ES2974721T3 - Intermedios para la preparación de inhibidores del extremo C-terminal de Hsp90 - Google Patents
Intermedios para la preparación de inhibidores del extremo C-terminal de Hsp90 Download PDFInfo
- Publication number
- ES2974721T3 ES2974721T3 ES19193576T ES19193576T ES2974721T3 ES 2974721 T3 ES2974721 T3 ES 2974721T3 ES 19193576 T ES19193576 T ES 19193576T ES 19193576 T ES19193576 T ES 19193576T ES 2974721 T3 ES2974721 T3 ES 2974721T3
- Authority
- ES
- Spain
- Prior art keywords
- nmr
- mhz
- cdcb
- acetamide
- biphenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 title abstract description 16
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 title abstract description 16
- 210000004899 c-terminal region Anatomy 0.000 title abstract description 11
- 239000003112 inhibitor Substances 0.000 title abstract description 8
- 239000000543 intermediate Substances 0.000 title description 4
- 238000002360 preparation method Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 40
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 44
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 235000010290 biphenyl Nutrition 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- BNQAFPFVQZIXSX-UHFFFAOYSA-N n-[2-[2-(4-fluorophenyl)-4-hydroxyphenyl]ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(O)C=C1C1=CC=C(F)C=C1 BNQAFPFVQZIXSX-UHFFFAOYSA-N 0.000 claims description 5
- VMGSBWSHWMLSJZ-UHFFFAOYSA-N n-[2-(4-hydroxy-2-pyridin-3-ylphenyl)ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(O)C=C1C1=CC=CN=C1 VMGSBWSHWMLSJZ-UHFFFAOYSA-N 0.000 claims description 4
- WXKPZXPFYQWGID-UHFFFAOYSA-N n-[2-[2-(1,3-benzodioxol-5-yl)-4-hydroxyphenyl]ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(O)C=C1C1=CC=C(OCO2)C2=C1 WXKPZXPFYQWGID-UHFFFAOYSA-N 0.000 claims description 4
- IGPUXJFWVWBZFA-UHFFFAOYSA-N n-[2-[2-(2-chlorophenyl)-4-hydroxyphenyl]ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(O)C=C1C1=CC=CC=C1Cl IGPUXJFWVWBZFA-UHFFFAOYSA-N 0.000 claims description 4
- ZTVZCXLVPCOWDC-UHFFFAOYSA-N n-[2-[4-hydroxy-2-(3-methoxyphenyl)phenyl]ethyl]acetamide Chemical compound COC1=CC=CC(C=2C(=CC=C(O)C=2)CCNC(C)=O)=C1 ZTVZCXLVPCOWDC-UHFFFAOYSA-N 0.000 claims description 4
- DXKGIXJPKVQBNL-UHFFFAOYSA-N n-[2-[4-hydroxy-2-(3-methylphenyl)phenyl]ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(O)C=C1C1=CC=CC(C)=C1 DXKGIXJPKVQBNL-UHFFFAOYSA-N 0.000 claims description 4
- JXLUYVLYUNZDMZ-UHFFFAOYSA-N n-[2-[4-hydroxy-2-[3-(trifluoromethyl)phenyl]phenyl]ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(O)C=C1C1=CC=CC(C(F)(F)F)=C1 JXLUYVLYUNZDMZ-UHFFFAOYSA-N 0.000 claims description 4
- LOWNRFVTPNIPSW-UHFFFAOYSA-N CC(=O)NCCc1ccc(O)cc1-c1cccc(Cl)c1 Chemical compound CC(=O)NCCc1ccc(O)cc1-c1cccc(Cl)c1 LOWNRFVTPNIPSW-UHFFFAOYSA-N 0.000 claims description 3
- BSRXTTUEGFOYST-UHFFFAOYSA-N n-[2-(4-hydroxy-2-pyridin-4-ylphenyl)ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(O)C=C1C1=CC=NC=C1 BSRXTTUEGFOYST-UHFFFAOYSA-N 0.000 claims description 3
- UIUSWANIMQYTSF-UHFFFAOYSA-N n-[2-[4-hydroxy-2-(2-methylsulfanylphenyl)phenyl]ethyl]acetamide Chemical compound CSC1=CC=CC=C1C1=CC(O)=CC=C1CCNC(C)=O UIUSWANIMQYTSF-UHFFFAOYSA-N 0.000 claims description 3
- COKHDQYUYVJHKB-UHFFFAOYSA-N n-[2-[2-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-4-hydroxyphenyl]ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(O)C=C1C1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1 COKHDQYUYVJHKB-UHFFFAOYSA-N 0.000 claims description 2
- LOJFQONZTSILOM-UHFFFAOYSA-N n-[2-[4-hydroxy-2-[4-(trifluoromethyl)phenyl]phenyl]ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(O)C=C1C1=CC=C(C(F)(F)F)C=C1 LOJFQONZTSILOM-UHFFFAOYSA-N 0.000 claims description 2
- TZQIIKOYVQAZSK-UHFFFAOYSA-N n-[2-[4-hydroxy-2-[3-(morpholin-4-ylmethyl)phenyl]phenyl]ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(O)C=C1C1=CC=CC(CN2CCOCC2)=C1 TZQIIKOYVQAZSK-UHFFFAOYSA-N 0.000 claims 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 abstract description 14
- 208000015122 neurodegenerative disease Diseases 0.000 abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 230000002265 prevention Effects 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 111
- 239000011734 sodium Substances 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 229940112879 novolog Drugs 0.000 description 16
- 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 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- -1 alkali metal salts Chemical class 0.000 description 15
