SK285433B6 - Spôsob prípravy bifenylových derivátov vhodných na prípravu 4-aryl-1-fenylalkyl-1,2,3,6-tetrahydropyridínov - Google Patents
Spôsob prípravy bifenylových derivátov vhodných na prípravu 4-aryl-1-fenylalkyl-1,2,3,6-tetrahydropyridínov Download PDFInfo
- Publication number
- SK285433B6 SK285433B6 SK593-2003A SK5932003A SK285433B6 SK 285433 B6 SK285433 B6 SK 285433B6 SK 5932003 A SK5932003 A SK 5932003A SK 285433 B6 SK285433 B6 SK 285433B6
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- formula
- compound
- ethyl
- tetrahydropyridine
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title abstract description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 117
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 238000012546 transfer Methods 0.000 claims abstract description 11
- 150000002940 palladium Chemical class 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- -1 cyano, amino Chemical group 0.000 claims description 46
- 238000002360 preparation method Methods 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 39
- 230000008569 process Effects 0.000 claims description 26
- 238000010992 reflux Methods 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 7
- 239000012736 aqueous medium Substances 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 4
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical group [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 4
- 150000007514 bases Chemical class 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 2
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 6
- 150000002367 halogens Chemical class 0.000 abstract description 6
- 150000001555 benzenes Chemical class 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract 2
- 239000001257 hydrogen Substances 0.000 abstract 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- 239000002904 solvent Substances 0.000 description 41
- 239000011541 reaction mixture Substances 0.000 description 40
- 239000000047 product Substances 0.000 description 35
- 239000000203 mixture Substances 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000002844 melting Methods 0.000 description 22
- 230000008018 melting Effects 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 239000012074 organic phase Substances 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 239000003480 eluent Substances 0.000 description 10
- SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 9
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- CNEWKIDCGDXBDE-UHFFFAOYSA-N 1-[2-(4-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=CC=CC=3)CC=2)=C1 CNEWKIDCGDXBDE-UHFFFAOYSA-N 0.000 description 4
- WALYRZRLDDOTJG-UHFFFAOYSA-N 2-chloro-6-[1-[2-(4-phenylphenyl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]pyridine Chemical compound ClC1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=CC=CC=3)CC=2)=N1 WALYRZRLDDOTJG-UHFFFAOYSA-N 0.000 description 4
- OWTUPHCOBJMOJX-UHFFFAOYSA-N Cl.C1=CC(CC(C)C)=CC=C1C(C)CN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 Chemical compound Cl.C1=CC(CC(C)C)=CC=C1C(C)CN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 OWTUPHCOBJMOJX-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 102000015336 Nerve Growth Factor Human genes 0.000 description 4
- 108010025020 Nerve Growth Factor Proteins 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940053128 nerve growth factor Drugs 0.000 description 4
- 230000000508 neurotrophic effect Effects 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- GEXQHZWNQSNYMQ-UHFFFAOYSA-N 1-[2-(3-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2H-pyridine hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C(C=CC=3)C=3C=CC=CC=3)CC=2)=C1 GEXQHZWNQSNYMQ-UHFFFAOYSA-N 0.000 description 3
- LAVVHCGEKVRBIR-UHFFFAOYSA-N 2-[3-chloro-4-(3-chlorophenyl)phenyl]acetic acid Chemical compound ClC1=CC(CC(=O)O)=CC=C1C1=CC=CC(Cl)=C1 LAVVHCGEKVRBIR-UHFFFAOYSA-N 0.000 description 3
- IZXWIWYERZDWOA-UHFFFAOYSA-N 2-[4-(2-methylpropyl)phenyl]propan-1-ol Chemical compound CC(C)CC1=CC=C(C(C)CO)C=C1 IZXWIWYERZDWOA-UHFFFAOYSA-N 0.000 description 3
