MXPA06002466A - Inhibidores heterociclicos de mek y metodos de uso de los mismos. - Google Patents
Inhibidores heterociclicos de mek y metodos de uso de los mismos.Info
- Publication number
- MXPA06002466A MXPA06002466A MXPA06002466A MXPA06002466A MXPA06002466A MX PA06002466 A MXPA06002466 A MX PA06002466A MX PA06002466 A MXPA06002466 A MX PA06002466A MX PA06002466 A MXPA06002466 A MX PA06002466A MX PA06002466 A MXPA06002466 A MX PA06002466A
- Authority
- MX
- Mexico
- Prior art keywords
- heteroaryl
- aryl
- heterocyclyl
- arylalkyl
- alkyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 101
- 125000000623 heterocyclic group Chemical group 0.000 title claims description 181
- 239000003112 inhibitor Substances 0.000 title description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 254
- 239000000651 prodrug Substances 0.000 claims abstract description 76
- 229940002612 prodrug Drugs 0.000 claims abstract description 76
- 150000003839 salts Chemical class 0.000 claims abstract description 54
- 241000124008 Mammalia Species 0.000 claims abstract description 52
- 238000011282 treatment Methods 0.000 claims abstract description 45
- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 28
- -1 phosphate ester Chemical class 0.000 claims description 175
- 125000001072 heteroaryl group Chemical group 0.000 claims description 162
- 125000003118 aryl group Chemical group 0.000 claims description 148
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 125
- 125000000217 alkyl group Chemical group 0.000 claims description 107
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 101
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 101
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 75
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 72
- 229910052801 chlorine Inorganic materials 0.000 claims description 66
- 229910052794 bromium Inorganic materials 0.000 claims description 64
- 125000003342 alkenyl group Chemical group 0.000 claims description 63
- 125000005843 halogen group Chemical group 0.000 claims description 63
- 229920006395 saturated elastomer Polymers 0.000 claims description 63
- 239000000203 mixture Substances 0.000 claims description 62
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 61
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 59
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 59
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 58
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 58
- 125000000304 alkynyl group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 35
- 125000002837 carbocyclic group Chemical group 0.000 claims description 28
- 125000004043 oxo group Chemical group O=* 0.000 claims description 28
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 23
- 125000004429 atom Chemical group 0.000 claims description 22
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 22
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims description 21
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims description 21
- 125000000539 amino acid group Chemical group 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 19
- 229910019142 PO4 Inorganic materials 0.000 claims description 17
- 239000012453 solvate Substances 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 239000010452 phosphate Substances 0.000 claims description 16
- 230000002401 inhibitory effect Effects 0.000 claims description 14
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 12
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 150000001413 amino acids Chemical class 0.000 claims description 6
- 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 claims description 5
- 102100039614 Nuclear receptor ROR-alpha Human genes 0.000 claims description 5
- 125000005647 linker group Chemical group 0.000 claims description 5
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 18
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 5
- 239000004474 valine Substances 0.000 claims 5
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 1
- 125000004946 alkenylalkyl group Chemical group 0.000 claims 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 37
- 206010028980 Neoplasm Diseases 0.000 abstract description 25
- 201000010099 disease Diseases 0.000 abstract description 23
- 201000011510 cancer Diseases 0.000 abstract description 12
- 229910052727 yttrium Inorganic materials 0.000 abstract description 11
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 abstract description 5
- 206010061218 Inflammation Diseases 0.000 abstract description 2
- 230000004054 inflammatory process Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 214
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 152
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 136
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
- 239000000243 solution Substances 0.000 description 109
- 239000000047 product Substances 0.000 description 103
- 230000015572 biosynthetic process Effects 0.000 description 92
- 238000006243 chemical reaction Methods 0.000 description 92
- 239000000460 chlorine Substances 0.000 description 91
- 238000002360 preparation method Methods 0.000 description 91
- 238000003786 synthesis reaction Methods 0.000 description 90
- 235000019439 ethyl acetate Nutrition 0.000 description 88
- 238000005481 NMR spectroscopy Methods 0.000 description 81
- 239000007787 solid Substances 0.000 description 79
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 79
- 239000011541 reaction mixture Substances 0.000 description 72
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 68
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 64
- 239000002253 acid Substances 0.000 description 62
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 53
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- 239000012267 brine Substances 0.000 description 50
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 50
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- 239000012044 organic layer Substances 0.000 description 37
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 34
- 238000003818 flash chromatography Methods 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 31
- 238000000746 purification Methods 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000000725 suspension Substances 0.000 description 29
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
- 238000003756 stirring Methods 0.000 description 28
- 150000002148 esters Chemical class 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 22
- 239000007788 liquid Substances 0.000 description 21
- 101150041968 CDC13 gene Proteins 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 17
- 239000008194 pharmaceutical composition Substances 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- 239000000284 extract Substances 0.000 description 16
- 150000004702 methyl esters Chemical class 0.000 description 16
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 14
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 14
- 150000001412 amines Chemical class 0.000 description 14
- 230000008878 coupling Effects 0.000 description 14
- 238000010168 coupling process Methods 0.000 description 14
- 238000005859 coupling reaction Methods 0.000 description 14
- 208000035475 disorder Diseases 0.000 description 14
- 239000003960 organic solvent Substances 0.000 description 14
- 238000010561 standard procedure Methods 0.000 description 14
- 239000007832 Na2SO4 Substances 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 238000007363 ring formation reaction Methods 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
- 230000002159 abnormal effect Effects 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- HSFNEBWXUWQGNW-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-n-(2-hydroxyethoxy)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound OCCONC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl HSFNEBWXUWQGNW-UHFFFAOYSA-N 0.000 description 11
- 230000010261 cell growth Effects 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 11
- 150000003254 radicals Chemical class 0.000 description 11
- RZRBEUMGDQTYNA-UHFFFAOYSA-N 4-(4-bromo-2-chloroanilino)-5,6-dichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)C(Cl)=C1NC1=CC=C(Br)C=C1Cl RZRBEUMGDQTYNA-UHFFFAOYSA-N 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 9
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
- 238000004293 19F NMR spectroscopy Methods 0.000 description 9
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- YLPFLKCGZGXPFI-UHFFFAOYSA-N methyl 6-amino-4-(4-bromo-2-chloroanilino)-5-chloropyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(N)C(Cl)=C1NC1=CC=C(Br)C=C1Cl YLPFLKCGZGXPFI-UHFFFAOYSA-N 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 8
