JP2006514691A - 炎症を抑制する医薬 - Google Patents
炎症を抑制する医薬 Download PDFInfo
- Publication number
- JP2006514691A JP2006514691A JP2005508625A JP2005508625A JP2006514691A JP 2006514691 A JP2006514691 A JP 2006514691A JP 2005508625 A JP2005508625 A JP 2005508625A JP 2005508625 A JP2005508625 A JP 2005508625A JP 2006514691 A JP2006514691 A JP 2006514691A
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- compound
- alkyl
- switch control
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 230000004054 inflammatory process Effects 0.000 title claims description 6
- 206010061218 Inflammation Diseases 0.000 title claims description 5
- 239000003814 drug Substances 0.000 title description 8
- 229940079593 drug Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 217
- 238000000034 method Methods 0.000 claims abstract description 54
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 35
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 35
- 230000004913 activation Effects 0.000 claims abstract description 11
- 239000003446 ligand Substances 0.000 claims description 59
- -1 β-trimethylsilylethyl Chemical group 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims description 42
- 230000027455 binding Effects 0.000 claims description 37
- 125000002947 alkylene group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 17
- 230000003197 catalytic effect Effects 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
- 125000000335 thiazolyl group Chemical group 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 125000001769 aryl amino group Chemical group 0.000 claims description 12
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 12
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000000539 amino acid group Chemical group 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000002971 oxazolyl group Chemical group 0.000 claims description 10
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 206010040070 Septic Shock Diseases 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000005110 aryl thio group Chemical group 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 7
- 102000001253 Protein Kinase Human genes 0.000 claims description 6
- 206010040047 Sepsis Diseases 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 239000004305 biphenyl Substances 0.000 claims description 6
- 235000010290 biphenyl Nutrition 0.000 claims description 6
- 239000002131 composite material Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 108060006633 protein kinase Proteins 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 4
- 125000002723 alicyclic group Chemical group 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- 125000002648 azanetriyl group Chemical group *N(*)* 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 4
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 201000005569 Gout Diseases 0.000 claims description 3
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 206010063837 Reperfusion injury Diseases 0.000 claims description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
- 208000007502 anemia Diseases 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 208000019664 bone resorption disease Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 208000024908 graft versus host disease Diseases 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 230000001537 neural effect Effects 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 230000001988 toxicity Effects 0.000 claims description 3
- 231100000419 toxicity Toxicity 0.000 claims description 3
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 2
- 206010014824 Endotoxic shock Diseases 0.000 claims description 2
- 239000000556 agonist Substances 0.000 claims description 2
- 239000005557 antagonist Substances 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 230000008733 trauma Effects 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 125000004185 ester group Chemical group 0.000 claims 1
- 230000002685 pulmonary effect Effects 0.000 claims 1
- 230000035939 shock Effects 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 abstract description 7
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 abstract description 7
- 230000004968 inflammatory condition Effects 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 description 80
- 102000004169 proteins and genes Human genes 0.000 description 79
- 238000006243 chemical reaction Methods 0.000 description 73
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- 150000001412 amines Chemical class 0.000 description 49
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 239000000543 intermediate Substances 0.000 description 36
- 239000000460 chlorine Substances 0.000 description 35
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 239000007787 solid Substances 0.000 description 23
- 239000000203 mixture Substances 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 17
- 239000003112 inhibitor Substances 0.000 description 16
- 230000003993 interaction Effects 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 229910000104 sodium hydride Inorganic materials 0.000 description 15
- 239000004202 carbamide Substances 0.000 description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- 150000003384 small molecules Chemical class 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 0 CCC[C@@](C=CC(O*(C)C)=*1C)C=C1N Chemical compound CCC[C@@](C=CC(O*(C)C)=*1C)C=C1N 0.000 description 12
- 239000013058 crude material Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 239000012948 isocyanate Substances 0.000 description 10
- 150000002513 isocyanates Chemical class 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000009471 action Effects 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 230000000975 bioactive effect Effects 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 8
- 150000002540 isothiocyanates Chemical class 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 8
- 238000007254 oxidation reaction Methods 0.000 description 8
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
- 230000002378 acidificating effect Effects 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 238000010511 deprotection reaction Methods 0.000 description 7
- 238000005984 hydrogenation reaction Methods 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000003039 volatile agent Substances 0.000 description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 6
- 238000007341 Heck reaction Methods 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 150000001336 alkenes Chemical class 0.000 description 6
- 230000029936 alkylation Effects 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 230000031018 biological processes and functions Effects 0.000 description 6
- 238000006555 catalytic reaction Methods 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000008030 elimination Effects 0.000 description 6
- 238000003379 elimination reaction Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
- ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 5
- BDQNKCYCTYYMAA-UHFFFAOYSA-N 1-isocyanatonaphthalene Chemical compound C1=CC=C2C(N=C=O)=CC=CC2=C1 BDQNKCYCTYYMAA-UHFFFAOYSA-N 0.000 description 5
- MXZMACXOMZKYHJ-UHFFFAOYSA-N 4,4-dimethyl-3-oxopentanenitrile Chemical compound CC(C)(C)C(=O)CC#N MXZMACXOMZKYHJ-UHFFFAOYSA-N 0.000 description 5
