ES2574927T3 - Piridinas bicíclicas y análogos como moduladores de sirtuina - Google Patents
Piridinas bicíclicas y análogos como moduladores de sirtuina Download PDFInfo
- Publication number
- ES2574927T3 ES2574927T3 ES10830519.4T ES10830519T ES2574927T3 ES 2574927 T3 ES2574927 T3 ES 2574927T3 ES 10830519 T ES10830519 T ES 10830519T ES 2574927 T3 ES2574927 T3 ES 2574927T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- substituted
- fluorine
- cr4r5
- independently selected
- 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
- -1 Bicyclic pyridines Chemical class 0.000 title abstract description 10
- 102000011990 Sirtuin Human genes 0.000 title description 67
- 108050002485 Sirtuin Proteins 0.000 title description 67
- 150000001875 compounds Chemical class 0.000 claims abstract description 64
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 34
- 229910052731 fluorine Inorganic materials 0.000 claims abstract 16
- 239000011737 fluorine Chemical group 0.000 claims abstract 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract 15
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract 15
- 229910052736 halogen Inorganic materials 0.000 claims abstract 8
- 150000002367 halogens Chemical group 0.000 claims abstract 6
- 125000001424 substituent group Chemical group 0.000 claims abstract 4
- 150000003839 salts Chemical class 0.000 abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract 8
- 239000001257 hydrogen Substances 0.000 abstract 8
- 125000000623 heterocyclic group Chemical group 0.000 abstract 7
- 150000002431 hydrogen Chemical group 0.000 abstract 6
- 229910052757 nitrogen Inorganic materials 0.000 abstract 6
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 abstract 4
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 4
- 229910052799 carbon Inorganic materials 0.000 abstract 3
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 abstract 2
- 125000005843 halogen group Chemical group 0.000 abstract 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 2
- 229910052717 sulfur Inorganic materials 0.000 abstract 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- 125000001931 aliphatic group Chemical group 0.000 abstract 1
- 125000004429 atom Chemical group 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 35
- 230000000694 effects Effects 0.000 description 29
- 238000000034 method Methods 0.000 description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 27
- 239000000203 mixture Substances 0.000 description 19
- 201000010099 disease Diseases 0.000 description 17
- 201000006417 multiple sclerosis Diseases 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 9
- 230000032683 aging Effects 0.000 description 8
- 230000004770 neurodegeneration Effects 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 208000015122 neurodegenerative disease Diseases 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 210000003491 skin Anatomy 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000002502 liposome Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 208000024827 Alzheimer disease Diseases 0.000 description 5
- 229920000858 Cyclodextrin Polymers 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 230000030833 cell death Effects 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- KOUVDKDABFOPIG-UHFFFAOYSA-N 2-oxa-6-azaspiro[3.3]heptane;oxalic acid Chemical compound OC(=O)C(O)=O.C1NCC11COC1 KOUVDKDABFOPIG-UHFFFAOYSA-N 0.000 description 4
- JMEWIFIVAHKVTL-UHFFFAOYSA-N 4,4-difluoro-n-pyridin-2-yl-7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1,8-naphthyridine-1-carboxamide Chemical compound FC(F)(F)C1=CC=CC(C=2N=C3C(C(CCN3C(=O)NC=3N=CC=CC=3)(F)F)=CC=2)=C1 JMEWIFIVAHKVTL-UHFFFAOYSA-N 0.000 description 4
- YZAIPNZQESMPAU-UHFFFAOYSA-N 4,4-difluoro-n-pyridin-4-yl-7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1,8-naphthyridine-1-carboxamide Chemical compound FC(F)(F)C1=CC=CC(C=2N=C3C(C(CCN3C(=O)NC=3C=CN=CC=3)(F)F)=CC=2)=C1 YZAIPNZQESMPAU-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- SSONGPPRCUORMZ-UHFFFAOYSA-N 4-methyl-n-pyridin-2-yl-7-[3-(trifluoromethyl)phenyl]-3,4-dihydro-2h-1,8-naphthyridine-1-carboxamide Chemical compound C12=NC(C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C(C)CCN1C(=O)NC1=CC=CC=N1 SSONGPPRCUORMZ-UHFFFAOYSA-N 0.000 description 4