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- ILMIEWNDXAKVNI-UHFFFAOYSA-N 4,6-dichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)C=C1Cl ILMIEWNDXAKVNI-UHFFFAOYSA-N 0.000 description 7
- SPWOSOVUCYTNGI-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-fluoroimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C(F)=C1NC1=CC=C(Br)C=C1Cl SPWOSOVUCYTNGI-UHFFFAOYSA-N 0.000 description 7
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 239000007859 condensation product Substances 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- 239000003102 growth factor Substances 0.000 description 7
- 150000002443 hydroxylamines Chemical class 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- YHNRUSMOYCDMJS-UHFFFAOYSA-N o-(cyclopropylmethyl)hydroxylamine Chemical compound NOCC1CC1 YHNRUSMOYCDMJS-UHFFFAOYSA-N 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- MIIQJAUWHSUTIT-UHFFFAOYSA-N 1,2-oxazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=NO1 MIIQJAUWHSUTIT-UHFFFAOYSA-N 0.000 description 6
- QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 6
- GONDNJRVKJZYEK-UHFFFAOYSA-N 3-benzyl-7-(4-bromo-2-chloroanilino)-8-chloro-n-(cyclopropylmethoxy)-[1,2,4]triazolo[4,3-a]pyridine-6-carboxamide Chemical compound ClC1=CC(Br)=CC=C1NC(C(=CN12)C(=O)NOCC3CC3)=C(Cl)C1=NN=C2CC1=CC=CC=C1 GONDNJRVKJZYEK-UHFFFAOYSA-N 0.000 description 6
- QPUQVLGZNFJHCD-UHFFFAOYSA-N 6-(2-chloroanilino)-7-fluoro-3-methyl-2,1-benzoxazole-5-carboxylic acid Chemical compound OC(=O)C1=CC2=C(C)ON=C2C(F)=C1NC1=CC=CC=C1Cl QPUQVLGZNFJHCD-UHFFFAOYSA-N 0.000 description 6
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 230000005595 deprotonation Effects 0.000 description 6
- 238000010537 deprotonation reaction Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 229930195733 hydrocarbon Natural products 0.000 description 6
- 230000000670 limiting effect Effects 0.000 description 6
- 239000002207 metabolite Substances 0.000 description 6
- SUUIBASDMLZZPY-UHFFFAOYSA-N methyl 5-acetyl-2-(2-chloroanilino)-3,4-difluorobenzoate Chemical compound COC(=O)C1=CC(C(C)=O)=C(F)C(F)=C1NC1=CC=CC=C1Cl SUUIBASDMLZZPY-UHFFFAOYSA-N 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 210000002307 prostate Anatomy 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 5
- ITYWODCTYSDDQT-UHFFFAOYSA-N 4-(4-bromo-2-chloroanilino)-6-chloropyridine-3-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CN=C(Cl)C=C1NC1=CC=C(Br)C=C1Cl ITYWODCTYSDDQT-UHFFFAOYSA-N 0.000 description 5
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 5
- CXNKXAGWACKPKC-UHFFFAOYSA-N 6-(4-bromo-2-chloroanilino)-7-fluoro-3-methyl-1,2-benzoxazole-5-carboxylic acid Chemical compound OC(=O)C=1C=C2C(C)=NOC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CXNKXAGWACKPKC-UHFFFAOYSA-N 0.000 description 5
- MTTNNRMJDBVLIC-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)imidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C=C1NC1=CC=C(Br)C=C1Cl MTTNNRMJDBVLIC-UHFFFAOYSA-N 0.000 description 5
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 5
- 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 5
- 241001274216 Naso Species 0.000 description 5
- 229910002666 PdCl2 Inorganic materials 0.000 description 5
- 102000001253 Protein Kinase Human genes 0.000 description 5
- 201000004681 Psoriasis Diseases 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 239000007900 aqueous suspension Substances 0.000 description 5
- MUTLQOJUSJVKRM-UHFFFAOYSA-N ethyl 4-(4-bromo-2-chloroanilino)-5-chloro-6-hydrazinylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(NN)C(Cl)=C1NC1=CC=C(Br)C=C1Cl MUTLQOJUSJVKRM-UHFFFAOYSA-N 0.000 description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- JEJMDUMJSZTJTI-UHFFFAOYSA-N methyl 4,6-dichloropyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(Cl)C=C1Cl JEJMDUMJSZTJTI-UHFFFAOYSA-N 0.000 description 5
- SVJXZVKROGVKAY-UHFFFAOYSA-N methyl 6-(2-chloroanilino)-7-fluoro-3-methyl-1,2-benzoxazole-5-carboxylate Chemical compound COC(=O)C1=CC=2C(C)=NOC=2C(F)=C1NC1=CC=CC=C1Cl SVJXZVKROGVKAY-UHFFFAOYSA-N 0.000 description 5
- LGIUQDSHXXLYCG-UHFFFAOYSA-N methyl 6-azido-4-(4-bromo-2-chloroanilino)-5-chloropyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(N=[N+]=[N-])C(Cl)=C1NC1=CC=C(Br)C=C1Cl LGIUQDSHXXLYCG-UHFFFAOYSA-N 0.000 description 5
- KHCYMZHRGVCYOE-UHFFFAOYSA-N n-(cyclopropylmethoxy)pyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)NOCC1CC1 KHCYMZHRGVCYOE-UHFFFAOYSA-N 0.000 description 5
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 235000021317 phosphate Nutrition 0.000 description 5
- 108060006633 protein kinase Proteins 0.000 description 5
- 238000007127 saponification reaction Methods 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 229940124530 sulfonamide Drugs 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 235000011149 sulphuric acid Nutrition 0.000 description 5
- IYCZHTKLJQLKMW-UHFFFAOYSA-N tert-butyl 6-amino-4-(4-bromo-2-chloroanilino)pyridine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CN=C(N)C=C1NC1=CC=C(Br)C=C1Cl IYCZHTKLJQLKMW-UHFFFAOYSA-N 0.000 description 5
- OAKQKBRICFLEPS-UHFFFAOYSA-N tert-butyl 6-azido-4-(4-bromo-2-chloroanilino)pyridine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CN=C(N=[N+]=[N-])C=C1NC1=CC=C(Br)C=C1Cl OAKQKBRICFLEPS-UHFFFAOYSA-N 0.000 description 5
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 5
- 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 4
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 4
- XQIATTAAVBLNAN-UHFFFAOYSA-N 5-bromo-2,3,4-trifluorobenzoic acid Chemical compound OC(=O)C1=CC(Br)=C(F)C(F)=C1F XQIATTAAVBLNAN-UHFFFAOYSA-N 0.000 description 4
- FVAGIKQSUOJNRT-UHFFFAOYSA-N 6-(2,4-dichloroanilino)-7-fluoro-3-methyl-1,2-benzoxazole-5-carboxylic acid Chemical compound OC(=O)C=1C=C2C(C)=NOC2=C(F)C=1NC1=CC=C(Cl)C=C1Cl FVAGIKQSUOJNRT-UHFFFAOYSA-N 0.000 description 4
- HDLYKTAZFYFKEW-UHFFFAOYSA-N 6-(2-chloroanilino)-7-fluoro-n-(2-hydroxyethoxy)-3-methyl-2,1-benzoxazole-5-carboxamide Chemical compound OCCONC(=O)C1=CC2=C(C)ON=C2C(F)=C1NC1=CC=CC=C1Cl HDLYKTAZFYFKEW-UHFFFAOYSA-N 0.000 description 4
- MCAHUWAGPMQWRK-UHFFFAOYSA-N 6-(4-bromo-2-chloroanilino)-7-fluoro-n-(2-hydroxyethoxy)-3-methyl-1,2-benzoxazole-5-carboxamide Chemical compound OCCONC(=O)C=1C=C2C(C)=NOC2=C(F)C=1NC1=CC=C(Br)C=C1Cl MCAHUWAGPMQWRK-UHFFFAOYSA-N 0.000 description 4
- ROIKTCFZWMIEEE-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-3-methyl-[1,2,4]triazolo[4,3-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C(C)=NN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl ROIKTCFZWMIEEE-UHFFFAOYSA-N 0.000 description 4
- MFPCSJJHFOEXPJ-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-n-(2-hydroxyethoxy)-3-methyl-[1,2,4]triazolo[4,3-a]pyridine-6-carboxamide Chemical compound OCCONC(=O)C1=CN2C(C)=NN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl MFPCSJJHFOEXPJ-UHFFFAOYSA-N 0.000 description 4
- DRRFUQMCLFJCDN-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl DRRFUQMCLFJCDN-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 4
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 4
- 102000043136 MAP kinase family Human genes 0.000 description 4
- 108091054455 MAP kinase family Proteins 0.000 description 4
- 229940124647 MEK inhibitor Drugs 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 4
- 150000003927 aminopyridines Chemical class 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
- 230000000340 anti-metabolite Effects 0.000 description 4
- 239000002256 antimetabolite Substances 0.000 description 4
- 229940100197 antimetabolite Drugs 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000000481 breast Anatomy 0.000 description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 229940043279 diisopropylamine Drugs 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 4
- 230000026030 halogenation Effects 0.000 description 4
- 238000005658 halogenation reaction Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- ILPCPKZAAQXHKL-UHFFFAOYSA-N methyl 1,2-oxazole-5-carboxylate Chemical compound COC(=O)C1=CC=NO1 ILPCPKZAAQXHKL-UHFFFAOYSA-N 0.000 description 4
- UPXZTUASRXFGEX-UHFFFAOYSA-N methyl 2-(2-chloroanilino)-5-cyano-3,4-difluorobenzoate Chemical compound COC(=O)C1=CC(C#N)=C(F)C(F)=C1NC1=CC=CC=C1Cl UPXZTUASRXFGEX-UHFFFAOYSA-N 0.000 description 4
- OVHUPKYGIWERSV-UHFFFAOYSA-N methyl 4-(4-bromo-2-chloroanilino)-5,6-dichloropyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(Cl)C(Cl)=C1NC1=CC=C(Br)C=C1Cl OVHUPKYGIWERSV-UHFFFAOYSA-N 0.000 description 4
- NETQKENPKCVDCZ-UHFFFAOYSA-N methyl 7-(4-bromo-2-chloroanilino)-8-chloro-3-formylimidazo[1,2-a]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN2C(C=O)=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl NETQKENPKCVDCZ-UHFFFAOYSA-N 0.000 description 4