- 239000008103 glucose Substances 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
- 230000000324 neuroprotective effect Effects 0.000 description 14
- 238000000034 method Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- YJQPYGGHQPGBLI-KGSXXDOSSA-N novobiocin Chemical compound O1C(C)(C)[C@H](OC)[C@@H](OC(N)=O)[C@@H](O)[C@@H]1OC1=CC=C(C(O)=C(NC(=O)C=2C=C(CC=C(C)C)C(O)=CC=2)C(=O)O2)C2=C1C YJQPYGGHQPGBLI-KGSXXDOSSA-N 0.000 description 10
- 210000003594 spinal ganglia Anatomy 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 206010012289 Dementia Diseases 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 229910052681 coesite Inorganic materials 0.000 description 8
- 229910052906 cristobalite Inorganic materials 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 235000012239 silicon dioxide Nutrition 0.000 description 8
- 229910052682 stishovite Inorganic materials 0.000 description 8
- 229910052905 tridymite Inorganic materials 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 230000001120 cytoprotective effect Effects 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 7
- YJQPYGGHQPGBLI-UHFFFAOYSA-N Novobiocin Natural products O1C(C)(C)C(OC)C(OC(N)=O)C(O)C1OC1=CC=C(C(O)=C(NC(=O)C=2C=C(CC=C(C)C)C(O)=CC=2)C(=O)O2)C2=C1C YJQPYGGHQPGBLI-UHFFFAOYSA-N 0.000 description 6
- 230000003833 cell viability Effects 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000004112 neuroprotection Effects 0.000 description 6
- 229960002950 novobiocin Drugs 0.000 description 6
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 210000001044 sensory neuron Anatomy 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- 201000001421 hyperglycemia Diseases 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 230000014759 maintenance of location Effects 0.000 description 5
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 5
- VXFVJCLMUVIKKX-LYFYHCNISA-N noviose Chemical compound CO[C@@H](C(C)(C)O)[C@@H](O)[C@@H](O)C=O VXFVJCLMUVIKKX-LYFYHCNISA-N 0.000 description 5
- 230000004224 protection Effects 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical group CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 239000004305 biphenyl Substances 0.000 description 4
- 125000005620 boronic acid group Chemical class 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- PIAOLBVUVDXHHL-UHFFFAOYSA-N 2-nitroethenylbenzene Chemical class [O-][N+](=O)C=CC1=CC=CC=C1 PIAOLBVUVDXHHL-UHFFFAOYSA-N 0.000 description 3
- ZNEQWGXPTHRHHW-UHFFFAOYSA-N 2-phenyl-4-phenylmethoxybenzaldehyde Chemical compound C1=C(C=2C=CC=CC=2)C(C=O)=CC=C1OCC1=CC=CC=C1 ZNEQWGXPTHRHHW-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 208000027747 Kennedy disease Diseases 0.000 description 3
- 108010006519 Molecular Chaperones Proteins 0.000 description 3
- 102000005431 Molecular Chaperones Human genes 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000003954 Spinal Muscular Atrophies of Childhood Diseases 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 239000000370 acceptor Substances 0.000 description 3
- 206010002022 amyloidosis Diseases 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000001028 anti-proliverative effect Effects 0.000 description 3
- 150000001543 aryl boronic acids Chemical class 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 150000005676 cyclic carbonates Chemical class 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000003119 immunoblot Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- FXVYLVMCPODKFN-UHFFFAOYSA-N n-[2-(2-phenyl-4-phenylmethoxyphenyl)ethyl]acetamide Chemical compound C1=C(C=2C=CC=CC=2)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 FXVYLVMCPODKFN-UHFFFAOYSA-N 0.000 description 3
- ZNFJDFYHYQOOEY-PZKXETHGSA-N n-[2-[4-[(3r,4s,5r)-3,4-dihydroxy-5-methoxy-6,6-dimethyloxan-2-yl]oxy-2-phenylphenyl]ethyl]acetamide Chemical compound O1C(C)(C)[C@H](OC)[C@@H](O)[C@@H](O)C1OC1=CC=C(CCNC(C)=O)C(C=2C=CC=CC=2)=C1 ZNFJDFYHYQOOEY-PZKXETHGSA-N 0.000 description 3
- UZCUPBRWTVBHAZ-DJQAVYROSA-N n-[2-[4-[(3r,4s,5r)-3,4-dihydroxy-5-methoxy-6,6-dimethyloxan-2-yl]oxy-2-pyridin-3-ylphenyl]ethyl]acetamide Chemical compound O1C(C)(C)[C@H](OC)[C@@H](O)[C@@H](O)C1OC1=CC=C(CCNC(C)=O)C(C=2C=NC=CC=2)=C1 UZCUPBRWTVBHAZ-DJQAVYROSA-N 0.000 description 3
- 239000004090 neuroprotective agent Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 208000002320 spinal muscular atrophy Diseases 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- ZNRLQJHZUGAULD-UHFFFAOYSA-N (2-formyl-5-phenylmethoxyphenyl) trifluoromethanesulfonate Chemical compound C1=C(C=O)C(OS(=O)(=O)C(F)(F)F)=CC(OCC=2C=CC=CC=2)=C1 ZNRLQJHZUGAULD-UHFFFAOYSA-N 0.000 description 2