- IFYKRMQORZOMNY-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCNCC=2)=C1 IFYKRMQORZOMNY-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- YKUYBNZXLWMPLS-UHFFFAOYSA-N Cl.C=1C=C(C=2C=C(Cl)C=CC=2)C=CC=1C(C)(C)CN(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 Chemical compound Cl.C=1C=C(C=2C=C(Cl)C=CC=2)C=CC=1C(C)(C)CN(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 YKUYBNZXLWMPLS-UHFFFAOYSA-N 0.000 description 3
- PPFNNYHYLUMPJR-UHFFFAOYSA-N Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C(=CC(=CC=3)C=3C=CC=CC=3)Cl)CC=2)=C1 Chemical compound Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C(=CC(=CC=3)C=3C=CC=CC=3)Cl)CC=2)=C1 PPFNNYHYLUMPJR-UHFFFAOYSA-N 0.000 description 3
- QBCWDWXXHYTFKT-UHFFFAOYSA-N Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C(Cl)C(=CC=3)C=3C=CC=CC=3)CC=2)=C1 Chemical compound Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C(Cl)C(=CC=3)C=3C=CC=CC=3)CC=2)=C1 QBCWDWXXHYTFKT-UHFFFAOYSA-N 0.000 description 3
- MMBHACFJXAJGDL-UHFFFAOYSA-N Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C(=CC=CC=3)C(F)(F)F)CC=2)=C1 Chemical compound Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C(=CC=CC=3)C(F)(F)F)CC=2)=C1 MMBHACFJXAJGDL-UHFFFAOYSA-N 0.000 description 3
- DHLKQRCCVKYQMF-UHFFFAOYSA-N Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=C(Cl)C=C(Cl)C=3)CC=2)=C1 Chemical compound Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=C(Cl)C=C(Cl)C=3)CC=2)=C1 DHLKQRCCVKYQMF-UHFFFAOYSA-N 0.000 description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- IYTUKSIOQKTZEG-UHFFFAOYSA-N (3-chloro-4-hydroxyphenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(O)C(Cl)=C1 IYTUKSIOQKTZEG-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- RWXUNIMBRXGNEP-UHFFFAOYSA-N 1-bromo-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1Br RWXUNIMBRXGNEP-UHFFFAOYSA-N 0.000 description 2
- PMOSJSPFNDUAFY-UHFFFAOYSA-N 2-(4-bromophenyl)ethanol Chemical compound OCCC1=CC=C(Br)C=C1 PMOSJSPFNDUAFY-UHFFFAOYSA-N 0.000 description 2
- XQHBVCWPLIENDJ-UHFFFAOYSA-N 2-chloro-6-[1-[2-(4-cyclohexylphenyl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]pyridine Chemical compound ClC1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C3CCCCC3)CC=2)=N1 XQHBVCWPLIENDJ-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LRSVQAHKPUSMQD-UHFFFAOYSA-N Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C(Cl)C(=CC=3)C=3C=C(Cl)C=CC=3)CC=2)=C1 Chemical compound Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C(Cl)C(=CC=3)C=3C=C(Cl)C=CC=3)CC=2)=C1 LRSVQAHKPUSMQD-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 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 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- LKVWHRHPCHSGSI-UHFFFAOYSA-N ethyl 2-[3-chloro-4-(trifluoromethylsulfonyl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=C(S(=O)(=O)C(F)(F)F)C(Cl)=C1 LKVWHRHPCHSGSI-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical class [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000005185 salting out Methods 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- QNEGDGPAXKYZHZ-UHFFFAOYSA-N (2,4-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1Cl QNEGDGPAXKYZHZ-UHFFFAOYSA-N 0.000 description 1
- DKYRKAIKWFHQHM-UHFFFAOYSA-N (3,5-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=CC(Cl)=C1 DKYRKAIKWFHQHM-UHFFFAOYSA-N 0.000 description 1
- WJDZZXIDQYKVDG-UHFFFAOYSA-N (3-chloro-4-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(Cl)=C1 WJDZZXIDQYKVDG-UHFFFAOYSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- 150000008083 1,2,3,6-tetrahydropyridines Chemical class 0.000 description 1
- IBIYQZBPDLOXIV-UHFFFAOYSA-N 1-(1,1-dimethoxyethyl)-4-[2-(trifluoromethyl)phenyl]benzene Chemical compound C1=CC(C(C)(OC)OC)=CC=C1C1=CC=CC=C1C(F)(F)F IBIYQZBPDLOXIV-UHFFFAOYSA-N 0.000 description 1
- JPYIJUCQMFRZDI-UHFFFAOYSA-N 1-(2-bromoethyl)-4-[2-(trifluoromethyl)phenyl]benzene Chemical compound FC(F)(F)C1=CC=CC=C1C1=CC=C(CCBr)C=C1 JPYIJUCQMFRZDI-UHFFFAOYSA-N 0.000 description 1
- WYECURVXVYPVAT-UHFFFAOYSA-N 1-(4-bromophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1 WYECURVXVYPVAT-UHFFFAOYSA-N 0.000 description 1
- VADDCANEJRSDNL-IBGZPJMESA-N 1-[(2r)-2-[4-(2-methylpropyl)phenyl]propyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(CC(C)C)=CC=C1[C@@H](C)CN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 VADDCANEJRSDNL-IBGZPJMESA-N 0.000 description 1
