TW201217362A - Heteroaryls and uses thereof - Google Patents
Heteroaryls and uses thereof Download PDFInfo
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- TW201217362A TW201217362A TW100128763A TW100128763A TW201217362A TW 201217362 A TW201217362 A TW 201217362A TW 100128763 A TW100128763 A TW 100128763A TW 100128763 A TW100128763 A TW 100128763A TW 201217362 A TW201217362 A TW 201217362A
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- sulfur
- nitrogen
- oxygen
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- 125000001072 heteroaryl group Chemical group 0.000 title claims description 69
- 150000001875 compounds Chemical class 0.000 claims abstract description 209
- 101000605630 Homo sapiens Phosphatidylinositol 3-kinase catalytic subunit type 3 Proteins 0.000 claims abstract description 28
- 102100038329 Phosphatidylinositol 3-kinase catalytic subunit type 3 Human genes 0.000 claims abstract description 28
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 11
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 10
- 230000002062 proliferating effect Effects 0.000 claims abstract description 10
- 108091007960 PI3Ks Proteins 0.000 claims abstract description 4
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 claims abstract 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 171
- 239000000203 mixture Substances 0.000 claims description 133
- 229910052757 nitrogen Inorganic materials 0.000 claims description 110
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 95
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 94
- 229910052760 oxygen Inorganic materials 0.000 claims description 94
- 239000001301 oxygen Substances 0.000 claims description 94
- -1 ethoxymethylene Chemical group 0.000 claims description 92
- 229910052717 sulfur Inorganic materials 0.000 claims description 85
- 239000011593 sulfur Substances 0.000 claims description 85
- 125000003118 aryl group Chemical group 0.000 claims description 84
- 125000001931 aliphatic group Chemical group 0.000 claims description 74
- 125000005842 heteroatom Chemical group 0.000 claims description 73
- 125000000623 heterocyclic group Chemical group 0.000 claims description 58
- 239000001257 hydrogen Substances 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 30
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 21
- 125000004429 atom Chemical group 0.000 claims description 20
- 239000007789 gas Substances 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 10
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
- 206010020751 Hypersensitivity Diseases 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 150000002923 oximes Chemical class 0.000 claims description 5
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 4
- 206010014733 Endometrial cancer Diseases 0.000 claims description 4
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 4
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 4
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 4
- JBCFJMYPJJWIRG-UHFFFAOYSA-N 1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC=N1 JBCFJMYPJJWIRG-UHFFFAOYSA-N 0.000 claims description 3
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 208000006029 Cardiomegaly Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 208000032612 Glial tumor Diseases 0.000 claims description 3
- 206010018338 Glioma Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 208000038016 acute inflammation Diseases 0.000 claims description 3
- 230000006022 acute inflammation Effects 0.000 claims description 3
- 230000000172 allergic effect Effects 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 208000037976 chronic inflammation Diseases 0.000 claims description 3
- 230000006020 chronic inflammation Effects 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 201000004101 esophageal cancer Diseases 0.000 claims description 3
- 125000004494 ethyl ester group Chemical group 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 239000002689 soil Substances 0.000 claims description 3
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 3
- 201000002510 thyroid cancer Diseases 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- VAELWSLNTRVXQS-UHFFFAOYSA-N 1,3-oxazole-4-carboxamide Chemical compound NC(=O)C1=COC=N1 VAELWSLNTRVXQS-UHFFFAOYSA-N 0.000 claims description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