- HBJLCNZDUBGXHR-UHFFFAOYSA-N 4-methyl-n-pyridin-4-yl-7-[3-(trifluoromethyl)phenyl]-3,4-dihydro-2h-1,8-naphthyridine-1-carboxamide Chemical compound C12=NC(C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C(C)CCN1C(=O)NC1=CC=NC=C1 HBJLCNZDUBGXHR-UHFFFAOYSA-N 0.000 description 4
- OTINAJBFOXELMP-UHFFFAOYSA-N 6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(N2CC3(COC3)C2)=N1 OTINAJBFOXELMP-UHFFFAOYSA-N 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 208000033808 peripheral neuropathy Diseases 0.000 description 4
- 238000012746 preparative thin layer chromatography Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000023105 Huntington disease Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 230000007845 axonopathy Effects 0.000 description 3
- 210000004958 brain cell Anatomy 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 208000015114 central nervous system disease Diseases 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- BKDIZUYZBKBSTG-UHFFFAOYSA-N 2-(3-chlorophenyl)-5-oxo-n-pyridin-3-yl-7,8-dihydro-6h-pyrido[2,3-b]azepine-9-carboxamide Chemical compound ClC1=CC=CC(C=2N=C3C(C(CCCN3C(=O)NC=3C=NC=CC=3)=O)=CC=2)=C1 BKDIZUYZBKBSTG-UHFFFAOYSA-N 0.000 description 2
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 2
- GPRCCHKJYRWMCI-UHFFFAOYSA-N 4,4-dimethyl-n-pyridin-4-yl-7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1,8-naphthyridine-1-carboxamide Chemical compound C12=NC(C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C(C)(C)CCN1C(=O)NC1=CC=NC=C1 GPRCCHKJYRWMCI-UHFFFAOYSA-N 0.000 description 2
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000031229 Cardiomyopathies Diseases 0.000 description 2
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 2
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 2
- 206010012442 Dermatitis contact Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 229930186217 Glycolipid Natural products 0.000 description 2
- 208000002720 Malnutrition Diseases 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- 206010034719 Personality change Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 210000003403 autonomic nervous system Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 230000010094 cellular senescence Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000002113 chemopreventative effect Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229940097362 cyclodextrins Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- 229960004979 fampridine Drugs 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 230000006984 memory degeneration Effects 0.000 description 2
- 208000023060 memory loss Diseases 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 201000005518 mononeuropathy Diseases 0.000 description 2
- 208000005264 motor neuron disease Diseases 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000009758 senescence Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000012049 topical pharmaceutical composition Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-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
- FQKMURZGUPNXOK-UHFFFAOYSA-N 4,4-difluoro-7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1h-1,8-naphthyridine Chemical compound FC(F)(F)C1=CC=CC(C=2N=C3C(C(CCN3)(F)F)=CC=2)=C1 FQKMURZGUPNXOK-UHFFFAOYSA-N 0.000 description 1
- RPJFOJQMTHLCAZ-UHFFFAOYSA-N 4-methyl-7-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-1,8-naphthyridine Chemical compound C=1C=C2C(C)CCNC2=NC=1C1=CC=CC(C(F)(F)F)=C1 RPJFOJQMTHLCAZ-UHFFFAOYSA-N 0.000 description 1
- KLRCTUOHTMRIQJ-UHFFFAOYSA-N 4-methyl-7-[3-(trifluoromethyl)phenyl]-1,2-dihydro-1,8-naphthyridine Chemical compound C=1C=C2C(C)=CCNC2=NC=1C1=CC=CC(C(F)(F)F)=C1 KLRCTUOHTMRIQJ-UHFFFAOYSA-N 0.000 description 1