- VADDCANEJRSDNL-LJQANCHMSA-N 1-[(2s)-2-[4-(2-methylpropyl)phenyl]propyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(CC(C)C)=CC=C1[C@H](C)CN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 VADDCANEJRSDNL-LJQANCHMSA-N 0.000 description 1
- VTGWBLWGKZUFSF-UHFFFAOYSA-N 1-[1-(4-phenoxyphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C=1C=C(OC=2C=CC=CC=2)C=CC=1C(C)N(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 VTGWBLWGKZUFSF-UHFFFAOYSA-N 0.000 description 1
- XKZARGAIMGEZSW-UHFFFAOYSA-N 1-[2-(2-chloro-4-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol Chemical compound C1CC(O)(C=2C=C(C=CC=2)C(F)(F)F)CCN1CCC(C(=C1)Cl)=CC=C1C1=CC=CC=C1 XKZARGAIMGEZSW-UHFFFAOYSA-N 0.000 description 1
- DRUFLWBKCQQARQ-UHFFFAOYSA-N 1-[2-(2-methoxy-5-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound COC1=CC=C(C=2C=CC=CC=2)C=C1CCN(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 DRUFLWBKCQQARQ-UHFFFAOYSA-N 0.000 description 1
- QRXBOJSFBITNAZ-UHFFFAOYSA-N 1-[2-(3,4-dipropylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=C(CCC)C(CCC)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 QRXBOJSFBITNAZ-UHFFFAOYSA-N 0.000 description 1
- QQYINFSTLSPFDL-UHFFFAOYSA-N 1-[2-(3-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C(C=CC=3)C=3C=CC=CC=3)CC=2)=C1 QQYINFSTLSPFDL-UHFFFAOYSA-N 0.000 description 1
- WCLDJGHFRWOPJG-UHFFFAOYSA-N 1-[2-(4-butoxyphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(OCCCC)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 WCLDJGHFRWOPJG-UHFFFAOYSA-N 0.000 description 1
- RWPHWFAGKMQMNQ-UHFFFAOYSA-N 1-[2-(4-butylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(CCCC)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 RWPHWFAGKMQMNQ-UHFFFAOYSA-N 0.000 description 1
- VALBFTWRAPRFAG-UHFFFAOYSA-N 1-[2-(4-cyclohexylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C3CCCCC3)CC=2)=C1 VALBFTWRAPRFAG-UHFFFAOYSA-N 0.000 description 1
- AABJKTOPLCMVDK-UHFFFAOYSA-N 1-[2-(4-propan-2-ylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(C(C)C)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 AABJKTOPLCMVDK-UHFFFAOYSA-N 0.000 description 1
- JLELFBXBGPMKRF-UHFFFAOYSA-N 1-[2-(4-tert-butylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(C(C)(C)C)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 JLELFBXBGPMKRF-UHFFFAOYSA-N 0.000 description 1
- CGZCRZXFJHZEIA-UHFFFAOYSA-N 1-[2-[3-chloro-4-(3-chlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol Chemical compound C1CC(O)(C=2C=C(C=CC=2)C(F)(F)F)CCN1CCC(C=C1Cl)=CC=C1C1=CC=CC(Cl)=C1 CGZCRZXFJHZEIA-UHFFFAOYSA-N 0.000 description 1
- CDLNSVYOVRTZMA-UHFFFAOYSA-N 1-[2-[4-(2,4-dichlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C(=CC(Cl)=CC=3)Cl)CC=2)=C1 CDLNSVYOVRTZMA-UHFFFAOYSA-N 0.000 description 1
- KQOJYUOTDQJAAV-UHFFFAOYSA-N 1-[2-[4-(2,4-dichlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C(=CC(Cl)=CC=3)Cl)CC=2)=C1 KQOJYUOTDQJAAV-UHFFFAOYSA-N 0.000 description 1
- PXDPEQSARDZRSU-UHFFFAOYSA-N 1-[2-[4-(2-chlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C(=CC=CC=3)Cl)CC=2)=C1 PXDPEQSARDZRSU-UHFFFAOYSA-N 0.000 description 1
- YKTMXPRKLNNHIY-UHFFFAOYSA-N 1-[2-[4-(2-methylpropyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(CC(C)C)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 YKTMXPRKLNNHIY-UHFFFAOYSA-N 0.000 description 1
- VADDCANEJRSDNL-UHFFFAOYSA-N 1-[2-[4-(2-methylpropyl)phenyl]propyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(CC(C)C)=CC=C1C(C)CN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 VADDCANEJRSDNL-UHFFFAOYSA-N 0.000 description 1
- WSPBZUSIEIUXCY-UHFFFAOYSA-N 1-[2-[4-(3,5-dichlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=C(Cl)C=C(Cl)C=3)CC=2)=C1 WSPBZUSIEIUXCY-UHFFFAOYSA-N 0.000 description 1
- WAFSHDHWRRPPSQ-UHFFFAOYSA-N 1-[2-[4-(4-chlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=CC(Cl)=CC=3)CC=2)=C1 WAFSHDHWRRPPSQ-UHFFFAOYSA-N 0.000 description 1
- CPNHRQSEIFVLQO-UHFFFAOYSA-N 1-[2-[4-(4-fluorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(F)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 CPNHRQSEIFVLQO-UHFFFAOYSA-N 0.000 description 1