- VYIBCOSBNVFEIW-UHFFFAOYSA-N 3-phenylpropanamide Chemical compound NC(=O)CCC1=CC=CC=C1 VYIBCOSBNVFEIW-UHFFFAOYSA-N 0.000 claims description 2
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 241000237536 Mytilus edulis Species 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 235000020638 mussel Nutrition 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- 102100035353 Cyclin-dependent kinase 2-associated protein 1 Human genes 0.000 claims 1
- 229910002651 NO3 Inorganic materials 0.000 claims 1
- 125000005418 aryl aryl group Chemical group 0.000 claims 1
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical group [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 claims 1
- 239000004519 grease Substances 0.000 claims 1
- 150000004702 methyl esters Chemical class 0.000 claims 1
- 125000006327 phenyl hydrazinyl group Chemical group [H]N(*)N([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 claims 1
- 238000004513 sizing Methods 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 10
- 208000027866 inflammatory disease Diseases 0.000 abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 124
- 239000000243 solution Substances 0.000 description 101
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 100
- 239000011541 reaction mixture Substances 0.000 description 85
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 78
- 235000019439 ethyl acetate Nutrition 0.000 description 61
- 238000000034 method Methods 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 37
- 238000004440 column chromatography Methods 0.000 description 37
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
- 239000002585 base Substances 0.000 description 31
- 210000004027 cell Anatomy 0.000 description 31
- 206010028980 Neoplasm Diseases 0.000 description 29
- 238000012552 review Methods 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
- 201000011510 cancer Diseases 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000002609 medium Substances 0.000 description 18
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 238000007876 drug discovery Methods 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 11
- 108091008611 Protein Kinase B Proteins 0.000 description 11
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 11
- 239000012267 brine Substances 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 125000001041 indolyl group Chemical group 0.000 description 11
- 229910052708 sodium Inorganic materials 0.000 description 11
- 235000015424 sodium Nutrition 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
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Classifications
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
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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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D405/14—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 three or more hetero rings
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- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
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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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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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
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- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Immunology (AREA)
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- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37255310P | 2010-08-11 | 2010-08-11 | |
| US37262810P | 2010-08-11 | 2010-08-11 | |
| US201161469157P | 2011-03-30 | 2011-03-30 |
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| TW201217362A true TW201217362A (en) | 2012-05-01 |
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Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8859768B2 (enExample) |
| EP (1) | EP2603216A4 (enExample) |
| JP (1) | JP2013533318A (enExample) |
| AR (1) | AR082666A1 (enExample) |
| TW (1) | TW201217362A (enExample) |
| WO (1) | WO2012021615A1 (enExample) |