- LAMQVIQMVKWXOC-UHFFFAOYSA-N 4-methyl-n-[2-[3-(morpholin-4-ylmethyl)imidazo[2,1-b][1,3]thiazol-6-yl]phenyl]-2-pyridin-3-yl-1,3-thiazole-5-carboxamide Chemical compound CC=1N=C(C=2C=NC=CC=2)SC=1C(=O)NC1=CC=CC=C1C(N=C1SC=2)=CN1C=2CN1CCOCC1 LAMQVIQMVKWXOC-UHFFFAOYSA-N 0.000 description 1
- DVSLPPSXVDZQHH-UHFFFAOYSA-N 6-(4-methylphenyl)sulfonyl-2-oxa-6-azaspiro[3.3]heptane Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CC2(COC2)C1 DVSLPPSXVDZQHH-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 201000010053 Alcoholic Cardiomyopathy Diseases 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 206010061666 Autonomic neuropathy Diseases 0.000 description 1
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 206010007637 Cardiomyopathy alcoholic Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 208000009043 Chemical Burns Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 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
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010012455 Dermatitis exfoliative Diseases 0.000 description 1
- 206010012643 Diabetic amyotrophy Diseases 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 206010069808 Electrical burn Diseases 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 206010015218 Erythema multiforme Diseases 0.000 description 1
- 206010015226 Erythema nodosum Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 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
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010058222 Hypertensive cardiomyopathy Diseases 0.000 description 1
- 206010021283 IIIrd nerve paralysis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 description 1
- KSMITTDZTTZFML-LURJTMIESA-N Jasminine Chemical compound C[C@@H]1NC(=O)CC2=C1C=NC=C2C(=O)OC KSMITTDZTTZFML-LURJTMIESA-N 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 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 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000001940 Massive Hepatic Necrosis Diseases 0.000 description 1
- 206010070909 Metabolic cardiomyopathy Diseases 0.000 description 1
- 206010027910 Mononeuritis Diseases 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 102100031455 NAD-dependent protein deacetylase sirtuin-1 Human genes 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 208000014723 Oculomotor Nerve disease Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 208000021811 Sandhoff disease Diseases 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- 108010041191 Sirtuin 1 Proteins 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010040799 Skin atrophy Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000022292 Tay-Sachs disease Diseases 0.000 description 1
- 206010053615 Thermal burn Diseases 0.000 description 1
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 208000009621 actinic keratosis Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000003679 aging effect Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 208000002353 alcoholic hepatitis Diseases 0.000 description 1
- 208000002029 allergic contact dermatitis Diseases 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 102000007478 beta-N-Acetylhexosaminidases Human genes 0.000 description 1
- 108010085377 beta-N-Acetylhexosaminidases Proteins 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 235000020827 calorie restriction Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 201000004559 cerebral degeneration Diseases 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000004970 emotional disturbance Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- TXHMGULJVNYTGV-UHFFFAOYSA-N ethyl 6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC(N2CC3(COC3)C2)=N1 TXHMGULJVNYTGV-UHFFFAOYSA-N 0.000 description 1
- OONBOXSIWCBAHZ-UHFFFAOYSA-N ethyl 6-bromopyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC(Br)=N1 OONBOXSIWCBAHZ-UHFFFAOYSA-N 0.000 description 1