- KRZBYJLACJFLEQ-UHFFFAOYSA-N 1-[2-[4-(4-methoxyphenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(OC)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 KRZBYJLACJFLEQ-UHFFFAOYSA-N 0.000 description 1
- UDDHPDJWOQQARE-UHFFFAOYSA-N 1-[2-methyl-2-[4-(2-methylpropyl)phenyl]propyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(CC(C)C)=CC=C1C(C)(C)CN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 UDDHPDJWOQQARE-UHFFFAOYSA-N 0.000 description 1
- SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 1
- OFMVBOQHPIGOIN-UHFFFAOYSA-N 1-bromo-4-(1,1-dimethoxyethyl)benzene Chemical compound COC(C)(OC)C1=CC=C(Br)C=C1 OFMVBOQHPIGOIN-UHFFFAOYSA-N 0.000 description 1
- NXDYRIDLOUSORJ-UHFFFAOYSA-N 1-cyclohexyl-4-ethylbenzene Chemical compound C1=CC(CC)=CC=C1C1CCCCC1 NXDYRIDLOUSORJ-UHFFFAOYSA-N 0.000 description 1
- FILKGCRCWDMBKA-UHFFFAOYSA-N 2,6-dichloropyridine Chemical compound ClC1=CC=CC(Cl)=N1 FILKGCRCWDMBKA-UHFFFAOYSA-N 0.000 description 1
- RPSRZPOMRDDSPQ-UHFFFAOYSA-N 2-(1-benzyl-3,6-dihydro-2h-pyridin-4-yl)-6-chloropyridine Chemical compound ClC1=CC=CC(C=2CCN(CC=3C=CC=CC=3)CC=2)=N1 RPSRZPOMRDDSPQ-UHFFFAOYSA-N 0.000 description 1
- MDTAULLCKGQYMK-UHFFFAOYSA-N 2-(2-chloro-4-hydroxyphenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1Cl MDTAULLCKGQYMK-UHFFFAOYSA-N 0.000 description 1
- GAJFHFSIBABSMM-UHFFFAOYSA-N 2-(2-chloro-4-phenylphenyl)-1-[4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]ethanone Chemical compound C1CC(O)(C=2C=C(C=CC=2)C(F)(F)F)CCN1C(=O)CC(C(=C1)Cl)=CC=C1C1=CC=CC=C1 GAJFHFSIBABSMM-UHFFFAOYSA-N 0.000 description 1
- AAMWFJUMCNIECU-UHFFFAOYSA-N 2-(2-chloro-4-phenylphenyl)acetic acid Chemical compound C1=C(Cl)C(CC(=O)O)=CC=C1C1=CC=CC=C1 AAMWFJUMCNIECU-UHFFFAOYSA-N 0.000 description 1
- GGFZLGAIHSRDFD-UHFFFAOYSA-N 2-(3-chloro-4-phenylphenyl)-1-[4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]ethanone Chemical compound C1CC(O)(C=2C=C(C=CC=2)C(F)(F)F)CCN1C(=O)CC(C=C1Cl)=CC=C1C1=CC=CC=C1 GGFZLGAIHSRDFD-UHFFFAOYSA-N 0.000 description 1
- YTUMWOBUZOYYJQ-UHFFFAOYSA-N 2-(4-cyclohexylphenyl)propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C1CCCCC1 YTUMWOBUZOYYJQ-UHFFFAOYSA-N 0.000 description 1
- NJVSGWJGTMOTKP-UHFFFAOYSA-N 2-[3-chloro-4-(trifluoromethylsulfonyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(S(=O)(=O)C(F)(F)F)C(Cl)=C1 NJVSGWJGTMOTKP-UHFFFAOYSA-N 0.000 description 1
- JLORCINISDJUDL-UHFFFAOYSA-N 2-[4-(2-methylpropyl)phenyl]propyl methanesulfonate Chemical compound CC(C)CC1=CC=C(C(C)COS(C)(=O)=O)C=C1 JLORCINISDJUDL-UHFFFAOYSA-N 0.000 description 1
- CVBPQTZKZQWEFX-UHFFFAOYSA-N 2-[4-(cyclohexen-1-yl)phenyl]propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C1=CCCCC1 CVBPQTZKZQWEFX-UHFFFAOYSA-N 0.000 description 1
- DXKIKFNSKJTQBC-KKXIITGPSA-N 2-[4-[(1r,2r)-2-methylcyclohexyl]phenyl]propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1[C@H]1[C@H](C)CCCC1 DXKIKFNSKJTQBC-KKXIITGPSA-N 0.000 description 1
- WPWMYNBPYHSLIR-UHFFFAOYSA-N 2-chloro-6-(1,2,3,6-tetrahydropyridin-4-yl)pyridine Chemical compound ClC1=CC=CC(C=2CCNCC=2)=N1 WPWMYNBPYHSLIR-UHFFFAOYSA-N 0.000 description 1
- YFEODRYLGVDDDC-UHFFFAOYSA-N 2-chloro-6-(1,2,3,6-tetrahydropyridin-4-yl)pyridine;hydrochloride Chemical compound Cl.ClC1=CC=CC(C=2CCNCC=2)=N1 YFEODRYLGVDDDC-UHFFFAOYSA-N 0.000 description 1
- GKZWPTSMKCVFMZ-UHFFFAOYSA-N 2-chloro-6-[1-[2-[4-(2-methylpropyl)phenyl]propyl]-3,6-dihydro-2h-pyridin-4-yl]pyridine Chemical compound C1=CC(CC(C)C)=CC=C1C(C)CN1CC=C(C=2N=C(Cl)C=CC=2)CC1 GKZWPTSMKCVFMZ-UHFFFAOYSA-N 0.000 description 1
- YKVPRNREJYTEKZ-UHFFFAOYSA-N 2-chloro-6-[1-[2-[4-(2-methylpropyl)phenyl]propyl]-3,6-dihydro-2h-pyridin-4-yl]pyridine;hydrochloride Chemical compound Cl.C1=CC(CC(C)C)=CC=C1C(C)CN1CC=C(C=2N=C(Cl)C=CC=2)CC1 YKVPRNREJYTEKZ-UHFFFAOYSA-N 0.000 description 1
- SVDDJQGVOFZBNX-UHFFFAOYSA-N 2-chloroethyl carbonochloridate Chemical compound ClCCOC(Cl)=O SVDDJQGVOFZBNX-UHFFFAOYSA-N 0.000 description 1
- 150000005749 2-halopyridines Chemical class 0.000 description 1
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
- RRTUHDMSMMCWNI-UHFFFAOYSA-N 4-[4-[2-[4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]ethyl]phenyl]phenol Chemical compound C1=CC(O)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 RRTUHDMSMMCWNI-UHFFFAOYSA-N 0.000 description 1