- IUNJCFABHJZSKB-UHFFFAOYSA-N 2,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C(O)=C1 IUNJCFABHJZSKB-UHFFFAOYSA-N 0.000 description 2
- IJUNTEHFEXHQFX-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)-4-phenylmethoxybenzaldehyde Chemical compound C1=C(C=2C=C3OCOC3=CC=2)C(C=O)=CC=C1OCC1=CC=CC=C1 IJUNTEHFEXHQFX-UHFFFAOYSA-N 0.000 description 2
- YCVUBILPOGITSP-UHFFFAOYSA-N 2-(2-methylsulfanylphenyl)-4-phenylmethoxybenzaldehyde Chemical compound CSC1=CC=CC=C1C1=CC(OCC=2C=CC=CC=2)=CC=C1C=O YCVUBILPOGITSP-UHFFFAOYSA-N 0.000 description 2
- ZHGZZMJTZOFCGL-UHFFFAOYSA-N 2-(3-fluorophenyl)-4-phenylmethoxybenzaldehyde Chemical compound FC1=CC=CC(C=2C(=CC=C(OCC=3C=CC=CC=3)C=2)C=O)=C1 ZHGZZMJTZOFCGL-UHFFFAOYSA-N 0.000 description 2
- RVUXOAQFIKQOND-UHFFFAOYSA-N 2-(3-methoxyphenyl)-4-phenylmethoxybenzaldehyde Chemical compound COC1=CC=CC(C=2C(=CC=C(OCC=3C=CC=CC=3)C=2)C=O)=C1 RVUXOAQFIKQOND-UHFFFAOYSA-N 0.000 description 2
- GMCQGZQKIPVSMM-UHFFFAOYSA-N 2-(3-methylphenyl)-4-phenylmethoxybenzaldehyde Chemical compound CC1=CC=CC(C=2C(=CC=C(OCC=3C=CC=CC=3)C=2)C=O)=C1 GMCQGZQKIPVSMM-UHFFFAOYSA-N 0.000 description 2
- KCYJYZHXGIFDMN-UHFFFAOYSA-N 2-(4-fluorophenyl)-4-phenylmethoxybenzaldehyde Chemical compound C1=CC(F)=CC=C1C1=CC(OCC=2C=CC=CC=2)=CC=C1C=O KCYJYZHXGIFDMN-UHFFFAOYSA-N 0.000 description 2
- IWKQSTVTIJVPPQ-ZRDIBKRKSA-N 3-[2-[(e)-2-nitroethenyl]-5-phenylmethoxyphenyl]pyridine Chemical compound C1=C(C=2C=NC=CC=2)C(/C=C/[N+](=O)[O-])=CC=C1OCC1=CC=CC=C1 IWKQSTVTIJVPPQ-ZRDIBKRKSA-N 0.000 description 2
- ZWPJRCPOAARPNR-JLHYYAGUSA-N 4-[2-[(e)-2-nitroethenyl]-5-phenylmethoxyphenyl]pyridine Chemical compound C1=C(C=2C=CN=CC=2)C(/C=C/[N+](=O)[O-])=CC=C1OCC1=CC=CC=C1 ZWPJRCPOAARPNR-JLHYYAGUSA-N 0.000 description 2
- JVJFIQYAHPMBBX-UHFFFAOYSA-N 4-hydroxynonenal Chemical compound CCCCCC(O)C=CC=O JVJFIQYAHPMBBX-UHFFFAOYSA-N 0.000 description 2
- HGSQBXKZTGTOGW-UHFFFAOYSA-N 4-phenylmethoxy-2-[3-(trifluoromethyl)phenyl]benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(C=2C(=CC=C(OCC=3C=CC=CC=3)C=2)C=O)=C1 HGSQBXKZTGTOGW-UHFFFAOYSA-N 0.000 description 2
- SICHNSZWAIEGDL-UHFFFAOYSA-N 4-phenylmethoxy-2-pyridin-3-ylbenzaldehyde Chemical compound C1=C(C=2C=NC=CC=2)C(C=O)=CC=C1OCC1=CC=CC=C1 SICHNSZWAIEGDL-UHFFFAOYSA-N 0.000 description 2
- JICDUZDKNJDTQW-UHFFFAOYSA-N 4-phenylmethoxy-2-pyridin-4-ylbenzaldehyde Chemical compound C1=C(C=2C=CN=CC=2)C(C=O)=CC=C1OCC1=CC=CC=C1 JICDUZDKNJDTQW-UHFFFAOYSA-N 0.000 description 2
- DQAAFPWICSEBRD-ZHACJKMWSA-N 5-[2-[(e)-2-nitroethenyl]-5-phenylmethoxyphenyl]-1,3-benzodioxole Chemical compound C1=C(C=2C=C3OCOC3=CC=2)C(/C=C/[N+](=O)[O-])=CC=C1OCC1=CC=CC=C1 DQAAFPWICSEBRD-ZHACJKMWSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 244000089409 Erythrina poeppigiana Species 0.000 description 2
- 101710113864 Heat shock protein 90 Proteins 0.000 description 2
- 238000006842 Henry reaction Methods 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 208000033526 Proximal spinal muscular atrophy type 3 Diseases 0.000 description 2
- 235000009776 Rathbunia alamosensis Nutrition 0.000 description 2
- 229910004161 SiNa Inorganic materials 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 2
- 150000003869 acetamides Chemical class 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 150000005347 biaryls Chemical group 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- OGKRDTQOLGDKCT-UHFFFAOYSA-N carbonic acid;2,2,2-trichloroacetamide Chemical compound OC(O)=O.OC(=N)C(Cl)(Cl)Cl OGKRDTQOLGDKCT-UHFFFAOYSA-N 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 231100000459 glucotoxic Toxicity 0.000 description 2
- 230000002145 glucotoxic effect Effects 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 230000003345 hyperglycaemic effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 201000004815 juvenile spinal muscular atrophy Diseases 0.000 description 2
- 150000002611 lead compounds Chemical class 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000006984 memory degeneration Effects 0.000 description 2
- 208000023060 memory loss Diseases 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000004065 mitochondrial dysfunction Effects 0.000 description 2
- 201000005518 mononeuropathy Diseases 0.000 description 2
- 208000005264 motor neuron disease Diseases 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- YEADYCJGBFBFBJ-UHFFFAOYSA-N n-[2-(4-phenylmethoxy-2-pyridin-3-ylphenyl)ethyl]acetamide Chemical compound C1=C(C=2C=NC=CC=2)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 YEADYCJGBFBFBJ-UHFFFAOYSA-N 0.000 description 2
