ZA200506614B - 1-phenylalkanecarboxylic acid derivatives for the treatment of neurodegenerative diseases - Google Patents
1-phenylalkanecarboxylic acid derivatives for the treatment of neurodegenerative diseases Download PDFInfo
- Publication number
- ZA200506614B ZA200506614B ZA200506614A ZA200506614A ZA200506614B ZA 200506614 B ZA200506614 B ZA 200506614B ZA 200506614 A ZA200506614 A ZA 200506614A ZA 200506614 A ZA200506614 A ZA 200506614A ZA 200506614 B ZA200506614 B ZA 200506614B
- Authority
- ZA
- South Africa
- Prior art keywords
- compounds
- chf
- alkyl
- branched
- linear
- Prior art date
Links
- 208000015122 neurodegenerative disease Diseases 0.000 title claims description 7
- 230000004770 neurodegeneration Effects 0.000 title claims description 5
- 239000002253 acid Substances 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims description 43
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 229910052731 fluorine Inorganic materials 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 239000011737 fluorine Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 208000024827 Alzheimer disease Diseases 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- LIYLTQQDABRNRX-UHFFFAOYSA-N 1-[4-(3,4-dichlorophenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=C(Cl)C(Cl)=CC=2)C(F)=CC=1C1(C(=O)O)CC1 LIYLTQQDABRNRX-UHFFFAOYSA-N 0.000 claims description 5
- 125000003289 ascorbyl group Chemical group [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 5
- -1 or a CONHSO Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical compound C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 claims description 4
- IYYZUPMFVPLQIF-UHFFFAOYSA-N dibenzothiophene Chemical compound C1=CC=C2C3=CC=CC=C3SC2=C1 IYYZUPMFVPLQIF-UHFFFAOYSA-N 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 2
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 2
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 claims description 2
- VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical compound C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 claims description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
- ODMMNALOCMNQJZ-UHFFFAOYSA-N 1H-pyrrolizine Chemical compound C1=CC=C2CC=CN21 ODMMNALOCMNQJZ-UHFFFAOYSA-N 0.000 claims description 2
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 2
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 2
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 claims description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000000126 in silico method Methods 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 150000003020 phtalazines Chemical class 0.000 claims description 2
- 230000003449 preventive effect Effects 0.000 claims description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 2
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical compound C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims 1
- 101000795849 Calliactis parasitica Delta-hormotoxin-Cpt1b Proteins 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 108010037464 Cyclooxygenase 1 Proteins 0.000 description 6
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 5
- 208000037259 Amyloid Plaque Diseases 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 3
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 235000010290 biphenyl Nutrition 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- KVWJVBSLLYGPIM-UHFFFAOYSA-N 1-(4-bromo-3-fluorophenyl)cyclopropane-1-carbonitrile Chemical compound C1=C(Br)C(F)=CC(C2(CC2)C#N)=C1 KVWJVBSLLYGPIM-UHFFFAOYSA-N 0.000 description 2
