MXPA02002319A - Derivados 2-hidroxi-2-metil-3,3,3-trifluoropropanamida con n-fenilo susbtituido que elevan la actividad de la deshidrogenasa de piruvato. - Google Patents
Derivados 2-hidroxi-2-metil-3,3,3-trifluoropropanamida con n-fenilo susbtituido que elevan la actividad de la deshidrogenasa de piruvato.Info
- Publication number
- MXPA02002319A MXPA02002319A MXPA02002319A MXPA02002319A MXPA02002319A MX PA02002319 A MXPA02002319 A MX PA02002319A MX PA02002319 A MXPA02002319 A MX PA02002319A MX PA02002319 A MXPA02002319 A MX PA02002319A MX PA02002319 A MXPA02002319 A MX PA02002319A
- Authority
- MX
- Mexico
- Prior art keywords
- optionally substituted
- hydroxy
- methyl
- phenyl
- formula
- Prior art date
Links
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims description 48
- 230000000694 effects Effects 0.000 title abstract description 50
- 125000002887 hydroxy group Chemical group [H]O* 0.000 title description 180
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 title description 8
- 101710088194 Dehydrogenase Proteins 0.000 title description 3
- ZVQPSVUIMCRLCY-UHFFFAOYSA-N 3,3,3-trifluoro-n-methylpropanamide Chemical class CNC(=O)CC(F)(F)F ZVQPSVUIMCRLCY-UHFFFAOYSA-N 0.000 title 1
- -1 chloro, fluoro, bromo, methyl Chemical group 0.000 claims abstract description 358
- 150000001875 compounds Chemical class 0.000 claims abstract description 210
- 238000000034 method Methods 0.000 claims abstract description 209
- 150000003839 salts Chemical class 0.000 claims abstract description 44
- 239000001257 hydrogen Substances 0.000 claims abstract description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 40
- 150000002148 esters Chemical class 0.000 claims abstract description 37
- 241001465754 Metazoa Species 0.000 claims abstract description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 18
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 107
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 106
- 229910052757 nitrogen Inorganic materials 0.000 claims description 87
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 229910052799 carbon Inorganic materials 0.000 claims description 81
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 79
- 125000005843 halogen group Chemical group 0.000 claims description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
- 238000011282 treatment Methods 0.000 claims description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 24
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 17
- 239000011737 fluorine Chemical group 0.000 claims description 17
- 229910052731 fluorine Chemical group 0.000 claims description 17
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000004193 piperazinyl group Chemical group 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 15
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 14
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 14
- 206010012601 diabetes mellitus Diseases 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 238000007254 oxidation reaction Methods 0.000 claims description 13
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 230000003647 oxidation Effects 0.000 claims description 12
- 238000005859 coupling reaction Methods 0.000 claims description 11
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 230000008878 coupling Effects 0.000 claims description 9
- 238000010168 coupling process Methods 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 208000031225 myocardial ischemia Diseases 0.000 claims description 7
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 6
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 6
- 238000010511 deprotection reaction Methods 0.000 claims description 6
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 125000006241 alcohol protecting group Chemical group 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 9
- FIBGGVTWOTYYME-OAHLLOKOSA-N (2r)-n-[2-chloro-3-(1,1-dioxo-1,4-thiazinan-4-yl)-4-ethylsulfonylphenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide Chemical compound CCS(=O)(=O)C1=CC=C(NC(=O)[C@@](C)(O)C(F)(F)F)C(Cl)=C1N1CCS(=O)(=O)CC1 FIBGGVTWOTYYME-OAHLLOKOSA-N 0.000 claims 1