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| US9029411B2 (en) | 2008-01-25 | 2015-05-12 | Millennium Pharmaceuticals, Inc. | Thiophenes and uses thereof |
| US9139589B2 (en) | 2009-01-30 | 2015-09-22 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| US8796314B2 (en) | 2009-01-30 | 2014-08-05 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| US9090601B2 (en) | 2009-01-30 | 2015-07-28 | Millennium Pharmaceuticals, Inc. | Thiazole derivatives |
| MA34797B1 (fr) | 2010-08-11 | 2014-01-02 | Millennium Pharm Inc | Hétéroaryles et leurs utilisations |
| US9062038B2 (en) | 2010-08-11 | 2015-06-23 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| PH12013500723A1 (en) | 2010-10-13 | 2017-08-23 | Millennium Pharm Inc | Heteroaryls and uses thereof |
| EP2882741B1 (en) * | 2012-08-10 | 2018-10-24 | Boehringer Ingelheim International GmbH | Heteroaromatic compounds as bruton's tyrosine kinase (btk) inhibitors |
| JP2017502092A (ja) | 2014-01-14 | 2017-01-19 | ミレニアム ファーマシューティカルズ, インコーポレイテッドMillennium Pharmaceuticals, Inc. | ヘテロアリール及びその使用 |
| TN2016000270A1 (en) * | 2014-01-14 | 2017-10-06 | Millennium Pharm Inc | Heteroaryls and uses thereof. |
| US9828364B2 (en) | 2014-01-29 | 2017-11-28 | Boehringer Ingelheim International Gmbh | Pyrazole compounds as BTK inhibitors |
| EP3156405A1 (en) | 2015-10-13 | 2017-04-19 | Boehringer Ingelheim International GmbH | Spirocyclic ether derivatives of pyrazolo[1,5-a]pyrimidine-3-carboxamide |
| KR102691112B1 (ko) | 2015-12-16 | 2024-08-05 | 베링거 인겔하임 인터내셔날 게엠베하 | 자가 면역 질환의 치료에 유용한 비피라졸릴 유도체 |
| EP3402789B1 (en) | 2016-01-13 | 2020-03-18 | Boehringer Ingelheim International Gmbh | Isoquinolones as btk inhibitors |
| WO2025054366A1 (en) * | 2023-09-06 | 2025-03-13 | Nico Therapeutics, Inc. | Compounds, compositions, and methods |
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| US3821384A (en) | 1972-10-06 | 1974-06-28 | Uniroyal Inc | Pharmaceutical compositions containing a4-aryl-2-(3-pyridyl)thiazole and methods of using same |
| DE3021590A1 (de) | 1980-06-09 | 1981-12-17 | Hoechst Ag, 6000 Frankfurt | 4-halogen-5-(halogenmethyl-phenyl)-oxazol-derivate, ein verfahren zu ihrer herstellung und sie enthaltenden strahlungsempfindliche massen |
| DD275870A1 (de) | 1988-09-27 | 1990-02-07 | Univ Leipzig | Verfahren zur herstellung von in 5-position verschiedenartig substituierten 3-aminothiophen-4-carbonitrilen |
| PH27357A (en) | 1989-09-22 | 1993-06-21 | Fujisawa Pharmaceutical Co | Pyrazole derivatives and pharmaceutical compositions comprising the same |
| WO1997012613A1 (en) | 1995-10-05 | 1997-04-10 | Warner-Lambert Company | Method for treating and preventing inflammation and atherosclerosis |
| WO1998008845A1 (en) | 1996-08-27 | 1998-03-05 | Novartis Ag | Herbicidal s-substituted 1,2,4,6-thiatriazines |
| JPH1087490A (ja) | 1996-09-10 | 1998-04-07 | Sagami Chem Res Center | インターロイキン6生産抑制剤、骨吸収抑制剤、抗骨粗鬆症剤、及びチアゾール化合物 |
| PT853083E (pt) | 1997-01-06 | 2001-12-28 | Pfizer | Composto de piridilfurano e piridiltiofeno e sua utilizacao farmaceutica |
| TR199802691T1 (xx) | 1997-04-24 | 1999-07-21 | Dow Agrosciences Llc | Pestisid etkili 3-(ikameli fenil)-5-(tienil ya da furil)-1,2,4-triazoller |
| JP2002520324A (ja) | 1998-07-10 | 2002-07-09 | メルク エンド カムパニー インコーポレーテッド | 新規な血管形成インヒビター |
| DE19858192A1 (de) | 1998-12-17 | 2000-06-21 | Aventis Cropscience Gmbh | 4-Trifluormethyl-3-oxazolylpyridine, Verfahren zu ihrer Herstellung, sie enthaltende Mittel und ihre Verwendung als Schädlingsbekämpfungsmittel |
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-
2011
- 2011-08-10 JP JP2013524201A patent/JP2013533318A/ja active Pending
- 2011-08-10 EP EP11816983.8A patent/EP2603216A4/en not_active Withdrawn
- 2011-08-10 US US13/206,671 patent/US8859768B2/en active Active
- 2011-08-10 WO PCT/US2011/047245 patent/WO2012021615A1/en not_active Ceased
- 2011-08-11 TW TW100128763A patent/TW201217362A/zh unknown
- 2011-08-11 AR ARP110102930A patent/AR082666A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013533318A (ja) | 2013-08-22 |
| US8859768B2 (en) | 2014-10-14 |
| EP2603216A4 (en) | 2013-12-18 |
| WO2012021615A1 (en) | 2012-02-16 |
| US20120142732A1 (en) | 2012-06-07 |
| AR082666A1 (es) | 2012-12-26 |
| EP2603216A1 (en) | 2013-06-19 |
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