- WKVFGGQPVGDERD-UHFFFAOYSA-N 1-(4-bromo-3-fluorophenyl)cyclopropane-1-carboxylic acid Chemical compound C=1C=C(Br)C(F)=CC=1C1(C(=O)O)CC1 WKVFGGQPVGDERD-UHFFFAOYSA-N 0.000 description 2
- GMVNLHLMJSMARX-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC(CBr)=CC=C1Br GMVNLHLMJSMARX-UHFFFAOYSA-N 0.000 description 2
- CGDCFGJXTOGEGD-UHFFFAOYSA-N 2-(4-bromo-3-fluorophenyl)acetonitrile Chemical compound FC1=CC(CC#N)=CC=C1Br CGDCFGJXTOGEGD-UHFFFAOYSA-N 0.000 description 2
- VENPPESRQUOIAN-UHFFFAOYSA-N 2-[3-fluoro-4-[4-(trifluoromethyl)phenyl]phenyl]-2-methylpropanoic acid Chemical compound FC1=CC(C(C)(C(O)=O)C)=CC=C1C1=CC=C(C(F)(F)F)C=C1 VENPPESRQUOIAN-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229960002390 flurbiprofen Drugs 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000003118 histopathologic effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 1
- FMNQRUKVXAQEAZ-JNRFBPFXSA-N (5z,8s,9r,10e,12s)-9,12-dihydroxy-8-[(1s)-1-hydroxy-3-oxopropyl]heptadeca-5,10-dienoic acid Chemical compound CCCCC[C@H](O)\C=C\[C@@H](O)[C@H]([C@@H](O)CC=O)C\C=C/CCCC(O)=O FMNQRUKVXAQEAZ-JNRFBPFXSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- XVWGBBAJYDIQRO-UHFFFAOYSA-N 1-(3-fluoro-4-phenylphenyl)cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC=CC=2)C(F)=CC=1C1(C(=O)O)CC1 XVWGBBAJYDIQRO-UHFFFAOYSA-N 0.000 description 1
- BHYFPOMNUGVUDU-UHFFFAOYSA-N 1-[3-fluoro-4-(4-hydroxyphenyl)phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC(O)=CC=2)C(F)=CC=1C1(C(=O)O)CC1 BHYFPOMNUGVUDU-UHFFFAOYSA-N 0.000 description 1
- KQMALGNGCXDBLN-UHFFFAOYSA-N 1-[3-fluoro-4-(4-phenylmethoxyphenyl)phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC(OCC=3C=CC=CC=3)=CC=2)C(F)=CC=1C1(C(=O)O)CC1 KQMALGNGCXDBLN-UHFFFAOYSA-N 0.000 description 1
- CTSCOBRUAALLDX-UHFFFAOYSA-N 1-[3-fluoro-4-(4-propan-2-yloxyphenyl)phenyl]cyclopropane-1-carboxylic acid Chemical compound C1=CC(OC(C)C)=CC=C1C1=CC=C(C2(CC2)C(O)=O)C=C1F CTSCOBRUAALLDX-UHFFFAOYSA-N 0.000 description 1
- MEPWDCFZPLOUHG-UHFFFAOYSA-N 1-[3-fluoro-4-[3-(trifluoromethoxy)phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=C(OC(F)(F)F)C=CC=2)C(F)=CC=1C1(C(=O)O)CC1 MEPWDCFZPLOUHG-UHFFFAOYSA-N 0.000 description 1
- MWVDEELEHXLNJV-UHFFFAOYSA-N 1-[3-fluoro-4-[3-(trifluoromethyl)phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=C(C=CC=2)C(F)(F)F)C(F)=CC=1C1(C(=O)O)CC1 MWVDEELEHXLNJV-UHFFFAOYSA-N 0.000 description 1
- GSVNIOVGZGDTOV-UHFFFAOYSA-N 1-[3-fluoro-4-[4-(4-oxocyclohexyl)phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)C2CCC(=O)CC2)C(F)=CC=1C1(C(=O)O)CC1 GSVNIOVGZGDTOV-UHFFFAOYSA-N 0.000 description 1
- KSEFZMXVRTYGAP-UHFFFAOYSA-N 1-[3-fluoro-4-[4-(oxan-4-yl)phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)C2CCOCC2)C(F)=CC=1C1(C(=O)O)CC1 KSEFZMXVRTYGAP-UHFFFAOYSA-N 0.000 description 1
- GQNQCMAXHUKUBW-UHFFFAOYSA-N 1-[3-fluoro-4-[4-(trifluoromethoxy)phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC(OC(F)(F)F)=CC=2)C(F)=CC=1C1(C(=O)O)CC1 GQNQCMAXHUKUBW-UHFFFAOYSA-N 0.000 description 1
- STSYUQWYKFKDNG-UHFFFAOYSA-N 1-[3-fluoro-4-[4-(trifluoromethyl)phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)C(F)(F)F)C(F)=CC=1C1(C(=O)O)CC1 STSYUQWYKFKDNG-UHFFFAOYSA-N 0.000 description 1
- UJEZCMCMAKNZKV-UHFFFAOYSA-N 1-[3-fluoro-4-[4-[4-(trifluoromethyl)cyclohexyl]oxyphenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC(OC3CCC(CC3)C(F)(F)F)=CC=2)C(F)=CC=1C1(C(=O)O)CC1 UJEZCMCMAKNZKV-UHFFFAOYSA-N 0.000 description 1
- OHASMRIPZSZDPE-UHFFFAOYSA-N 1-[4-(1-benzothiophen-3-yl)-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C3=CC=CC=C3SC=2)C(F)=CC=1C1(C(=O)O)CC1 OHASMRIPZSZDPE-UHFFFAOYSA-N 0.000 description 1
- JWFWTNVXMREUBB-UHFFFAOYSA-N 1-[4-(2-cyclohexylphenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C(=CC=CC=2)C2CCCCC2)C(F)=CC=1C1(C(=O)O)CC1 JWFWTNVXMREUBB-UHFFFAOYSA-N 0.000 description 1