- 208000004526 exfoliative dermatitis Diseases 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 208000037957 feline spongiform encephalopathy Diseases 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- GIVLTTJNORAZON-HDBOBKCLSA-N ganglioside GM2 (18:0) Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 GIVLTTJNORAZON-HDBOBKCLSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 231100000652 hormesis Toxicity 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 208000022368 idiopathic cardiomyopathy Diseases 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 208000001875 irritant dermatitis Diseases 0.000 description 1
- 208000023589 ischemic disease Diseases 0.000 description 1
- 230000003780 keratinization Effects 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000013734 mononeuritis simplex Diseases 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- VSPPONOIKZXUBJ-UHFFFAOYSA-N n,n-diethylethanamine;oxolane Chemical compound C1CCOC1.CCN(CC)CC VSPPONOIKZXUBJ-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000006764 neuronal dysfunction Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 235000018343 nutrient deficiency Nutrition 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- IDQIVMAVPVTKGL-UHFFFAOYSA-N phenyl n-pyridin-2-ylcarbamate Chemical compound C=1C=CC=CC=1OC(=O)NC1=CC=CC=N1 IDQIVMAVPVTKGL-UHFFFAOYSA-N 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000021283 resveratrol Nutrition 0.000 description 1
- 229940016667 resveratrol Drugs 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 208000008864 scrapie Diseases 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008833 sun damage Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- VLYYWMYAPRLZIC-UHFFFAOYSA-N tert-butyl n-[6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyridin-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(N2CC3(COC3)C2)=N1 VLYYWMYAPRLZIC-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25626909P | 2009-10-29 | 2009-10-29 | |
| US256269P | 2009-10-29 | ||
| PCT/US2010/054880 WO2011059839A1 (en) | 2009-10-29 | 2010-10-29 | Bicyclic pyridines and analogs as sirtuin modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2574927T3 true ES2574927T3 (es) | 2016-06-23 |
Family
ID=43991957
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10830519.4T Active ES2574927T3 (es) | 2009-10-29 | 2010-10-29 | Piridinas bicíclicas y análogos como moduladores de sirtuina |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US9556201B2 (enExample) |
| EP (1) | EP2493888B1 (enExample) |
| JP (1) | JP2013509442A (enExample) |
| KR (1) | KR20120092141A (enExample) |
| CN (1) | CN102725291B (enExample) |
| AU (1) | AU2010319842A1 (enExample) |
| BR (1) | BR112012010010A2 (enExample) |
| CA (1) | CA2779303A1 (enExample) |
| ES (1) | ES2574927T3 (enExample) |
| IL (1) | IL219372A0 (enExample) |
| IN (1) | IN2012DN03799A (enExample) |
| MX (1) | MX2012004995A (enExample) |
| RU (1) | RU2550821C2 (enExample) |
| WO (1) | WO2011059839A1 (enExample) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2231280B1 (en) | 2007-12-10 | 2016-08-10 | Novartis AG | Amiloride-like Pyrazine-carboxamides as ENaC blockers |
| CA2738809C (en) | 2008-09-29 | 2015-11-24 | Sirtris Pharmaceuticals, Inc. | Quinazolinone, quinolone and related analogs as sirtuin modulators |
| AU2013253516B2 (en) | 2012-04-25 | 2017-10-12 | Takeda Pharmaceutical Company Limited | Nitrogenated heterocyclic compound |
| CA2871514C (en) | 2012-05-08 | 2020-08-25 | Merck Sharp & Dohme Corp. | Tetrahydronaphthyridine and related bicyclic compounds for inhibition of ror.gamma.activity and the treatment of disease |
| AU2013259624B2 (en) | 2012-05-08 | 2017-10-19 | Lycera Corporation | Tetrahydro[1,8]naphthyridine sulfonamide and related compounds for use as agonists of RORy and the treatment of disease |
| WO2014010732A1 (ja) | 2012-07-13 | 2014-01-16 | 武田薬品工業株式会社 | 複素環化合物 |
| KR101697444B1 (ko) * | 2012-08-30 | 2017-01-17 | 에프. 호프만-라 로슈 아게 | 다이옥시노- 및 옥사진-[2,3-d]피리미딘 pi3k 억제제 화합물 및 사용 방법 |
| CN102977117A (zh) * | 2012-11-26 | 2013-03-20 | 盛世泰科生物医药技术(苏州)有限公司 | 一种6-溴-2,2-二甲基-2h-吡啶并[3,2-b][1,4]恶嗪-3(4h)-酮的合成方法 |