- BTSBNMAXVSFLMH-UHFFFAOYSA-N n-[2-(4-phenylmethoxy-2-pyridin-4-ylphenyl)ethyl]acetamide Chemical compound C1=C(C=2C=CN=CC=2)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 BTSBNMAXVSFLMH-UHFFFAOYSA-N 0.000 description 2
- FEKRHVNJCYAFDY-DVZSQSHLSA-N n-[2-[2-(1,3-benzodioxol-5-yl)-4-[(3r,4s,5r)-3,4-dihydroxy-5-methoxy-6,6-dimethyloxan-2-yl]oxyphenyl]ethyl]acetamide Chemical compound O1C(C)(C)[C@H](OC)[C@@H](O)[C@@H](O)C1OC1=CC=C(CCNC(C)=O)C(C=2C=C3OCOC3=CC=2)=C1 FEKRHVNJCYAFDY-DVZSQSHLSA-N 0.000 description 2
- KHBINXDCYOUFRK-UHFFFAOYSA-N n-[2-[2-(1,3-benzodioxol-5-yl)-4-phenylmethoxyphenyl]ethyl]acetamide Chemical compound C1=C(C=2C=C3OCOC3=CC=2)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 KHBINXDCYOUFRK-UHFFFAOYSA-N 0.000 description 2
- SGCBVAURWZNEQM-PZKXETHGSA-N n-[2-[2-(2-chlorophenyl)-4-[(3r,4s,5r)-3,4-dihydroxy-5-methoxy-6,6-dimethyloxan-2-yl]oxyphenyl]ethyl]acetamide Chemical compound O1C(C)(C)[C@H](OC)[C@@H](O)[C@@H](O)C1OC1=CC=C(CCNC(C)=O)C(C=2C(=CC=CC=2)Cl)=C1 SGCBVAURWZNEQM-PZKXETHGSA-N 0.000 description 2
- LXWYLILOPPSCGE-UHFFFAOYSA-N n-[2-[2-(2-chlorophenyl)-4-phenylmethoxyphenyl]ethyl]acetamide Chemical compound C1=C(C=2C(=CC=CC=2)Cl)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 LXWYLILOPPSCGE-UHFFFAOYSA-N 0.000 description 2
- PCMQZUKDGACDJD-UHFFFAOYSA-N n-[2-[2-(2-methylsulfanylphenyl)-4-phenylmethoxyphenyl]ethyl]acetamide Chemical compound CSC1=CC=CC=C1C1=CC(OCC=2C=CC=CC=2)=CC=C1CCNC(C)=O PCMQZUKDGACDJD-UHFFFAOYSA-N 0.000 description 2
- WCMDBIBPDWXHLO-PZKXETHGSA-N n-[2-[2-(3-chlorophenyl)-4-[(3r,4s,5r)-3,4-dihydroxy-5-methoxy-6,6-dimethyloxan-2-yl]oxyphenyl]ethyl]acetamide Chemical compound O1C(C)(C)[C@H](OC)[C@@H](O)[C@@H](O)C1OC1=CC=C(CCNC(C)=O)C(C=2C=C(Cl)C=CC=2)=C1 WCMDBIBPDWXHLO-PZKXETHGSA-N 0.000 description 2
- JSYQQGDIOSSIHD-UHFFFAOYSA-N n-[2-[2-(3-chlorophenyl)-4-phenylmethoxyphenyl]ethyl]acetamide Chemical compound C1=C(C=2C=C(Cl)C=CC=2)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 JSYQQGDIOSSIHD-UHFFFAOYSA-N 0.000 description 2
- USKDPVVZNFTUID-UHFFFAOYSA-N n-[2-[2-(3-methylphenyl)-4-phenylmethoxyphenyl]ethyl]acetamide Chemical compound C1=C(C=2C=C(C)C=CC=2)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 USKDPVVZNFTUID-UHFFFAOYSA-N 0.000 description 2
- XBUIZXZNSVTLHF-UHFFFAOYSA-N n-[2-[2-(4-fluorophenyl)-4-phenylmethoxyphenyl]ethyl]acetamide Chemical compound C1=C(C=2C=CC(F)=CC=2)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 XBUIZXZNSVTLHF-UHFFFAOYSA-N 0.000 description 2
- PDBWOHBMJQOBHL-PZKXETHGSA-N n-[2-[4-[(3r,4s,5r)-3,4-dihydroxy-5-methoxy-6,6-dimethyloxan-2-yl]oxy-2-(3-fluorophenyl)phenyl]ethyl]acetamide Chemical compound O1C(C)(C)[C@H](OC)[C@@H](O)[C@@H](O)C1OC1=CC=C(CCNC(C)=O)C(C=2C=C(F)C=CC=2)=C1 PDBWOHBMJQOBHL-PZKXETHGSA-N 0.000 description 2
- VMQCJCYASMOABW-DJQAVYROSA-N n-[2-[4-[(3r,4s,5r)-3,4-dihydroxy-5-methoxy-6,6-dimethyloxan-2-yl]oxy-2-pyridin-4-ylphenyl]ethyl]acetamide Chemical compound O1C(C)(C)[C@H](OC)[C@@H](O)[C@@H](O)C1OC1=CC=C(CCNC(C)=O)C(C=2C=CN=CC=2)=C1 VMQCJCYASMOABW-DJQAVYROSA-N 0.000 description 2
- RLRAMODAJJGEEF-UHFFFAOYSA-N n-[2-[4-phenylmethoxy-2-[3-(trifluoromethyl)phenyl]phenyl]ethyl]acetamide Chemical compound C1=C(C=2C=C(C=CC=2)C(F)(F)F)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 RLRAMODAJJGEEF-UHFFFAOYSA-N 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 210000000578 peripheral nerve Anatomy 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 210000002248 primary sensory neuron Anatomy 0.000 description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000012846 protein folding Effects 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 208000032527 type III spinal muscular atrophy Diseases 0.000 description 2
- 229910052727 yttrium Inorganic materials 0.000 description 2
- RRCMGJCFMJBHQC-UHFFFAOYSA-N (2-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1Cl RRCMGJCFMJBHQC-UHFFFAOYSA-N 0.000 description 1
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 1
- QXBWTYBCNFKURT-UHFFFAOYSA-N (2-methylsulfanylphenyl)boronic acid Chemical compound CSC1=CC=CC=C1B(O)O QXBWTYBCNFKURT-UHFFFAOYSA-N 0.000 description 1
- KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 description 1
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 1
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 1
