NO325160B1 - 1,2-dihydropyridinforbindelser, fremgangsmate for fremstilling av de samme og anvendelse derav - Google Patents
1,2-dihydropyridinforbindelser, fremgangsmate for fremstilling av de samme og anvendelse derav Download PDFInfo
- Publication number
- NO325160B1 NO325160B1 NO20025955A NO20025955A NO325160B1 NO 325160 B1 NO325160 B1 NO 325160B1 NO 20025955 A NO20025955 A NO 20025955A NO 20025955 A NO20025955 A NO 20025955A NO 325160 B1 NO325160 B1 NO 325160B1
- Authority
- NO
- Norway
- Prior art keywords
- pyridyl
- dihydropyridin
- phenyl
- cyanophenyl
- group
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 191
- 230000008569 process Effects 0.000 title claims description 21
- MMWRGWQTAMNAFC-UHFFFAOYSA-N 1,2-dihydropyridine Chemical class C1NC=CC=C1 MMWRGWQTAMNAFC-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 405
- 150000003839 salts Chemical class 0.000 claims abstract description 150
- 125000003118 aryl group Chemical group 0.000 claims abstract description 36
- 102000003678 AMPA Receptors Human genes 0.000 claims abstract description 27
- 108090000078 AMPA Receptors Proteins 0.000 claims abstract description 27
- 238000002360 preparation method Methods 0.000 claims abstract description 27
- 125000005843 halogen group Chemical group 0.000 claims abstract description 19
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 175
- 239000002904 solvent Substances 0.000 claims description 166
- -1 piperidyloxy Chemical group 0.000 claims description 164
- 238000006243 chemical reaction Methods 0.000 claims description 149
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 75
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 68
- 239000002585 base Substances 0.000 claims description 65
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 58
- 238000005859 coupling reaction Methods 0.000 claims description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
- 239000003054 catalyst Substances 0.000 claims description 50
- 239000003795 chemical substances by application Substances 0.000 claims description 35
- 229910052763 palladium Inorganic materials 0.000 claims description 34
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 31
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 30
- 150000004677 hydrates Chemical class 0.000 claims description 29
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 239000003153 chemical reaction reagent Substances 0.000 claims description 27
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 24
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 23
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 23
- 238000004519 manufacturing process Methods 0.000 claims description 23
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 23
- 125000004076 pyridyl group Chemical group 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 22
- 125000001544 thienyl group Chemical group 0.000 claims description 22
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 21
- 239000005749 Copper compound Substances 0.000 claims description 21
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 21
- 150000001880 copper compounds Chemical class 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 20
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 20
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 19
- 125000001624 naphthyl group Chemical group 0.000 claims description 19
- 125000005493 quinolyl group Chemical group 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 125000002541 furyl group Chemical group 0.000 claims description 18
- 238000005658 halogenation reaction Methods 0.000 claims description 18