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 5
- 229910010082 LiAlH Inorganic materials 0.000 description 5
- 238000006751 Mitsunobu reaction Methods 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 238000011065 in-situ storage Methods 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 238000005932 reductive alkylation reaction Methods 0.000 description 5
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 4
- YOELZIQOLWZLQC-UHFFFAOYSA-N 6-(4-fluorophenyl)-5-pyridin-4-yl-2,3-dihydroimidazo[2,1-b]thiazole Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)N2CCSC2=N1 YOELZIQOLWZLQC-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 238000005576 amination reaction Methods 0.000 description 4
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- PGBXZDDHDXRVAV-UHFFFAOYSA-N 4,4-dimethylpyrazolidine-3,5-dione Chemical compound CC1(C)C(=O)NNC1=O PGBXZDDHDXRVAV-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 206010044248 Toxic shock syndrome Diseases 0.000 description 3
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 229940127010 p38α kinase inhibitor Drugs 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 150000003222 pyridines Chemical class 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- MNOALXGAYUJNKX-UHFFFAOYSA-N s-chloro chloromethanethioate Chemical compound ClSC(Cl)=O MNOALXGAYUJNKX-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 3
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 3
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 2
- UDATXMIGEVPXTR-UHFFFAOYSA-N 1,2,4-triazolidine-3,5-dione Chemical compound O=C1NNC(=O)N1 UDATXMIGEVPXTR-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- TVEKGJQYELHDJM-UHFFFAOYSA-N 1-[5-tert-butyl-2-[4-[(1,1-dioxo-1,4-thiazinan-4-yl)methyl]phenyl]pyrazol-3-yl]-3-(4-chlorophenyl)urea Chemical compound C=1C=C(CN2CCS(=O)(=O)CC2)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=C(Cl)C=C1 TVEKGJQYELHDJM-UHFFFAOYSA-N 0.000 description 2
- LNMBCRKRCIMQLW-UHFFFAOYSA-N 2-tert-butylsulfanyl-2-methylpropane Chemical compound CC(C)(C)SC(C)(C)C LNMBCRKRCIMQLW-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 2
- 241000698776 Duma Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229940100389 Sulfonylurea Drugs 0.000 description 2
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 2
- 239000012042 active reagent Substances 0.000 description 2
- 125000006242 amine protecting group Chemical group 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 238000006254 arylation reaction Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- 150000001540 azides Chemical group 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 238000012925 biological evaluation Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 239000006225 natural substrate Substances 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 150000003138 primary alcohols Chemical class 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000004853 protein function Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- QAZLUNIWYYOJPC-UHFFFAOYSA-M sulfenamide Chemical compound [Cl-].COC1=C(C)C=[N+]2C3=NC4=CC=C(OC)C=C4N3SCC2=C1C QAZLUNIWYYOJPC-UHFFFAOYSA-M 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
- 125000002348 vinylic group Chemical group 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- QHFKWIKCUHNXAU-UHFFFAOYSA-N (4-nitrophenyl) carbamate Chemical compound NC(=O)OC1=CC=C([N+]([O-])=O)C=C1 QHFKWIKCUHNXAU-UHFFFAOYSA-N 0.000 description 1
- DHAKCNQDRGJAQU-UHFFFAOYSA-N (4-nitrophenyl) n-(4-chlorophenyl)carbamate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)NC1=CC=C(Cl)C=C1 DHAKCNQDRGJAQU-UHFFFAOYSA-N 0.000 description 1
- JSZAZZQHDRHICK-UHFFFAOYSA-N 1,1-dioxo-1,2,5-thiadiazolidin-3-one Chemical compound O=C1CNS(=O)(=O)N1 JSZAZZQHDRHICK-UHFFFAOYSA-N 0.000 description 1
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 description 1
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- NFYWQFPRQBYKOK-UHFFFAOYSA-N 1-[2-[3-(2-aminoethyl)phenyl]-5-tert-butylpyrazol-3-yl]-3-naphthalen-1-ylurea Chemical compound N1=C(C(C)(C)C)C=C(NC(=O)NC=2C3=CC=CC=C3C=CC=2)N1C1=CC=CC(CCN)=C1 NFYWQFPRQBYKOK-UHFFFAOYSA-N 0.000 description 1
- BFSQEYSMVLRBBS-UHFFFAOYSA-N 1-[2-[3-(azidomethyl)phenyl]-5-tert-butylpyrazol-3-yl]-3-naphthalen-1-ylurea Chemical compound N1=C(C(C)(C)C)C=C(NC(=O)NC=2C3=CC=CC=C3C=CC=2)N1C1=CC=CC(CN=[N+]=[N-])=C1 BFSQEYSMVLRBBS-UHFFFAOYSA-N 0.000 description 1
- QPSGMYVAAPQTEC-UHFFFAOYSA-N 1-[2-[4-(aminomethyl)phenyl]-5-tert-butylpyrazol-3-yl]-3-(4-chlorophenyl)urea Chemical compound C=1C=C(CN)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=C(Cl)C=C1 QPSGMYVAAPQTEC-UHFFFAOYSA-N 0.000 description 1
- WKEIAJKTSFSIHK-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-hydroxyphenyl)pyrazol-3-yl]-3-naphthalen-1-ylurea Chemical compound N1=C(C(C)(C)C)C=C(NC(=O)NC=2C3=CC=CC=C3C=CC=2)N1C1=CC=CC(O)=C1 WKEIAJKTSFSIHK-UHFFFAOYSA-N 0.000 description 1
- JFKYKCZHDGUZOM-UHFFFAOYSA-N 1-[5-tert-butyl-2-[3-(chloromethyl)phenyl]pyrazol-3-yl]-3-(4-chlorophenyl)urea Chemical compound C=1C=CC(CCl)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=C(Cl)C=C1 JFKYKCZHDGUZOM-UHFFFAOYSA-N 0.000 description 1
- VTQNEBMXGHCOND-UHFFFAOYSA-N 1-[5-tert-butyl-2-[3-[(1-methyl-3,5-dioxo-1,2,4-triazolidin-4-yl)methyl]phenyl]pyrazol-3-yl]-3-(4-chlorophenyl)urea Chemical compound O=C1N(C)NC(=O)N1CC1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NC=2C=CC(Cl)=CC=2)=C1 VTQNEBMXGHCOND-UHFFFAOYSA-N 0.000 description 1
- UYTPVMBHOKRVBE-UHFFFAOYSA-N 1-[5-tert-butyl-2-[3-[(4,4-dimethyl-3,5-dioxopyrazolidin-1-yl)methyl]phenyl]pyrazol-3-yl]-3-(4-chlorophenyl)urea Chemical compound C=1C=CC(CN2C(C(C)(C)C(=O)N2)=O)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=C(Cl)C=C1 UYTPVMBHOKRVBE-UHFFFAOYSA-N 0.000 description 1
- OSBLOSVKWUYEJJ-UHFFFAOYSA-N 1-[5-tert-butyl-2-[3-[(4,4-dimethyl-3,5-dioxopyrazolidin-1-yl)methyl]phenyl]pyrazol-3-yl]-3-naphthalen-1-ylurea Chemical compound N1=C(C(C)(C)C)C=C(NC(=O)NC=2C3=CC=CC=C3C=CC=2)N1C(C=1)=CC=CC=1CN1NC(=O)C(C)(C)C1=O OSBLOSVKWUYEJJ-UHFFFAOYSA-N 0.000 description 1
- PIEXCQIOSMOEOU-UHFFFAOYSA-N 1-bromo-3-chloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Br)C(=O)N(Cl)C1=O PIEXCQIOSMOEOU-UHFFFAOYSA-N 0.000 description 1
- PTCSLGONLAYNQB-UHFFFAOYSA-N 1-isocyanonaphthalene Chemical compound C1=CC=C2C([N+]#[C-])=CC=CC2=C1 PTCSLGONLAYNQB-UHFFFAOYSA-N 0.000 description 1
- NENDRBATLNDSTO-UHFFFAOYSA-N 1-methyl-1,2,4-triazolidine-3,5-dione Chemical compound CN1NC(=O)NC1=O NENDRBATLNDSTO-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- LBWKDTFSPUMSAT-UHFFFAOYSA-N 2-(3-aminophenyl)acetamide Chemical compound NC(=O)CC1=CC=CC(N)=C1 LBWKDTFSPUMSAT-UHFFFAOYSA-N 0.000 description 1
- ATDMUOUARWAVEW-UHFFFAOYSA-N 2-(3-nitrophenyl)acetamide Chemical compound NC(=O)CC1=CC=CC([N+]([O-])=O)=C1 ATDMUOUARWAVEW-UHFFFAOYSA-N 0.000 description 1
- WUKHOVCMWXMOOA-UHFFFAOYSA-N 2-(3-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC([N+]([O-])=O)=C1 WUKHOVCMWXMOOA-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- RLGMQRQJTXNWRX-UHFFFAOYSA-N 2-[3-(5-amino-3-tert-butylpyrazol-1-yl)phenyl]acetamide Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=CC(CC(N)=O)=C1 RLGMQRQJTXNWRX-UHFFFAOYSA-N 0.000 description 1
- OCGWSRHYGBLTTK-UHFFFAOYSA-N 2-[3-(azidomethyl)phenyl]-5-tert-butylpyrazol-3-amine Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=CC(CN=[N+]=[N-])=C1 OCGWSRHYGBLTTK-UHFFFAOYSA-N 0.000 description 1
