ES2444777T3 - Compuestos de nicotinamida útiles como moduladores de quinasas - Google Patents
Compuestos de nicotinamida útiles como moduladores de quinasas Download PDFInfo
- Publication number
- ES2444777T3 ES2444777T3 ES10724657.1T ES10724657T ES2444777T3 ES 2444777 T3 ES2444777 T3 ES 2444777T3 ES 10724657 T ES10724657 T ES 10724657T ES 2444777 T3 ES2444777 T3 ES 2444777T3
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- Prior art keywords
- alkyl
- phenyl
- nrb
- crbrb
- nrbc
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- 108091000080 Phosphotransferase Proteins 0.000 title description 13
- 102000020233 phosphotransferase Human genes 0.000 title description 13
- 150000005480 nicotinamides Chemical class 0.000 title description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 334
- -1 -OH Chemical group 0.000 claims abstract description 317
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 259
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 218
- 150000001875 compounds Chemical class 0.000 claims abstract description 154
- 125000001424 substituent group Chemical group 0.000 claims abstract description 137
- 125000005843 halogen group Chemical group 0.000 claims abstract description 128
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 100
- 150000003839 salts Chemical class 0.000 claims abstract description 99
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 98
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 82
- 125000003118 aryl group Chemical group 0.000 claims abstract description 65
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 58
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 58
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 57
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 53
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 49
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 45
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 41
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 38
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 35
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims abstract description 30
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 27
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 26
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 25
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 15
- 235000010290 biphenyl Nutrition 0.000 claims abstract description 15
- 239000004305 biphenyl Substances 0.000 claims abstract description 15
- 125000001207 fluorophenyl group Chemical group 0.000 claims abstract description 14
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 12
- 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 250
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 211
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 55
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 54
- 125000004076 pyridyl group Chemical group 0.000 claims description 42
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 38
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 37
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 34
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 32
- 125000001624 naphthyl group Chemical group 0.000 claims description 29
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 29
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 26
- 125000001188 haloalkyl group Chemical group 0.000 claims description 25
- 125000000335 thiazolyl group Chemical group 0.000 claims description 24
- 125000001041 indolyl group Chemical group 0.000 claims description 23
- 125000002757 morpholinyl group Chemical group 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 21
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 20
- 125000002883 imidazolyl group Chemical group 0.000 claims description 19
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 19
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 18
- 125000002541 furyl group Chemical group 0.000 claims description 18
- 125000003386 piperidinyl group Chemical group 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 16
- 208000035475 disorder Diseases 0.000 claims description 15
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 14
- 125000001544 thienyl group Chemical group 0.000 claims description 14
- 208000023275 Autoimmune disease Diseases 0.000 claims description 13
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 13
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 13
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 11
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 11
- 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 10
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 10
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 9
- 230000000172 allergic effect Effects 0.000 claims description 9
- 208000010668 atopic eczema Diseases 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 9
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 8
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 7
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 125000004965 chloroalkyl group Chemical group 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 5
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 5
- 125000005059 halophenyl group Chemical group 0.000 claims description 5
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 5
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 5
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 5
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 4
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 4
- 125000003566 oxetanyl group Chemical group 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 3
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 3
- BHNHHSOHWZKFOX-UHFFFAOYSA-N 2-methyl-1H-indole Chemical compound C1=CC=C2NC(C)=CC2=C1 BHNHHSOHWZKFOX-UHFFFAOYSA-N 0.000 claims description 3
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 3
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 3
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 2
- 208000037979 autoimmune inflammatory disease Diseases 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 214
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 119
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- 239000007787 solid Substances 0.000 description 81
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 58
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 56
- 239000000243 solution Substances 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- 235000019439 ethyl acetate Nutrition 0.000 description 38
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 35
- 238000000034 method Methods 0.000 description 34
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 33
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 30
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 24
- 239000000725 suspension Substances 0.000 description 24
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- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 19
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- 210000003719 b-lymphocyte Anatomy 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- 239000003814 drug Substances 0.000 description 17
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
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- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 12
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- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- 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
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- 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
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
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- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US186417P | 2000-03-02 | ||
| US18641709P | 2009-06-12 | 2009-06-12 | |
| PCT/US2010/038079 WO2010144647A1 (en) | 2009-06-12 | 2010-06-10 | Nicotinamide compounds useful as kinase modulators |
Publications (1)
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| ES2444777T3 true ES2444777T3 (es) | 2014-02-26 |
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| ES10724657.1T Active ES2444777T3 (es) | 2009-06-12 | 2010-06-10 | Compuestos de nicotinamida útiles como moduladores de quinasas |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8586751B2 (enExample) |
| EP (1) | EP2440204B1 (enExample) |
| JP (1) | JP2012529535A (enExample) |
| CN (1) | CN102458402B (enExample) |
| ES (1) | ES2444777T3 (enExample) |
| WO (1) | WO2010144647A1 (enExample) |
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| US8110581B2 (en) | 2004-11-10 | 2012-02-07 | Incyte Corporation | Lactam compounds and their use as pharmaceuticals |
| MY177250A (en) * | 2010-06-30 | 2020-09-10 | Fujifilm Corp | Novel nicotinamide derivative or salt thereof |
| JP2014501705A (ja) * | 2010-11-01 | 2014-01-23 | ポートラ ファーマシューティカルズ, インコーポレイテッド | Syk調節剤としてのベンズアミドおよびニコチンアミド |
| SG10201604682VA (en) * | 2011-06-10 | 2016-07-28 | Merck Patent Gmbh | Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity |
| US9782406B2 (en) | 2011-10-25 | 2017-10-10 | Peking University Shenzhen Graduate School | Kinase inhibitor and method for treatment of related diseases |
| CN103073508B (zh) | 2011-10-25 | 2016-06-01 | 北京大学深圳研究生院 | 激酶抑制剂及治疗相关疾病的方法 |
| MY188000A (en) | 2011-12-28 | 2021-11-08 | Fujifilm Corp | Novel nicotinamide derivative or salt thereof |
| US9242976B2 (en) | 2012-01-13 | 2016-01-26 | Bristol-Myers Squibb Company | Thiazolyl- or thiadiazolyl-substituted pyridyl compounds useful as kinase inhibitors |
| WO2013106614A1 (en) | 2012-01-13 | 2013-07-18 | Bristol-Myers Squibb Company | Triazolyl-substituted pyridyl compounds useful as kinase inhibitors |
| JP6109195B2 (ja) | 2012-01-13 | 2017-04-05 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | キナーゼ阻害剤として有用な複素環置換されたピリジル化合物 |
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| TW202340204A (zh) * | 2022-01-07 | 2023-10-16 | 日商中外製藥股份有限公司 | 具有Nrf2活化作用的含氮雜環化合物 |
| US11786531B1 (en) | 2022-06-08 | 2023-10-17 | Beigene Switzerland Gmbh | Methods of treating B-cell proliferative disorder |
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- 2010-06-10 EP EP10724657.1A patent/EP2440204B1/en not_active Not-in-force
- 2010-06-10 WO PCT/US2010/038079 patent/WO2010144647A1/en not_active Ceased
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- 2010-06-10 JP JP2012515123A patent/JP2012529535A/ja active Pending
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| CN102458402A (zh) | 2012-05-16 |
| JP2012529535A (ja) | 2012-11-22 |
| WO2010144647A1 (en) | 2010-12-16 |
| US20120082702A1 (en) | 2012-04-05 |
| US8586751B2 (en) | 2013-11-19 |
| EP2440204A1 (en) | 2012-04-18 |
| EP2440204B1 (en) | 2013-12-18 |
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