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 17
- 102000000079 Kainic Acid Receptors Human genes 0.000 claims description 16
- 108010069902 Kainic Acid Receptors Proteins 0.000 claims description 16
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims description 16
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 16
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 16
- 229910052721 tungsten Inorganic materials 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 15
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 15
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 15
- 125000005945 imidazopyridyl group Chemical group 0.000 claims description 15
- 125000002524 organometallic group Chemical group 0.000 claims description 15
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 15
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 15
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 15
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 14
- 229910052723 transition metal Inorganic materials 0.000 claims description 14
- 150000003624 transition metals Chemical class 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000001041 indolyl group Chemical group 0.000 claims description 13
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 13
- 125000000335 thiazolyl group Chemical group 0.000 claims description 13
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 239000011630 iodine Substances 0.000 claims description 11
- 229910052740 iodine Inorganic materials 0.000 claims description 11
- 230000003449 preventive effect Effects 0.000 claims description 11
- 230000001225 therapeutic effect Effects 0.000 claims description 11
- 238000010511 deprotection reaction Methods 0.000 claims description 10
- 125000003386 piperidinyl group Chemical group 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 9
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 claims description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
- VAYWXCQNXGTBAQ-UHFFFAOYSA-N 2-[1-(3-aminophenyl)-2-oxo-5-pyridin-2-ylpyridin-3-yl]benzonitrile Chemical compound NC1=CC=CC(N2C(C(C=3C(=CC=CC=3)C#N)=CC(=C2)C=2N=CC=CC=2)=O)=C1 VAYWXCQNXGTBAQ-UHFFFAOYSA-N 0.000 claims description 8
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 8
- 208000018737 Parkinson disease Diseases 0.000 claims description 8
- QJTAAHJJXWYZSK-UHFFFAOYSA-N [Br].CC(O)=O Chemical compound [Br].CC(O)=O QJTAAHJJXWYZSK-UHFFFAOYSA-N 0.000 claims description 8
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 8
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 206010015037 epilepsy Diseases 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 150000001340 alkali metals Chemical group 0.000 claims description 6
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 6
- 238000006192 iodination reaction Methods 0.000 claims description 6
- PRMWGUBFXWROHD-UHFFFAOYSA-N perampanel Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=CN1C1=CC=CC=C1 PRMWGUBFXWROHD-UHFFFAOYSA-N 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 6
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 5
- XJEGKWQBBPBZBM-UHFFFAOYSA-N 2-[5-(2-formylthiophen-3-yl)-2-oxo-1-phenylpyridin-3-yl]benzonitrile Chemical compound S1C=CC(C2=CN(C(=O)C(C=3C(=CC=CC=3)C#N)=C2)C=2C=CC=CC=2)=C1C=O XJEGKWQBBPBZBM-UHFFFAOYSA-N 0.000 claims description 5
- KTUDVOUKZFBMAG-UHFFFAOYSA-N 3-(2-oxo-1-phenyl-5-pyridin-2-ylpyridin-3-yl)thiophene-2-carbaldehyde Chemical compound S1C=CC(C=2C(N(C=3C=CC=CC=3)C=C(C=2)C=2N=CC=CC=2)=O)=C1C=O KTUDVOUKZFBMAG-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
