JP2011529918A - Ｊａｋ３阻害剤としてのピペリジン誘導体 - Google Patents
Ｊａｋ３阻害剤としてのピペリジン誘導体 Download PDFInfo
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- JP2011529918A JP2011529918A JP2011521361A JP2011521361A JP2011529918A JP 2011529918 A JP2011529918 A JP 2011529918A JP 2011521361 A JP2011521361 A JP 2011521361A JP 2011521361 A JP2011521361 A JP 2011521361A JP 2011529918 A JP2011529918 A JP 2011529918A
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- heteroaryl
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- 229940123241 Janus kinase 3 inhibitor Drugs 0.000 title 1
- 150000003053 piperidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 141
- 150000003839 salts Chemical class 0.000 claims abstract description 55
- 230000004913 activation Effects 0.000 claims abstract description 13
- 230000001575 pathological effect Effects 0.000 claims abstract description 13
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 241000124008 Mammalia Species 0.000 claims abstract description 11
- 238000011282 treatment Methods 0.000 claims abstract description 8
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 5
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 5
- 201000011510 cancer Diseases 0.000 claims abstract description 4
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 125000003118 aryl group Chemical group 0.000 claims description 50
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 5
- 230000028993 immune response Effects 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 230000036210 malignancy Effects 0.000 claims description 2
- 238000013160 medical therapy Methods 0.000 claims description 2
- 150000001717 carbocyclic compounds Chemical class 0.000 claims 2
- 206010066476 Haematological malignancy Diseases 0.000 claims 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims 1
- 230000001629 suppression Effects 0.000 claims 1
- 230000001506 immunosuppresive effect Effects 0.000 abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 180
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- 238000005481 NMR spectroscopy Methods 0.000 description 71
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- -1 cyclooctadienyl Chemical group 0.000 description 46
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
- 238000003818 flash chromatography Methods 0.000 description 38
- 239000000741 silica gel Substances 0.000 description 37
- 229910002027 silica gel Inorganic materials 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 239000012267 brine Substances 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
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- 239000000543 intermediate Substances 0.000 description 18
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 18
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 17
- 239000005695 Ammonium acetate Substances 0.000 description 17
- 235000019257 ammonium acetate Nutrition 0.000 description 17
- 229940043376 ammonium acetate Drugs 0.000 description 17
- 239000000872 buffer Substances 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- BOUIZPWBFIVJPD-UHFFFAOYSA-N 3h-1,2,4-triazin-4-amine Chemical compound NN1CN=NC=C1 BOUIZPWBFIVJPD-UHFFFAOYSA-N 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 235000019441 ethanol Nutrition 0.000 description 11
- OZLIBRFWDOSHRS-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-cyanoacetate Chemical compound N#CCC(=O)ON1C(=O)CCC1=O OZLIBRFWDOSHRS-UHFFFAOYSA-N 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 10
- 239000002552 dosage form Substances 0.000 description 10
- 125000005842 heteroatom Chemical group 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- AMJBBOMXPFXGQM-RJUBDTSPSA-N 3-[(3r,4r)-4-methyl-3-(methylamino)piperidin-1-yl]-3-oxopropanenitrile;hydrochloride Chemical compound Cl.CN[C@H]1CN(C(=O)CC#N)CC[C@H]1C AMJBBOMXPFXGQM-RJUBDTSPSA-N 0.000 description 8
- ONTLBVKRDUFQFP-UHFFFAOYSA-N 4-chloropyrrolo[2,1-f][1,2,4]triazine Chemical compound ClC1=NC=NN2C=CC=C12 ONTLBVKRDUFQFP-UHFFFAOYSA-N 0.000 description 8