- UHODZRKJYJILTL-SSDOTTSWSA-N (3r)-5-methoxy-3,4-dihydro-2h-chromen-3-amine Chemical compound O1C[C@H](N)CC2=C1C=CC=C2OC UHODZRKJYJILTL-SSDOTTSWSA-N 0.000 description 1
- COIQUVGFTILYGA-UHFFFAOYSA-N (4-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=C(O)C=C1 COIQUVGFTILYGA-UHFFFAOYSA-N 0.000 description 1
- CMHPUBKZZPSUIQ-UHFFFAOYSA-N 1,3-benzodioxol-5-ylboronic acid Chemical compound OB(O)C1=CC=C2OCOC2=C1 CMHPUBKZZPSUIQ-UHFFFAOYSA-N 0.000 description 1
- WLVZUTZEJLYLRB-BUHFOSPRSA-N 1-[(e)-2-nitroethenyl]-2-phenyl-4-phenylmethoxybenzene Chemical group C1=C(C=2C=CC=CC=2)C(/C=C/[N+](=O)[O-])=CC=C1OCC1=CC=CC=C1 WLVZUTZEJLYLRB-BUHFOSPRSA-N 0.000 description 1
- ZXKBNSNAWWVQST-BUHFOSPRSA-N 2-(2-methoxyphenyl)-1-[(e)-2-nitroethenyl]-4-phenylmethoxybenzene Chemical group COC1=CC=CC=C1C1=CC(OCC=2C=CC=CC=2)=CC=C1\C=C\[N+]([O-])=O ZXKBNSNAWWVQST-BUHFOSPRSA-N 0.000 description 1
- UUXLEJUSVITYOE-UHFFFAOYSA-N 2-(2-methoxyphenyl)-4-phenylmethoxybenzaldehyde Chemical compound COC1=CC=CC=C1C1=CC(OCC=2C=CC=CC=2)=CC=C1C=O UUXLEJUSVITYOE-UHFFFAOYSA-N 0.000 description 1
- HSEWKGJTRMTNQB-OUKQBFOZSA-N 2-(3-methoxyphenyl)-1-[(e)-2-nitroethenyl]-4-phenylmethoxybenzene Chemical group COC1=CC=CC(C=2C(=CC=C(OCC=3C=CC=CC=3)C=2)\C=C\[N+]([O-])=O)=C1 HSEWKGJTRMTNQB-OUKQBFOZSA-N 0.000 description 1
- MSYKIBBVIJIVQF-UHFFFAOYSA-N 2-[3-(morpholin-4-ylmethyl)phenyl]-4-phenylmethoxybenzaldehyde Chemical compound C1=C(C=2C=C(CN3CCOCC3)C=CC=2)C(C=O)=CC=C1OCC1=CC=CC=C1 MSYKIBBVIJIVQF-UHFFFAOYSA-N 0.000 description 1
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 1
- NRQBTNARWALYSB-UHFFFAOYSA-N 4,6-dimethoxy-1h-indole Chemical class COC1=CC(OC)=C2C=CNC2=C1 NRQBTNARWALYSB-UHFFFAOYSA-N 0.000 description 1
- DXYCMSJBONBULL-VAWYXSNFSA-N 4-[[3-[2-[(e)-2-nitroethenyl]-5-phenylmethoxyphenyl]phenyl]methyl]morpholine Chemical compound C1=C(C=2C=C(CN3CCOCC3)C=CC=2)C(/C=C/[N+](=O)[O-])=CC=C1OCC1=CC=CC=C1 DXYCMSJBONBULL-VAWYXSNFSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- OBQWKNNBNWALJG-UHFFFAOYSA-N 4-phenylmethoxy-2-[4-(trifluoromethyl)phenyl]benzaldehyde Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC(OCC=2C=CC=CC=2)=CC=C1C=O OBQWKNNBNWALJG-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 208000036487 Arthropathies Diseases 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 102000007371 Ataxin-3 Human genes 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000029402 Bulbospinal muscular atrophy Diseases 0.000 description 1
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010007509 Cardiac amyloidosis Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 208000033647 Classic progressive supranuclear palsy syndrome Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 108010054814 DNA Gyrase Proteins 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 206010012643 Diabetic amyotrophy Diseases 0.000 description 1
- 206010012645 Diabetic autonomic neuropathy Diseases 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010016207 Familial Mediterranean fever Diseases 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 description 1
- 206010072075 Gerstmann-Straussler-Scheinker syndrome Diseases 0.000 description 1
- 206010018985 Haemorrhage intracranial Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000013016 Hypoglycemia 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
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 208000008574 Intracranial Hemorrhages Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 208000034693 Laceration Diseases 0.000 description 1
- 208000034800 Leukoencephalopathies Diseases 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000002569 Machado-Joseph Disease Diseases 0.000 description 1
- 208000019090 Machado-Joseph disease type 3 Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 description 1
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 201000002795 Muckle-Wells syndrome Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 101100440286 Mus musculus Cntrl gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- RNNNVOFHVXDEQR-UHFFFAOYSA-N Oc1ccc(cc1)-c1cc(OCc2ccccc2)ccc1C=O Chemical compound Oc1ccc(cc1)-c1cc(OCc2ccccc2)ccc1C=O RNNNVOFHVXDEQR-UHFFFAOYSA-N 0.000 description 1
- 208000014723 Oculomotor Nerve disease Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010033885 Paraparesis Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 208000032225 Proximal spinal muscular atrophy type 1 Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000021811 Sandhoff disease Diseases 0.000 description 1