| GEP201606554B (en) * | 2012-12-26 | 2016-10-10 | Takeda Pharmaceuticals Co | Nitrogenated heterocyclic compound |
| WO2014142255A1 (ja) | 2013-03-14 | 2014-09-18 | 武田薬品工業株式会社 | 複素環化合物 |
| CN105392788B (zh) * | 2013-05-13 | 2018-10-23 | 葛兰素史密斯克莱有限责任公司 | 用作沉默调节蛋白调节剂的取代的桥连脲类似物 |
| WO2016081692A2 (en) * | 2014-11-19 | 2016-05-26 | Glaxosmithkline Llc | Substituted bridged urea analogs as sirtuin modulators |
| WO2015002231A1 (ja) | 2013-07-03 | 2015-01-08 | 武田薬品工業株式会社 | 複素環化合物 |
| WO2015002230A1 (ja) | 2013-07-03 | 2015-01-08 | 武田薬品工業株式会社 | アミド化合物 |
| FI3929196T3 (fi) | 2013-09-24 | 2023-10-02 | Fujifilm Corp | Typpeä sisältävän yhdisteen tai sen suolan tai niiden metallikompleksin farmaseuttinen koostumus |
| US10172915B2 (en) | 2013-10-20 | 2019-01-08 | Duke University | Methods and compositions for activation of sirtuins with Annexin A1 peptides |
| TR201810944T4 (tr) | 2013-10-25 | 2018-08-27 | Novartis Ag | Fgfr4 inhibitörleri olarak halka-füzyonlu bisiklik piridil türevleri. |
| US9783511B2 (en) | 2013-12-20 | 2017-10-10 | Lycera Corporation | Carbamate benzoxazine propionic acids and acid derivatives for modulation of RORgamma activity and the treatment of disease |
| WO2015095795A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | TETRAHYDRONAPHTHYRIDINE, BENZOXAZINE, AZA-BENZOXAZINE, AND RELATED BICYCLIC COMPOUNDS FOR INHIBITION OF RORgamma ACTIVITY AND THE TREATMENT OF DISEASE |
| US9663502B2 (en) | 2013-12-20 | 2017-05-30 | Lycera Corporation | 2-Acylamidomethyl and sulfonylamidomethyl benzoxazine carbamates for inhibition of RORgamma activity and the treatment of disease |
| US10087151B2 (en) | 2014-01-09 | 2018-10-02 | The J. David Gladstone Institutes, A Testimentary Trust Established Under The Will Of J. David Gladstone | Substituted benzoxazine and related compounds |
| AU2015222917A1 (en) | 2014-02-27 | 2016-09-15 | Lycera Corporation | Adoptive cellular therapy using an agonist of retinoic acid receptor-related orphan receptor gamma and related therapeutic methods |
| JP2017114764A (ja) * | 2014-04-25 | 2017-06-29 | 武田薬品工業株式会社 | 片頭痛治療剤 |
| WO2015171558A2 (en) | 2014-05-05 | 2015-11-12 | Lycera Corporation | BENZENESULFONAMIDO AND RELATED COMPOUNDS FOR USE AS AGONISTS OF RORγ AND THE TREATEMENT OF DISEASE |
| JP6728061B2 (ja) | 2014-05-05 | 2020-07-22 | リセラ・コーポレイションＬｙｃｅｒａ Ｃｏｒｐｏｒａｔｉｏｎ | ＲＯＲγアゴニストとして用いるテトラヒドロキノリンスルホンアミド及び関連化合物ならびに疾患の治療 |
| WO2015186068A1 (en) | 2014-06-02 | 2015-12-10 | Glaxosmithkline Intellectual Property (No.2) Limited | Preparation and use of crystalline beta-d-nicotinamide riboside |
| RU2016149767A (ru) | 2014-06-06 | 2018-07-16 | Глэксосмитклайн Интеллекчуал Проперти (Но.2) Лимитед | Аналоги никотинамидрибозида и фармацевтические композиции и их применение |
| JP6585167B2 (ja) | 2014-10-03 | 2019-10-02 | ノバルティス アーゲー | Ｆｇｆｒ４阻害剤としての縮環二環式ピリジル誘導体の使用 |
| CN107207509B (zh) * | 2014-11-19 | 2020-04-21 | 葛兰素史密斯克莱知识产权（第2 号）有限公司 | 作为沉默调节蛋白调节剂的取代的桥环脲类似物 |
| EP3256450B1 (en) | 2015-02-11 | 2020-12-02 | Merck Sharp & Dohme Corp. | Substituted pyrazole compounds as ror-gamma-t inhibitors and uses thereof |
| US9802917B2 (en) | 2015-03-25 | 2017-10-31 | Novartis Ag | Particles of N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide |
| EP3292119A4 (en) | 2015-05-05 | 2018-10-03 | Lycera Corporation | DIHYDRO-2H-BENZO[b][1,4]OXAZINE SULFONAMIDE AND RELATED COMPOUNDS FOR USE AS AGONISTS OF RORy AND THE TREATMENT OF DISEASE |
| KR20180025894A (ko) | 2015-06-11 | 2018-03-09 | 라이세라 코퍼레이션 | Rory의 작용제로서 사용하기 위한 아릴 디히드로-2h-벤조[b][1,4]옥사진 술폰아미드 및 관련 화합물 및 질환의 치료 |
| AU2016344115A1 (en) | 2015-10-27 | 2018-05-10 | Merck Sharp & Dohme Corp. | Substituted indazole compounds as rorgammat inhibitors and uses thereof |
| CA3002846A1 (en) | 2015-10-27 | 2017-05-04 | Merck Sharp & Dohme Corp. | Substituted bicyclic pyrazole compounds as rorgammat inhibitors and uses thereof |
| WO2017075185A1 (en) | 2015-10-27 | 2017-05-04 | Merck Sharp & Dohme Corp. | Heteroaryl substituted benzoic acids as rorgammat inhibitors and uses thereof |