- VHNBCNJMJRBOAN-UHFFFAOYSA-N methyl 7-(4-bromo-2-chloroanilino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl VHNBCNJMJRBOAN-UHFFFAOYSA-N 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 230000002611 ovarian Effects 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 238000005897 peptide coupling reaction Methods 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 150000003335 secondary amines Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 4
- 238000001665 trituration Methods 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 3
- 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 3
- GDRLWCPMLULBNF-UHFFFAOYSA-N 4,5,6-trichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)C(Cl)=C1Cl GDRLWCPMLULBNF-UHFFFAOYSA-N 0.000 description 3
- KWQACFCLUAMPDU-UHFFFAOYSA-N 6-(2-chloroanilino)-n-(cyclopropylmethoxy)-7-fluoro-3-methyl-2,1-benzoxazole-5-carboxamide Chemical compound C1CC1CONC(=O)C1=CC2=C(C)ON=C2C(F)=C1NC1=CC=CC=C1Cl KWQACFCLUAMPDU-UHFFFAOYSA-N 0.000 description 3
- CGRHABYUCHONCD-UHFFFAOYSA-N 6-(4-bromo-2-chloroanilino)-n-(cyclopropylmethoxy)-7-fluoro-3-methyl-1,2-benzoxazole-5-carboxamide Chemical compound C1CC1CONC(=O)C=1C=C2C(C)=NOC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CGRHABYUCHONCD-UHFFFAOYSA-N 0.000 description 3
- SXBDEFJKOQZBQW-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-n-(cyclopropylmethoxy)-3-(dimethylamino)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound C1CC1CONC(=O)C1=CN2C(N(C)C)=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl SXBDEFJKOQZBQW-UHFFFAOYSA-N 0.000 description 3
- JSQBQOZYGDHQLG-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-n-(cyclopropylmethoxy)-3-morpholin-4-ylimidazo[1,2-a]pyridine-6-carboxamide Chemical compound ClC1=CC(Br)=CC=C1NC(C(=CN12)C(=O)NOCC3CC3)=C(Cl)C1=NC=C2N1CCOCC1 JSQBQOZYGDHQLG-UHFFFAOYSA-N 0.000 description 3
- UIEJDMATSWMGJD-UHFFFAOYSA-N 7-(4-bromo-2-fluoroanilino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1F UIEJDMATSWMGJD-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- 229940123587 Cell cycle inhibitor Drugs 0.000 description 3
- 229940127007 Compound 39 Drugs 0.000 description 3
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 206010018338 Glioma Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- OIGHAIBXVRBMFR-UHFFFAOYSA-N N-(2-hydroxyethoxy)-1,2-oxazole-5-carboxamide Chemical compound OCCONC(=O)C1=CC=NO1 OIGHAIBXVRBMFR-UHFFFAOYSA-N 0.000 description 3
- UQAWZDHISJKWTF-UHFFFAOYSA-N N-(2-hydroxyethoxy)pyridine-3-carboxamide Chemical compound OCCONC(=O)c1cccnc1 UQAWZDHISJKWTF-UHFFFAOYSA-N 0.000 description 3
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 230000001594 aberrant effect Effects 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000002280 anti-androgenic effect Effects 0.000 description 3
- 230000003388 anti-hormonal effect Effects 0.000 description 3
- 239000000051 antiandrogen Substances 0.000 description 3
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 229940126086 compound 21 Drugs 0.000 description 3
- 229940125877 compound 31 Drugs 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 238000009830 intercalation Methods 0.000 description 3
- 230000002687 intercalation Effects 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 208000017169 kidney disease Diseases 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- UNMJABFHYFLOMR-UHFFFAOYSA-N methyl 3-amino-6-(4-bromo-2-chloroanilino)-7-fluoro-1,2-benzoxazole-5-carboxylate Chemical compound COC(=O)C1=CC=2C(N)=NOC=2C(F)=C1NC1=CC=C(Br)C=C1Cl UNMJABFHYFLOMR-UHFFFAOYSA-N 0.000 description 3
- NHHCTYLYMAUZHD-UHFFFAOYSA-N methyl 5-bromo-2-(2-chloroanilino)-3,4-difluorobenzoate Chemical compound COC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=CC=C1Cl NHHCTYLYMAUZHD-UHFFFAOYSA-N 0.000 description 3
- BCVUYRQUEVYBBX-UHFFFAOYSA-N methyl 6-(2-chloroanilino)-7-fluoro-3-methyl-2,1-benzoxazole-5-carboxylate Chemical compound COC(=O)C1=CC2=C(C)ON=C2C(F)=C1NC1=CC=CC=C1Cl BCVUYRQUEVYBBX-UHFFFAOYSA-N 0.000 description 3
- AQMLRZVAIFMUFA-UHFFFAOYSA-N methyl 7-(4-bromo-2-chloroanilino)-8-chloro-3-(methylaminomethyl)imidazo[1,2-a]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN2C(CNC)=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl AQMLRZVAIFMUFA-UHFFFAOYSA-N 0.000 description 3
- 230000000394 mitotic effect Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- MDNVANLCJLEKMY-MRVPVSSYSA-N o-[(2r)-2-[tert-butyl(dimethyl)silyl]oxypropyl]hydroxylamine Chemical compound NOC[C@@H](C)O[Si](C)(C)C(C)(C)C MDNVANLCJLEKMY-MRVPVSSYSA-N 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical class C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- NWELCUKYUCBVKK-UHFFFAOYSA-N pyridin-2-ylhydrazine Chemical compound NNC1=CC=CC=N1 NWELCUKYUCBVKK-UHFFFAOYSA-N 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 208000037803 restenosis Diseases 0.000 description 3
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 3
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- CPBNOLFQEDHRCM-UHFFFAOYSA-N tert-butyl 4-(4-bromo-2-chloroanilino)-6-chloropyridine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CN=C(Cl)C=C1NC1=CC=C(Br)C=C1Cl CPBNOLFQEDHRCM-UHFFFAOYSA-N 0.000 description 3
- YAELKEVWDOOJJX-UHFFFAOYSA-N tert-butyl 6-amino-4-(4-bromo-2-chloroanilino)-5-fluoropyridine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CN=C(N)C(F)=C1NC1=CC=C(Br)C=C1Cl YAELKEVWDOOJJX-UHFFFAOYSA-N 0.000 description 3
- FESDUDPSRMWIDL-UHFFFAOYSA-N tert-butyl n,n'-di(propan-2-yl)carbamimidate Chemical compound CC(C)NC(OC(C)(C)C)=NC(C)C FESDUDPSRMWIDL-UHFFFAOYSA-N 0.000 description 3
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- PMHHCLXJMNLEIE-GSVOUGTGSA-N (2r)-1-iodopropan-2-ol Chemical compound C[C@@H](O)CI PMHHCLXJMNLEIE-GSVOUGTGSA-N 0.000 description 2
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 2
- MLEHKULMJMDXGA-UHFFFAOYSA-N (3-hydroxy-2,2-dimethylpropyl)carbamic acid Chemical compound OCC(C)(C)CNC(O)=O MLEHKULMJMDXGA-UHFFFAOYSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- RBACIKXCRWGCBB-UHFFFAOYSA-N 1,2-Epoxybutane Chemical compound CCC1CO1 RBACIKXCRWGCBB-UHFFFAOYSA-N 0.000 description 2
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 2
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 2
- MUUAQFJJUGVBGB-UHFFFAOYSA-N 1-bromo-2,3,4-trifluorobenzene Chemical compound FC1=CC=C(Br)C(F)=C1F MUUAQFJJUGVBGB-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- KQFJLRSPVMTBLE-UHFFFAOYSA-N 2-(2-hydroxy-3,3-dimethylbutoxy)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(OCC(O)C(C)(C)C)C(=O)C2=C1 KQFJLRSPVMTBLE-UHFFFAOYSA-N 0.000 description 2
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical class ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 2
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- VGOALPIDEXVYQI-UHFFFAOYSA-N 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-n-[3-imidazol-1-yl-5-(trifluoromethyl)phenyl]-4-methylbenzamide Chemical compound C1=C(C#CC=2N3N=CC=CC3=NC=2)C(C)=CC=C1C(=O)NC(C=C(C=1)C(F)(F)F)=CC=1N1C=CN=C1 VGOALPIDEXVYQI-UHFFFAOYSA-N 0.000 description 2
- AGMZSYQMSHMXLT-UHFFFAOYSA-N 3-aminobutan-1-ol Chemical compound CC(N)CCO AGMZSYQMSHMXLT-UHFFFAOYSA-N 0.000 description 2
- OQEBBZSWEGYTPG-UHFFFAOYSA-N 3-aminobutanoic acid Chemical compound CC(N)CC(O)=O OQEBBZSWEGYTPG-UHFFFAOYSA-N 0.000 description 2
- NWPNIMOHYUWBAW-UHFFFAOYSA-N 3-chloro-7-(2,4-dichloroanilino)-8-fluoro-n-(2-hydroxyethoxy)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound OCCONC(=O)C1=CN2C(Cl)=CN=C2C(F)=C1NC1=CC=C(Cl)C=C1Cl NWPNIMOHYUWBAW-UHFFFAOYSA-N 0.000 description 2
- IMZQLFVADHUXFO-UHFFFAOYSA-N 3-chloro-7-(2,4-dichloroanilino)-n-(2-ethenoxyethoxy)-8-fluoroimidazo[1,2-a]pyridine-6-carboxamide Chemical compound C=COCCONC(=O)C1=CN2C(Cl)=CN=C2C(F)=C1NC1=CC=C(Cl)C=C1Cl IMZQLFVADHUXFO-UHFFFAOYSA-N 0.000 description 2
- WCDLCPLAAKUJNY-UHFFFAOYSA-N 4-[4-[3-(1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C2=CNN=C2)C=C1 WCDLCPLAAKUJNY-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- INMZDDDQLHKGPF-UHFFFAOYSA-N 4-bromo-2-chloroaniline Chemical compound NC1=CC=C(Br)C=C1Cl INMZDDDQLHKGPF-UHFFFAOYSA-N 0.000 description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- KUZSBKJSGSKPJH-VXGBXAGGSA-N 5-[(9R)-6-[(3R)-3-methylmorpholin-4-yl]-11-oxa-1,3,5-triazatricyclo[7.4.0.02,7]trideca-2,4,6-trien-4-yl]pyrazin-2-amine Chemical compound C[C@@H]1COCCN1c1nc(nc2N3CCOC[C@H]3Cc12)-c1cnc(N)cn1 KUZSBKJSGSKPJH-VXGBXAGGSA-N 0.000 description 2
- WNPQZVIIAQRYMK-UHFFFAOYSA-N 5-chloro-4-hydroxy-6-oxo-1H-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CNC(=O)C(Cl)=C1O WNPQZVIIAQRYMK-UHFFFAOYSA-N 0.000 description 2