- 208000009106 Shy-Drager Syndrome Diseases 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 208000002548 Spastic Paraparesis Diseases 0.000 description 1
- 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
- 208000032859 Synucleinopathies Diseases 0.000 description 1
- 208000022292 Tay-Sachs disease Diseases 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
- 206010063661 Vascular encephalopathy Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 208000026481 Werdnig-Hoffmann disease Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- WOAORAPRPVIATR-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(F)(F)F)=C1 WOAORAPRPVIATR-UHFFFAOYSA-N 0.000 description 1
- ALMFIOZYDASRRC-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)C=C1 ALMFIOZYDASRRC-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000002210 biocatalytic effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- RAROSYAOUZEARD-OUKQBFOZSA-N c1c(C)cccc1-c1cc(OCc2ccccc2)ccc1\C=C\[N+]([O-])=O Chemical group c1c(C)cccc1-c1cc(OCc2ccccc2)ccc1\C=C\[N+]([O-])=O RAROSYAOUZEARD-OUKQBFOZSA-N 0.000 description 1
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- AEULIVPVIDOLIN-UHFFFAOYSA-N cep-11981 Chemical compound C1=C2C3=C4CNC(=O)C4=C4C5=CN(C)N=C5CCC4=C3N(CC(C)C)C2=CC=C1NC1=NC=CC=N1 AEULIVPVIDOLIN-UHFFFAOYSA-N 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 208000017004 dementia pugilistica Diseases 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000003073 embolic effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 201000006061 fatal familial insomnia Diseases 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 210000000609 ganglia Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 208000008675 hereditary spastic paraplegia Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 206010023497 kuru Diseases 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 201000000564 macroglobulinemia Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- WPXNRRRAWSQDNI-UHFFFAOYSA-N n-[2-[2-(2-methoxyphenyl)-4-phenylmethoxyphenyl]ethyl]acetamide Chemical compound COC1=CC=CC=C1C1=CC(OCC=2C=CC=CC=2)=CC=C1CCNC(C)=O WPXNRRRAWSQDNI-UHFFFAOYSA-N 0.000 description 1
- QFCBTASYZWUOTM-UHFFFAOYSA-N n-[2-[2-[3-(morpholin-4-ylmethyl)phenyl]-4-phenylmethoxyphenyl]ethyl]acetamide Chemical compound C1=C(C=2C=C(CN3CCOCC3)C=CC=2)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 QFCBTASYZWUOTM-UHFFFAOYSA-N 0.000 description 1
- VUFKOBNUTBCFBM-UHFFFAOYSA-N n-[2-[4-hydroxy-2-(2-methoxyphenyl)phenyl]ethyl]acetamide Chemical compound COC1=CC=CC=C1C1=CC(O)=CC=C1CCNC(C)=O VUFKOBNUTBCFBM-UHFFFAOYSA-N 0.000 description 1
- NVMXSXZDWJCDLM-UHFFFAOYSA-N n-[2-[4-phenylmethoxy-2-[4-(trifluoromethyl)phenyl]phenyl]ethyl]acetamide Chemical compound C1=C(C=2C=CC(=CC=2)C(F)(F)F)C(CCNC(=O)C)=CC=C1OCC1=CC=CC=C1 NVMXSXZDWJCDLM-UHFFFAOYSA-N 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000012316 non-parametric ANOVA Methods 0.000 description 1
- 230000001019 normoglycemic effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 208000031237 olivopontocerebellar atrophy Diseases 0.000 description 1
- 229940127017 oral antidiabetic Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 208000001282 primary progressive aphasia Diseases 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 208000032207 progressive 1 supranuclear palsy Diseases 0.000 description 1
- 201000002241 progressive bulbar palsy Diseases 0.000 description 1
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 230000007129 protein targeting to mitochondrion Effects 0.000 description 1
- 201000000196 pseudobulbar palsy Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010916 retrosynthetic analysis Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- MQTUXRKNJYPMCG-CYBMUJFWSA-N robalzotan Chemical compound C1CCC1N([C@H]1COC=2C(F)=CC=C(C=2C1)C(=O)N)C1CCC1 MQTUXRKNJYPMCG-CYBMUJFWSA-N 0.000 description 1
- 229950003023 robalzotan Drugs 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 208000003755 striatonigral degeneration Diseases 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- QCIWZIYBBNEPKB-UHFFFAOYSA-N tert-butyl(dimethyl)silane Chemical compound C[SiH](C)C(C)(C)C QCIWZIYBBNEPKB-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 208000032471 type 1 spinal muscular atrophy Diseases 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/16—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings other than six-membered aromatic rings