- DFJGLZRYGZSQOR-UHFFFAOYSA-N 1-[4-(3,5-dichlorophenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=C(Cl)C=C(Cl)C=2)C(F)=CC=1C1(C(=O)O)CC1 DFJGLZRYGZSQOR-UHFFFAOYSA-N 0.000 description 1
- YHUIIJKTOAGXJM-UHFFFAOYSA-N 1-[4-(3-chloro-4-fluorophenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=C(Cl)C(F)=CC=2)C(F)=CC=1C1(C(=O)O)CC1 YHUIIJKTOAGXJM-UHFFFAOYSA-N 0.000 description 1
- GZGHHENIMUQAFG-UHFFFAOYSA-N 1-[4-(4-cyclohexyloxyphenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC(OC3CCCCC3)=CC=2)C(F)=CC=1C1(C(=O)O)CC1 GZGHHENIMUQAFG-UHFFFAOYSA-N 0.000 description 1
- CBZPNTGBQQEKFH-UHFFFAOYSA-N 1-[4-(4-cyclohexylphenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)C2CCCCC2)C(F)=CC=1C1(C(=O)O)CC1 CBZPNTGBQQEKFH-UHFFFAOYSA-N 0.000 description 1
- NFFLHZLUGWGPDS-UHFFFAOYSA-N 1-[4-(4-cyclopentylphenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)C2CCCC2)C(F)=CC=1C1(C(=O)O)CC1 NFFLHZLUGWGPDS-UHFFFAOYSA-N 0.000 description 1
- JCHOEKYPSFUGTA-UHFFFAOYSA-N 1-[4-[4-(4,4-dimethylcyclohexyl)oxyphenyl]-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound C1CC(C)(C)CCC1OC1=CC=C(C=2C(=CC(=CC=2)C2(CC2)C(O)=O)F)C=C1 JCHOEKYPSFUGTA-UHFFFAOYSA-N 0.000 description 1
- SLFNGVGRINFJLK-UHFFFAOYSA-N 1-bromo-2-fluoro-4-methylbenzene Chemical compound CC1=CC=C(Br)C(F)=C1 SLFNGVGRINFJLK-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- PAQRNRXJRSCEOL-UHFFFAOYSA-N 2-[3-fluoro-4-[4-(trifluoromethyl)phenyl]phenyl]propanoic acid Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=C(C(F)(F)F)C=C1 PAQRNRXJRSCEOL-UHFFFAOYSA-N 0.000 description 1
- 125000002999 4-(trifluoromethyl)benzoyl group Chemical group FC(C1=CC=C(C(=O)*)C=C1)(F)F 0.000 description 1
- HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 1
- IJIBRSFAXRFPPN-UHFFFAOYSA-N 5-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC=C(Br)C=C1C=O IJIBRSFAXRFPPN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 229940124638 COX inhibitor Drugs 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000031124 Dementia Alzheimer type Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102100024304 Protachykinin-1 Human genes 0.000 description 1
- 101800003906 Substance P Proteins 0.000 description 1
- XNRNNGPBEPRNAR-UHFFFAOYSA-N Thromboxane B2 Natural products CCCCCC(O)C=CC1OC(O)CC(O)C1CC=CCCCC(O)=O XNRNNGPBEPRNAR-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 229930189065 blasticidin Natural products 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 125000005621 boronate group Chemical class 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 150000002066 eicosanoids Chemical class 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical class OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- MOTRZVVGCFFABN-UHFFFAOYSA-N hexane;2-propan-2-yloxypropane Chemical compound CCCCCC.CC(C)OC(C)C MOTRZVVGCFFABN-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- NVXFJGJJJOIRPE-UHFFFAOYSA-N methyl 2-[3-fluoro-4-[4-(trifluoromethyl)phenyl]phenyl]propanoate Chemical compound FC=1C(=CC=C(C=1)C(C(=O)OC)C)C1=CC=C(C=C1)C(F)(F)F NVXFJGJJJOIRPE-UHFFFAOYSA-N 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000008807 pathological lesion Effects 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 150000003304 ruthenium compounds Chemical class 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI20030311 ITMI20030311A1 (it) | 2003-02-21 | 2003-02-21 | Acidi 2-fenil-2-dialchil-acetici per il trattamento della malattia di alzheimer. |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200506614B true ZA200506614B (en) | 2006-12-27 |