- 238000005893 bromination reaction Methods 0.000 claims description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- HAWPVMCOOMZUTD-UHFFFAOYSA-N 2-(2-oxo-1-phenyl-5-pyrimidin-2-ylpyridin-3-yl)benzonitrile Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CN=2)=CN1C1=CC=CC=C1 HAWPVMCOOMZUTD-UHFFFAOYSA-N 0.000 claims description 4
- UYJJATPPJOSNFM-UHFFFAOYSA-N 2-(2-oxo-5-pyridin-2-yl-1-pyridin-3-ylpyridin-3-yl)benzonitrile Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=CN1C1=CC=CN=C1 UYJJATPPJOSNFM-UHFFFAOYSA-N 0.000 claims description 4
- SRIBOAOQCACOFW-UHFFFAOYSA-N 2-[1-(3-hydroxyphenyl)-2-oxo-5-pyridin-2-ylpyridin-3-yl]benzonitrile Chemical compound OC1=CC=CC(N2C(C(C=3C(=CC=CC=3)C#N)=CC(=C2)C=2N=CC=CC=2)=O)=C1 SRIBOAOQCACOFW-UHFFFAOYSA-N 0.000 claims description 4
- UZUVMMADDOPENK-UHFFFAOYSA-N 2-[1-(3-nitrophenyl)-2-oxo-5-pyridin-2-ylpyridin-3-yl]benzonitrile Chemical compound [O-][N+](=O)C1=CC=CC(N2C(C(C=3C(=CC=CC=3)C#N)=CC(=C2)C=2N=CC=CC=2)=O)=C1 UZUVMMADDOPENK-UHFFFAOYSA-N 0.000 claims description 4
- SBAHNGRZWCURSP-UHFFFAOYSA-N 2-[1-(4-methylsulfanylphenyl)-2-oxo-5-pyridin-2-ylpyridin-3-yl]benzonitrile Chemical compound C1=CC(SC)=CC=C1N1C(=O)C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=C1 SBAHNGRZWCURSP-UHFFFAOYSA-N 0.000 claims description 4
- 150000005749 2-halopyridines Chemical class 0.000 claims description 4
- YWVMGZYXPNDLRV-UHFFFAOYSA-N 3-(2-chlorophenyl)-1-(4-hydroxyphenyl)-5-pyridin-2-ylpyridin-2-one Chemical compound C1=CC(O)=CC=C1N1C(=O)C(C=2C(=CC=CC=2)Cl)=CC(C=2N=CC=CC=2)=C1 YWVMGZYXPNDLRV-UHFFFAOYSA-N 0.000 claims description 4
- AISWTIWIIAADRP-UHFFFAOYSA-N 3-(2-chloropyridin-3-yl)-1-phenyl-5-pyridin-2-ylpyridin-2-one Chemical compound ClC1=NC=CC=C1C(C1=O)=CC(C=2N=CC=CC=2)=CN1C1=CC=CC=C1 AISWTIWIIAADRP-UHFFFAOYSA-N 0.000 claims description 4
- BMXYEXPMZDKGCR-UHFFFAOYSA-N 3-(2-fluoropyridin-3-yl)-1-phenyl-5-pyridin-2-ylpyridin-2-one Chemical compound FC1=NC=CC=C1C(C1=O)=CC(C=2N=CC=CC=2)=CN1C1=CC=CC=C1 BMXYEXPMZDKGCR-UHFFFAOYSA-N 0.000 claims description 4
- BGTNYGOBNLWJRT-UHFFFAOYSA-N 3-(2-fluoropyridin-3-yl)-5-pyridin-2-yl-1-pyridin-3-ylpyridin-2-one Chemical compound FC1=NC=CC=C1C(C1=O)=CC(C=2N=CC=CC=2)=CN1C1=CC=CN=C1 BGTNYGOBNLWJRT-UHFFFAOYSA-N 0.000 claims description 4
- 206010034010 Parkinsonism Diseases 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 4
- XAEMOTNPVLUMRS-UHFFFAOYSA-N methyl 3-[3-(2-cyanophenyl)-2-oxo-5-pyridin-2-ylpyridin-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2C(C(C=3C(=CC=CC=3)C#N)=CC(=C2)C=2N=CC=CC=2)=O)=C1 XAEMOTNPVLUMRS-UHFFFAOYSA-N 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
- OBRUTSCSGNDVDC-UHFFFAOYSA-N 1,3-diphenyl-5-pyridin-2-ylpyridin-2-one Chemical compound O=C1C(C=2C=CC=CC=2)=CC(C=2N=CC=CC=2)=CN1C1=CC=CC=C1 OBRUTSCSGNDVDC-UHFFFAOYSA-N 0.000 claims description 3
- HBVRDIGMVDCZRS-UHFFFAOYSA-N 1-(3-fluorophenyl)-3-(2-fluoropyridin-3-yl)-5-pyridin-2-ylpyridin-2-one Chemical compound FC1=CC=CC(N2C(C(C=3C(=NC=CC=3)F)=CC(=C2)C=2N=CC=CC=2)=O)=C1 HBVRDIGMVDCZRS-UHFFFAOYSA-N 0.000 claims description 3
- NUWRPCHEZDSDPK-UHFFFAOYSA-N 1-(3-fluorophenyl)-3-phenyl-5-pyridin-2-ylpyridin-2-one Chemical compound FC1=CC=CC(N2C(C(C=3C=CC=CC=3)=CC(=C2)C=2N=CC=CC=2)=O)=C1 NUWRPCHEZDSDPK-UHFFFAOYSA-N 0.000 claims description 3
- ORJCITCNJVUPSP-UHFFFAOYSA-N 2-(1-benzyl-2-oxo-5-pyridin-2-ylpyridin-3-yl)benzonitrile Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=CN1CC1=CC=CC=C1 ORJCITCNJVUPSP-UHFFFAOYSA-N 0.000 claims description 3
- UXUALQPGAMIQLC-UHFFFAOYSA-N 2-(2-oxo-1,5-diphenylpyridin-3-yl)benzonitrile Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2C=CC=CC=2)=CN1C1=CC=CC=C1 UXUALQPGAMIQLC-UHFFFAOYSA-N 0.000 claims description 3