| SG11201806302RA (en) | 2016-02-05 | 2018-08-30 | Denali Therapeutics Inc | Inhibitors of receptor-interacting protein kinase 1 |
| CN106243045A (zh) * | 2016-07-27 | 2016-12-21 | 常州大学 | 一种2,5‑二甲氧基‑4‑氨基嘧啶的制备方法 |
| JOP20190053A1 (ar) | 2016-09-23 | 2019-03-21 | Novartis Ag | مركبات أزا إندازول للاستخدام في إصابات الأوتار و/ أو الرباط |
| WO2018089353A1 (en) | 2016-11-08 | 2018-05-17 | Bristol-Myers Squibb Company | 3-substituted propionic acids as alpha v integrin inhibitors |
| LT3552017T (lt) | 2016-12-09 | 2022-05-10 | Denali Therapeutics Inc. | Junginiai, naudotini kaip ripk1 inhibitoriai |
| US9969768B1 (en) | 2017-11-16 | 2018-05-15 | King Saud University | Oleanolic acid methyl ester derivatives |
| GB201817047D0 (en) | 2018-10-19 | 2018-12-05 | Heptares Therapeutics Ltd | H4 antagonist compounds |
| GB202019667D0 (en) * | 2020-12-14 | 2021-01-27 | Heptares Therapeutics Ltd | H4 antagonist comnpounds |
| CN116354937B (zh) * | 2021-12-27 | 2025-07-11 | 江苏恩华药业股份有限公司 | 吡啶(嘧啶)胺类衍生物及其应用 |
| IL314082A (en) | 2022-01-12 | 2024-09-01 | Denali Therapeutics Inc | Crystal forms of (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazapin-3-yl)- H4- 1,2,4-triazole-3-carboxamide |
| CN117362286B (zh) * | 2023-12-08 | 2024-03-12 | 清华大学 | 具有sirt6激动活性的化合物及其用途 |
Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1108698B (de) | 1959-09-03 | 1961-06-15 | Hoechst Ag | Verfahren zur Herstellung von 2-(2'-Aminoaryl)-4, 5-arylen-1, 2, 3-triazolen |
| WO2005000846A1 (en) * | 2003-06-20 | 2005-01-06 | F.Hoffmann-La Roche Ag | Hexahydropyridoisoqinolines as dpp-iv inhibitors |
| CA2588384A1 (en) * | 2004-11-23 | 2006-06-22 | Ptc Therapeutics, Inc. | Tetrahydrocarbazoles as active agents for inhibiting vegf production by translational control |
| ATE544071T1 (de) | 2005-03-03 | 2012-02-15 | Sirtris Pharmaceuticals Inc | Fluoreszenzpolarisationstests für die acetyltransferase-deacetylase-aktivität |
| WO2006094248A1 (en) | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | Aryl-substituted cyclic sirtuin modulators |
| WO2006094233A1 (en) | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | N,n'-dicyclic isothiourea sirtuin modulators |
| WO2006094246A2 (en) | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | N-arylmethyl benzamide sirtuin modulators |
| US7998974B2 (en) * | 2005-03-03 | 2011-08-16 | Sirtris Pharmaceuticals, Inc. | Fused heterocyclic compounds and their use as sirtuin modulators |
| US20090069301A1 (en) * | 2005-03-03 | 2009-03-12 | Sirtris Pharmaceuticals, Inc. | Acridine and Quinoline Derivatives as Sirtuin Modulators |
| WO2006094210A2 (en) * | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | Tetrahydroquinoxalinone sirtuin modulators |
| WO2006094236A1 (en) | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | N-phenyl benzamide derivatives as sirtuin modulators |
| US20060229265A1 (en) | 2005-03-30 | 2006-10-12 | Sirtris Pharmaceuticals, Inc. | Nicotinamide riboside and analogues thereof |
| US20070014833A1 (en) | 2005-03-30 | 2007-01-18 | Sirtris Pharmaceuticals, Inc. | Treatment of eye disorders with sirtuin modulators |
| EP1928440A2 (en) | 2005-05-25 | 2008-06-11 | Sirtris Pharmaceuticals, Inc. | Treatment of eye disorders with sirtuin modulators |
| DE102005026762A1 (de) * | 2005-06-09 | 2006-12-21 | Sanofi-Aventis Deutschland Gmbh | Azolopyridin-2-on-derivate als Inhibitoren von Lipasen und Phospholipasen |
| CN103055313A (zh) | 2005-07-07 | 2013-04-24 | 西特里斯药业公司 | 用于治疗或预防肥胖、胰岛素抵抗障碍和线粒体相关障碍的方法和相关组合物 |
| US8088928B2 (en) | 2005-08-04 | 2012-01-03 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US7855289B2 (en) | 2005-08-04 | 2010-12-21 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| WO2007019345A1 (en) | 2005-08-04 | 2007-02-15 | Sirtris Pharmaceuticals, Inc. | Imidazopyridine derivatives as sirtuin modulating agents |
| US8093401B2 (en) | 2005-08-04 | 2012-01-10 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| EP1955077B1 (en) | 2005-12-02 | 2012-06-13 | Sirtris Pharmaceuticals, Inc. | Mass spectrometry assays for acetyltransferase/deacetylase activity |