- ONJUOZSSNDIVPJ-UHFFFAOYSA-N 6-(4-bromo-2-chloroanilino)-7-fluoro-3-methyl-n-methylsulfonyl-1,2-benzoxazole-5-carboxamide Chemical compound CS(=O)(=O)NC(=O)C=1C=C2C(C)=NOC2=C(F)C=1NC1=CC=C(Br)C=C1Cl ONJUOZSSNDIVPJ-UHFFFAOYSA-N 0.000 description 2
- FICOZADEPHTOPW-UHFFFAOYSA-N 6-(4-bromo-2-chloroanilino)-7-fluoro-n-(2-hydroxyethoxy)pyrazolo[1,5-a]pyridine-5-carboxamide Chemical compound OCCONC(=O)C1=CC2=CC=NN2C(F)=C1NC1=CC=C(Br)C=C1Cl FICOZADEPHTOPW-UHFFFAOYSA-N 0.000 description 2
- NTZRVCRYSYJTOK-UHFFFAOYSA-N 6-(4-bromo-2-chloroanilino)-n-(2-ethenoxyethoxy)-7-fluoro-3-methyl-1,2-benzoxazole-5-carboxamide Chemical compound C=COCCONC(=O)C=1C=C2C(C)=NOC2=C(F)C=1NC1=CC=C(Br)C=C1Cl NTZRVCRYSYJTOK-UHFFFAOYSA-N 0.000 description 2
- PJJWOWSVCJNOGV-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-3-[[[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]methyl]imidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C(CNCC(=O)OC(C)(C)C)=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl PJJWOWSVCJNOGV-UHFFFAOYSA-N 0.000 description 2
- JKAKPGNWHYCSCW-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-n-(cyclopropylmethoxy)-3-(methylaminomethyl)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound C1CC1CONC(=O)C1=CN2C(CNC)=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl JKAKPGNWHYCSCW-UHFFFAOYSA-N 0.000 description 2
- NORGQDQXQJVLCT-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-n-(cyclopropylmethoxy)-3-[(4-methylpiperazin-1-yl)methyl]imidazo[1,2-a]pyridine-6-carboxamide Chemical compound C1CN(C)CCN1CC1=CN=C2N1C=C(C(=O)NOCC1CC1)C(NC=1C(=CC(Br)=CC=1)Cl)=C2Cl NORGQDQXQJVLCT-UHFFFAOYSA-N 0.000 description 2
- ZMDRKWQVFLNVQB-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-n-(cyclopropylmethoxy)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound ClC1=CC(Br)=CC=C1NC1=C(Cl)C2=NC=CN2C=C1C(=O)NOCC1CC1 ZMDRKWQVFLNVQB-UHFFFAOYSA-N 0.000 description 2
- SBXOHQFXNRTVGM-UHFFFAOYSA-N 7-(4-bromo-2-fluoroanilino)-8-chloro-n'-(2-chloroacetyl)imidazo[1,2-a]pyridine-6-carbohydrazide Chemical compound FC1=CC(Br)=CC=C1NC1=C(Cl)C2=NC=CN2C=C1C(=O)NNC(=O)CCl SBXOHQFXNRTVGM-UHFFFAOYSA-N 0.000 description 2
- YZQQNOIYCZLLID-UHFFFAOYSA-N 7-(4-bromo-2-fluoroanilino)-8-chloroimidazo[1,2-a]pyridine-6-carbohydrazide Chemical compound NNC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1F YZQQNOIYCZLLID-UHFFFAOYSA-N 0.000 description 2
- MITGKKFYIJJQGL-UHFFFAOYSA-N 9-(4-chlorobenzoyl)-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one Chemical compound ClC1=CC=C(C(=O)N2C3=CC=C(C=C3C=3C(CCCC2=3)=O)S(=O)(=O)C)C=C1 MITGKKFYIJJQGL-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- ZHGNHOOVYPHPNJ-UHFFFAOYSA-N Amigdalin Chemical compound FC(F)(F)C(=O)OCC1OC(OCC2OC(OC(C#N)C3=CC=CC=C3)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C2OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C1OC(=O)C(F)(F)F ZHGNHOOVYPHPNJ-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- QUMCIHKVKQYNPA-RUZDIDTESA-N C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC Chemical compound C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC QUMCIHKVKQYNPA-RUZDIDTESA-N 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- 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 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 238000006683 Mannich reaction Methods 0.000 description 2
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 2
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 206010033645 Pancreatitis Diseases 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- GOOHAUXETOMSMM-GSVOUGTGSA-N R-propylene oxide Chemical compound C[C@@H]1CO1 GOOHAUXETOMSMM-GSVOUGTGSA-N 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- GOOHAUXETOMSMM-VKHMYHEASA-N S-propylene oxide Chemical compound C[C@H]1CO1 GOOHAUXETOMSMM-VKHMYHEASA-N 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000009468 active modified atmosphere packaging Methods 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 238000012382 advanced drug delivery Methods 0.000 description 2
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000004037 angiogenesis inhibitor Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 2
- 239000012964 benzotriazole Substances 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 150000001723 carbon free-radicals Chemical class 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 229940125807 compound 37 Drugs 0.000 description 2
- 229940127573 compound 38 Drugs 0.000 description 2
- 230000006552 constitutive activation Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000006880 cross-coupling reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 2
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000032692 embryo implantation Effects 0.000 description 2
- IADRZSLECZWZIT-UHFFFAOYSA-N ethyl 4-(4-bromo-2-chloroanilino)-5,6-dichloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C(Cl)=C1NC1=CC=C(Br)C=C1Cl IADRZSLECZWZIT-UHFFFAOYSA-N 0.000 description 2
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000007306 functionalization reaction Methods 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 229940015043 glyoxal Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 201000011066 hemangioma Diseases 0.000 description 2
- 125000004404 heteroalkyl group Chemical group 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- HMKNKWJIRCGBBP-UHFFFAOYSA-N imidazo[1,2-a]pyridin-3-ylmethanamine Chemical class C1=CC=CN2C(CN)=CN=C21 HMKNKWJIRCGBBP-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- HHAMGFVBGIBWEJ-UHFFFAOYSA-N methyl 2-(2-chloroanilino)-3,4-difluoro-5-(2-trimethylsilylethynyl)benzoate Chemical compound COC(=O)C1=CC(C#C[Si](C)(C)C)=C(F)C(F)=C1NC1=CC=CC=C1Cl HHAMGFVBGIBWEJ-UHFFFAOYSA-N 0.000 description 2
- NTMDDLGPSVALQQ-UHFFFAOYSA-N methyl 3-amino-6-(2-chloroanilino)-7-fluoro-1,2-benzoxazole-5-carboxylate Chemical compound COC(=O)C1=CC=2C(N)=NOC=2C(F)=C1NC1=CC=CC=C1Cl NTMDDLGPSVALQQ-UHFFFAOYSA-N 0.000 description 2
- KWRYQZBIAVVSMG-UHFFFAOYSA-N methyl 3-ethyl-8-fluoro-7-(2-fluoro-4-methylanilino)imidazo[1,2-a]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN2C(CC)=CN=C2C(F)=C1NC1=CC=C(C)C=C1F KWRYQZBIAVVSMG-UHFFFAOYSA-N 0.000 description 2
- HXUFRHFJGUHIAG-UHFFFAOYSA-N methyl 3-ethynyl-8-fluoro-7-(2-fluoro-4-methylanilino)imidazo[1,2-a]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN2C(C#C)=CN=C2C(F)=C1NC1=CC=C(C)C=C1F HXUFRHFJGUHIAG-UHFFFAOYSA-N 0.000 description 2
- 229940050176 methyl chloride Drugs 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 2
- MNWYVVFHNHMOQJ-UHFFFAOYSA-N n-(cyclopropylmethyl)hydroxylamine Chemical compound ONCC1CC1 MNWYVVFHNHMOQJ-UHFFFAOYSA-N 0.000 description 2
- VMFMUJZRXZXYAH-UHFFFAOYSA-N n-[5-[[5-chloro-4-[2-[2-(dimethylamino)-2-oxoacetyl]anilino]pyrimidin-2-yl]amino]-4-methoxy-2-(4-methylpiperazin-1-yl)phenyl]prop-2-enamide Chemical compound C=CC(=O)NC=1C=C(NC=2N=C(NC=3C(=CC=CC=3)C(=O)C(=O)N(C)C)C(Cl)=CN=2)C(OC)=CC=1N1CCN(C)CC1 VMFMUJZRXZXYAH-UHFFFAOYSA-N 0.000 description 2
- YRCHYHRCBXNYNU-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]pyridin-2-yl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-(4-fluorophenyl)acetamide Chemical compound N1=CC(CNCCOC)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC(F)=CC=4)=CC=3)F)=C2S1 YRCHYHRCBXNYNU-UHFFFAOYSA-N 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 210000003739 neck Anatomy 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- XZTSFVPMMQNIAJ-UHFFFAOYSA-N o-(2-ethenoxyethyl)hydroxylamine Chemical compound NOCCOC=C XZTSFVPMMQNIAJ-UHFFFAOYSA-N 0.000 description 2
- YWNYAUCCVBZMPH-VIFPVBQESA-N o-[(2s)-2-[tert-butyl(dimethyl)silyl]oxybutyl]hydroxylamine Chemical compound NOC[C@H](CC)O[Si](C)(C)C(C)(C)C YWNYAUCCVBZMPH-VIFPVBQESA-N 0.000 description 2
- MDNVANLCJLEKMY-QMMMGPOBSA-N o-[(2s)-2-[tert-butyl(dimethyl)silyl]oxypropyl]hydroxylamine Chemical compound NOC[C@H](C)O[Si](C)(C)C(C)(C)C MDNVANLCJLEKMY-QMMMGPOBSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 150000002924 oxiranes Chemical group 0.000 description 2
- 239000001301 oxygen Chemical group 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 108010077182 raf Kinases Proteins 0.000 description 2
- 102000009929 raf Kinases Human genes 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000001235 sensitizing effect Effects 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 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 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 150000003871 sulfonates Chemical class 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 230000002381 testicular Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 230000005747 tumor angiogenesis Effects 0.000 description 2