- 208000002381 Brain Hypoxia Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- TZTLZMRICCAZOA-UHFFFAOYSA-N C1CN(C(CC1C2=CC(=CC=C2)C(F)(F)F)O)C(=O)CC3=CC(=C(C=C3)C4=CC(=CC=C4)Cl)Cl Chemical compound C1CN(C(CC1C2=CC(=CC=C2)C(F)(F)F)O)C(=O)CC3=CC(=C(C=C3)C4=CC(=CC=C4)Cl)Cl TZTLZMRICCAZOA-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- STQMGVHJJYKZDT-UHFFFAOYSA-N Cl.C1(=CC(=CC=C1)CCO)C1=CC=CC=C1 Chemical compound Cl.C1(=CC(=CC=C1)CCO)C1=CC=CC=C1 STQMGVHJJYKZDT-UHFFFAOYSA-N 0.000 description 1
- FWVQMQXFDGFBPX-UHFFFAOYSA-N Cl.C1=C(Cl)C(F)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 Chemical compound Cl.C1=C(Cl)C(F)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 FWVQMQXFDGFBPX-UHFFFAOYSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical compound NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 description 1
- 208000008348 Post-Concussion Syndrome Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- JNSBEPKGFVENFS-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC=C1C(F)(F)F JNSBEPKGFVENFS-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- ARHWPKZXBHOEEE-UHFFFAOYSA-N alclofenac Chemical compound OC(=O)CC1=CC=C(OCC=C)C(Cl)=C1 ARHWPKZXBHOEEE-UHFFFAOYSA-N 0.000 description 1
- 229960005142 alclofenac Drugs 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- QRZAKQDHEVVFRX-UHFFFAOYSA-N biphenyl-4-ylacetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1C1=CC=CC=C1 QRZAKQDHEVVFRX-UHFFFAOYSA-N 0.000 description 1
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical class [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 125000005619 boric acid group Chemical class 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000005111 carboxyalkoxy group Chemical group 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000000718 cholinopositive effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000004981 cycloalkylmethyl group Chemical group 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- RLARTPYAWIPQME-UHFFFAOYSA-N ethyl 2-(2-chloro-4-phenylphenyl)acetate Chemical compound C1=C(Cl)C(CC(=O)OCC)=CC=C1C1=CC=CC=C1 RLARTPYAWIPQME-UHFFFAOYSA-N 0.000 description 1
- FOQCNUUYQWIJPZ-UHFFFAOYSA-N ethyl 2-(3-chloro-4-hydroxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(O)C(Cl)=C1 FOQCNUUYQWIJPZ-UHFFFAOYSA-N 0.000 description 1
- XTSCLIBGCPXCLH-UHFFFAOYSA-N ethyl 2-(4-bromophenyl)-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)C1=CC=C(Br)C=C1 XTSCLIBGCPXCLH-UHFFFAOYSA-N 0.000 description 1
- ZFDCWHPNBWPPHG-UHFFFAOYSA-N ethyl 2-(4-bromophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(Br)C=C1 ZFDCWHPNBWPPHG-UHFFFAOYSA-N 0.000 description 1
- QZGCQJSFPRWMJF-UHFFFAOYSA-N ethyl 2-[3-chloro-4-(3-chlorophenyl)phenyl]acetate Chemical compound ClC1=CC(CC(=O)OCC)=CC=C1C1=CC=CC(Cl)=C1 QZGCQJSFPRWMJF-UHFFFAOYSA-N 0.000 description 1
- HXTFUVWJFLDLJP-UHFFFAOYSA-N ethyl 2-[4-(2-methylpropyl)phenyl]propanoate Chemical compound CCOC(=O)C(C)C1=CC=C(CC(C)C)C=C1 HXTFUVWJFLDLJP-UHFFFAOYSA-N 0.000 description 1
- LKGFRTZVCPEBMJ-UHFFFAOYSA-N ethyl 5-[4-[4-[2-[4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]ethyl]phenyl]phenoxy]pentanoate Chemical compound C1=CC(OCCCCC(=O)OCC)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 LKGFRTZVCPEBMJ-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- IDKAXRLETRCXKS-UHFFFAOYSA-N fenclofenac Chemical compound OC(=O)CC1=CC=CC=C1OC1=CC=C(Cl)C=C1Cl IDKAXRLETRCXKS-UHFFFAOYSA-N 0.000 description 1
- 229950006236 fenclofenac Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 229950004679 hexaprofen Drugs 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- CYWFCPPBTWOZSF-UHFFFAOYSA-N ibufenac Chemical compound CC(C)CC1=CC=C(CC(O)=O)C=C1 CYWFCPPBTWOZSF-UHFFFAOYSA-N 0.000 description 1
- 229950009183 ibufenac Drugs 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229950005150 mexoprofen Drugs 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960004526 piracetam Drugs 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000002186 septum of brain Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229950001676 tetriprofen Drugs 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- 125000002827 triflate group Chemical class FC(S(=O)(=O)O*)(F)F 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9507760A FR2736053B1 (fr) | 1995-06-28 | 1995-06-28 | Nouvelles 1-phenylalkyl-1,2,3,6-tetrahydropyridines |