- NYDCMPAJIMDYCJ-UHFFFAOYSA-N 2-[3-[3-tert-butyl-5-(naphthalen-1-ylcarbamoylamino)pyrazol-1-yl]phenyl]propanoic acid Chemical compound OC(=O)C(C)C1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NC=2C3=CC=CC=C3C=CC=2)=C1 NYDCMPAJIMDYCJ-UHFFFAOYSA-N 0.000 description 1
- UMYOSVRLKQFYGA-UHFFFAOYSA-N 2-[benzyl-(2-ethoxy-2-oxoethyl)amino]acetic acid Chemical compound CCOC(=O)CN(CC(O)=O)Cc1ccccc1 UMYOSVRLKQFYGA-UHFFFAOYSA-N 0.000 description 1
- XJCXXSOSJXRDTP-UHFFFAOYSA-N 2-[benzyl-[2-(methylamino)-2-oxoethyl]amino]-n-methylacetamide Chemical compound CNC(=O)CN(CC(=O)NC)CC1=CC=CC=C1 XJCXXSOSJXRDTP-UHFFFAOYSA-N 0.000 description 1
- LOUVEYUQIGQTHC-UHFFFAOYSA-N 2-[benzyl-[2-(methylamino)-2-oxoethyl]amino]acetic acid Chemical compound CNC(=O)CN(CC(O)=O)CC1=CC=CC=C1 LOUVEYUQIGQTHC-UHFFFAOYSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 1
- WDGCBNTXZHJTHJ-UHFFFAOYSA-N 2h-1,3-oxazol-2-id-4-one Chemical class O=C1CO[C-]=N1 WDGCBNTXZHJTHJ-UHFFFAOYSA-N 0.000 description 1
- LIUJJVCUIDFKSW-UHFFFAOYSA-N 3-(5-amino-3-tert-butylpyrazol-1-yl)benzoic acid Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=CC(C(O)=O)=C1 LIUJJVCUIDFKSW-UHFFFAOYSA-N 0.000 description 1
- XFDUHJPVQKIXHO-UHFFFAOYSA-N 3-aminobenzoic acid Chemical compound NC1=CC=CC(C(O)=O)=C1 XFDUHJPVQKIXHO-UHFFFAOYSA-N 0.000 description 1
- YONFQPJFIKYVLO-UHFFFAOYSA-N 3-hydrazinylbenzoic acid;hydrochloride Chemical compound Cl.NNC1=CC=CC(C(O)=O)=C1 YONFQPJFIKYVLO-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- MNMSEDATXVLFAV-UHFFFAOYSA-N 5-tert-butyl-2-[3-(chloromethyl)phenyl]pyrazol-3-amine Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=CC(CCl)=C1 MNMSEDATXVLFAV-UHFFFAOYSA-N 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 239000007989 BIS-Tris Propane buffer Substances 0.000 description 1
- FORHBRYTXDXZKO-UHFFFAOYSA-N CC(C)(C)OC(=O)N(N)S(N)(=O)=O Chemical compound CC(C)(C)OC(=O)N(N)S(N)(=O)=O FORHBRYTXDXZKO-UHFFFAOYSA-N 0.000 description 1
- MVIMQODHEHIMNL-UHFFFAOYSA-N CC(C)(C)c(cc1N)n[n]1-c1cc(CCNC(OC(C)(C)C)=O)ccc1 Chemical compound CC(C)(C)c(cc1N)n[n]1-c1cc(CCNC(OC(C)(C)C)=O)ccc1 MVIMQODHEHIMNL-UHFFFAOYSA-N 0.000 description 1
- NEYMXPNCERHYAJ-UHFFFAOYSA-N CC(C)(C)c(cc1NC(Nc(cc2)c(cccc3)c3c2OCCc2cccnc2)=O)n[n]1-c1ccc(COC(NS(N(C)C)(=O)=O)=O)cc1 Chemical compound CC(C)(C)c(cc1NC(Nc(cc2)c(cccc3)c3c2OCCc2cccnc2)=O)n[n]1-c1ccc(COC(NS(N(C)C)(=O)=O)=O)cc1 NEYMXPNCERHYAJ-UHFFFAOYSA-N 0.000 description 1
- DDHWHCGCUDELGS-UHFFFAOYSA-N CC(C)(C)c(cc1NC(Nc(cc2)ccc2Cl)=O)n[n]1-c(cc1)ccc1C(NS(C)(=O)=O)=O Chemical compound CC(C)(C)c(cc1NC(Nc(cc2)ccc2Cl)=O)n[n]1-c(cc1)ccc1C(NS(C)(=O)=O)=O DDHWHCGCUDELGS-UHFFFAOYSA-N 0.000 description 1
- NGLOSHORSKGYLC-UHFFFAOYSA-N CC(C)(C)c(cc1NC(Nc(cc2)ccc2Cl)=O)n[n]1-c1ccc(CN(C(C2(O)O)=O)N(C)C2=O)cc1 Chemical compound CC(C)(C)c(cc1NC(Nc(cc2)ccc2Cl)=O)n[n]1-c1ccc(CN(C(C2(O)O)=O)N(C)C2=O)cc1 NGLOSHORSKGYLC-UHFFFAOYSA-N 0.000 description 1
- QVGCXIRKEVPWOX-UHFFFAOYSA-N CC(C)(C)c(cc1NC(Nc(cc2)ccc2OCCc2cccnc2)=O)n[n]1-c1ccc(C[O](C(NS(N(C)C)(=O)=O)=O)=C)cc1 Chemical compound CC(C)(C)c(cc1NC(Nc(cc2)ccc2OCCc2cccnc2)=O)n[n]1-c1ccc(C[O](C(NS(N(C)C)(=O)=O)=O)=C)cc1 QVGCXIRKEVPWOX-UHFFFAOYSA-N 0.000 description 1
- SCFCTJMNOFTXDW-UHFFFAOYSA-N CC(C)(C)c(cc1NC(Nc(cc2)ccc2OCCc2ccncc2)=O)n[n]1-c1ccc(COC(NS(N(C)C)(=O)=O)=O)cc1 Chemical compound CC(C)(C)c(cc1NC(Nc(cc2)ccc2OCCc2ccncc2)=O)n[n]1-c1ccc(COC(NS(N(C)C)(=O)=O)=O)cc1 SCFCTJMNOFTXDW-UHFFFAOYSA-N 0.000 description 1
- ILSQCXNPYTVKCC-UHFFFAOYSA-N CC(C)(C)c(cc1NC(Nc2c(cccc3)c3ccc2)=O)n[n]1-c1cccc(CCC(O)=O)c1 Chemical compound CC(C)(C)c(cc1NC(Nc2c(cccc3)c3ccc2)=O)n[n]1-c1cccc(CCC(O)=O)c1 ILSQCXNPYTVKCC-UHFFFAOYSA-N 0.000 description 1
- MVPALSJSNSNZAS-UHFFFAOYSA-N CC(NS(N(C)C)(=O)=O)OCc(cc1)ccc1-[n]1nc(C(C)(C)C)cc1NC(Nc(cc1)c(cccc2)c2c1OCCN1CCOCC1)=O Chemical compound CC(NS(N(C)C)(=O)=O)OCc(cc1)ccc1-[n]1nc(C(C)(C)C)cc1NC(Nc(cc1)c(cccc2)c2c1OCCN1CCOCC1)=O MVPALSJSNSNZAS-UHFFFAOYSA-N 0.000 description 1
- AMJIVVJFADZSNZ-UHFFFAOYSA-N CCCCCNCCCC Chemical compound CCCCCNCCCC AMJIVVJFADZSNZ-UHFFFAOYSA-N 0.000 description 1
- CKMRVKWJCOOIFK-UHFFFAOYSA-N CNC(Oc(cc1)ccc1[N+]([O-])=O)=O Chemical compound CNC(Oc(cc1)ccc1[N+]([O-])=O)=O CKMRVKWJCOOIFK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N Di-tert-butyl dicarbonate Substances CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 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 1
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 description 1
- AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- RYSXSKPGMGXJJP-UHFFFAOYSA-N [3-(5-amino-3-tert-butylpyrazol-1-yl)phenyl]methanol Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=CC(CO)=C1 RYSXSKPGMGXJJP-UHFFFAOYSA-N 0.000 description 1
- VELBEPGJCGEZMC-UHFFFAOYSA-N [Br-].C1(=CC=C([NH3+])C=C1)C1=CC=C(N)C=C1 Chemical compound [Br-].C1(=CC=C([NH3+])C=C1)C1=CC=C(N)C=C1 VELBEPGJCGEZMC-UHFFFAOYSA-N 0.000 description 1
- LRHVEGCJASOOIG-UHFFFAOYSA-N acetic acid;bromoethane Chemical compound CCBr.CC(O)=O LRHVEGCJASOOIG-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000007080 aromatic substitution reaction Methods 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
- ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 1
- 238000012362 drug development process Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- NRPMBSHHBFFYBF-VMPITWQZSA-N ethyl (e)-3-(4-aminophenyl)prop-2-enoate Chemical compound CCOC(=O)\C=C\C1=CC=C(N)C=C1 NRPMBSHHBFFYBF-VMPITWQZSA-N 0.000 description 1
- HIZZJSBSOJLOQQ-UHFFFAOYSA-N ethyl 2-[benzyl-(2-ethoxy-2-oxoethyl)amino]acetate Chemical compound CCOC(=O)CN(CC(=O)OCC)CC1=CC=CC=C1 HIZZJSBSOJLOQQ-UHFFFAOYSA-N 0.000 description 1
- NEXFMPAUGJAIHE-UHFFFAOYSA-N ethyl 3-(4-aminophenyl)propanoate Chemical compound CCOC(=O)CCC1=CC=C(N)C=C1 NEXFMPAUGJAIHE-UHFFFAOYSA-N 0.000 description 1
- UJDSJBSXNQSBRO-UHFFFAOYSA-N ethyl 3-(4-hydrazinylphenyl)propanoate Chemical compound CCOC(=O)CCC1=CC=C(NN)C=C1 UJDSJBSXNQSBRO-UHFFFAOYSA-N 0.000 description 1
- PLWTXWBKKPXFNQ-UHFFFAOYSA-N ethyl 3-[3-tert-butyl-5-[(4-chlorophenyl)carbamoylamino]pyrazol-1-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NC=2C=CC(Cl)=CC=2)=C1 PLWTXWBKKPXFNQ-UHFFFAOYSA-N 0.000 description 1
- YQJUZZZTDREFQT-UHFFFAOYSA-N ethyl 3-[4-[3-tert-butyl-5-(naphthalen-1-ylcarbamoylamino)pyrazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OCC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C=CC=2)=CC(C(C)(C)C)=N1 YQJUZZZTDREFQT-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229920001973 fluoroelastomer Polymers 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229910052740 iodine Chemical group 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- CBEQRNSPHCCXSH-UHFFFAOYSA-N iodine monobromide Chemical group IBr CBEQRNSPHCCXSH-UHFFFAOYSA-N 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- JYJVVHFRSFVEJM-UHFFFAOYSA-N iodosobenzene Chemical compound O=IC1=CC=CC=C1 JYJVVHFRSFVEJM-UHFFFAOYSA-N 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- VCSGRXIKJCLEAN-UHFFFAOYSA-N methyl 3-(3-aminophenyl)prop-2-enoate Chemical compound COC(=O)C=CC1=CC=CC(N)=C1 VCSGRXIKJCLEAN-UHFFFAOYSA-N 0.000 description 1
- PITMSNMLUXCPLM-UHFFFAOYSA-N methyl 3-(3-aminophenyl)propanoate Chemical compound COC(=O)CCC1=CC=CC(N)=C1 PITMSNMLUXCPLM-UHFFFAOYSA-N 0.000 description 1