- 238000002835 absorbance Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- DSKHBLMKLTZNRU-UHFFFAOYSA-N 2-(oxetan-3-ylidene)acetonitrile Chemical compound N#CC=C1COC1 DSKHBLMKLTZNRU-UHFFFAOYSA-N 0.000 description 7
- OVOINUKCVYVMEF-UHFFFAOYSA-N 4-chlorofuro[3,2-d]pyrimidine Chemical compound ClC1=NC=NC2=C1OC=C2 OVOINUKCVYVMEF-UHFFFAOYSA-N 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- XRIARWQZLGCQDM-KOLCDFICSA-N n-methyl-n-[(3r,4r)-4-methylpiperidin-3-yl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C[C@@H]1CCNC[C@@H]1N(C)C1=NC=NC2=C1C=CN2 XRIARWQZLGCQDM-KOLCDFICSA-N 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- NVKDDQBZODSEIN-UHFFFAOYSA-N 1-benzyl-n,4-dimethylpiperidin-3-amine Chemical compound C1CC(C)C(NC)CN1CC1=CC=CC=C1 NVKDDQBZODSEIN-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
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- 239000011734 sodium Substances 0.000 description 6
- 229910052717 sulfur Chemical group 0.000 description 6
- JKTHBYNKZDJPQV-OLZOCXBDSA-N tert-butyl (3r,4r)-4-methyl-3-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]piperidine-1-carboxylate Chemical compound C[C@@H]1CCN(C(=O)OC(C)(C)C)C[C@@H]1N(C)C(=O)OC(C)(C)C JKTHBYNKZDJPQV-OLZOCXBDSA-N 0.000 description 6
- GWQZTLKKZAHNAH-WBVHZDCISA-N tert-butyl n-[(3r,4r)-1-benzyl-4-methylpiperidin-3-yl]-n-methylcarbamate Chemical compound C1[C@H](N(C)C(=O)OC(C)(C)C)[C@H](C)CCN1CC1=CC=CC=C1 GWQZTLKKZAHNAH-WBVHZDCISA-N 0.000 description 6
- RYUDJOMESUSKEK-YPMHNXCESA-N 3-[(3r,4r)-3-[furo[3,2-d]pyrimidin-4-yl(methyl)amino]-4-methylpiperidin-1-yl]-3-oxopropanenitrile Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1OC=C2 RYUDJOMESUSKEK-YPMHNXCESA-N 0.000 description 5
- XALREJZOVRBCPN-YPMHNXCESA-N 3-[(3r,4r)-4-methyl-3-[methyl(thieno[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CS2 XALREJZOVRBCPN-YPMHNXCESA-N 0.000 description 5
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- 102000006500 Janus Kinase 3 Human genes 0.000 description 5
- 108010019421 Janus Kinase 3 Proteins 0.000 description 5
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- NBNMAHFMRYJNGS-OCCSQVGLSA-N 1-[(3r,4r)-4-methyl-3-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidine-1-carbonyl]cyclopropane-1-carbonitrile Chemical compound C([C@H]([C@H](C1)N(C)C=2C=3C=CNC=3N=CN=2)C)CN1C(=O)C1(C#N)CC1 NBNMAHFMRYJNGS-OCCSQVGLSA-N 0.000 description 4
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- QMFPURRPZZSJPF-UHFFFAOYSA-N 1h-imidazo[2,1-f][1,2,4]triazin-4-one Chemical compound O=C1N=CNN2C=CN=C12 QMFPURRPZZSJPF-UHFFFAOYSA-N 0.000 description 4
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- DEOXAVJVEZNAPW-NEPJUHHUSA-N 3-[(3r,4r)-3-[(7-chloroimidazo[1,2-a]pyrimidin-5-yl)-methylamino]-4-methylpiperidin-1-yl]-3-oxopropanenitrile Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=CC(Cl)=NC2=NC=CN12 DEOXAVJVEZNAPW-NEPJUHHUSA-N 0.000 description 4
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- DANQCJZYOJHPPW-NEPJUHHUSA-N 3-[(3r,4r)-4-methyl-3-[methyl([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)amino]piperidin-1-yl]-3-oxopropanenitrile Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=CC=NC2=NC=NN12 DANQCJZYOJHPPW-NEPJUHHUSA-N 0.000 description 4
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- RREIDOPAHNBHLZ-PBHICJAKSA-N 4-n-[(3r,4r)-1-benzyl-4-methylpiperidin-3-yl]-4-n-methyl-7h-pyrrolo[2,3-d]pyrimidine-2,4-diamine Chemical compound C([C@H]([C@H](C1)N(C)C=2C=3C=CNC=3N=C(N)N=2)C)CN1CC1=CC=CC=C1 RREIDOPAHNBHLZ-PBHICJAKSA-N 0.000 description 4
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- INVVMIXYILXINW-UHFFFAOYSA-N 5-methyl-1h-[1,2,4]triazolo[1,5-a]pyrimidin-7-one Chemical compound CC1=CC(=O)N2NC=NC2=N1 INVVMIXYILXINW-UHFFFAOYSA-N 0.000 description 4
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- VUEWVPSSFIXDKG-UHFFFAOYSA-N ethyl 1-aminoimidazole-2-carboxylate Chemical compound CCOC(=O)C1=NC=CN1N VUEWVPSSFIXDKG-UHFFFAOYSA-N 0.000 description 4
- AHKACZDKUNMFBD-UHFFFAOYSA-N ethyl 2-cyano-4,4-diethoxybutanoate Chemical compound CCOC(OCC)CC(C#N)C(=O)OCC AHKACZDKUNMFBD-UHFFFAOYSA-N 0.000 description 4
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- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 4