| PCT/FR1996/000995 WO1997001536A1 (fr) | 1995-06-28 | 1996-06-26 | 4-aryl-1-phenylalkyl-1,2,3,6-tetrahydropyridines ayant une activite neurotrophique et neuroprotectrice |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK285433B6 true SK285433B6 (sk) | 2007-01-04 |
Family
ID=9480466
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK593-2003A SK285433B6 (sk) | 1995-06-28 | 1996-06-26 | Spôsob prípravy bifenylových derivátov vhodných na prípravu 4-aryl-1-fenylalkyl-1,2,3,6-tetrahydropyridínov |
| SK1781-97A SK283707B6 (sk) | 1995-06-28 | 1996-06-26 | 4-Aryl-1-fenylalkyl-1,2,3,6-tetrahydropyridínová zlúčenina, spôsob jej prípravy, medziprodukty a farmaceutický prostriedok obsahujúci túto zlúčeninu |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1781-97A SK283707B6 (sk) | 1995-06-28 | 1996-06-26 | 4-Aryl-1-fenylalkyl-1,2,3,6-tetrahydropyridínová zlúčenina, spôsob jej prípravy, medziprodukty a farmaceutický prostriedok obsahujúci túto zlúčeninu |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US5981754A (cs) |
| EP (2) | EP1216996A3 (cs) |
| JP (2) | JP3147906B2 (cs) |
| KR (1) | KR100460581B1 (cs) |
| CN (1) | CN1153765C (cs) |
| AT (1) | ATE223897T1 (cs) |
| AU (1) | AU715090B2 (cs) |
| BR (1) | BR9608662A (cs) |
| CA (1) | CA2225746C (cs) |
| CY (1) | CY2312B1 (cs) |
| CZ (1) | CZ291075B6 (cs) |
| DE (1) | DE69623631T2 (cs) |
| DK (1) | DK0837848T3 (cs) |
| EE (1) | EE03870B1 (cs) |
| ES (1) | ES2183965T3 (cs) |
| FR (1) | FR2736053B1 (cs) |
| HU (1) | HUP9900055A3 (cs) |
| IL (1) | IL122159A (cs) |
| IS (1) | IS1999B (cs) |
| NO (1) | NO310144B1 (cs) |
| NZ (1) | NZ312723A (cs) |
| PL (2) | PL187087B1 (cs) |
| PT (1) | PT837848E (cs) |
| RU (1) | RU2163237C2 (cs) |
| SK (2) | SK285433B6 (cs) |
| TR (1) | TR199701710T1 (cs) |
| UA (1) | UA62914C2 (cs) |
| WO (1) | WO1997001536A1 (cs) |
| ZA (1) | ZA965527B (cs) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2762514B1 (fr) * | 1997-04-29 | 1999-10-22 | Sanofi Sa | Utilisation de derives de la tetrahydropyridine pour la preparation de medicaments pour le traitement des maladies entrainant une demyelinisation |
| FR2763847B1 (fr) * | 1997-05-28 | 2003-06-06 | Sanofi Sa | Utilisation de tetrahydropyridines 4-substituees pour fabriquer des medicaments agissant sur le tgf-beta-1 |
| CO4980891A1 (es) * | 1997-11-14 | 2000-11-27 | Sanofi Sa | Asociacion de principios activos para el tratamiento de la demencia senil de tipo azheimer |
| FR2771006B1 (fr) * | 1997-11-14 | 2000-12-01 | Sanofi Sa | Association de principes actifs pour le traitement de la demence senile du type alzheimer |
| FR2771007B1 (fr) * | 1997-11-14 | 2000-12-01 | Sanofi Sa | Association de principes actifs pour le traitement de la demence senile du type alzheimer |
| WO1999065896A1 (en) * | 1998-06-19 | 1999-12-23 | Eli Lilly And Company | Preparation of heteroaryl compounds |
| FR2803593B1 (fr) * | 2000-01-06 | 2002-02-15 | Sanofi Synthelabo | Nouvelles tetrahydropyridines, procede pour leur preparation et compositions pharmaceutiques les contenant |
| FR2823748B1 (fr) * | 2001-04-20 | 2004-02-20 | Sanofi Synthelabo | Tetrahydropyridyl-alkyl-benzodiazines, procede pour leur preparation et compositions pharmaceutiques les contenant |
| JP4324382B2 (ja) * | 2001-04-20 | 2009-09-02 | サノフィ−アベンティス | テトラヒドロピリジル−アルキル−複素環、その製造方法およびそれを含む医薬組成物 |
| FR2840896B1 (fr) * | 2002-06-18 | 2005-04-08 | Sanofi Synthelabo | Phenyl-et pyridyl-piperazines, procede pour leur preparation et compositions pharmaceutiques les contenant |
| WO2004055007A1 (en) * | 2002-12-16 | 2004-07-01 | Mitsubishi Pharma Corporation | 3-substituted-4-pyrimidone derivatives |
| EP1657240A4 (en) | 2003-08-18 | 2009-04-08 | Fujifilm Finechemicals Co Ltd | PYRIDYLTETRAHYDROPYRIDINE, PYRIDYLPIPERIDINE AND METHOD FOR THE PRODUCTION THEREOF |
| TWI350168B (en) * | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| JP2008504275A (ja) * | 2004-06-24 | 2008-02-14 | インサイト・コーポレイション | Ｎ−置換ピペリジンおよびその医薬としての使用 |
| JP2008504279A (ja) * | 2004-06-24 | 2008-02-14 | インサイト・コーポレイション | アミド化合物およびその医薬としての使用 |