- 230000004862 vasculogenesis Effects 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- QENMPTUFXWVPQZ-UHFFFAOYSA-N (2-hydroxyethylazaniumyl)formate Chemical compound OCCNC(O)=O QENMPTUFXWVPQZ-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- RBACIKXCRWGCBB-SCSAIBSYSA-N (2r)-2-ethyloxirane Chemical compound CC[C@@H]1CO1 RBACIKXCRWGCBB-SCSAIBSYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- PMHHCLXJMNLEIE-VKHMYHEASA-N (2s)-1-iodopropan-2-ol Chemical compound C[C@H](O)CI PMHHCLXJMNLEIE-VKHMYHEASA-N 0.000 description 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
- JVJWUBBUFDYWOO-UHFFFAOYSA-N (3-aminooxy-2,2-dimethylpropyl)carbamic acid Chemical compound NOCC(CNC(O)=O)(C)C JVJWUBBUFDYWOO-UHFFFAOYSA-N 0.000 description 1
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- AHFMSNDOYCFEPH-UHFFFAOYSA-N 1,2-difluoroethane Chemical compound FCCF AHFMSNDOYCFEPH-UHFFFAOYSA-N 0.000 description 1
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical class [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
- FZKCAHQKNJXICB-UHFFFAOYSA-N 2,1-benzoxazole Chemical group C1=CC=CC2=CON=C21 FZKCAHQKNJXICB-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- GCUNXHWKISRLSW-GFCCVEGCSA-N 2-[(2r)-2-[tert-butyl(dimethyl)silyl]oxypropoxy]isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(OC[C@@H](C)O[Si](C)(C)C(C)(C)C)C(=O)C2=C1 GCUNXHWKISRLSW-GFCCVEGCSA-N 0.000 description 1
- GCUNXHWKISRLSW-LBPRGKRZSA-N 2-[(2s)-2-[tert-butyl(dimethyl)silyl]oxypropoxy]isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(OC[C@H](C)O[Si](C)(C)C(C)(C)C)C(=O)C2=C1 GCUNXHWKISRLSW-LBPRGKRZSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
- UKQGSVWBONLFAR-UHFFFAOYSA-N 2-aminooxy-2-methylpropan-1-ol Chemical compound OCC(C)(C)ON UKQGSVWBONLFAR-UHFFFAOYSA-N 0.000 description 1
- HTGQQGJLZPSAAP-UHFFFAOYSA-N 2-aminooxyethyl(methyl)carbamic acid Chemical compound OC(=O)N(C)CCON HTGQQGJLZPSAAP-UHFFFAOYSA-N 0.000 description 1
- XIHMVBYRFOJGLN-UHFFFAOYSA-N 2-aminooxyethylcarbamic acid Chemical compound NOCCNC(O)=O XIHMVBYRFOJGLN-UHFFFAOYSA-N 0.000 description 1
- SZVUPDRKOWDKAR-UHFFFAOYSA-N 2-aminooxypropan-1-ol Chemical compound OCC(C)ON SZVUPDRKOWDKAR-UHFFFAOYSA-N 0.000 description 1
- GRWKNBPOGBTZMN-UHFFFAOYSA-N 2-benzyl-3-phenylpropane-1,2-diamine Chemical compound C=1C=CC=CC=1CC(N)(CN)CC1=CC=CC=C1 GRWKNBPOGBTZMN-UHFFFAOYSA-N 0.000 description 1
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 description 1
- HWZUMEVIIGNXGM-UHFFFAOYSA-N 2-chloro-4-methyl-5-nitropyridine Chemical compound CC1=CC(Cl)=NC=C1[N+]([O-])=O HWZUMEVIIGNXGM-UHFFFAOYSA-N 0.000 description 1
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical class OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- KTRZQCIGJUWSGE-UHFFFAOYSA-N 2-chloropropanedial Chemical compound O=CC(Cl)C=O KTRZQCIGJUWSGE-UHFFFAOYSA-N 0.000 description 1
- MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 description 1
- HEAYDCIZOFDHRM-UHFFFAOYSA-N 2-tert-butyloxirane Chemical compound CC(C)(C)C1CO1 HEAYDCIZOFDHRM-UHFFFAOYSA-N 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- FPENCTDAQQQKNY-UHFFFAOYSA-N 3,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(F)=C1 FPENCTDAQQQKNY-UHFFFAOYSA-N 0.000 description 1
- BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
- NHFDRBXTEDBWCZ-ZROIWOOFSA-N 3-[2,4-dimethyl-5-[(z)-(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoic acid Chemical compound OC(=O)CCC1=C(C)NC(\C=C/2C3=CC=CC=C3NC\2=O)=C1C NHFDRBXTEDBWCZ-ZROIWOOFSA-N 0.000 description 1
- FNVOFDGAASRDQY-UHFFFAOYSA-N 3-amino-2,2-dimethylpropan-1-ol Chemical compound NCC(C)(C)CO FNVOFDGAASRDQY-UHFFFAOYSA-N 0.000 description 1
- UNYHAFYVPBNWGT-UHFFFAOYSA-N 3-aminooxy-1,1,1-trifluoropropan-2-ol Chemical compound NOCC(O)C(F)(F)F UNYHAFYVPBNWGT-UHFFFAOYSA-N 0.000 description 1
- KAHKXUXOXXKPLO-UHFFFAOYSA-N 3-aminooxypropan-1-ol Chemical compound NOCCCO KAHKXUXOXXKPLO-UHFFFAOYSA-N 0.000 description 1
- CBSLZQNXEWOWKZ-UHFFFAOYSA-N 3-aminooxypropylcarbamic acid Chemical compound NOCCCNC(O)=O CBSLZQNXEWOWKZ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- SXAXZLYJPLISIP-UHFFFAOYSA-N 3-bromo-7-(4-bromo-2-chloroanilino)-8-chloro-n-(2-hydroxyethoxy)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound OCCONC(=O)C1=CN2C(Br)=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl SXAXZLYJPLISIP-UHFFFAOYSA-N 0.000 description 1
- GKHIYZYURHIGSB-UHFFFAOYSA-N 3-ethyl-8-fluoro-7-(2-fluoro-4-methylanilino)-n-(2-hydroxyethoxy)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound OCCONC(=O)C1=CN2C(CC)=CN=C2C(F)=C1NC1=CC=C(C)C=C1F GKHIYZYURHIGSB-UHFFFAOYSA-N 0.000 description 1
- IFVNEJLHHCHXGX-UHFFFAOYSA-N 3-hydroxypropylcarbamic acid Chemical compound OCCCNC(O)=O IFVNEJLHHCHXGX-UHFFFAOYSA-N 0.000 description 1
- UVCDOAAKEDNFOE-UHFFFAOYSA-N 3-iodoimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound C1=C(C(=O)O)C=CC2=NC=C(I)N21 UVCDOAAKEDNFOE-UHFFFAOYSA-N 0.000 description 1
- QFCJSANSFSOSQM-UHFFFAOYSA-N 3-methyl-1,2-benzoxazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(C)=NOC2=C1 QFCJSANSFSOSQM-UHFFFAOYSA-N 0.000 description 1
- ZOQDGMRYMRFKRV-UHFFFAOYSA-N 3-methyl-2,1-benzoxazole Chemical class C1=CC=CC2=C(C)ON=C21 ZOQDGMRYMRFKRV-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- UYTWCEYZEQBILY-UHFFFAOYSA-N 4,6-dichloro-5-fluoropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)C(F)=C1Cl UYTWCEYZEQBILY-UHFFFAOYSA-N 0.000 description 1
- SNZTWTPHAOXTON-UHFFFAOYSA-N 4-(4-bromo-2-chloroanilino)-5-chloro-6-(2-hydroxypropylamino)pyridine-3-carboxylic acid Chemical compound BrC1=CC(=C(C=C1)NC1=C(C(=NC=C1C(=O)O)NCC(C)O)Cl)Cl SNZTWTPHAOXTON-UHFFFAOYSA-N 0.000 description 1
- WHJJXZHUNYRNMF-UHFFFAOYSA-N 4-(4-bromo-2-chloroanilino)-5-chloro-6-(2-oxopropylamino)pyridine-3-carboxylic acid Chemical compound BrC1=CC(=C(C=C1)NC1=C(C(=NC=C1C(=O)O)NCC(C)=O)Cl)Cl WHJJXZHUNYRNMF-UHFFFAOYSA-N 0.000 description 1
- ACKWHPURNTYNOA-UHFFFAOYSA-N 4-(4-bromo-2-chloroanilino)-6-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)C=C1NC1=CC=C(Br)C=C1Cl ACKWHPURNTYNOA-UHFFFAOYSA-N 0.000 description 1
- AZOZVJKRVNSUIW-UHFFFAOYSA-N 4-aminooxybutan-2-ylcarbamic acid Chemical compound NOCCC(C)NC(O)=O AZOZVJKRVNSUIW-UHFFFAOYSA-N 0.000 description 1
- QJLHSJRQOWSNMD-UHFFFAOYSA-N 4-hydroxy-6-oxo-1h-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CNC(O)=CC1=O QJLHSJRQOWSNMD-UHFFFAOYSA-N 0.000 description 1
- 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
- YWDBFEUMTBHUQK-UHFFFAOYSA-N 5-[7-(4-bromo-2-fluoroanilino)-8-chloroimidazo[1,2-a]pyridin-6-yl]-1,3,4-oxadiazol-2-amine Chemical compound O1C(N)=NN=C1C(C(=C1Cl)NC=2C(=CC(Br)=CC=2)F)=CN2C1=NC=C2 YWDBFEUMTBHUQK-UHFFFAOYSA-N 0.000 description 1
- FAZBYWAFKABYKV-UHFFFAOYSA-N 5-[7-(4-bromo-2-fluoroanilino)-8-chloroimidazo[1,2-a]pyridin-6-yl]-3h-1,3,4-oxadiazole-2-thione Chemical compound FC1=CC(Br)=CC=C1NC1=C(Cl)C2=NC=CN2C=C1C1=NN=C(S)O1 FAZBYWAFKABYKV-UHFFFAOYSA-N 0.000 description 1
- VNHBYKHXBCYPBJ-UHFFFAOYSA-N 5-ethynylimidazo[1,2-a]pyridine Chemical compound C#CC1=CC=CC2=NC=CN12 VNHBYKHXBCYPBJ-UHFFFAOYSA-N 0.000 description 1
- LLXZNFYIVVPKQQ-UHFFFAOYSA-N 6-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]-n-(4-bromo-2-fluorophenyl)-8-chloroimidazo[1,2-a]pyridin-7-amine Chemical compound O1C(CN)=NN=C1C(C(=C1Cl)NC=2C(=CC(Br)=CC=2)F)=CN2C1=NC=C2 LLXZNFYIVVPKQQ-UHFFFAOYSA-N 0.000 description 1
- AGEVDPUWKBBHBY-UHFFFAOYSA-N 6-amino-4-(4-bromo-2-chloroanilino)pyridine-3-carboxylic acid Chemical compound C1=NC(N)=CC(NC=2C(=CC(Br)=CC=2)Cl)=C1C(O)=O AGEVDPUWKBBHBY-UHFFFAOYSA-N 0.000 description 1
- YUVIXTURSBAVTQ-UHFFFAOYSA-N 6-azido-4-(4-bromo-2-chloroanilino)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C(N=[N+]=[N-])C=C1NC1=CC=C(Br)C=C1Cl YUVIXTURSBAVTQ-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- LWGWOMXZROJDGC-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-3-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound C1CN(C)CCN1C1=CN=C2N1C=C(C(O)=O)C(NC=1C(=CC(Br)=CC=1)Cl)=C2Cl LWGWOMXZROJDGC-UHFFFAOYSA-N 0.000 description 1
- SXGSZAKAUGOPFL-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-3-[(dimethylamino)methyl]imidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C(CN(C)C)=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl SXGSZAKAUGOPFL-UHFFFAOYSA-N 0.000 description 1
- WPQHKPZQJXYOOG-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-3-methylimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C(C)=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl WPQHKPZQJXYOOG-UHFFFAOYSA-N 0.000 description 1
- WYOCLSQMNYYDAE-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-n-(cyclopropylmethoxy)-3-(morpholin-4-ylmethyl)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound ClC1=CC(Br)=CC=C1NC(C(=CN12)C(=O)NOCC3CC3)=C(Cl)C1=NC=C2CN1CCOCC1 WYOCLSQMNYYDAE-UHFFFAOYSA-N 0.000 description 1