- VSSVPRRVRYAVQU-UHFFFAOYSA-N 2-(2-oxo-1-phenyl-5-thiophen-2-ylpyridin-3-yl)benzonitrile Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2SC=CC=2)=CN1C1=CC=CC=C1 VSSVPRRVRYAVQU-UHFFFAOYSA-N 0.000 claims description 3
- PYEKXHCYVSBIMU-UHFFFAOYSA-N 2-(2-oxo-1-phenyl-5-thiophen-3-ylpyridin-3-yl)benzonitrile Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C2=CSC=C2)=CN1C1=CC=CC=C1 PYEKXHCYVSBIMU-UHFFFAOYSA-N 0.000 claims description 3
- BDAUQVDIEIVKDH-UHFFFAOYSA-N 2-(2-oxo-5-phenyl-1-pyridin-2-ylpyridin-3-yl)benzonitrile Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2C=CC=CC=2)=CN1C1=CC=CC=N1 BDAUQVDIEIVKDH-UHFFFAOYSA-N 0.000 claims description 3
- UNSTVPJCWLUIPT-UHFFFAOYSA-N 2-(2-oxo-5-pyridin-2-yl-1-pyridin-4-ylpyridin-3-yl)benzonitrile Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=CN1C1=CC=NC=C1 UNSTVPJCWLUIPT-UHFFFAOYSA-N 0.000 claims description 3
- OVMRJNJAFNMBJT-UHFFFAOYSA-N 2-(2-oxo-5-pyridin-2-yl-1-thiophen-3-ylpyridin-3-yl)benzonitrile Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=CN1C=1C=CSC=1 OVMRJNJAFNMBJT-UHFFFAOYSA-N 0.000 claims description 3
- RPXOWGJZXRBGDS-UHFFFAOYSA-N 2-[1-(2-amino-1,3-benzothiazol-6-yl)-2-oxo-5-pyridin-2-ylpyridin-3-yl]benzonitrile Chemical compound C1=C2SC(N)=NC2=CC=C1N(C1=O)C=C(C=2N=CC=CC=2)C=C1C1=CC=CC=C1C#N RPXOWGJZXRBGDS-UHFFFAOYSA-N 0.000 claims description 3
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- PXKNDCRXLYKBJZ-UHFFFAOYSA-N 2-[1-(2-methoxyphenyl)-2-oxo-5-pyridin-2-ylpyridin-3-yl]benzonitrile Chemical compound COC1=CC=CC=C1N1C(=O)C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=C1 PXKNDCRXLYKBJZ-UHFFFAOYSA-N 0.000 claims description 3
- FSVBNVCEZCRHIY-UHFFFAOYSA-N 2-[1-(3-amino-4-methylphenyl)-2-oxo-5-pyridin-2-ylpyridin-3-yl]benzonitrile Chemical compound C1=C(N)C(C)=CC=C1N1C(=O)C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=C1 FSVBNVCEZCRHIY-UHFFFAOYSA-N 0.000 claims description 3
- AWPTWYZHDCDVGD-UHFFFAOYSA-N 2-[1-(3-aminophenyl)-2-oxo-5-pyrimidin-2-ylpyridin-3-yl]benzonitrile Chemical compound NC1=CC=CC(N2C(C(C=3C(=CC=CC=3)C#N)=CC(=C2)C=2N=CC=CN=2)=O)=C1 AWPTWYZHDCDVGD-UHFFFAOYSA-N 0.000 claims description 3
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- UJHRNXLFCMDWRB-UHFFFAOYSA-N tert-butyl 4-[[3-(2-cyanophenyl)-2-oxo-5-pyridin-2-ylpyridin-1-yl]methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CN1C(=O)C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=C1 UJHRNXLFCMDWRB-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- REDSKZBUUUQMSK-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC REDSKZBUUUQMSK-UHFFFAOYSA-N 0.000 description 1
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Classifications
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PCT/JP2001/004857 WO2001096308A1 (fr) | 2000-06-12 | 2001-06-08 | Composes 1,2-dihydropyridine, leur procede de preparation et leur utilisation |
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KR100850728B1 (ko) * | 2000-06-12 | 2008-08-06 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 1,2-디하이드로피리딘 화합물, 그의 제조 방법 및 그의 용도 |
AU2002237664A1 (en) * | 2000-11-20 | 2002-05-27 | Bristol-Myers Squibb Company | Pyridone derivatives as AP2 inhibitors |
US20030105144A1 (en) | 2001-04-17 | 2003-06-05 | Ping Gao | Stabilized oral pharmaceutical composition |
JP4119114B2 (ja) * | 2001-11-28 | 2008-07-16 | 広栄化学工業株式会社 | 新規なジヒドロキシ(3−ピリジル)ボラン類 |
GB0129260D0 (en) * | 2001-12-06 | 2002-01-23 | Eisai London Res Lab Ltd | Pharmaceutical compositions and their uses |