- C07C211/17—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings other than six-membered aromatic rings containing only non-condensed rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/18—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/08—1,3-Dioxanes; Hydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/207—Cyclohexane rings not substituted by nitrogen atoms, e.g. kasugamycins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Emergency Medicine (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261597004P | 2012-02-09 | 2012-02-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2974721T3 true ES2974721T3 (es) | 2024-07-01 |
Family
ID=47754998
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES19193576T Active ES2974721T3 (es) | 2012-02-09 | 2013-02-08 | Intermedios para la preparación de inhibidores del extremo C-terminal de Hsp90 |
| ES13706822T Active ES2755093T3 (es) | 2012-02-09 | 2013-02-08 | Inhibidores del extremo C-terminal de Hsp90 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13706822T Active ES2755093T3 (es) | 2012-02-09 | 2013-02-08 | Inhibidores del extremo C-terminal de Hsp90 |
Country Status (24)
| Country | Link |
|---|---|
| US (7) | US9422320B2 (enExample) |
| EP (3) | EP2812341B1 (enExample) |
| JP (1) | JP6121450B2 (enExample) |
| KR (1) | KR102124109B1 (enExample) |
| CN (2) | CN104271587B (enExample) |
| AU (1) | AU2013216858C1 (enExample) |
| BR (1) | BR112014019704B1 (enExample) |
| CA (1) | CA2866814C (enExample) |
| CY (1) | CY1122358T1 (enExample) |
| DK (2) | DK3656758T3 (enExample) |
| EA (1) | EA027147B1 (enExample) |
| ES (2) | ES2974721T3 (enExample) |
| FI (1) | FI3656758T3 (enExample) |
| HR (2) | HRP20191940T1 (enExample) |
| HU (2) | HUE046939T2 (enExample) |
| LT (2) | LT3656758T (enExample) |
| MX (1) | MX361233B (enExample) |
| NZ (1) | NZ629778A (enExample) |
| PL (2) | PL3656758T3 (enExample) |
| PT (2) | PT3656758T (enExample) |
| RS (2) | RS59719B1 (enExample) |
| SI (2) | SI3656758T1 (enExample) |
| SM (2) | SMT201900660T1 (enExample) |
| WO (1) | WO2013119985A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104271587B (zh) | 2012-02-09 | 2017-09-12 | 堪萨斯大学 | Hsp90C端抑制剂 |
| CA2951270C (en) | 2014-06-13 | 2023-07-04 | The University Of Kansas | Triazole modified coumarin and biphenyl amide-based hsp90 inhibitors |
| CA3289739A1 (en) * | 2014-06-24 | 2025-11-29 | The Univ Of Kansas | Biphenyl amides with modified ether groups as hsp90 inhibitors and hsp70 inducers |
| WO2016145219A1 (en) * | 2015-03-10 | 2016-09-15 | University Of Florida Research Foundation, Inc. | Treatment of peripheral neuropathies |
| CN111479815A (zh) * | 2017-12-20 | 2020-07-31 | 默克专利有限公司 | 杂芳族化合物 |
| IL276583B2 (en) * | 2018-02-07 | 2025-03-01 | Reata Pharmaceuticals Inc | Crystal structures of proline and a novobiocin analog |
| US11827664B2 (en) * | 2018-05-14 | 2023-11-28 | Reata Pharmaceuticals, Inc | Biaryl amides with modified sugar groups for treatment of diseases associated with heat shock protein pathway |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| US20250049810A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7622451B2 (en) | 2004-11-03 | 2009-11-24 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
| US9120774B2 (en) | 2004-11-03 | 2015-09-01 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
| US8212011B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues |
| US8212012B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
| AU2005301957B2 (en) | 2004-11-03 | 2012-02-23 | Department Of Health And Human Services | Novobiocin analogues as anticancer agents |
| US8846742B2 (en) * | 2006-02-14 | 2014-09-30 | The Trustees Of Columbia University In The City Of New York | Neuronal pain pathway modulators |
| GB0620259D0 (en) * | 2006-10-12 | 2006-11-22 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| CA2669687C (en) | 2006-11-15 | 2013-09-10 | Forest Laboratories Holdings Limited | Phthalazine derivatives |
| MX2009009936A (es) | 2007-03-20 | 2010-02-11 | Curis Inc | Amino piridina fusionada como inhibidores de hsp90. |
| US7960353B2 (en) * | 2007-05-10 | 2011-06-14 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
| JP5766617B2 (ja) * | 2009-02-20 | 2015-08-19 | ユニバーシティ・オブ・カンザス | 修飾された糖部分を有するノボビオシン類似体 |
| US20110082098A1 (en) | 2009-09-30 | 2011-04-07 | University Of Kansas | Novobiocin analogues and treatment of polycystic kidney disease |
| EP2594554A4 (en) | 2010-07-13 | 2014-01-15 | Dainippon Sumitomo Pharma Co | BIARYLAMID DERIVATIVES BZW. PHARMACEUTICALLY PERMITTED SALT FROM THIS |