- LJDLEEKULCGTLS-UHFFFAOYSA-N methyl 4-(5-amino-3-tert-butylpyrazol-1-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(N)=CC(C(C)(C)C)=N1 LJDLEEKULCGTLS-UHFFFAOYSA-N 0.000 description 1
- AIUQARONZYCSPI-UHFFFAOYSA-N methyl 4-[3-tert-butyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]pyrazol-1-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(NC(=O)OC(C)(C)C)=CC(C(C)(C)C)=N1 AIUQARONZYCSPI-UHFFFAOYSA-N 0.000 description 1
- PUVXAQCVNJUHKG-UHFFFAOYSA-N methyl 4-hydrazinylbenzoate Chemical compound COC(=O)C1=CC=C(NN)C=C1 PUVXAQCVNJUHKG-UHFFFAOYSA-N 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- ZKWFSTHEYLJLEL-UHFFFAOYSA-N morpholine-4-carboxamide Chemical class NC(=O)N1CCOCC1 ZKWFSTHEYLJLEL-UHFFFAOYSA-N 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- JKRHDMPWBFBQDZ-UHFFFAOYSA-N n'-hexylmethanediimine Chemical compound CCCCCCN=C=N JKRHDMPWBFBQDZ-UHFFFAOYSA-N 0.000 description 1
- XCVNDBIXFPGMIW-UHFFFAOYSA-N n-ethylpropan-1-amine Chemical compound CCCNCC XCVNDBIXFPGMIW-UHFFFAOYSA-N 0.000 description 1
- QWLISCJHYITNQF-UHFFFAOYSA-N n-methoxy-1-phenylmethanamine Chemical compound CONCC1=CC=CC=C1 QWLISCJHYITNQF-UHFFFAOYSA-N 0.000 description 1
- KVJUDCHMRDCBMY-UHFFFAOYSA-N n-methyl-2-[[2-(methylamino)-2-oxoethyl]amino]acetamide Chemical compound CNC(=O)CNCC(=O)NC KVJUDCHMRDCBMY-UHFFFAOYSA-N 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 239000003909 protein kinase inhibitor Substances 0.000 description 1
- 229940076155 protein modulator Drugs 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- XWJAPBHPAQSTCT-UHFFFAOYSA-N tert-butyl carbamoylsulfamoylformate Chemical compound CC(C)(C)OC(=O)S(=O)(=O)NC(N)=O XWJAPBHPAQSTCT-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WMXCDAVJEZZYLT-UHFFFAOYSA-N tert-butylthiol Chemical compound CC(C)(C)S WMXCDAVJEZZYLT-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 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
- 125000003944 tolyl group Chemical group 0.000 description 1
- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- QFDUTPNKBRXHTC-UHFFFAOYSA-N zinc diazide Chemical compound [Zn++].[N-]=[N+]=[N-].[N-]=[N+]=[N-] QFDUTPNKBRXHTC-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D295/10—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 doubly bound oxygen or sulphur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/04—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- 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
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43730402P | 2002-12-31 | 2002-12-31 | |
| US43740302P | 2002-12-31 | 2002-12-31 | |
| US43741502P | 2002-12-31 | 2002-12-31 | |
| US43748702P | 2002-12-31 | 2002-12-31 | |
| US46380403P | 2003-04-18 | 2003-04-18 | |
| US10/746,460 US7144911B2 (en) | 2002-12-31 | 2003-12-24 | Anti-inflammatory medicaments |
| PCT/US2003/041449 WO2004060306A2 (en) | 2002-12-31 | 2003-12-26 | Anti-inflammatory medicaments |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006514691A true JP2006514691A (ja) | 2006-05-11 |
| JP2006514691A5 JP2006514691A5 (https=) | 2009-04-02 |
Family
ID=32719725
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2005508625A Withdrawn JP2006514691A (ja) | 2002-12-31 | 2003-12-26 | 炎症を抑制する医薬 |
Country Status (9)
| Country | Link |
|---|---|
| US (7) | US7144911B2 (https=) |
| EP (2) | EP1585734A4 (https=) |
| JP (1) | JP2006514691A (https=) |
| AU (1) | AU2003303641A1 (https=) |
| BR (1) | BR0317872A (https=) |
| CA (1) | CA2513627A1 (https=) |
| MX (1) | MXPA05007236A (https=) |
| TW (1) | TW200427672A (https=) |
| WO (2) | WO2004060306A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021132577A1 (ja) * | 2019-12-27 | 2021-07-01 | 日本たばこ産業株式会社 | アシルスルファミド化合物及びその医薬用途 |
Families Citing this family (116)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7144911B2 (en) * | 2002-12-31 | 2006-12-05 | Deciphera Pharmaceuticals Llc | Anti-inflammatory medicaments |
| US7202257B2 (en) * | 2003-12-24 | 2007-04-10 | Deciphera Pharmaceuticals, Llc | Anti-inflammatory medicaments |
| US20080045706A1 (en) * | 2002-12-31 | 2008-02-21 | Flynn Daniel L | Anti-inflammatory medicaments |
| JP2006518738A (ja) * | 2003-02-12 | 2006-08-17 | トランス テック ファーマ,インコーポレイテッド | 治療薬としての置換アゾール誘導体 |
| JP2006522130A (ja) | 2003-04-03 | 2006-09-28 | メルク エンド カムパニー インコーポレーテッド | ナトリウムチャンネル遮断薬としてのビアリール置換ピラゾール |
| AU2004246800B2 (en) * | 2003-06-13 | 2008-12-04 | Novartis Ag | 2-aminopyrimidine derivatives as Raf kinase inhibitors |
| PL2256106T3 (pl) | 2003-07-22 | 2015-08-31 | Astex Therapeutics Ltd | Związki 3,4-pochodne 1h-pirazolu i ich zastosowanie jako kinazy zależne od cyklin (cdk) i modulatory kinazy syntazy glikogenu-3 (gsk-3) |
| KR100854211B1 (ko) * | 2003-12-18 | 2008-08-26 | 동아제약주식회사 | 신규한 옥사졸리디논 유도체, 그의 제조방법 및 이를유효성분으로 하는 항생제용 약학 조성물 |
| JP4898458B2 (ja) * | 2004-02-12 | 2012-03-14 | トランス テック ファーマ,インコーポレイテッド | 置換アゾール誘導体、組成物及び使用方法 |
| KR20070011458A (ko) | 2004-04-08 | 2007-01-24 | 탈자진 인코포레이티드 | 키나제의 벤조트리아진 억제제 |
| US7459562B2 (en) | 2004-04-23 | 2008-12-02 | Bristol-Myers Squibb Company | Monocyclic heterocycles as kinase inhibitors |
| TW200538453A (en) | 2004-04-26 | 2005-12-01 | Bristol Myers Squibb Co | Bicyclic heterocycles as kinase inhibitors |
| US7439246B2 (en) | 2004-06-28 | 2008-10-21 | Bristol-Myers Squibb Company | Fused heterocyclic kinase inhibitors |
| US7173031B2 (en) | 2004-06-28 | 2007-02-06 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
| US7432373B2 (en) | 2004-06-28 | 2008-10-07 | Bristol-Meyers Squibb Company | Processes and intermediates useful for preparing fused heterocyclic kinase inhibitors |
| EP1768984B1 (en) | 2004-07-16 | 2010-10-20 | Sunesis Pharmaceuticals, Inc. | Thienopyrimidines useful as aurora kinase inhibitors |
| PL382308A1 (pl) | 2004-08-25 | 2007-08-20 | Targegen, Inc. | Związki heterocykliczne i sposoby stosowania |
| WO2006045581A1 (en) * | 2004-10-21 | 2006-05-04 | Neuropharma, S.A. | The use of 1, 2, 4-thiadiazolidine-3, 5-diones as ppar activators |
| EP1824843A2 (en) | 2004-12-07 | 2007-08-29 | Locus Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| JP2008523071A (ja) | 2004-12-07 | 2008-07-03 | ルーカス ファーマシューティカルズ, インコーポレイテッド | Mapキナーゼの尿素インヒビター |
| WO2006068591A1 (en) * | 2004-12-20 | 2006-06-29 | Astrazeneca Ab | Novel pyrazole derivatives and their use as modulators of nicotinic acetylcholine receptors |
| WO2006071940A2 (en) | 2004-12-23 | 2006-07-06 | Deciphera Pharmaceuticals, Llc | Enzyme modulators and treatments |
| AU2005325676A1 (en) * | 2004-12-23 | 2006-08-03 | Deciphera Pharmaceuticals, Llc | Anti-inflammatory medicaments |
| AR054425A1 (es) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
| ES2524922T3 (es) | 2005-05-10 | 2014-12-15 | Intermune, Inc. | Derivados de piridona para modular el sistema de proteína cinasa activada por estrés |
| WO2006137421A1 (ja) * | 2005-06-21 | 2006-12-28 | Kyowa Hakko Kogyo Co., Ltd. | 局所投与剤 |
| CN103626742B (zh) | 2005-11-01 | 2017-04-26 | 塔格根公司 | 激酶的联-芳基间-嘧啶抑制剂 |
| US8604042B2 (en) | 2005-11-01 | 2013-12-10 | Targegen, Inc. | Bi-aryl meta-pyrimidine inhibitors of kinases |
| BRPI0707338A2 (pt) | 2006-01-30 | 2011-05-03 | Transtech Pharma Inc | derivados de imidazol, composições, e métodos substituìdos de uso como inibidores de ptpase |
| US8188113B2 (en) | 2006-09-14 | 2012-05-29 | Deciphera Pharmaceuticals, Inc. | Dihydropyridopyrimidinyl, dihydronaphthyidinyl and related compounds useful as kinase inhibitors for the treatment of proliferative diseases |