US7482366B2 (en) | 2001-12-21 | 2009-01-27 | X-Ceptor Therapeutics, Inc. | Modulators of LXR |
WO2003059884A1 (en) * | 2001-12-21 | 2003-07-24 | X-Ceptor Therapeutics, Inc. | Modulators of lxr |
AU2003220401A1 (en) | 2002-03-18 | 2003-10-08 | Bristol-Myers Squibb Company | Uracil derivatives as inhibitors of tnf-alpha converting enzyme (tace) and matrix metalloproteinases |
DE60326223D1 (de) * | 2002-04-19 | 2009-04-02 | Glaxo Group Ltd | Verbindungen mit affinität zum 5ht2c-rezeptor und deren therapeutische verwendung |
JP4208512B2 (ja) | 2002-07-23 | 2009-01-14 | 株式会社クラレ | 5−(2’−ピリジル)−2−ピリドン誘導体の製造方法 |
AU2003274022A1 (en) * | 2002-10-17 | 2004-05-04 | Syngenta Participations Ag | 3-heterocyclylpyridine derivatives useful as herbicides |
ZA200505258B (en) * | 2002-12-16 | 2006-09-27 | Mitsubishi Pharma Corp | 3-Substituted-4-pyrimidone derivatives |
EP1581539A4 (de) * | 2003-01-03 | 2007-09-19 | Bristol Myers Squibb Co | Neue tyrosinkinase-hemmer |
GB0305024D0 (en) * | 2003-03-05 | 2003-04-09 | Glaxo Group Ltd | Compounds |
SE0302323D0 (sv) * | 2003-08-28 | 2003-08-28 | Astrazeneca Ab | Novel compounds |
SE0302324D0 (sv) * | 2003-08-28 | 2003-08-28 | Astrazeneca Ab | Novel compounds |
SE0302486D0 (sv) | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | Novel compounds |
US7897607B2 (en) | 2004-04-07 | 2011-03-01 | Takeda Pharmaceutical Company Limited | Cyclic compounds |
JP2007099781A (ja) * | 2004-07-06 | 2007-04-19 | Eisai R & D Management Co Ltd | 1,2−ジヒドロピリジン化合物の結晶の製造方法 |
MY148809A (en) | 2004-07-06 | 2013-05-31 | Eisai R&D Man Co Ltd | Crystals of 1,2-dihydropyridine compound and their production process |
GB0420722D0 (en) * | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
US20060069260A1 (en) * | 2004-09-28 | 2006-03-30 | Huiping Zhang | Preparation of N-aryl pyridones |
RU2423351C2 (ru) | 2004-12-16 | 2011-07-10 | Вертекс Фармасьютикалз Инкорпорейтед | Пирид-2-оны, применимые как ингибиторы протеинкиназ семейства тес для лечения воспалительных, пролиферативных и иммунологически-опосредованных заболеваний |
AU2006203819A1 (en) * | 2005-01-07 | 2006-07-13 | Roskamp Research Llc | Compounds for inhibiting beta-amyloid production and methods of identifying the compounds |
TW200700392A (en) * | 2005-03-16 | 2007-01-01 | Astrazeneca Ab | Novel compounds |
US20060270709A1 (en) | 2005-04-04 | 2006-11-30 | Eisai Co. Ltd. | Dihydropyridine compounds and compositions for headaches |
US20090030017A1 (en) * | 2005-04-08 | 2009-01-29 | Eisai R & D Management Co., Ltd | Therapeutic agent for dyskinesia |
MX2007014114A (es) | 2005-05-10 | 2008-03-14 | Intermune Inc | Derivados de piridona para modular el sistema de proteina cinasa activada por estres. |
GB0510141D0 (en) | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds B3 |
JP2009503103A (ja) * | 2005-08-02 | 2009-01-29 | レキシコン・ファーマシューティカルズ・インコーポレーテッド | アリールピリジン及びその使用方法 |
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US7786130B2 (en) | 2005-08-29 | 2010-08-31 | Vertex Pharmaceuticals Incorporated | Pyridones useful as inhibitors of kinases |
ES2361338T3 (es) * | 2005-08-29 | 2011-06-16 | Vertex Pharmaceuticals Incorporated | Pirid-2-onas 3,5-disustituidas útiles como inhibidores de la familia tec de tirosina quinasas no ligadas a receptor. |
RU2008112691A (ru) | 2005-10-03 | 2009-10-10 | Оно Фармасьютикал Ко., Лтд. (Jp) | Азотсодержащее гетероциклическое соединение и его фармацевтическое применение |
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GB0129260D0 (en) | 2001-12-06 | 2002-01-23 | Eisai London Res Lab Ltd | Pharmaceutical compositions and their uses |
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