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- 235000019359 magnesium stearate Nutrition 0.000 description 4
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- 229910052740 iodine Inorganic materials 0.000 description 1
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- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
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- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
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- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
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- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
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- 229920005862 polyol Polymers 0.000 description 1
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
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- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
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- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- CTDQAGUNKPRERK-UHFFFAOYSA-N spirodecane Chemical compound C1CCCC21CCCCC2 CTDQAGUNKPRERK-UHFFFAOYSA-N 0.000 description 1
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- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
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- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
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- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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- 238000002054 transplantation Methods 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- POFDSYGXHVPQNX-UHFFFAOYSA-N triazolo[1,5-a]pyrimidine Chemical compound C1=CC=NC2=CN=NN21 POFDSYGXHVPQNX-UHFFFAOYSA-N 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
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- 235000012431 wafers Nutrition 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8570508P | 2008-08-01 | 2008-08-01 | |
| US61/085,705 | 2008-08-01 | ||
| US9856208P | 2008-09-19 | 2008-09-19 | |
| US61/098,562 | 2008-09-19 | ||
| PCT/US2009/052449 WO2010014930A2 (en) | 2008-08-01 | 2009-07-31 | Therapeutic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011529918A true JP2011529918A (ja) | 2011-12-15 |
| JP2011529918A5 JP2011529918A5 (OSRAM) | 2012-09-06 |
Family
ID=41170025
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011521361A Pending JP2011529918A (ja) | 2008-08-01 | 2009-07-31 | Ｊａｋ３阻害剤としてのピペリジン誘導体 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20110165183A1 (OSRAM) |
| EP (1) | EP2324020A2 (OSRAM) |
| JP (1) | JP2011529918A (OSRAM) |
| KR (1) | KR20110050654A (OSRAM) |
| CN (1) | CN102171211A (OSRAM) |
| AU (1) | AU2009276420A1 (OSRAM) |
| BR (1) | BRPI0916931A2 (OSRAM) |
| CA (1) | CA2732628A1 (OSRAM) |
| IL (1) | IL210990A0 (OSRAM) |
| MX (1) | MX2011001259A (OSRAM) |
| NZ (1) | NZ590922A (OSRAM) |
| RU (1) | RU2011105768A (OSRAM) |
| WO (1) | WO2010014930A2 (OSRAM) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AR077346A1 (es) | 2009-07-31 | 2011-08-17 | Biocryst Pharm Inc | Compuestos heterociclicos como inhibidores de janus quinasa |
| BR112012029994A2 (pt) * | 2010-05-28 | 2019-09-24 | Biocryst Pharm Inc | composto heterocíclicos como inibidores de janus quinase |
| EP2710006A1 (en) | 2011-05-17 | 2014-03-26 | Principia Biopharma Inc. | Azaindole derivatives as tyrosine kinase inhibitors |
| EP2825533B1 (en) | 2012-03-13 | 2016-10-19 | Basf Se | Fungicidal pyrimidine compounds |
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Also Published As
| Publication number | Publication date |
|---|---|
| AU2009276420A1 (en) | 2010-02-04 |
| CA2732628A1 (en) | 2010-02-04 |
| EP2324020A2 (en) | 2011-05-25 |
| WO2010014930A2 (en) | 2010-02-04 |
| NZ590922A (en) | 2012-09-28 |
| BRPI0916931A2 (pt) | 2015-11-24 |
| IL210990A0 (en) | 2011-04-28 |
| CN102171211A (zh) | 2011-08-31 |
| MX2011001259A (es) | 2011-03-15 |
| RU2011105768A (ru) | 2012-09-10 |
| KR20110050654A (ko) | 2011-05-16 |
| WO2010014930A3 (en) | 2010-07-29 |
| US20110165183A1 (en) | 2011-07-07 |
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