- LDOCDEIZNYVEOX-CQSZACIVSA-N (2r)-n-[2-chloro-3-(1,1-dioxo-1,4-thiazinan-4-yl)-4-methylsulfonylphenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide Chemical compound FC(F)(F)[C@@](O)(C)C(=O)NC1=CC=C(S(C)(=O)=O)C(N2CCS(=O)(=O)CC2)=C1Cl LDOCDEIZNYVEOX-CQSZACIVSA-N 0.000 claims 1
- YVFKGEVOGBEGBA-OAHLLOKOSA-N (2r)-n-[2-chloro-4-ethylsulfonyl-3-(1-oxo-1,4-thiazinan-4-yl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide Chemical compound CCS(=O)(=O)C1=CC=C(NC(=O)[C@@](C)(O)C(F)(F)F)C(Cl)=C1N1CCS(=O)CC1 YVFKGEVOGBEGBA-OAHLLOKOSA-N 0.000 claims 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 11
- 238000001727 in vivo Methods 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 222
- 235000019439 ethyl acetate Nutrition 0.000 description 111
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- 239000000243 solution Substances 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 73
- 238000005481 NMR spectroscopy Methods 0.000 description 72
- 239000000463 material Substances 0.000 description 70
- 238000001704 evaporation Methods 0.000 description 65
- 230000008020 evaporation Effects 0.000 description 65
- 239000007787 solid Substances 0.000 description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
- 206010012812 Diffuse cutaneous mastocytosis Diseases 0.000 description 54
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 43
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 42
- 239000012267 brine Substances 0.000 description 42
- 238000004587 chromatography analysis Methods 0.000 description 41
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 38
- 239000007858 starting material Substances 0.000 description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- 238000003756 stirring Methods 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000000377 silicon dioxide Substances 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 21
- 229910052786 argon Inorganic materials 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000000284 extract Substances 0.000 description 17
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 16
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 16
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 16
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 239000006260 foam Substances 0.000 description 14
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- 101150041968 CDC13 gene Proteins 0.000 description 12
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 11
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 11
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 11
- 239000005909 Kieselgur Substances 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 239000008103 glucose Substances 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
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- 125000001589 carboacyl group Chemical group 0.000 description 9
- 239000012362 glacial acetic acid Substances 0.000 description 9
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 9
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- 125000001422 pyrrolinyl group Chemical group 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 8
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- 239000003795 chemical substances by application Substances 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
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- LMJXSOYPAOSIPZ-UHFFFAOYSA-N 4-sulfanylbenzoic acid Chemical compound OC(=O)C1=CC=C(S)C=C1 LMJXSOYPAOSIPZ-UHFFFAOYSA-N 0.000 description 7
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- 125000004429 atom Chemical group 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 125000002883 imidazolyl group Chemical group 0.000 description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 7
- 125000000168 pyrrolyl group Chemical group 0.000 description 7
- 229940076788 pyruvate Drugs 0.000 description 7
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- 210000001519 tissue Anatomy 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
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- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 6
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- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 6
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
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- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