| CN101967125B (zh) * | 2010-10-08 | 2012-07-04 | 广州暨南生物医药研究开发基地有限公司 | 一种Hsp90抑制剂Xbj-B16-1及其制备方法与应用 |
| EP2694506B1 (en) | 2011-04-05 | 2017-09-20 | Sloan-kettering Institute For Cancer Research | Hsp90 inhibitors |
| US9056104B2 (en) | 2011-05-20 | 2015-06-16 | The University Of Kansas | Dynamic inhibitors of heat shock protein 90 |
| CN104271587B (zh) | 2012-02-09 | 2017-09-12 | 堪萨斯大学 | Hsp90C端抑制剂 |
| EP3066072B1 (en) | 2013-11-07 | 2021-11-03 | The University of Kansas | Biphenylamide derivative hsp90 inhibitors |
| WO2015070238A2 (en) | 2013-11-11 | 2015-05-14 | The University Of Kansas | Coumarin based hsp90 inhibitors with urea and ether substituents |
| CA2951270C (en) | 2014-06-13 | 2023-07-04 | The University Of Kansas | Triazole modified coumarin and biphenyl amide-based hsp90 inhibitors |
| CA3289739A1 (en) | 2014-06-24 | 2025-11-29 | The Univ Of Kansas | Biphenyl amides with modified ether groups as hsp90 inhibitors and hsp70 inducers |
| US11827664B2 (en) | 2018-05-14 | 2023-11-28 | Reata Pharmaceuticals, Inc | Biaryl amides with modified sugar groups for treatment of diseases associated with heat shock protein pathway |
-
2013
- 2013-02-08 CN CN201380019057.XA patent/CN104271587B/zh active Active
- 2013-02-08 US US14/377,616 patent/US9422320B2/en active Active
- 2013-02-08 KR KR1020147025348A patent/KR102124109B1/ko active Active
- 2013-02-08 PL PL19193576.6T patent/PL3656758T3/pl unknown
- 2013-02-08 EP EP13706822.7A patent/EP2812341B1/en active Active
- 2013-02-08 CN CN201710729038.6A patent/CN107474085B/zh active Active
- 2013-02-08 WO PCT/US2013/025387 patent/WO2013119985A1/en not_active Ceased
- 2013-02-08 LT LTEP19193576.6T patent/LT3656758T/lt unknown
- 2013-02-08 SM SM20190660T patent/SMT201900660T1/it unknown
- 2013-02-08 HR HRP20191940TT patent/HRP20191940T1/hr unknown
- 2013-02-08 SM SM20240145T patent/SMT202400145T1/it unknown
- 2013-02-08 HU HUE13706822A patent/HUE046939T2/hu unknown
- 2013-02-08 ES ES19193576T patent/ES2974721T3/es active Active
- 2013-02-08 BR BR112014019704-0A patent/BR112014019704B1/pt active IP Right Grant
- 2013-02-08 EA EA201491496A patent/EA027147B1/ru unknown
- 2013-02-08 HU HUE19193576A patent/HUE066259T2/hu unknown
- 2013-02-08 SI SI201332079T patent/SI3656758T1/sl unknown
- 2013-02-08 CA CA2866814A patent/CA2866814C/en active Active
- 2013-02-08 EP EP19193576.6A patent/EP3656758B1/en active Active
- 2013-02-08 AU AU2013216858A patent/AU2013216858C1/en active Active
- 2013-02-08 SI SI201331622T patent/SI2812341T1/sl unknown
- 2013-02-08 NZ NZ629778A patent/NZ629778A/en unknown
- 2013-02-08 PL PL13706822T patent/PL2812341T3/pl unknown
- 2013-02-08 LT LT13706822T patent/LT2812341T/lt unknown
- 2013-02-08 FI FIEP19193576.6T patent/FI3656758T3/fi active
- 2013-02-08 MX MX2014009608A patent/MX361233B/es active IP Right Grant
- 2013-02-08 HR HRP20240514TT patent/HRP20240514T1/hr unknown
- 2013-02-08 RS RS20191454A patent/RS59719B1/sr unknown
- 2013-02-08 DK DK19193576.6T patent/DK3656758T3/da active
- 2013-02-08 ES ES13706822T patent/ES2755093T3/es active Active
- 2013-02-08 PT PT191935766T patent/PT3656758T/pt unknown
- 2013-02-08 DK DK13706822T patent/DK2812341T3/da active
- 2013-02-08 JP JP2014556739A patent/JP6121450B2/ja active Active
- 2013-02-08 PT PT137068227T patent/PT2812341T/pt unknown
- 2013-02-08 RS RS20240452A patent/RS65412B1/sr unknown
- 2013-02-08 EP EP24161059.1A patent/EP4403552A3/en active Pending
-
2016
- 2016-08-03 US US15/227,230 patent/US10030041B2/en active Active
-
2018
- 2018-06-26 US US16/018,401 patent/US10590157B2/en active Active
-
2019
- 2019-11-11 CY CY20191101180T patent/CY1122358T1/el unknown
-
2020
- 2020-02-05 US US16/783,025 patent/US10882881B2/en active Active
- 2020-12-04 US US17/112,060 patent/US11390640B2/en active Active
-
2022
- 2022-07-12 US US17/863,135 patent/US12024536B2/en active Active
-
2024
- 2024-05-17 US US18/667,496 patent/US20240417419A1/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2974721T3 (es) | Intermedios para la preparación de inhibidores del extremo C-terminal de Hsp90 | |
| US10590065B2 (en) | Biphenyl amides with modified ether groups as HSP90 inhibitors and HSP70 inducers | |
| KR102388412B1 (ko) | 페노티아진 유도체 및 이의 사용 방법 | |
| HK1249519B (zh) | Hsp90 c端抑制剂及其医药组合物和用途 | |
| HK1205131B (en) | C-terminal hsp90 inhibitors | |
| CN120398981A (zh) | 具有HIF-1α蛋白抑制活性的红景天苷衍生物及其合成和应用 | |
| JP2025517814A (ja) | 新規インデノン誘導体及びその用途 | |
| EA041727B1 (ru) | Бифениламиды, содержащие модифицированные простые эфирные группы, в качестве ингибиторов hsp90 и стимуляторов hsp70 |