| US7687665B2 (en) | 2004-06-24 | 2010-03-30 | Incyte Corporation | 2-methylprop anamides and their use as pharmaceuticals |
| EP1758582A4 (en) * | 2004-06-24 | 2008-01-09 | Incyte Corp | AMIDO COMPOUNDS AND THEIR USE AS PHARMACEUTICAL PRODUCTS |
| MXPA06014573A (es) * | 2004-06-24 | 2007-03-12 | Incyte Corp | Compuestos amido y su uso como farmaceuticos. |
| KR20070050076A (ko) * | 2004-08-10 | 2007-05-14 | 인사이트 산 디에고 인코포레이티드 | 아미도 화합물 및 약제로서의 이의 용도 |
| BRPI0518022A (pt) * | 2004-11-10 | 2008-10-21 | Incyte Corp | compostos de lactam e seu uso como produtos farmacêuticos |
| US8110581B2 (en) * | 2004-11-10 | 2012-02-07 | Incyte Corporation | Lactam compounds and their use as pharmaceuticals |
| WO2006055752A2 (en) * | 2004-11-18 | 2006-05-26 | Incyte Corporation | INHIBITORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1 AND METHODS OF USING THE SAME |
| FR2883285B1 (fr) * | 2005-03-17 | 2007-05-18 | Sanofi Aventis Sa | Sel besylate de la 7-(2-(4-(3-trifluoromethyl-phenyl) -1,2,3,6-tetrahudro-pyrid-1-yl)ethyl) isoquinoleine, sa preparation et son utilisation en therapeutique |
| JP4864342B2 (ja) * | 2005-04-27 | 2012-02-01 | 北興化学工業株式会社 | ビアリール化合物の製造方法 |
| US20070066584A1 (en) * | 2005-09-21 | 2007-03-22 | Wenqing Yao | Amido compounds and their use as pharmaceuticals |
| KR101415861B1 (ko) * | 2005-12-05 | 2014-07-04 | 인사이트 코포레이션 | 락탐 화합물 및 이를 사용하는 방법 |
| WO2007084314A2 (en) * | 2006-01-12 | 2007-07-26 | Incyte Corporation | MODULATORS OF 11-ß HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| WO2007089683A1 (en) * | 2006-01-31 | 2007-08-09 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| TW200808807A (en) * | 2006-03-02 | 2008-02-16 | Incyte Corp | Modulators of 11-β hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| US20070208001A1 (en) * | 2006-03-03 | 2007-09-06 | Jincong Zhuo | Modulators of 11- beta hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| JP2009535420A (ja) * | 2006-05-01 | 2009-10-01 | インサイト・コーポレイション | １１−βヒドロキシルステロイドデヒドロゲナーゼタイプ１のモジュレーターとしてのテトラ置換ウレア |
| US7838544B2 (en) * | 2006-05-17 | 2010-11-23 | Incyte Corporation | Heterocyclic inhibitors of 11-β hydroxyl steroid dehydrogenase type 1 and methods of using the same |
| CL2008001839A1 (es) * | 2007-06-21 | 2009-01-16 | Incyte Holdings Corp | Compuestos derivados de 2,7-diazaespirociclos, inhibidores de 11-beta hidroxil esteroide deshidrogenasa tipo 1; composicion farmaceutica que comprende a dichos compuestos; utiles para tratar la obesidad, diabetes, intolerancia a la glucosa, diabetes tipo ii, entre otras enfermedades. |
| CA2710477A1 (en) | 2007-12-20 | 2009-07-09 | Envivo Pharmaceuticals, Inc. | Tetrasubstituted benzenes |
| KR101773070B1 (ko) * | 2010-01-19 | 2017-09-12 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | 아릴 및 헤테로아릴아세트산 유도체의 제조방법 |
| US10858351B2 (en) | 2017-04-26 | 2020-12-08 | Alberta Research Chemicals Inc. | Substituted tetrahydropyridine derivatives as IDO-1 inhibitors and uses thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2098248T3 (es) * | 1989-05-17 | 1997-05-01 | Pfizer | Derivados de 2-piperidino-1-alcanoles como agentes antiisquemicos. |
| FR2650505B1 (fr) * | 1989-08-07 | 1994-06-03 | Midy Spa | Utilisation de trifluoromethylphenyltetrahydropyridines pour la preparation de medicaments destines a combattre les troubles de la motricite intestinale |
| FR2662355B1 (fr) * | 1990-05-22 | 1994-11-10 | Sanofi Sa | Utilisation de la 1-[2-(2-naphtyl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyridine pour la preparation de medicaments destines au traitement de troubles cerebraux et neuronaux. |
| HU211019B (en) * | 1991-12-02 | 1995-09-28 | Richter Gedeon Vegyeszet | Process for producing new 1,2,3,6-tetrahydropyridine and piperidine derivatives substituted with n-(hydroxylalkyl) group and compositions comprising such compounds |
| DE4325855A1 (de) * | 1993-08-02 | 1995-02-09 | Boehringer Ingelheim Kg | Neue Benzoesäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
-
1995
- 1995-06-28 FR FR9507760A patent/FR2736053B1/fr not_active Expired - Fee Related
-
1996
- 1996-06-26 CA CA002225746A patent/CA2225746C/en not_active Expired - Fee Related
- 1996-06-26 EP EP02006482A patent/EP1216996A3/fr not_active Withdrawn