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- 239000002609 medium Substances 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 6
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Classifications
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/64—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton
- C07C323/65—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton containing sulfur atoms of sulfone or sulfoxide groups bound to the carbon skeleton
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9920814.2A GB9920814D0 (en) | 1999-09-04 | 1999-09-04 | Chemical compounds |
| GB0006641A GB0006641D0 (en) | 2000-03-21 | 2000-03-21 | Chemical compounds |
| PCT/GB2000/003314 WO2001017956A1 (en) | 1999-09-04 | 2000-08-30 | Substituted n-phenyl 2-hydroxy-2-methyl-3,3,3-trifluoropropanamide derivatives which elevate pyruvate dehydrogenase activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA02002319A true MXPA02002319A (es) | 2002-07-30 |
Family
ID=26243905
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA02002319A MXPA02002319A (es) | 1999-09-04 | 2000-08-30 | Derivados 2-hidroxi-2-metil-3,3,3-trifluoropropanamida con n-fenilo susbtituido que elevan la actividad de la deshidrogenasa de piruvato. |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US6689909B1 (enExample) |
| EP (1) | EP1214296B1 (enExample) |
| JP (1) | JP2003508515A (enExample) |
| KR (1) | KR100692232B1 (enExample) |
| CN (1) | CN1235877C (enExample) |
| AR (1) | AR035163A1 (enExample) |
| AT (1) | ATE262507T1 (enExample) |
| AU (1) | AU760061B2 (enExample) |
| BG (1) | BG65099B1 (enExample) |
| BR (1) | BR0013694A (enExample) |
| CA (1) | CA2381581A1 (enExample) |
| CO (1) | CO5190690A1 (enExample) |
| CZ (1) | CZ2002773A3 (enExample) |
| DE (1) | DE60009319T2 (enExample) |
| DK (1) | DK1214296T3 (enExample) |
| EE (1) | EE05080B1 (enExample) |
| ES (1) | ES2216940T3 (enExample) |
| HK (1) | HK1045496B (enExample) |
| HU (1) | HUP0202725A3 (enExample) |
| IL (2) | IL148111A0 (enExample) |
| IS (1) | IS2069B (enExample) |
| MX (1) | MXPA02002319A (enExample) |
| MY (1) | MY127036A (enExample) |
| NO (1) | NO20021040L (enExample) |
| NZ (1) | NZ517147A (enExample) |
| PL (1) | PL353887A1 (enExample) |
| PT (1) | PT1214296E (enExample) |
| RU (1) | RU2255085C2 (enExample) |
| SK (1) | SK286774B6 (enExample) |
| TR (1) | TR200200550T2 (enExample) |
| TW (1) | TW577867B (enExample) |
| WO (1) | WO2001017956A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE399753T1 (de) | 1999-09-04 | 2008-07-15 | Astrazeneca Ab | Amide als pyruvatdehydrogenaseinhibitoren |
| GB0012012D0 (en) * | 2000-05-19 | 2000-07-05 | Astrazeneca Ab | Chemical compound |
| GB0120471D0 (en) * | 2001-08-23 | 2001-10-17 | Astrazeneca Ab | Chemical compounds |
| CA2471943C (en) * | 2001-12-27 | 2011-09-20 | Daiichi Pharmaceutical Co., Ltd. | .beta.-amyloid protein production-secretion inhibitors |
| WO2012151448A1 (en) * | 2011-05-03 | 2012-11-08 | Agios Pharmaceuticals, Inc. | Pyruvate kinase activators for use in therapy |
| EP2917207A1 (en) | 2012-11-08 | 2015-09-16 | Agios Pharmaceuticals, Inc. | Therapeutic compounds and compositions and their use as pkm2 modulators |
| WO2014139144A1 (en) | 2013-03-15 | 2014-09-18 | Agios Pharmaceuticals, Inc. | Therapeutic compounds and compositions |
| SG11202001353PA (en) | 2017-08-15 | 2020-03-30 | Agios Pharmaceuticals Inc | Pyruvate kinase modulators and use thereof |
| CN109096186B (zh) * | 2018-09-29 | 2020-08-04 | 中南大学 | 一种2-芳磺酰基喹啉衍生物的合成方法 |
| EP4438040A4 (en) * | 2021-09-01 | 2025-08-20 | Japan Tobacco Inc | NITROGEN-CONTAINING TRICYCLIC COMPOUND AND ITS PHARMACEUTICAL USE |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0002309B1 (en) | 1977-10-12 | 1982-12-01 | Imperial Chemical Industries Plc | Acylanilides, process for their manufacture and pharmaceutical and veterinary compositions containing them |
| US4191775A (en) | 1977-12-15 | 1980-03-04 | Imperial Chemical Industries Limited | Amide derivatives |
| NZ197008A (en) | 1980-05-22 | 1984-10-19 | Ici Ltd | Acylanilide derivatives and pharmaceutical compositions |
| AU8961382A (en) | 1981-11-06 | 1983-05-12 | Imperial Chemical Industries Plc | Amide derivatives |
