPXVRC-UHFFFAOYSA-N 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 239000011812 mixed powder Substances 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• 230000003387 muscular Effects 0.000 description 1
• 201000000585 muscular atrophy Diseases 0.000 description 1
• 125000005487 naphthalate group Chemical group 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 210000000478 neocortex Anatomy 0.000 description 1
• 150000002828 nitro derivatives Chemical class 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 229940039748 oxalate Drugs 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 230000005298 paramagnetic effect Effects 0.000 description 1
• 239000003182 parenteral nutrition solution Substances 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000006919 peptide aggregation Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 229960003742 phenol Drugs 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229960004063 propylene glycol Drugs 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 230000000171 quenching effect Effects 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 238000002603 single-photon emission computed tomography Methods 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• CIJQGPVMMRXSQW-UHFFFAOYSA-M sodium;2-aminoacetic acid;hydroxide Chemical compound O.[Na+].NCC([O-])=O CIJQGPVMMRXSQW-UHFFFAOYSA-M 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000012289 standard assay Methods 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 229940070710 valerate Drugs 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1