Family
ID=36605990
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200506614A ZA200506614B (en) | 2003-02-21 | 2004-02-19 | 1-phenylalkanecarboxylic acid derivatives for the treatment of neurodegenerative diseases |
Country Status (3)
Country | Link |
---|---|
CN (2) | CN100398506C (zh) |
IT (1) | ITMI20030311A1 (zh) |
ZA (1) | ZA200506614B (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2133322A1 (en) * | 2008-06-11 | 2009-12-16 | CHIESI FARMACEUTICI S.p.A. | Process of preparing derivatives of 1-(2-halobiphenyl-4-yl)-cyclopropanecarboxylic acid |
CN102596879B (zh) * | 2009-08-04 | 2015-01-28 | 奇斯药制品公司 | 制备1-(2-卤代联苯-4-基)-环丙烷羧酸的衍生物的方法 |
CN102869643A (zh) * | 2010-04-01 | 2013-01-09 | 奇斯药制品公司 | 新的多晶型物和盐 |
CN105658615A (zh) * | 2013-06-24 | 2016-06-08 | 奇斯药制品公司 | 用于制备1-(2-氟[1,1′-联苯]-4-基)-环丙烷甲酸衍生物的改进方法 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4994680A (zh) * | 1973-01-22 | 1974-09-09 | ||
JPS5046669A (zh) * | 1973-03-28 | 1975-04-25 | ||
GB1442707A (en) * | 1973-07-07 | 1976-07-14 | Yoshitomi Pharmaceutical | Substituted phenylalkanoic acids and their derivatives and pharma ceutical compositions thereof |
JPS58177977A (ja) * | 1982-04-09 | 1983-10-18 | Grelan Pharmaceut Co Ltd | 4−フエニルピラゾ−ル類 |
US5994379A (en) * | 1998-02-13 | 1999-11-30 | Merck Frosst Canada, Inc. | Bisaryl COX-2 inhibiting compounds, compositions and methods of use |
DE10123884A1 (de) * | 2001-05-16 | 2002-11-21 | Bayer Ag | Herstellung und Verwendung von Palladium-Katalysatoren für Kreuzkupplungsreaktionen |
-
2003
- 2003-02-21 IT ITMI20030311 patent/ITMI20030311A1/it unknown
-
2004
- 2004-02-19 CN CNB2004800047290A patent/CN100398506C/zh not_active Expired - Fee Related
- 2004-02-19 CN CN200810100704.0A patent/CN101328117B/zh not_active Expired - Fee Related
- 2004-02-19 ZA ZA200506614A patent/ZA200506614B/en unknown
Also Published As
Publication number | Publication date |
---|---|
CN100398506C (zh) | 2008-07-02 |
CN101328117B (zh) | 2014-04-23 |
ITMI20030311A1 (it) | 2004-08-22 |
CN1751018A (zh) | 2006-03-22 |
CN101328117A (zh) | 2008-12-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2004213145B2 (en) | 1-Phenylalkanecarboxylic acid derivatives for the treatment of neurodegenerative diseases | |
JP4390563B2 (ja) | 置換フェニルアルカン酸誘導体及びその用途 | |
AU2005270949B2 (en) | Derivatives of 1-phenylalkanecarboxylic acids for the treatment of neurodegenerative diseases | |
WO2004073705A1 (en) | 1-phenyl-2- monoalkyl carboxylic acid derivatives for the treatment of neurodegenerative diseases | |
CN103848798A (zh) | 2-芳基硒唑化合物及其药物组合物 | |
ZA200506614B (en) | 1-phenylalkanecarboxylic acid derivatives for the treatment of neurodegenerative diseases | |
MX2008012393A (es) | Material cristalino mejorado. | |
Peretto et al. | Raveglia et al.(45) Date of Patent: Feb. 16, 2010 | |
Peretto et al. | Raveglia et al.(45) Date of Patent: Nov. 20, 2012 | |
Peretto et al. | Raveglia et a].(45) Date of Patent: Sep. 20, 2011 | |
WO2024114665A1 (zh) | 取代的三嗪-2,4-二酮类衍生物中间体及其制备方法 | |
FI58629B (fi) | Foerfarande foer framstaellning av en hypokolesterolemiskt och hypotriglyseridemiskt aktiv foerening | |
Qing et al. | Synthesis of the trifluoromethylated retinoial aromatic amide—4-[1-(5, 6, 7, 8-tetrahydro-3-trifluoromethyl-5, 5, 8, 8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid | |
CN118619885A (zh) | 芳基并咪唑类化合物及其医药用途 | |
CA2578332A1 (en) | Derivatives of pyrazoline, procedure for obtaining them and use thereof as therapeutic agents | |
JPS6154015B2 (zh) | ||
JPH03115254A (ja) | α―(1―カルボキシエチル)アミノ―γ―フエニル酪酸エチルの製造法 | |
JPS61271262A (ja) | フエニルアルカン酸誘導体 | |
KR20120017367A (ko) | (에스)-(+)-1-아미노인단을 이용한 광학활성을 갖는 2-아릴프로피온산 계열 약물들의 제조 방법 |