| US7790756B2 (en) | 2006-10-11 | 2010-09-07 | Deciphera Pharmaceuticals, Llc | Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases |
| KR20100014811A (ko) * | 2007-04-20 | 2010-02-11 | 데시페라 파마슈티칼스, 엘엘씨. | 골수증식성 질환 및 기타 증식성 질환의 치료에 유용한 키나제 억제제 |
| US20110189167A1 (en) * | 2007-04-20 | 2011-08-04 | Flynn Daniel L | Methods and Compositions for the Treatment of Myeloproliferative Diseases and other Proliferative Diseases |
| US8242271B2 (en) | 2007-06-04 | 2012-08-14 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
| WO2008153959A1 (en) * | 2007-06-07 | 2008-12-18 | Intra-Cellular Therapies, Inc. | Novel heterocycle compounds and uses thereof |
| US20100286280A1 (en) * | 2007-09-26 | 2010-11-11 | The University Of North Carolina At Chapel Hill | Inhibitors of eppin/semenogelin binding as male contraceptives |
| JP5567481B2 (ja) | 2007-10-09 | 2014-08-06 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | グルコキナーゼアクチベーターとして有用なピリジン誘導体 |
| AU2008335709A1 (en) * | 2007-12-13 | 2009-06-18 | Amgen Inc. | Gamma secretase modulators |
| UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
| CA2726588C (en) | 2008-06-03 | 2019-04-16 | Karl Kossen | Compounds and methods for treating inflammatory and fibrotic disorders |
| GB0818033D0 (en) | 2008-10-02 | 2008-11-05 | Respivert Ltd | Novel compound |
| MY159230A (en) | 2008-10-02 | 2016-12-30 | Respivert Ltd | P38 map kinase inhibitors |
| WO2010042887A2 (en) * | 2008-10-10 | 2010-04-15 | Trius Therapeutics | Methods for preparing oxazolidinones and compositions containing them |
| CN102256493A (zh) * | 2008-10-29 | 2011-11-23 | 迪赛孚尔制药有限公司 | 表现出抗癌活性和抗增殖活性的环丙烷酰胺及其类似物 |
| JP5670912B2 (ja) | 2008-12-11 | 2015-02-18 | レスピバート・リミテツド | p38MAPキナーゼ阻害剤 |
| KR101918678B1 (ko) | 2009-02-03 | 2018-11-14 | 머크 샤프 앤드 돔 코포레이션 | R)-3-(4-(2-(2-메틸테트라졸-5-일)피리딘-5-일)-3-플루오로페닐)-5-히드록시메틸 옥사졸리딘-2-온 디히드로겐 포스페이트의 결정형 |
| GB0905955D0 (en) | 2009-04-06 | 2009-05-20 | Respivert Ltd | Novel compounds |
| US8580767B2 (en) * | 2009-05-28 | 2013-11-12 | Trius Therapeutics, Inc. | Oxazolidinone containing dimer compounds, compositions and methods to make and use |
| WO2011150198A1 (en) | 2010-05-27 | 2011-12-01 | Ambit Biosciences Corporation | Azolyl urea compounds and methods of use thereof |
| CA2816957A1 (en) | 2010-11-07 | 2012-05-10 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
| AU2012256237B2 (en) | 2011-05-13 | 2017-01-05 | Array Biopharma Inc. | Pyrrolidinyl urea and pyrrolidinyl thiourea compounds as TrkA kinase inhibitors |
| JP6378171B2 (ja) | 2012-04-24 | 2018-08-22 | バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated | Dna−pk阻害剤 |
| US8461179B1 (en) | 2012-06-07 | 2013-06-11 | Deciphera Pharmaceuticals, Llc | Dihydronaphthyridines and related compounds useful as kinase inhibitors for the treatment of proliferative diseases |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| US9790210B2 (en) | 2012-11-13 | 2017-10-17 | Array Biopharma Inc. | N-(monocyclic aryl),N'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| US9809578B2 (en) | 2012-11-13 | 2017-11-07 | Array Biopharma Inc. | Pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trkA kinase inhibitors |
| WO2014078372A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| US9981959B2 (en) | 2012-11-13 | 2018-05-29 | Array Biopharma Inc. | Thiazolyl and oxazolyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| HRP20161613T1 (hr) | 2012-11-13 | 2017-01-13 | Array Biopharma, Inc. | Tvari bicikličke ureje, tioureje, gvanidina i cijanogvanidina korisne za liječenje boli |
| US9969694B2 (en) | 2012-11-13 | 2018-05-15 | Array Biopharma Inc. | N-(arylalkyl)-N′-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| WO2014078328A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-bicyclic aryl,n'-pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| MY178262A (en) | 2012-11-13 | 2020-10-07 | Array Biopharma Inc | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078378A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078408A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Bicyclic heteroaryl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| SI3527563T1 (sl) | 2013-03-12 | 2022-01-31 | Vertex Pharmaceuticals Incorporated | Inhibitorji DNA-PK |
| RU2675270C2 (ru) | 2013-10-17 | 2018-12-18 | Вертекс Фармасьютикалз Инкорпорейтед | Сокристаллы и содержащие их фармацевтические композиции |
| MX382781B (es) | 2014-04-02 | 2025-03-13 | Intermune Inc | Piridinonas anti-fibroticas. |
| CA2949160C (en) | 2014-05-15 | 2023-03-21 | Array Biopharma Inc. | 1-((3s,4r)-4-(3-fluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)-3-(4-methyl-3-(2-methylpyrimidin-5-yl)-1-phenyl-1h-pyrazol-5-yl)urea as a trka kinase inhibitor |
| HRP20220522T1 (hr) | 2014-08-04 | 2022-06-10 | Nuevolution A/S | Proizvoljno kondenzirani heterociklil-supstituirani derivati pirimidina koji su korisni za liječenje upalnih, metaboličkih, onkoloških i autoimunih bolesti |
| US11214565B2 (en) | 2015-11-20 | 2022-01-04 | Denali Therapeutics Inc. | Compound, compositions, and methods |
| WO2017151409A1 (en) | 2016-02-29 | 2017-09-08 | University Of Florida Research Foundation, Incorporated | Chemotherapeutic methods |
| US11028080B2 (en) | 2016-03-11 | 2021-06-08 | Denali Therapeutics Inc. | Substituted pyrimidines as LRKK2 inhibitors |
| MD3472153T2 (ro) | 2016-06-16 | 2022-03-31 | Denali Therapeutics Inc | Pirimidin-2-ilamino-1H-pirazoli în calitate de inhibitori L RRK2 pentru utilizare în tratamentul tulburărilor neurodegenerative |
| RU2758669C2 (ru) | 2016-09-27 | 2021-11-01 | Вертекс Фармасьютикалз Инкорпорейтед | Способ лечения рака с применением сочетания днк-поражающих агентов и ингибиторов днк-пк |
| CN108203450B (zh) * | 2016-12-19 | 2020-05-19 | 南京工业大学 | 一种含氨基膦酸酯芳基吡唑类化合物的制备方法及应用 |
| GB201721185D0 (en) | 2017-12-18 | 2018-01-31 | Nodthera Ltd | Sulphonyl urea derivatives |
| KR102708177B1 (ko) | 2018-01-31 | 2024-09-23 | 데시페라 파마슈티칼스, 엘엘씨. | 위장관 기질 종양의 치료를 위한 병용 요법 |
| IL276398B2 (en) | 2018-01-31 | 2026-03-01 | Deciphera Pharmaceuticals Llc | Combination therapy for mastocytosis |
| TWI767148B (zh) | 2018-10-10 | 2022-06-11 | 美商弗瑪治療公司 | 抑制脂肪酸合成酶(fasn) |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| WO2020113094A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| SMT202500389T1 (it) | 2018-12-28 | 2025-11-10 | Deciphera Pharmaceuticals Llc | Inibitori di csf1r per l'uso nel trattamento di tumori tenosinoviali a cellule giganti |
| WO2020168197A1 (en) | 2019-02-15 | 2020-08-20 | Incyte Corporation | Pyrrolo[2,3-d]pyrimidinone compounds as cdk2 inhibitors |
| WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| EP3938363A1 (en) | 2019-03-11 | 2022-01-19 | Teva Pharmaceuticals International GmbH | Solid state forms of ripretinib |
| WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
| US11440914B2 (en) | 2019-05-01 | 2022-09-13 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| WO2020223558A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | Tricyclic amine compounds as cdk2 inhibitors |
| MX2021013662A (es) | 2019-05-10 | 2022-03-11 | Deciphera Pharmaceuticals Llc | Inhibidores de la autofagia de heteroarilaminopirimidina amida y metodos de uso de estos. |
| EP3966207B1 (en) | 2019-05-10 | 2023-11-01 | Deciphera Pharmaceuticals, LLC | Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereof |
| PL3983387T3 (pl) | 2019-06-12 | 2024-08-19 | NodThera Limited | Pochodne sulfonylomocznika i ich zastosowania |
| IL325201A (en) | 2019-06-17 | 2026-02-01 | Deciphera Pharmaceuticals Llc | Aminopyrimidine amide autophagy inhibitors and methods of using them |
| PT4013412T (pt) | 2019-08-12 | 2026-03-18 | Deciphera Pharmaceuticals Llc | Ripretinib para o tratamento de tumores estromais gastrointestinais |
| LT4013412T (lt) | 2019-08-12 | 2026-03-25 | Deciphera Pharmaceuticals, Llc | Ripretinibas, skirtas virškinamojo trakto stromos navikų gydymui |
| TW202115024A (zh) | 2019-08-14 | 2021-04-16 | 美商英塞特公司 | 作為cdk2 抑制劑之咪唑基嘧啶基胺化合物 |
| CN112574201B (zh) * | 2019-09-29 | 2024-04-19 | 四川科伦博泰生物医药股份有限公司 | 芳基胺类化合物、包含其的药物组合物及其制备方法和用途 |
| AU2020364007A1 (en) | 2019-10-11 | 2022-04-28 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| US11685727B2 (en) | 2019-12-20 | 2023-06-27 | Nuevolution A/S | Compounds active towards nuclear receptors |
| MX2022007265A (es) | 2019-12-20 | 2022-09-09 | Nuevolution As | Compuestos activos frente a receptores nucleares. |
| CN115243681B (zh) | 2019-12-30 | 2024-08-16 | 德西费拉制药有限责任公司 | 1-(4-溴-5-(1-乙基-7-(甲氨基)-2-侧氧基-1,2-二氢-1,6-萘啶-3-基)-2-氟苯基)-3-苯基脲的组合物 |
| HRP20231699T1 (hr) | 2019-12-30 | 2024-05-10 | Deciphera Pharmaceuticals, Llc | Formulacije inhibitora amorfne kinaze i postupci njihove primjene |
| EP4126874A1 (en) | 2020-03-31 | 2023-02-08 | Nuevolution A/S | Compounds active towards nuclear receptors |
| CA3174176A1 (en) | 2020-03-31 | 2021-10-07 | Sanne Schroder Glad | Compounds active towards nuclear receptors |
| MX2023005747A (es) | 2020-11-18 | 2023-07-28 | Deciphera Pharmaceuticals Llc | Inhibidores de gcn2 y perk quinasas y metodos de uso de los mismos. |
| BR112023026747A2 (pt) | 2021-06-18 | 2024-03-12 | Aligos Therapeutics Inc | Métodos e composições para direcionamento de pd-l1 |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| KR20240113496A (ko) | 2021-12-03 | 2024-07-22 | 데시페라 파마슈티칼스, 엘엘씨. | Gcn2 및 perk 키나아제 억제제로서의 헤테로고리 화합물 |
| US12319655B2 (en) | 2021-12-09 | 2025-06-03 | Deciphera Pharmaceuticals, Llc | RAF kinase inhibitors and methods of use thereof |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| CA3240346A1 (en) | 2021-12-16 | 2023-06-22 | Aligos Therapeutics, Inc. | Methods and compositions for targeting pd-l1 |
| EP4448492B1 (en) | 2021-12-17 | 2026-03-04 | Reglagene, Inc. | Compositions and methods of making and using small molecules in the treatment of cancer |
| US11779572B1 (en) | 2022-09-02 | 2023-10-10 | Deciphera Pharmaceuticals, Llc | Methods of treating gastrointestinal stromal tumors |
| US12215102B2 (en) | 2023-02-28 | 2025-02-04 | Reglagene, Inc. | Compositions and methods for making and using small molecules for tubulin-targeted therapy in the treatment of cancers and related conditions |
| WO2025122952A1 (en) | 2023-12-08 | 2025-06-12 | Deciphera Pharmaceuticals, Llc | Formulations of vimseltinib |
| US20250206720A1 (en) | 2023-12-08 | 2025-06-26 | Deciphera Pharmaceuticals, Llc | Solid forms of an ulk inhibitor |
| WO2025231106A1 (en) | 2024-05-01 | 2025-11-06 | Deciphera Pharmaceuticals, Llc | Csf-1r inhibitors and methods of use thereof |
Family Cites Families (123)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US186221A (en) * | 1877-01-16 | Improvement in time-locks | ||
| US181411A (en) * | 1876-08-22 | Improvement in frame-squaring tools | ||
| US8898A (en) * | 1852-04-20 | Improved device for casting circle-plates, roses | ||
| DE1115350B (de) | 1959-04-17 | 1961-10-19 | Siemens Ag | Selbstschalter, insbesondere Leitungsschutz-schalter, mit einem aus einem Kniegelenk bestehenden Antriebsmechanismus fuer das Schaltorgan |
| GB971307A (en) | 1961-03-02 | 1964-09-30 | Wellcome Found | 5-anilinopyrimidines |
| DE1670701A1 (de) | 1966-05-23 | 1970-11-12 | Bayer Ag | Verfahren zur Darstellung von Thiaimidazolidinen |
| GB1127875A (en) | 1967-03-23 | 1968-09-18 | Parke Davis & Co | 4-(5-nitro-2-furyl) thiazolyl hydantoins and hydrouracils |
| DE2156343A1 (de) | 1970-11-13 | 1972-05-18 | Ici Ltd | Aromatische Polymere und Verfahren zu deren Herstellung |
| US3818024A (en) * | 1972-02-16 | 1974-06-18 | Velsicol Chemical Corp | Benzothiazol substituted thiadiazolidines |
| CH565887A5 (https=) | 1972-08-22 | 1975-08-29 | Ciba Geigy Ag | |
| US3939122A (en) * | 1973-04-11 | 1976-02-17 | Bayer Aktiengesellschaft | Process for the preparation of compounds which contain hydantoin rings |
| FR2337554A1 (fr) | 1976-01-08 | 1977-08-05 | Buzas Andre | Nouveaux derives de la pyrazolidinedione |
| US4093624A (en) * | 1977-01-31 | 1978-06-06 | Icn Pharmaceuticals, Inc. | 1,2,4-Thiadiazolidine-3,5-dione |
| FR2396549A2 (fr) | 1977-07-06 | 1979-02-02 | Buzas Andre | Nouveaux derives de la pyrazolidinedione |
| GB2036480B (en) | 1977-08-02 | 1982-06-03 | Western Electric Co | Reversible analogue to digital converter with high precision |
| US4256758A (en) | 1979-06-11 | 1981-03-17 | Merck & Co., Inc. | 4-Substituted-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase |
| US4296237A (en) * | 1979-09-11 | 1981-10-20 | Merck & Co., Inc. | 4-(Pyridyl, piperazinyl and thiazolyl substituted thiazolyl)-3-hydroxy-3-pyrroline-2,5-diones |
| US4298743A (en) | 1979-09-11 | 1981-11-03 | Merck & Co., Inc. | 4-(Substituted phenyl thiazolyl)-3-hydroxy-3-pyrroline-2,5-diones |
| US4432992A (en) * | 1979-11-05 | 1984-02-21 | Merck & Co., Inc. | 4-[5(and 4)-Substituted-2-thienyl]-3-hydroxy-3-pyrroline-2,5-dione inhibitors of glycolic acid oxidase |
| US4366189A (en) | 1979-12-21 | 1982-12-28 | Ciba-Geigy Corporation | 4-Heterocyclyl-4'-vinylstilbenes |
| JPS5915247A (ja) | 1982-07-16 | 1984-01-26 | Mitsubishi Paper Mills Ltd | 画像形成方法 |
| JPS59177557A (ja) | 1983-03-28 | 1984-10-08 | Fuji Photo Film Co Ltd | ハロゲン化銀カラ−写真感光材料 |
| DE3406329A1 (de) | 1984-02-22 | 1985-08-22 | Merck Patent Gmbh, 6100 Darmstadt | Pyridone |
| US4816454A (en) * | 1984-09-21 | 1989-03-28 | Cassella Aktiengesellschaft | 4,5-dihydro-3(2H)-pyridazinones and their pharmacological use |
| US5103014A (en) * | 1987-09-30 | 1992-04-07 | American Home Products Corporation | Certain 3,3'-[[[(2-phenyl-4-thiazolyl)methoxy]phenyl]methylene]dithiobis-propanoic acid derivatives |
| AU606808B2 (en) | 1988-06-29 | 1991-02-14 | Otsuka Pharmaceutical Factory, Inc. | Arylcarboxamide substituted by alkylphosphonates, process for preparing the same and a pharmaceutical composition containing the same |
| US5235786A (en) * | 1989-11-06 | 1993-08-17 | Mitsubishi Jukogyo Kabushiki Kaisha | Hourglass worm gear |
| GB9012936D0 (en) | 1990-06-11 | 1990-08-01 | Fujisawa Pharmaceutical Co | Thiophene derivatives,processes for preparation thereof and pharmaceutical composition comprising the same |
| US5254715A (en) | 1990-11-07 | 1993-10-19 | Warner-Lambert Company | Aminosulfonyl carbamates |
| ATE157355T1 (de) | 1991-01-21 | 1997-09-15 | Shionogi & Co | 3-benzyliden-1-carbamoyl-2-pyrrolidon-analoga |
| US5162360A (en) | 1991-06-24 | 1992-11-10 | Warner-Lambert Company | 2-heteroatom containing urea and thiourea ACAT inhibitors |
| GB9816837D0 (en) | 1998-08-04 | 1998-09-30 | Zeneca Ltd | Amide derivatives |
| TW225528B (https=) * | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| EP0656768A4 (en) | 1992-08-20 | 1996-03-06 | Lipomatrix Inc | PENIAL IMPLANT WITH TRIGLYCERIDIC LOAD. |