- FLJZZQWXKCDADK-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-n-(cyclopropylmethoxy)-3-methylimidazo[1,2-a]pyridine-6-carboxamide Chemical compound C1CC1CONC(=O)C1=CN2C(C)=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl FLJZZQWXKCDADK-UHFFFAOYSA-N 0.000 description 1
- MFWFYLMFYYBAIX-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-fluoro-n-(2-hydroxyethoxy)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound OCCONC(=O)C1=CN2C=CN=C2C(F)=C1NC1=CC=C(Br)C=C1Cl MFWFYLMFYYBAIX-UHFFFAOYSA-N 0.000 description 1
- LYQFMWLOPXCZMH-UHFFFAOYSA-N 7-(4-bromo-2-fluoroanilino)-8-fluoroimidazo[1,2-a]pyridine-6-carbohydrazide Chemical compound NNC(=O)C1=CN2C=CN=C2C(F)=C1NC1=CC=C(Br)C=C1F LYQFMWLOPXCZMH-UHFFFAOYSA-N 0.000 description 1
- IGMGMXNHPLPUQX-UHFFFAOYSA-N 7-(4-bromo-2-fluoroanilino)-8-fluoroimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C(F)=C1NC1=CC=C(Br)C=C1F IGMGMXNHPLPUQX-UHFFFAOYSA-N 0.000 description 1
- JLVYNMNYWOKTJK-UHFFFAOYSA-N 7-(4-bromo-2-fluoroanilino)-n-(2-hydroxyethoxy)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound OCCONC(=O)C1=CN2C=CN=C2C=C1NC1=CC=C(Br)C=C1F JLVYNMNYWOKTJK-UHFFFAOYSA-N 0.000 description 1
- DDLNUXKHROXSMM-UHFFFAOYSA-N 7-(4-bromo-2-fluoroanilino)-n-(cyclopropylmethoxy)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound FC1=CC(Br)=CC=C1NC1=CC2=NC=CN2C=C1C(=O)NOCC1CC1 DDLNUXKHROXSMM-UHFFFAOYSA-N 0.000 description 1
- MFHQCHJYBVTHEB-UHFFFAOYSA-N 7-(4-bromo-2-fluoroanilino)-n-ethoxy-8-fluoro-3-(morpholin-4-ylmethyl)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound C=1N=C2C(F)=C(NC=3C(=CC(Br)=CC=3)F)C(C(=O)NOCC)=CN2C=1CN1CCOCC1 MFHQCHJYBVTHEB-UHFFFAOYSA-N 0.000 description 1
- MUOSTNSOWIMQDO-UHFFFAOYSA-N 7-(4-bromo-2-fluoroanilino)-n-ethoxy-8-fluoroimidazo[1,2-a]pyridine-6-carboxamide Chemical compound CCONC(=O)C1=CN2C=CN=C2C(F)=C1NC1=CC=C(Br)C=C1F MUOSTNSOWIMQDO-UHFFFAOYSA-N 0.000 description 1
- POQWRBZNQLHZFX-UHFFFAOYSA-N 7-(4-bromo-2-fluoroanilino)imidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C=C1NC1=CC=C(Br)C=C1F POQWRBZNQLHZFX-UHFFFAOYSA-N 0.000 description 1
- MTBJRAXTUBUCJA-UHFFFAOYSA-N 7-(4-bromo-2-methylanilino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound CC1=CC(Br)=CC=C1NC1=C(Cl)C2=NC=CN2C=C1C(O)=O MTBJRAXTUBUCJA-UHFFFAOYSA-N 0.000 description 1
- ZXQDMIUHFBAYSF-UHFFFAOYSA-N 7-(4-bromo-2-methylanilino)-8-fluoroimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound CC1=CC(Br)=CC=C1NC1=C(F)C2=NC=CN2C=C1C(O)=O ZXQDMIUHFBAYSF-UHFFFAOYSA-N 0.000 description 1
- BRWCKXQUWVPMFP-UHFFFAOYSA-N 7-(4-chloro-2-fluoroanilino)-8-fluoroimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C(F)=C1NC1=CC=C(Cl)C=C1F BRWCKXQUWVPMFP-UHFFFAOYSA-N 0.000 description 1
- NVBNSACTYLGCLA-UHFFFAOYSA-N 8-chloro-7-(2,4-dichloroanilino)imidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(Cl)C=C1Cl NVBNSACTYLGCLA-UHFFFAOYSA-N 0.000 description 1
- CFHJETVTEOGFGW-UHFFFAOYSA-N 8-chloro-7-(2,4-difluoroanilino)imidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(F)C=C1F CFHJETVTEOGFGW-UHFFFAOYSA-N 0.000 description 1
- MKRRRVQPVQNQDA-UHFFFAOYSA-N 8-chloro-7-(2-fluoro-4-iodoanilino)imidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(I)C=C1F MKRRRVQPVQNQDA-UHFFFAOYSA-N 0.000 description 1
- CCEULDNBSVWLLU-UHFFFAOYSA-N 8-chloro-7-(2-fluoroanilino)-n-(2-hydroxyethoxy)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound OCCONC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=CC=C1F CCEULDNBSVWLLU-UHFFFAOYSA-N 0.000 description 1
- DZHRPTKXTBKICM-UHFFFAOYSA-N 8-chloro-7-(4-chloro-2-fluoroanilino)imidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(Cl)C=C1F DZHRPTKXTBKICM-UHFFFAOYSA-N 0.000 description 1
- JQLDTKUUHGCPSZ-UHFFFAOYSA-N 8-chloro-n-(cyclopropylmethoxy)-7-(2-fluoroanilino)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound FC1=CC=CC=C1NC1=C(Cl)C2=NC=CN2C=C1C(=O)NOCC1CC1 JQLDTKUUHGCPSZ-UHFFFAOYSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- UTJOBHLTUKZZBA-UHFFFAOYSA-N C(C)=O.[Br] Chemical compound C(C)=O.[Br] UTJOBHLTUKZZBA-UHFFFAOYSA-N 0.000 description 1
- 229910014585 C2-Ce Inorganic materials 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 102100027995 Collagenase 3 Human genes 0.000 description 1
- 108050005238 Collagenase 3 Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-YMDCURPLSA-N D-galactopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-YMDCURPLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 102100023266 Dual specificity mitogen-activated protein kinase kinase 2 Human genes 0.000 description 1
- 101710146529 Dual specificity mitogen-activated protein kinase kinase 2 Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 208000009849 Female Genital Neoplasms Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 101000797623 Homo sapiens Protein AMBP Proteins 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 208000004454 Hyperalgesia Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 102400001240 Inter-alpha-trypsin inhibitor light chain Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 206010061252 Intraocular melanoma Diseases 0.000 description 1
- LNQCUTNLHUQZLR-VNPYQEQNSA-N Iridin Natural products O(C)c1c(O)c2C(=O)C(c3cc(OC)c(OC)c(O)c3)=COc2cc1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 LNQCUTNLHUQZLR-VNPYQEQNSA-N 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 206010052178 Lymphocytic lymphoma Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102100027998 Macrophage metalloelastase Human genes 0.000 description 1
- 101710187853 Macrophage metalloelastase Proteins 0.000 description 1
- 102100030417 Matrilysin Human genes 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical class CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 1
- FZBPBLMUNZUMJG-UHFFFAOYSA-N N-(2-hydroxyethoxy)pyridine-2-carboxamide Chemical compound OCCONC(=O)c1ccccn1 FZBPBLMUNZUMJG-UHFFFAOYSA-N 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- POFVJRKJJBFPII-UHFFFAOYSA-N N-cyclopentyl-5-[2-[[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1(CCCC1)NC=1SC(=C(N=1)C)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)CC POFVJRKJJBFPII-UHFFFAOYSA-N 0.000 description 1
- FTFRZXFNZVCRSK-UHFFFAOYSA-N N4-(3-chloro-4-fluorophenyl)-N6-(1-methyl-4-piperidinyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(C)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 FTFRZXFNZVCRSK-UHFFFAOYSA-N 0.000 description 1
- 229910017974 NH40H Inorganic materials 0.000 description 1
- 102100030411 Neutrophil collagenase Human genes 0.000 description 1
- 101710118230 Neutrophil collagenase Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 108010047956 Nucleosomes Proteins 0.000 description 1
- ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical class COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000002471 Penile Neoplasms Diseases 0.000 description 1
- IGVPBCZDHMIOJH-UHFFFAOYSA-N Phenyl butyrate Chemical class CCCC(=O)OC1=CC=CC=C1 IGVPBCZDHMIOJH-UHFFFAOYSA-N 0.000 description 1
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical class [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 102100030416 Stromelysin-1 Human genes 0.000 description 1
- 101710108790 Stromelysin-1 Proteins 0.000 description 1
- 102100028848 Stromelysin-2 Human genes 0.000 description 1
- 101710108792 Stromelysin-2 Proteins 0.000 description 1
- 102100028847 Stromelysin-3 Human genes 0.000 description 1
- 108050005271 Stromelysin-3 Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000023915 Ureteral Neoplasms Diseases 0.000 description 1
- 206010046458 Urethral neoplasms Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 201000003761 Vaginal carcinoma Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- XMACCNOGDFVTGY-UHFFFAOYSA-N [2-amino-1-[7-(4-bromo-2-chloroanilino)-8-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-3-yl]-2-oxoethyl]-methylcarbamic acid Chemical compound BrC1=CC(=C(C=C1)NC1=C(C=2N(C=C1OCC1CC1)C(=CN2)C(C(N)=O)N(C(O)=O)C)Cl)Cl XMACCNOGDFVTGY-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000000475 acetylene derivatives Chemical class 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 206010053552 allodynia Diseases 0.000 description 1
- 229940061720 alpha hydroxy acid Drugs 0.000 description 1
- 150000001280 alpha hydroxy acids Chemical class 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 238000010936 aqueous wash Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- WGQKYBSKWIADBV-UHFFFAOYSA-O benzylaminium Chemical compound [NH3+]CC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-O 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- DHCLVCXQIBBOPH-UHFFFAOYSA-N beta-glycerol phosphate Natural products OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 1