| US4537618A (en) | 1982-05-26 | 1985-08-27 | Ciba Geigy Corporation | N-phenylsulfonyl-N'-pyrimidinylureas |
| EP0100172B1 (en) | 1982-07-23 | 1987-08-12 | Imperial Chemical Industries Plc | Amide derivatives |
| GB8617652D0 (en) | 1986-07-18 | 1986-08-28 | Ici Plc | Acylanilide derivatives |
| GB8617653D0 (en) | 1986-07-18 | 1986-08-28 | Ici Plc | Amide derivatives |
| GB9116069D0 (en) * | 1991-07-25 | 1991-09-11 | Ici Plc | Therapeutic amides |
| GB9214120D0 (en) * | 1991-07-25 | 1992-08-12 | Ici Plc | Therapeutic amides |
| EP0539329A1 (de) | 1991-10-25 | 1993-04-28 | Ciba-Geigy Ag | Acetylen-Verbindungen, verwendbar als Leukotrien-Antagonisten |
| SE9103397D0 (sv) | 1991-11-18 | 1991-11-18 | Kabi Pharmacia Ab | Nya substituerade salicylsyror |
| IL105558A (en) | 1992-05-18 | 1998-04-05 | Zeneca Ltd | Tertiary carbinols having potassium channel activity, process for their preparation and pharmaceutical compositions containing them |
| GB9305295D0 (en) | 1993-03-15 | 1993-05-05 | Zeneca Ltd | Therapeutic compounds |
| GB9309716D0 (en) | 1993-05-12 | 1993-06-23 | Zeneca Ltd | Heterocyclic derivatives |
| GB9310095D0 (en) | 1993-05-17 | 1993-06-30 | Zeneca Ltd | Therapeutic compounds |
| GB9310069D0 (en) | 1993-05-17 | 1993-06-30 | Zeneca Ltd | Heterocyclic compounds |
| GB2278054A (en) | 1993-05-18 | 1994-11-23 | Zeneca Ltd | Compounds for the treatment of urinary incontinence |
| GB9505082D0 (en) | 1995-03-14 | 1995-05-03 | Zeneca Ltd | Medicament |
| GB9607458D0 (en) | 1996-04-10 | 1996-06-12 | Zeneca Ltd | Enzymatic process for stereoselective preparation of therapeutic amides |
| GB9804648D0 (en) | 1998-03-06 | 1998-04-29 | Zeneca Ltd | Chemical compounds |
| GB9805520D0 (en) * | 1998-03-17 | 1998-05-13 | Zeneca Ltd | Chemical compounds |
| GB9811427D0 (en) | 1998-05-29 | 1998-07-22 | Zeneca Ltd | Chemical compounds |
-
2000
- 2000-08-30 CA CA002381581A patent/CA2381581A1/en not_active Abandoned
- 2000-08-30 CZ CZ2002773A patent/CZ2002773A3/cs unknown
- 2000-08-30 HU HU0202725A patent/HUP0202725A3/hu unknown
- 2000-08-30 BR BR0013694-8A patent/BR0013694A/pt not_active Application Discontinuation
- 2000-08-30 MX MXPA02002319A patent/MXPA02002319A/es active IP Right Grant
- 2000-08-30 US US10/069,994 patent/US6689909B1/en not_active Expired - Fee Related
- 2000-08-30 ES ES00956672T patent/ES2216940T3/es not_active Expired - Lifetime
- 2000-08-30 NZ NZ517147A patent/NZ517147A/en unknown
- 2000-08-30 RU RU2002108508/04A patent/RU2255085C2/ru not_active IP Right Cessation
- 2000-08-30 EP EP00956672A patent/EP1214296B1/en not_active Expired - Lifetime
- 2000-08-30 PT PT00956672T patent/PT1214296E/pt unknown
- 2000-08-30 CN CNB008152446A patent/CN1235877C/zh not_active Expired - Fee Related
- 2000-08-30 AT AT00956672T patent/ATE262507T1/de not_active IP Right Cessation
- 2000-08-30 MY MYPI20004037 patent/MY127036A/en unknown
- 2000-08-30 JP JP2001521703A patent/JP2003508515A/ja active Pending
- 2000-08-30 EE EEP200200113A patent/EE05080B1/xx not_active IP Right Cessation
- 2000-08-30 IL IL14811100A patent/IL148111A0/xx active IP Right Grant
- 2000-08-30 PL PL00353887A patent/PL353887A1/xx not_active Application Discontinuation
- 2000-08-30 WO PCT/GB2000/003314 patent/WO2001017956A1/en not_active Ceased
- 2000-08-30 DK DK00956672T patent/DK1214296T3/da active
- 2000-08-30 TR TR2002/00550T patent/TR200200550T2/xx unknown
- 2000-08-30 HK HK02107004.7A patent/HK1045496B/en not_active IP Right Cessation
- 2000-08-30 AU AU68543/00A patent/AU760061B2/en not_active Ceased
- 2000-08-30 KR KR1020027002841A patent/KR100692232B1/ko not_active Expired - Fee Related
- 2000-08-30 SK SK300-2002A patent/SK286774B6/sk not_active IP Right Cessation
- 2000-08-30 DE DE60009319T patent/DE60009319T2/de not_active Expired - Fee Related
- 2000-09-01 CO CO00065992A patent/CO5190690A1/es not_active Application Discontinuation
- 2000-09-04 TW TW089118053A patent/TW577867B/zh not_active IP Right Cessation
- 2000-09-04 AR ARP000104623A patent/AR035163A1/es unknown
-
2002
- 2002-02-11 IL IL148111A patent/IL148111A/en not_active IP Right Cessation
- 2002-02-26 IS IS6285A patent/IS2069B/xx unknown
- 2002-03-01 NO NO20021040A patent/NO20021040L/no not_active Application Discontinuation
- 2002-03-14 BG BG106520A patent/BG65099B1/bg unknown
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