- 1996-06-26 WO PCT/FR1996/000995 patent/WO1997001536A1/fr not_active Ceased
- 1996-06-26 CZ CZ19974222A patent/CZ291075B6/cs not_active IP Right Cessation
- 1996-06-26 DE DE69623631T patent/DE69623631T2/de not_active Expired - Fee Related
- 1996-06-26 IL IL12215996A patent/IL122159A/en not_active IP Right Cessation
- 1996-06-26 RU RU98101492/04A patent/RU2163237C2/ru not_active IP Right Cessation
- 1996-06-26 EE EE9700348A patent/EE03870B1/xx not_active IP Right Cessation
- 1996-06-26 TR TR97/01710T patent/TR199701710T1/xx unknown
- 1996-06-26 PL PL96324216A patent/PL187087B1/pl not_active IP Right Cessation
- 1996-06-26 PL PL357052A patent/PL192353B1/pl not_active IP Right Cessation
- 1996-06-26 US US08/973,712 patent/US5981754A/en not_active Expired - Fee Related
- 1996-06-26 EP EP96924023A patent/EP0837848B1/fr not_active Expired - Lifetime
- 1996-06-26 AT AT96924023T patent/ATE223897T1/de not_active IP Right Cessation
- 1996-06-26 SK SK593-2003A patent/SK285433B6/sk unknown
- 1996-06-26 BR BR9608662A patent/BR9608662A/pt not_active IP Right Cessation
- 1996-06-26 SK SK1781-97A patent/SK283707B6/sk unknown
- 1996-06-26 CN CNB961950900A patent/CN1153765C/zh not_active Expired - Fee Related
- 1996-06-26 HU HU9900055A patent/HUP9900055A3/hu unknown
- 1996-06-26 PT PT96924023T patent/PT837848E/pt unknown
- 1996-06-26 KR KR1019970709747A patent/KR100460581B1/ko not_active Expired - Fee Related
- 1996-06-26 JP JP50420697A patent/JP3147906B2/ja not_active Expired - Fee Related
- 1996-06-26 UA UA97126360A patent/UA62914C2/uk unknown
- 1996-06-26 AU AU64619/96A patent/AU715090B2/en not_active Ceased
- 1996-06-26 DK DK96924023T patent/DK0837848T3/da active
- 1996-06-26 NZ NZ312723A patent/NZ312723A/en unknown
- 1996-06-26 ES ES96924023T patent/ES2183965T3/es not_active Expired - Lifetime
- 1996-06-28 ZA ZA965527A patent/ZA965527B/xx unknown
-
1997
- 1997-12-23 NO NO19976079A patent/NO310144B1/no unknown
- 1997-12-23 IS IS4641A patent/IS1999B/is unknown
-
2000
- 2000-07-31 JP JP2000231069A patent/JP3302351B2/ja not_active Expired - Fee Related
-
2003
- 2003-01-15 CY CY0300004A patent/CY2312B1/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK285433B6 (sk) | Spôsob prípravy bifenylových derivátov vhodných na prípravu 4-aryl-1-fenylalkyl-1,2,3,6-tetrahydropyridínov | |
| US6610711B2 (en) | 4-phenylpiperidines for the treatment of pruritic dermatoses | |
| HUT58078A (en) | Process for producing new benzopyran derivatives and pharmaceutical compositions comprising same | |
| HUT65837A (en) | Process for producing phenoxy- and phenoxyalkyl-piperidines and pharmaceutical preparations containing them | |
| NZ233645A (en) | 3-(hetero)aryl-substituted-3,4 dehydropiperidine derivatives; preparatory processes and pharmaceutical compositions | |
| SK9622002A3 (en) | Novel tetrahydropyridines, preparation method and pharmaceutical compositions containing same | |
| US4598086A (en) | α2 antagonistic 2-(4,5-dihydro-2-1H-imidazolyl)-2,3-dihydro-1H-indoles | |
| US5773448A (en) | Pharmaceutical compounds | |
| JP4831908B2 (ja) | Ｔｎｆ阻害活性を有するフェニル−およびピリジル−テトラヒドロピリジン類 | |
| JPH06220045A (ja) | 薬理化合物 | |
| CA2274946C (en) | Diphenylalkyl-tetrahydropyridines, process for their preparation, and pharmaceutical compositions containing them | |
| EP0698601B1 (en) | Process for the preparation of the (-)-N-methyl-N-[4-(4-phenyl-4-acetyl-aminopiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-benzamide and its pharmaceutically acceptable salts | |
| US4518713A (en) | Analgesic substituted-1-aminoalkylamino-4-aryloxypiperidines | |
| MXPA96006531A (en) | Pharmaceutical compounds | |
| CZ291185B6 (cs) | Způsob přípravy bifenylových derivátů vhodných pro přípravu 4-aryl-1-fenylalkyl-1,2,3,6-tetrahydropyridinů | |
| AU606314B2 (en) | Hydropyridine derivatives | |
| US7326720B2 (en) | Phenyl- and pyridylpiperidines with TNF activity | |
| CA2420620A1 (en) | 4-aryl-1-phenylalkyl-1,2,3,6-tetrahydropyridines having neurotrophic and neuroprotective activity | |
| MXPA97010472A (en) | 4-aril-phenylalkil-1,2,3,6-tetrahydropiridines that have a neuroprophic activity and neuroprotect | |
| HU211690A9 (hu) | Az átmeneti oltalom az 1—18. igénypontokra vonatkozik. | |
| JP2010535837A (ja) | 新規調製方法 |