- GHRQXJHBXKYCLZ-UHFFFAOYSA-L beta-glycerolphosphate Chemical compound [Na+].[Na+].CC(CO)OOP([O-])([O-])=O GHRQXJHBXKYCLZ-UHFFFAOYSA-L 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-O bis(2-hydroxyethyl)azanium Chemical compound OCC[NH2+]CCO ZBCBWPMODOFKDW-UHFFFAOYSA-O 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 150000004768 bromobenzenes Chemical class 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004452 carbocyclyl group Chemical group 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229940097647 casodex Drugs 0.000 description 1
- 229940047495 celebrex Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000024207 chronic leukemia Diseases 0.000 description 1
- 235000019506 cigar Nutrition 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940125878 compound 36 Drugs 0.000 description 1
- 229940125936 compound 42 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000030944 contact inhibition Effects 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 208000030381 cutaneous melanoma Diseases 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 125000005534 decanoate group Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
- ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical compound OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- 125000005883 dithianyl group Chemical group 0.000 description 1
- 125000005411 dithiolanyl group Chemical group S1SC(CC1)* 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 229940121647 egfr inhibitor Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- XWJXULFLZWQHML-UHFFFAOYSA-N ethyl 4,5,6-trichloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C(Cl)=C1Cl XWJXULFLZWQHML-UHFFFAOYSA-N 0.000 description 1
- AAUBVINEXCCXOK-UHFFFAOYSA-N ethyl 4,6-dichloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C=C1Cl AAUBVINEXCCXOK-UHFFFAOYSA-N 0.000 description 1
- QDHHLXABEXNRJX-UHFFFAOYSA-N ethyl 4-hydroxy-6-oxo-1h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=CNC(O)=CC1=O QDHHLXABEXNRJX-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
- 229960004945 etoricoxib Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 201000001343 fallopian tube carcinoma Diseases 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N homoserine Chemical compound OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 1
- KIMZVDLDHKECSU-UHFFFAOYSA-N imidazo[1,2-a]pyridine-3-carbaldehyde Chemical compound C1=CC=CN2C(C=O)=CN=C21 KIMZVDLDHKECSU-UHFFFAOYSA-N 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- LNQCUTNLHUQZLR-OZJWLQQPSA-N iridin Chemical compound OC1=C(OC)C(OC)=CC(C=2C(C3=C(O)C(OC)=C(O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)C=C3OC=2)=O)=C1 LNQCUTNLHUQZLR-OZJWLQQPSA-N 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 150000003903 lactic acid esters Chemical class 0.000 description 1
- 239000011967 lanthanide triflate Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960000994 lumiracoxib Drugs 0.000 description 1
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910000372 mercury(II) sulfate Inorganic materials 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- SPJQBGGHUDNAIC-UHFFFAOYSA-N methyl 2,5-dichlorobenzoate Chemical compound COC(=O)C1=CC(Cl)=CC=C1Cl SPJQBGGHUDNAIC-UHFFFAOYSA-N 0.000 description 1
- JMOYQSBCBHBDNO-UHFFFAOYSA-N methyl 3-chloro-7-(2,4-dichloroanilino)-8-fluoroimidazo[1,2-a]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN2C(Cl)=CN=C2C(F)=C1NC1=CC=C(Cl)C=C1Cl JMOYQSBCBHBDNO-UHFFFAOYSA-N 0.000 description 1
- NEPVQFNYWYBUFR-UHFFFAOYSA-N methyl 4-(4-bromo-2-chloroanilino)-5-chloro-6-hydrazinylpyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(NN)C(Cl)=C1NC1=CC=C(Br)C=C1Cl NEPVQFNYWYBUFR-UHFFFAOYSA-N 0.000 description 1
- YRIXOKHFULWNHE-UHFFFAOYSA-N methyl 4-hydroxy-6-oxo-1h-pyridine-3-carboxylate Chemical compound COC(=O)C1=CNC(O)=CC1=O YRIXOKHFULWNHE-UHFFFAOYSA-N 0.000 description 1
- IJFWKXRSFRXNPH-UHFFFAOYSA-N methyl 5-acetyl-2-(2-chloroanilino)-3-fluoro-4-(propan-2-ylideneamino)oxybenzoate Chemical compound COC(=O)C1=CC(C(C)=O)=C(ON=C(C)C)C(F)=C1NC1=CC=CC=C1Cl IJFWKXRSFRXNPH-UHFFFAOYSA-N 0.000 description 1
- IGLBCFCDAJIRMO-UHFFFAOYSA-N methyl 6-(2,4-dichloroanilino)-7-fluoro-3-methyl-1,2-benzoxazole-5-carboxylate Chemical compound COC(=O)C1=CC=2C(C)=NOC=2C(F)=C1NC1=CC=C(Cl)C=C1Cl IGLBCFCDAJIRMO-UHFFFAOYSA-N 0.000 description 1
- PLMMRPBAGASMIR-UHFFFAOYSA-N methyl 7-(2,4-dichloroanilino)-8-fluoroimidazo[1,2-a]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN2C=CN=C2C(F)=C1NC1=CC=C(Cl)C=C1Cl PLMMRPBAGASMIR-UHFFFAOYSA-N 0.000 description 1
- KXIQCNMUCPYEES-UHFFFAOYSA-N methyl 7-(4-bromo-2-fluoroanilino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1F KXIQCNMUCPYEES-UHFFFAOYSA-N 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- SXKLNBJCHYEPDL-UHFFFAOYSA-N n,n-difluorosulfamoyl fluoride Chemical compound FN(F)S(F)(=O)=O SXKLNBJCHYEPDL-UHFFFAOYSA-N 0.000 description 1
- ACXLZQQEGRXRJF-UHFFFAOYSA-N n-(4-bromo-2-fluorophenyl)-8-chloro-6-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]imidazo[1,2-a]pyridin-7-amine Chemical compound FC1=CC(Br)=CC=C1NC1=C(Cl)C2=NC=CN2C=C1C1=NN=C(CCl)O1 ACXLZQQEGRXRJF-UHFFFAOYSA-N 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- YGFLCNPXEPDANQ-UHFFFAOYSA-N n-[bis[(2-methylpropan-2-yl)oxy]phosphanyl]-n-propan-2-ylpropan-2-amine Chemical compound CC(C)N(C(C)C)P(OC(C)(C)C)OC(C)(C)C YGFLCNPXEPDANQ-UHFFFAOYSA-N 0.000 description 1
- HSZCJVZRHXPCIA-UHFFFAOYSA-N n-benzyl-n-ethylaniline Chemical compound C=1C=CC=CC=1N(CC)CC1=CC=CC=C1 HSZCJVZRHXPCIA-UHFFFAOYSA-N 0.000 description 1
- PAVLETGHAKGMBG-UHFFFAOYSA-N n-ethoxy-7-(4-ethyl-2-fluoroanilino)-8-fluoroimidazo[1,2-a]pyridine-6-carboxamide Chemical compound CCONC(=O)C1=CN2C=CN=C2C(F)=C1NC1=CC=C(CC)C=C1F PAVLETGHAKGMBG-UHFFFAOYSA-N 0.000 description 1
- KNIJJZFXBMLOPC-UHFFFAOYSA-N n-ethoxypyridine-2-carboxamide Chemical compound CCONC(=O)C1=CC=CC=N1 KNIJJZFXBMLOPC-UHFFFAOYSA-N 0.000 description 1
- IUVIGVRSTLVOQI-UHFFFAOYSA-N n-methoxypropan-1-amine Chemical compound CCCNOC IUVIGVRSTLVOQI-UHFFFAOYSA-N 0.000 description 1
- IOXXVNYDGIXMIP-UHFFFAOYSA-N n-methylprop-2-en-1-amine Chemical compound CNCC=C IOXXVNYDGIXMIP-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229940085033 nolvadex Drugs 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000025308 nuclear transport Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 210000001623 nucleosome Anatomy 0.000 description 1
- KVGGSRKAJYWCQS-UHFFFAOYSA-N o-(2-methoxyethyl)hydroxylamine Chemical compound COCCON KVGGSRKAJYWCQS-UHFFFAOYSA-N 0.000 description 1
- OOHKBWPOLBTKMR-UHFFFAOYSA-N o-(4-nitrophenyl)hydroxylamine Chemical compound NOC1=CC=C([N+]([O-])=O)C=C1 OOHKBWPOLBTKMR-UHFFFAOYSA-N 0.000 description 1
- YWNYAUCCVBZMPH-SECBINFHSA-N o-[(2r)-2-[tert-butyl(dimethyl)silyl]oxybutyl]hydroxylamine Chemical compound NOC[C@@H](CC)O[Si](C)(C)C(C)(C)C YWNYAUCCVBZMPH-SECBINFHSA-N 0.000 description 1
- VHWNHUXVBBOJFQ-UHFFFAOYSA-N o-[2-[tert-butyl(dimethyl)silyl]oxy-3-methylbutyl]hydroxylamine Chemical compound NOCC(C(C)C)O[Si](C)(C)C(C)(C)C VHWNHUXVBBOJFQ-UHFFFAOYSA-N 0.000 description 1
- NUXCOKIYARRTDC-UHFFFAOYSA-N o-ethylhydroxylamine;hydron;chloride Chemical compound Cl.CCON NUXCOKIYARRTDC-UHFFFAOYSA-N 0.000 description 1
- HLYVNXRHROOICH-UHFFFAOYSA-N o-propan-2-ylhydroxylamine Chemical compound CC(C)ON HLYVNXRHROOICH-UHFFFAOYSA-N 0.000 description 1
- PRAARDGLAWZXML-UHFFFAOYSA-N o-propylhydroxylamine Chemical compound CCCON PRAARDGLAWZXML-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000002575 ocular melanoma Diseases 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000003901 oxalic acid esters Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003551 oxepanyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- QARVLSVVCXYDNA-UHFFFAOYSA-N phenyl bromide Natural products BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 125000005541 phosphonamide group Chemical group 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001184 polypeptide Chemical group 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical group C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 108090000765 processed proteins & peptides Chemical group 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 201000008171 proliferative glomerulonephritis Diseases 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- GHTCDIMLJVTPEP-UHFFFAOYSA-N pyrazolo[1,5-a]pyridin-2-amine Chemical compound C1=CC=CN2N=C(N)C=C21 GHTCDIMLJVTPEP-UHFFFAOYSA-N 0.000 description 1
- DVUBDHRTVYLIPA-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine Chemical compound C1=CC=CN2N=CC=C21 DVUBDHRTVYLIPA-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 201000007444 renal pelvis carcinoma Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 229910052706 scandium Inorganic materials 0.000 description 1