| DE4302702A1 (de) | 1993-02-01 | 1994-08-04 | Bayer Ag | Arylaminosulfonylharnstoffe |
| CA2159344A1 (en) | 1993-03-30 | 1994-10-13 | Minoru Moriwaki | Cell adhesion inhibitor and thienotriazolodiazepine compound |
| WO1994024095A1 (en) | 1993-04-16 | 1994-10-27 | Abbott Laboratories | Immunosuppressive agents |
| CA2123728A1 (en) * | 1993-05-21 | 1994-11-22 | Noriyoshi Sueda | Urea derivatives and their use as acat inhibitors |
| NO932986L (no) | 1993-08-20 | 1995-02-21 | Leiv Sandvik | Anordning ved nakkestötte |
| DE4337847A1 (de) | 1993-11-05 | 1995-05-11 | Bayer Ag | Substituierte Phenylaminosulfonylharnstoffe |
| EP0733048A1 (en) | 1993-12-07 | 1996-09-25 | Smithkline Beecham Plc | Heterocyclic biphenylylamides useful as 5ht1d antagonists |
| DE4343831A1 (de) | 1993-12-22 | 1995-06-29 | Magyar Tudomanyos Akademia | Substituierte Sulfonylharnstoffe |
| FR2715155B1 (fr) | 1994-01-19 | 1996-07-26 | Mayoly Spindler | Inhibiteurs de la monoamine oxydase B et leurs procédés de préparation. |
| DE4414840A1 (de) | 1994-04-28 | 1995-11-02 | Bayer Ag | Substituierte Phenylaminosulfonylharnstoffe |
| ES2199251T3 (es) | 1994-06-15 | 2004-02-16 | Otsuka Pharmaceutical Company, Limited | Derivados benzoheterociclicos utilizables como moduladores de vasopresina o de oxitocina. |
| ES2193205T3 (es) | 1994-11-24 | 2003-11-01 | Basilea Pharmaceutica Ag | Nuevas bencil pirimidinas. |
| US5494925A (en) * | 1994-12-02 | 1996-02-27 | Sterling Winthrop Inc. | 2-heterocyclyloxymethyl and 2-heterocyclylthiomethyl-1,2,5-thiadiazolidin-3-one 1,1-dioxides and compositions and method of use thereof |
| PL321048A1 (en) | 1994-12-22 | 1997-11-24 | Smithkline Beecham Plc | Tetracyclic spiro- compounds, method of obtaining them and their application as antagonists of 5ht1d receptors |
| KR100423818B1 (ko) | 1995-04-24 | 2004-07-05 | 가부시키가이샤 한도오따이 에네루기 켄큐쇼 | 액정화합물및이를함유하는액정조성물 |
| JPH09221476A (ja) | 1995-12-15 | 1997-08-26 | Otsuka Pharmaceut Co Ltd | 医薬組成物 |
| GB9605945D0 (en) | 1996-03-21 | 1996-05-22 | Smithkline Beecham Plc | Novel compounds |
| JPH107804A (ja) | 1996-06-25 | 1998-01-13 | Japan Synthetic Rubber Co Ltd | 熱硬化性樹脂組成物 |
| US6174905B1 (en) * | 1996-09-30 | 2001-01-16 | Mitsui Chemicals, Inc. | Cell differentiation inducer |
| GB9623833D0 (en) | 1996-11-16 | 1997-01-08 | Zeneca Ltd | Chemical compound |
| US6020357A (en) * | 1996-12-23 | 2000-02-01 | Dupont Pharmaceuticals Company | Nitrogen containing heteroaromatics as factor Xa inhibitors |
| ATE230742T1 (de) | 1997-03-27 | 2003-01-15 | Great Lakes Chemical Europ | 2-(2'-hydroxphenyl)-benzotriazole und ihre verwendung als lichtschutzmittel für organische polymere |
| WO1998052558A1 (en) | 1997-05-23 | 1998-11-26 | Bayer Corporation | INHIBITION OF p38 KINASE ACTIVITY BY ARYL UREAS |
| US6235786B1 (en) | 1997-08-06 | 2001-05-22 | Abbott Laboratories | Reverse hydroxamate inhibitors of matrix metalloproteinases |
| US6294573B1 (en) * | 1997-08-06 | 2001-09-25 | Abbott Laboratories | Reverse hydroxamate inhibitors of matrix metalloproteinases |
| AU739066B2 (en) | 1997-09-23 | 2001-10-04 | Astrazeneca Ab | Amide derivatives for the treatment of diseases mediated by cytokines |
| IT1295933B1 (it) | 1997-10-30 | 1999-05-28 | Great Lakes Chemical Italia | 2-(2'-idrossifenil)benzotriazoli e procedimento per la loro preparazione |
| WO1999023091A1 (en) | 1997-11-03 | 1999-05-14 | Boehringer Ingelheim Pharmaceuticals, Inc. | Aromatic heterocyclic compounds as anti-inflammatory agents |
| MXPA00006233A (es) | 1997-12-22 | 2002-09-18 | Bayer Ag | Inhibicion de la actividad de la cinasa p38 utilizando ureas heterociclicas sustituidas. |
| DE69836563T2 (de) | 1997-12-22 | 2007-05-16 | Bayer Pharmaceuticals Corp., West Haven | INHIBIERUNG DER p38 KINASE-AKTIVITÄT DURCH DIE VERWENDUNG VON ARYL- UND HETEROARYL-SUBSTITUIERTEN HARNSTOFFEN |
| ID26328A (id) | 1997-12-22 | 2000-12-14 | Bayer Ag | Penghambat raf kinase menggunakan urea heterosiklik tersubstitusi aril dan heteroaril |
| SK286213B6 (sk) | 1997-12-22 | 2008-05-06 | Bayer Corporation | Substituované heterocyklické močoviny, farmaceutický prípravok ich obsahujúci a ich použitie |
| US6887893B1 (en) | 1997-12-24 | 2005-05-03 | Sankyo Company, Limited | Methods and compositions for treatment and prevention of tumors, tumor-related disorders and cachexia |
| JPH11209350A (ja) | 1998-01-26 | 1999-08-03 | Eisai Co Ltd | 含窒素複素環誘導体およびその医薬 |
| ES2189079T3 (es) | 1998-04-24 | 2003-07-01 | Leuven K U Res & Dev | Efectos inmunosupresores de derivados de xantina 8-sustituidos. |
| CA2328927C (en) | 1998-05-15 | 2008-02-19 | Astrazeneca Ab | Benzamide derivatives for the treatment of diseases mediated by cytokines |
| CN1332943C (zh) | 1998-07-08 | 2007-08-22 | 萨诺费-阿文蒂斯德国有限公司 | 硫取代的磺酰基氨基羧酸n-芳基酰胺,其制备方法、用途以及含有该化合物的药物制剂 |
| US6197599B1 (en) | 1998-07-30 | 2001-03-06 | Guorong Chin | Method to detect proteins |
| WO2000006550A1 (en) | 1998-07-31 | 2000-02-10 | Nippon Soda Co., Ltd. | Phenylazole compounds, process for producing the same and drugs for hyperlipemia |
| JP3602343B2 (ja) * | 1998-09-02 | 2004-12-15 | アルプス電気株式会社 | 表示装置 |
| EP1115707B1 (en) | 1998-09-25 | 2003-11-12 | AstraZeneca AB | Benzamide derivatives and ther use as cytokine inhibitors |
| ATE284387T1 (de) | 1998-10-08 | 2004-12-15 | Smithkline Beecham Plc | 3-(3-chloro-4-hydroxyphenylamino)-4-(2- nitrophenyl)-1h-pyrrol-2,5-dion als glykogen synthase kinase-3 inhibitor (gsk-3) |
| ATE538794T1 (de) | 1999-01-13 | 2012-01-15 | Bayer Healthcare Llc | Gamma carboxyarylsubstituierte diphenylharnstoffverbindungen als p38 kinasehemmer |
| UA73492C2 (en) | 1999-01-19 | 2005-08-15 | Aromatic heterocyclic compounds as antiinflammatory agents | |
| NZ528846A (en) * | 1999-03-12 | 2005-05-27 | Boehringer Ingelheim Pharma | Compounds useful as anti-inflammatory agents |
| JP2000275886A (ja) | 1999-03-23 | 2000-10-06 | Konica Corp | 電子写真感光体、それを用いたプロセスカートリッジ及び画像形成装置 |
| US6548529B1 (en) | 1999-04-05 | 2003-04-15 | Bristol-Myers Squibb Company | Heterocyclic containing biphenyl aP2 inhibitors and method |
| US6410254B1 (en) | 1999-05-18 | 2002-06-25 | Cytokinetics | Compositions and assays utilizing ADP or phosphate for detecting protein modulators |
| JP3972163B2 (ja) | 1999-06-18 | 2007-09-05 | 株式会社大塚製薬工場 | ホスホン酸ジエステル誘導体 |
| US6441005B1 (en) * | 1999-07-28 | 2002-08-27 | Pharmacia & Upjohn Company | Oxazolidinone compounds and compositions, and methods of using the same |
| MXPA02001565A (es) | 1999-08-13 | 2005-07-14 | Vertex Pharma | Inhibidores de cinasas c-jun n-terminal (jnk) y de otras cinasas proteicas. |
| AR035016A1 (es) | 1999-08-25 | 2004-04-14 | Takeda Chemical Industries Ltd | Composicion de azol promotor de produccion/secrecion de neurotrofina, compuesto prodroga del mismo, composicion farmaceutica que lo comprende y uso del mismo para preparar esta ultima. |
| JP4316787B2 (ja) | 2000-01-11 | 2009-08-19 | 壽製薬株式会社 | エーテル又はアミド誘導体、その製法並びにそれを含有する糖尿病治療剤、 |
| US6525046B1 (en) | 2000-01-18 | 2003-02-25 | Boehringer Ingelheim Pharmaceuticals, Inc. | Aromatic heterocyclic compounds as antiinflammatory agents |
| GB0008264D0 (en) | 2000-04-04 | 2000-05-24 | Smithkline Beecham Plc | Novel method and compounds |
| US6500628B1 (en) | 2000-05-25 | 2002-12-31 | Millennium Pharmaceuticals, Inc. | Nucleic acid molecules encoding human kinase and phosphatase homologues and uses therefor |