| JP2009521408A (ja) | 2005-12-02 | 2009-06-04 | サートリス ファーマシューティカルズ， インコーポレイテッド | Ｃｄｃ２様キナーゼ（ＣＬＫ）のモジュレータおよびその使用方法 |
| DE102006014685A1 (de) * | 2006-03-28 | 2007-10-04 | Sanofi-Aventis | Imidazo-pyridin-2-on-derivate als Inhibitoren von Lipasen und Phospholiphasen |
| WO2008027379A2 (en) | 2006-08-29 | 2008-03-06 | Sirtris Pharmaceuticals, Inc. | Indicators of sirtuin activity and methods of use thereof |
| US20080249103A1 (en) | 2006-11-15 | 2008-10-09 | Sirtris Pharmaceuticals, Inc. | Sirtuin polymorphisms and methods of use thereof |
| WO2008073451A2 (en) | 2006-12-11 | 2008-06-19 | Sirtris Pharmaceuticals, Inc. | Benzoimidazole derivatives as sirtuin (sir) modulating compounds |
| WO2008100423A1 (en) | 2007-02-09 | 2008-08-21 | Sirtris Pharmaceuticals, Inc. | Gut microsomal triglyceride transport protein inhibitors |
| WO2008100376A2 (en) | 2007-02-15 | 2008-08-21 | Sirtris Pharmaceuticals, Inc. | Truncation variants of sirt1 and methods of use thereof |
| EP2126109A2 (en) | 2007-03-19 | 2009-12-02 | Sirtris Pharmaceuticals, Inc. | Biomarkers of sirtuin activity and methods of use thereof |
| TW200916472A (en) | 2007-06-20 | 2009-04-16 | Sirtris Pharmaceuticals Inc | Sirtuin modulating compounds |
| CL2008001821A1 (es) | 2007-06-20 | 2009-03-13 | Sirtris Pharmaceuticals Inc | Compuestos derivados de imidazo[2,1-b]-tiazol; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento de diabetes, sindrome metabolico, resistencia a la insulina, entre otras. |
| EP2215066A1 (en) | 2007-11-01 | 2010-08-11 | Sirtris Pharmaceuticals, Inc. | Amide derivatives as sirtuin modulators |
| MX2010005186A (es) | 2007-11-08 | 2010-05-27 | Sirtris Pharmaceuticals Inc | Tiazolopiridinas solubilizadas. |
| WO2009085226A2 (en) | 2007-12-21 | 2009-07-09 | Sirtris Pharmaceuticals, Inc. | Inhibitors of cdc2-like kinases (clks) and methods of use thereof |
| EP2249806A2 (en) | 2008-01-08 | 2010-11-17 | Sirtris Pharmaceuticals, Inc. | Resveratrol formulations |
| CA2723135A1 (en) | 2008-05-01 | 2009-11-05 | Sirtris Pharmaceuticals, Inc. | Quenolines and related analogs as sirtuin modulators |
| US20110113498A1 (en) | 2008-05-15 | 2011-05-12 | Westphal Christoph H | Sirt1 polymorphic variants and methods of use thereof |
| BRPI0913117A2 (pt) | 2008-05-29 | 2016-01-05 | Sirtris Pharmaceuticals Inc | imidazopiridina e análogos relacionados como moduladores de sirtuína |
| US8846947B2 (en) | 2008-07-03 | 2014-09-30 | Glaxosmithkline Llc | Benzimidazoles and related analogs as sirtuin modulators |
| RU2011109190A (ru) | 2008-08-12 | 2012-09-20 | Сертрис Фармасьютикалз, Инк. (Us) | Бензоксазолы, бензтиазолы и родственные аналоги в качестве модуляторов сиртуина |
| EP2341052A4 (en) * | 2008-09-05 | 2011-10-12 | Shionogi & Co | RING-CONDENSED MORPHOLINE DERIVATIVITY WITH PI3K-INHIBITING EFFECT |
| CA2738809C (en) | 2008-09-29 | 2015-11-24 | Sirtris Pharmaceuticals, Inc. | Quinazolinone, quinolone and related analogs as sirtuin modulators |
| EP2350051A4 (en) | 2008-10-29 | 2012-05-30 | Sirtris Pharmaceuticals Inc | PYRIDINE, BICYCLIC PYRIDINE AND ITS ANALOGS AS SIRTUINE MODULATORS |
| EP2365809B8 (en) * | 2008-11-12 | 2018-10-10 | Ariad Pharmaceuticals, Inc. | Pyrazinopyrazines and derivatives as kinase inhibitors |
| EP2373645A4 (en) | 2008-12-08 | 2012-05-02 | Sirtris Pharmaceuticals Inc | ISOINDOLINONE AND RELATED ANALOGUES AS SIRTUIN MODULATORS |
| BRPI0922597A8 (pt) | 2008-12-16 | 2018-09-25 | Sirtris Pharmaceuticals Inc | ftalazinona e análogos relacionados como moduladores de sirtuína |
| CN102388054B (zh) | 2008-12-19 | 2015-03-04 | 西特里斯药业公司 | 噻唑并吡啶沉默调节蛋白调节剂的化合物 |
| WO2010088574A1 (en) | 2009-01-30 | 2010-08-05 | Sirtris Pharmaceuticals, Inc. | Azabenzimidazoles and related analogs as sirtuin modulators |
| BRPI1011477A2 (pt) | 2009-03-02 | 2016-03-22 | Sirtris Pharmaceuticals Inc | quinolinas 8-substituidas e analogos relacionados como moduladores de sirtuina |
| US8735406B2 (en) * | 2009-09-09 | 2014-05-27 | Dainippon Sumitomo Pharma Co., Ltd. | 8-oxodihydropurine derivative |
| WO2011116176A1 (en) | 2010-03-17 | 2011-09-22 | Sirtris Pharmaceuticals Inc. | 3-substitued imidazo (4, 5-b) pyridines and analogs as sirtuin modulators |
-
2010
- 2010-10-29 KR KR1020127013635A patent/KR20120092141A/ko not_active Ceased
- 2010-10-29 RU RU2012122065/04A patent/RU2550821C2/ru not_active IP Right Cessation
- 2010-10-29 MX MX2012004995A patent/MX2012004995A/es not_active Application Discontinuation
- 2010-10-29 CA CA2779303A patent/CA2779303A1/en not_active Abandoned
- 2010-10-29 JP JP2012537157A patent/JP2013509442A/ja not_active Ceased
- 2010-10-29 US US13/504,134 patent/US9556201B2/en not_active Expired - Fee Related
- 2010-10-29 ES ES10830519.4T patent/ES2574927T3/es active Active
- 2010-10-29 IN IN3799DEN2012 patent/IN2012DN03799A/en unknown
- 2010-10-29 EP EP10830519.4A patent/EP2493888B1/en active Active
- 2010-10-29 WO PCT/US2010/054880 patent/WO2011059839A1/en not_active Ceased
- 2010-10-29 AU AU2010319842A patent/AU2010319842A1/en not_active Abandoned
- 2010-10-29 CN CN201080060180.2A patent/CN102725291B/zh not_active Expired - Fee Related
- 2010-10-29 BR BR112012010010A patent/BR112012010010A2/pt not_active IP Right Cessation
-
2012
- 2012-04-23 IL IL219372A patent/IL219372A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RU2012122065A (ru) | 2013-12-10 |
| AU2010319842A1 (en) | 2012-05-17 |
| CA2779303A1 (en) | 2011-05-19 |
| CN102725291B (zh) | 2016-12-21 |
| JP2013509442A (ja) | 2013-03-14 |
| EP2493888B1 (en) | 2016-04-06 |
| US20120252780A1 (en) | 2012-10-04 |
| EP2493888A4 (en) | 2013-05-01 |
| CN102725291A (zh) | 2012-10-10 |
| RU2550821C2 (ru) | 2015-05-20 |
| KR20120092141A (ko) | 2012-08-20 |
| MX2012004995A (es) | 2012-10-03 |
| IL219372A0 (en) | 2012-06-28 |
| US9556201B2 (en) | 2017-01-31 |
| WO2011059839A1 (en) | 2011-05-19 |
| EP2493888A1 (en) | 2012-09-05 |
| BR112012010010A2 (pt) | 2018-03-20 |
| IN2012DN03799A (enExample) | 2015-08-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2574927T3 (es) | Piridinas bicíclicas y análogos como moduladores de sirtuina | |
| ES2957159T3 (es) | Estimuladores de SGC fusionados bicíclicos | |
| ES2733092T3 (es) | Derivados de benzodioxol como inhibidores de la fosfodiesterasa | |
| CN109152933B (zh) | 诱导抗细胞凋亡bcl-2家族蛋白的降解的化合物及其用途 | |
| ES2670927T3 (es) | Composiciones de nicotinoil ribósido y métodos de uso | |
| ES2470673T3 (es) | Composiciones y métodos para el tratamiento de la isquemia y de la lesión por isquemia y reperfusi�n | |
| ES2552764T3 (es) | Métodos para el tratamiento de varias enfermedades y afecciones, y compuestos útiles para los mismos | |
| ES2733214T3 (es) | Derivados de cromolina y métodos relacionados de formación de imágenes y tratamiento | |
| ES2733502T3 (es) | Compuestos de imidazopiridazina | |
| ES2576484T3 (es) | Aza-heterociclos bicíclicos sustituidos y análogos como moduladores de sirtuina | |
| JP2020503379A (ja) | ラノステロールプロドラッグ化合物、その製造方法及び応用 | |
| ES2792149T3 (es) | Composiciones farmacéuticas que tienen estabilidad de almacenamiento mejorada | |
| KR20170008320A (ko) | 니코틴아미드 리보시드 유사체 및 그의 제약 조성물 및 용도 | |
| ES2898836T3 (es) | Compuestos de amino-naft[1,2-d]imidazol-5-ona 2-sustituida o sales farmacéuticamente aceptables de los mismos | |
| CA3117216A1 (en) | Deuterated compounds, compositions, and uses | |
| ES2289159T3 (es) | Derivados tetraciclicos sustituidos de pirroloquinolona utilizados como inhibidores de fosfodiesterasa. | |
| KR20140147819A (ko) | 염증성 질환의 치료에 사용하기 위한 n-아실에탄올아민에 특이적인 아미다제의 조절용 조성물 및 조절 방법 | |
| WO2020216152A1 (en) | 8-substituted aryl vinyl xanthine derivatives and uses thereof | |
| JP2015513317A (ja) | プロテアソーム活性を増強する化合物 | |
| CN102241674A (zh) | 1,1-二甲基-β-咔啉-3-甲酰基氨基酸苄酯的合成和抗肿瘤活性评价 | |
| DK2151439T3 (en) | Nitrogenated AROMATIC 6-membered RINGDERIVAT, AND THIS pharmaceutical composition comprising | |
| US11225460B2 (en) | Pyrrolidineamide derivatives and uses thereof | |
| ES2728932T3 (es) | Compuestos orgánicos | |
| TW201516034A (zh) | 犬尿氨酸－３－單加氧酶抑制劑、藥物組合物及其使用方法 | |
| KR20140105598A (ko) | [1,2,4]트리아졸로피리딘 및 포스포디에스테라제 억제제로서의 이의 용도 |