| CA2411495A1 (en) | 2000-06-14 | 2001-12-20 | Warner-Lambert Company | 1,2,4-trisubstituted benzenes as inhibitors of 15-lipoxygenase |
| US6787552B2 (en) | 2000-08-11 | 2004-09-07 | Nippon Chemiphar Co., Ltd. | PPAR delta activators |
| US6645990B2 (en) * | 2000-08-15 | 2003-11-11 | Amgen Inc. | Thiazolyl urea compounds and methods of uses |
| US20020173507A1 (en) * | 2000-08-15 | 2002-11-21 | Vincent Santora | Urea compounds and methods of uses |
| PL362546A1 (en) | 2000-10-05 | 2004-11-02 | Fujisawa Pharmaceutical Co, Ltd. | Benzamide compounds as apo b secretion inhibitors |
| JP2004530648A (ja) | 2000-10-19 | 2004-10-07 | スミスクライン・ビーチャム・コーポレイション | 炎症により促進される咳の治療のためのp38阻害剤の使用 |
| AU1826202A (en) | 2000-10-27 | 2002-05-06 | Novartis Ag | Treatment of gastrointestinal stromal tumors |
| CA2429426A1 (en) | 2000-11-17 | 2002-05-23 | Takeda Chemical Industries, Ltd. | Isoxazole derivatives |
| JP2002226464A (ja) | 2001-01-30 | 2002-08-14 | Sumitomo Pharmaceut Co Ltd | トリアリール類縁体およびその利用 |
| EP1362037A1 (en) * | 2001-02-15 | 2003-11-19 | Boehringer Ingelheim Pharmaceuticals Inc. | Process for synthesis of heteroaryl-substituted urea compounds useful as antiinflammatory agents |
| DE60239097D1 (de) | 2001-03-02 | 2011-03-17 | Gpc Biotech Ag | Drei-hybrid-assaysystem |
| WO2003000189A2 (en) | 2001-06-21 | 2003-01-03 | Baylor College Of Medicine | Prediction, diagnosis and treatment of endocrine resistant breast cancer, using p38 mapk pathway |
| EP1281399A3 (en) | 2001-08-01 | 2004-02-11 | Warner-Lambert Company | Dual inhibitors of wax ester and cholesteryl ester synthesis for inhibiting sebum production |
| JP2005503400A (ja) * | 2001-09-13 | 2005-02-03 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | サイトカイン媒介病の治療方法 |
| CN1596240A (zh) | 2001-12-19 | 2005-03-16 | 阿特罗吉尼克斯公司 | 查耳酮衍生物及其治疗疾病的用途 |
| AU2003207961A1 (en) | 2002-01-16 | 2003-07-30 | Ramot At Tel Aviv University Ltd. | Compositions and their use for enhancing and inhibiting fertilization |
| KR100611854B1 (ko) | 2002-02-28 | 2006-08-11 | 에프. 호프만-라 로슈 아게 | 신경 펩타이드 y(npy) 수용체 길항제로서의 티아졸유도체 |
| DE60319073T2 (de) | 2002-03-20 | 2009-02-05 | Elan Pharma International Ltd. | Nanopartikelzusammensetzungen von mitogen-aktivierten protein (map) kinase inhibitoren |
| US20030186221A1 (en) | 2002-04-02 | 2003-10-02 | Lockhart David J. | Phage display affinity filter and forward screen |
| US20030225089A1 (en) * | 2002-04-10 | 2003-12-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and p38 kinase inhibitors |
| TWI298478B (en) * | 2002-06-15 | 2008-07-01 | Samsung Electronics Co Ltd | Method of driving a shift register, a shift register, a liquid crystal display device having the shift register |
| US20040138216A1 (en) | 2002-12-23 | 2004-07-15 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Process for the preparation of an essentially pure polymorph of an n-pyrazolyl-n'-naphthyl-urea |
| US20080045706A1 (en) | 2002-12-31 | 2008-02-21 | Flynn Daniel L | Anti-inflammatory medicaments |
| US20040171075A1 (en) | 2002-12-31 | 2004-09-02 | Flynn Daniel L | Modulation of protein functionalities |
| US7202257B2 (en) | 2003-12-24 | 2007-04-10 | Deciphera Pharmaceuticals, Llc | Anti-inflammatory medicaments |
| US7144911B2 (en) | 2002-12-31 | 2006-12-05 | Deciphera Pharmaceuticals Llc | Anti-inflammatory medicaments |
| KR100705617B1 (ko) * | 2003-03-31 | 2007-04-11 | 비오이 하이디스 테크놀로지 주식회사 | 액정구동장치 |
| WO2004113352A1 (en) | 2003-06-19 | 2004-12-29 | Amedis Pharmaceuticals Ltd. | Silylated heterocyclylurea derivatives as cytokine-inhibitors |
| US20080220497A1 (en) | 2003-12-24 | 2008-09-11 | Flynn Daniel L | Modulation of protein functionalities |
| US20070191336A1 (en) | 2003-12-24 | 2007-08-16 | Flynn Daniel L | Anti-inflammatory medicaments |
| WO2006071940A2 (en) | 2004-12-23 | 2006-07-06 | Deciphera Pharmaceuticals, Llc | Enzyme modulators and treatments |
| US20080248487A1 (en) | 2007-04-09 | 2008-10-09 | Flynn Daniel L | Modulation of protein functionalities |
| US20080248548A1 (en) | 2007-04-09 | 2008-10-09 | Flynn Daniel L | Modulation of protein functionalities |
-
2003
- 2003-12-24 US US10/746,460 patent/US7144911B2/en not_active Expired - Fee Related
- 2003-12-26 AU AU2003303641A patent/AU2003303641A1/en not_active Abandoned
- 2003-12-26 EP EP03808576A patent/EP1585734A4/en not_active Withdrawn
- 2003-12-26 EP EP03814980A patent/EP1590344A4/en not_active Withdrawn
- 2003-12-26 BR BR0317872-2A patent/BR0317872A/pt not_active IP Right Cessation
- 2003-12-26 WO PCT/US2003/041449 patent/WO2004060306A2/en not_active Ceased
- 2003-12-26 MX MXPA05007236A patent/MXPA05007236A/es unknown
- 2003-12-26 WO PCT/US2003/041425 patent/WO2004060305A2/en not_active Ceased
- 2003-12-26 JP JP2005508625A patent/JP2006514691A/ja not_active Withdrawn
- 2003-12-26 CA CA002513627A patent/CA2513627A1/en not_active Abandoned
- 2003-12-30 TW TW092137451A patent/TW200427672A/zh unknown
-
2006
- 2006-01-20 US US11/337,245 patent/US20080187978A1/en not_active Abandoned
- 2006-06-09 US US11/450,851 patent/US20090137021A1/en not_active Abandoned
- 2006-06-09 US US11/450,842 patent/US20090105230A1/en not_active Abandoned
- 2006-06-09 US US11/450,850 patent/US7666895B2/en not_active Expired - Fee Related
- 2006-06-09 US US11/450,852 patent/US20090069310A1/en not_active Abandoned
- 2006-06-09 US US11/450,849 patent/US7737283B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021132577A1 (ja) * | 2019-12-27 | 2021-07-01 | 日本たばこ産業株式会社 | アシルスルファミド化合物及びその医薬用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20040180906A1 (en) | 2004-09-16 |
| US20080299639A1 (en) | 2008-12-04 |
| WO2004060306A3 (en) | 2005-07-28 |
| US20090075986A1 (en) | 2009-03-19 |
| EP1590344A4 (en) | 2007-08-29 |
| TW200427672A (en) | 2004-12-16 |
| CA2513627A1 (en) | 2004-07-22 |
| WO2004060306A2 (en) | 2004-07-22 |
| US20090069310A1 (en) | 2009-03-12 |
| WO2004060305A2 (en) | 2004-07-22 |
| EP1590344A2 (en) | 2005-11-02 |
| US7666895B2 (en) | 2010-02-23 |
| BR0317872A (pt) | 2005-12-06 |
| US20090105230A1 (en) | 2009-04-23 |
| US7737283B2 (en) | 2010-06-15 |
| MXPA05007236A (es) | 2006-04-27 |
| US20090137021A1 (en) | 2009-05-28 |
| WO2004060305A3 (en) | 2005-02-10 |
| EP1585734A4 (en) | 2007-09-19 |
| US7144911B2 (en) | 2006-12-05 |
| AU2003303641A1 (en) | 2004-07-29 |
| EP1585734A2 (en) | 2005-10-19 |
| US20080187978A1 (en) | 2008-08-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2006514691A (ja) | 炎症を抑制する医薬 | |
| US7202257B2 (en) | Anti-inflammatory medicaments | |
| US7279576B2 (en) | Anti-cancer medicaments | |
| US20090312349A1 (en) | Anti-inflammatory medicaments | |
| US20070191336A1 (en) | Anti-inflammatory medicaments | |
| US12522601B2 (en) | 1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same | |
| CA2531418A1 (en) | Benzenesulfonylamino compounds and pharmaceutical compositions containing these compounds | |
| US20080045706A1 (en) | Anti-inflammatory medicaments | |
| JP2008526910A (ja) | 3,4,(5)−置換テトラヒドロピリジン | |
| CN1756747A (zh) | 抗炎症药物 | |
| CA2511840A1 (en) | Anti-cancer medicaments | |
| ZA200505268B (en) | Anti-inflammatory medicaments |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060608 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060803 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090209 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20090930 |