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical compound [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012363 selectfluor Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000003708 skin melanoma Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- FQZYTYWMLGAPFJ-OQKDUQJOSA-N tamoxifen citrate Chemical compound [H+].[H+].[H+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 FQZYTYWMLGAPFJ-OQKDUQJOSA-N 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- YTNBLLVHFGPKPA-UHFFFAOYSA-N tert-butyl 4-(4-bromo-2-chloroanilino)-5,6-dichloropyridine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CN=C(Cl)C(Cl)=C1NC1=CC=C(Br)C=C1Cl YTNBLLVHFGPKPA-UHFFFAOYSA-N 0.000 description 1
- ZQYFABUNLUEERU-UHFFFAOYSA-N tert-butyl 4-(4-bromo-2-chloroanilino)-5-chloro-6-(2-hydroxypropylamino)pyridine-3-carboxylate Chemical compound CC(O)CNC1=NC=C(C(=O)OC(C)(C)C)C(NC=2C(=CC(Br)=CC=2)Cl)=C1Cl ZQYFABUNLUEERU-UHFFFAOYSA-N 0.000 description 1
- XRFVAZGLTPAMKQ-UHFFFAOYSA-N tert-butyl 4-[[7-(4-bromo-2-chloroanilino)-8-chloro-6-(cyclopropylmethoxycarbamoyl)imidazo[1,2-a]pyridin-3-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=CN=C2N1C=C(C(=O)NOCC1CC1)C(NC=1C(=CC(Br)=CC=1)Cl)=C2Cl XRFVAZGLTPAMKQ-UHFFFAOYSA-N 0.000 description 1
- LZSWYRVYQPBKBJ-UHFFFAOYSA-N tert-butyl n-[3-(1,3-dioxoisoindol-2-yl)oxy-2,2-dimethylpropyl]carbamate Chemical compound C1=CC=C2C(=O)N(OCC(C)(CNC(=O)OC(C)(C)C)C)C(=O)C2=C1 LZSWYRVYQPBKBJ-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- YJKBMRIXPNAHBN-MRVPVSSYSA-N tert-butyl-[(2r)-1-iodopropan-2-yl]oxy-dimethylsilane Chemical compound IC[C@@H](C)O[Si](C)(C)C(C)(C)C YJKBMRIXPNAHBN-MRVPVSSYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000006173 tetrahydropyranylmethyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- AQWOIRBQLOOZGX-UHFFFAOYSA-N triazolo[1,5-a]pyridine Chemical class C1=CC=CC2=CN=NN21 AQWOIRBQLOOZGX-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 208000037965 uterine sarcoma Diseases 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
- 239000002525 vasculotropin inhibitor Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- HOFQVRTUGATRFI-XQKSVPLYSA-N vinblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 HOFQVRTUGATRFI-XQKSVPLYSA-N 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 208000013013 vulvar carcinoma Diseases 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/654,580 US7144907B2 (en) | 2003-09-03 | 2003-09-03 | Heterocyclic inhibitors of MEK and methods of use thereof |
| US10/929,295 US7230099B2 (en) | 2003-09-03 | 2004-08-30 | Heterocyclic inhibitors of MEK and methods of use thereof |
| PCT/US2004/028649 WO2005023759A2 (en) | 2003-09-03 | 2004-09-01 | Heterocyclic inhibitors of mek and methods of use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA06002466A true MXPA06002466A (es) | 2006-06-20 |
Family
ID=34218110
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA06002466A MXPA06002466A (es) | 2003-09-03 | 2004-09-01 | Inhibidores heterociclicos de mek y metodos de uso de los mismos. |
Country Status (18)
| Country | Link |
|---|---|
| US (5) | US7144907B2 (OSRAM) |
| EP (1) | EP1673339B1 (OSRAM) |
| JP (1) | JP4131741B2 (OSRAM) |
| KR (1) | KR20060070558A (OSRAM) |
| CN (1) | CN1874769A (OSRAM) |
| AR (1) | AR046081A1 (OSRAM) |
| AU (1) | AU2004270699B2 (OSRAM) |
| BR (1) | BRPI0414111A (OSRAM) |
| CA (1) | CA2537321A1 (OSRAM) |
| IL (4) | IL173936A (OSRAM) |
| IS (1) | IS8392A (OSRAM) |
| MX (1) | MXPA06002466A (OSRAM) |
| NO (1) | NO20061506L (OSRAM) |
| PT (1) | PT1673339E (OSRAM) |
| RU (1) | RU2006109599A (OSRAM) |
| TW (1) | TW200526607A (OSRAM) |
| WO (1) | WO2005023759A2 (OSRAM) |
| ZA (1) | ZA200602581B (OSRAM) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010068738A1 (en) | 2008-12-10 | 2010-06-17 | Dana-Farber Cancer Institute, Inc. | Mek mutations conferring resistance to mek inhibitors |
| WO2011106298A1 (en) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| WO2013169858A1 (en) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
Families Citing this family (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7488823B2 (en) * | 2003-11-10 | 2009-02-10 | Array Biopharma, Inc. | Cyanoguanidines and cyanoamidines as ErbB2 and EGFR inhibitors |
| US7538120B2 (en) * | 2003-09-03 | 2009-05-26 | Array Biopharma Inc. | Method of treating inflammatory diseases |
| US7144907B2 (en) * | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| TW200520745A (en) * | 2003-09-19 | 2005-07-01 | Chugai Pharmaceutical Co Ltd | Novel 4-phenylamino-benzaldoxime derivatives and uses thereof as mitogen-activated protein kinase kinase (MEK) inhibitors |
| ATE495155T1 (de) * | 2003-11-19 | 2011-01-15 | Array Biopharma Inc | Heterocyclische inhibitoren von mek |
| US7517994B2 (en) * | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| MY144232A (en) | 2004-07-26 | 2011-08-15 | Chugai Pharmaceutical Co Ltd | 5-substituted-2-phenylamino benzamides as mek inhibitors |
| AU2005311451A1 (en) * | 2004-12-01 | 2006-06-08 | Merck Serono Sa | [1,2,4]triazolo[4,3-a]pyridine derivatives for the treatment of hyperproliferative diseases |
| US7666880B2 (en) | 2005-03-21 | 2010-02-23 | S*Bio Pte Ltd. | Imidazo[1,2-A]pyridine derivatives: preparation and pharmaceutical applications |
| MX2007011710A (es) * | 2005-03-21 | 2007-11-20 | S Bio Pte Ltd | Derivados de imidazo[1,2-a]piridina, preparacion y aplicaciones farmaceuticas. |
| TW201238952A (en) * | 2005-05-18 | 2012-10-01 | Array Biopharma Inc | Heterocyclic inhibitors of MEK and methods of use thereof |
| US20070155738A1 (en) | 2005-05-20 | 2007-07-05 | Alantos Pharmaceuticals, Inc. | Heterobicyclic metalloprotease inhibitors |
| AU2006251989B2 (en) * | 2005-05-20 | 2010-05-27 | Alantos-Pharmaceuticals, Inc. | Pyrimidine or triazine fused bicyclic metalloprotease inhibitors |
| US7572807B2 (en) * | 2005-06-09 | 2009-08-11 | Bristol-Myers Squibb Company | Heteroaryl 11-beta-hydroxysteroid dehydrogenase type I inhibitors |
| US7579360B2 (en) * | 2005-06-09 | 2009-08-25 | Bristol-Myers Squibb Company | Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| US8101799B2 (en) | 2005-07-21 | 2012-01-24 | Ardea Biosciences | Derivatives of N-(arylamino) sulfonamides as inhibitors of MEK |
| WO2007025090A2 (en) * | 2005-08-25 | 2007-03-01 | Kalypsys, Inc. | Heterobicyclic and - tricyclic inhibitors of mapk/erk kinase |
| AU2013203939B2 (en) * | 2005-10-07 | 2015-08-13 | Exelixis, Inc. | Azetidines as MEK inhibitors for the treatment of proliferative diseases |
| AU2012261703B2 (en) * | 2005-10-07 | 2015-08-13 | Exelixis, Inc. | Azetidines as MEK inhibitors for the treatment of proliferative diseases |
| ATE504565T1 (de) * | 2005-10-07 | 2011-04-15 | Exelixis Inc | Azetidine als mek-inhibitoren bei der behandlung proliferativer erkrankungen |
| GB0601962D0 (en) | 2006-01-31 | 2006-03-15 | Ucb Sa | Therapeutic agents |
| GB0616214D0 (en) * | 2006-08-15 | 2006-09-27 | Ucb Sa | Therapeutic Agents |
| KR101475088B1 (ko) * | 2006-08-21 | 2014-12-23 | 제넨테크, 인크. | 아자-벤조티오페닐 화합물 및 사용 방법 |
| MX2009001878A (es) * | 2006-08-21 | 2009-03-03 | Genentech Inc | Compuestos de aza-benzofuranilo y metodos de uso. |
| RU2444524C2 (ru) * | 2006-08-21 | 2012-03-10 | Дженентек, Инк. | Азабензотиофенильные соединения и способы применения |
| US7563797B2 (en) | 2006-08-28 | 2009-07-21 | Forest Laboratories Holding Limited | Substituted imidazo(1,2-A)pyrimidines and imidazo(1,2-A) pyridines as cannabinoid receptor ligands |
| US8236841B2 (en) * | 2006-09-13 | 2012-08-07 | Kyowa Hakko Kirin Co., Ltd. | Fused heterocycle derivative |
| KR20090094336A (ko) * | 2006-11-27 | 2009-09-04 | 하. 룬트벡 아크티에 셀스카브 | 헤테로아릴 아미드 유도체 |
| CN105106199A (zh) * | 2006-12-14 | 2015-12-02 | 埃克塞利希斯股份有限公司 | 使用mek抑制剂的方法 |
| EP2155744A1 (en) * | 2007-04-10 | 2010-02-24 | Lundbeck, H., A/S | Heteroaryl amide analogues as p2x7 antagonists |
| CA2689109A1 (en) | 2007-06-25 | 2008-12-31 | Novartis Ag | N5-(2-ethoxyethyl)-n3-(2-pyridinyl) -3,5-piperidinedicarboxamide derivatives for use as renin inhibitors |
| GB0714384D0 (en) | 2007-07-23 | 2007-09-05 | Ucb Pharma Sa | theraputic agents |
| US8119658B2 (en) | 2007-10-01 | 2012-02-21 | Bristol-Myers Squibb Company | Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| WO2009064675A1 (en) * | 2007-11-12 | 2009-05-22 | Takeda Pharmaceutical Company Limited | Mapk/erk kinase inhibitors |
| BRPI0819529A2 (pt) | 2007-12-19 | 2015-05-26 | Genentech Inc | "composto de fórmula i, composição farmacêutica, método para inibir o crescimento celular anormal ou tratar um distúrbio hiperproliferativo em um mamífero e método para tratar uma doença inflamatória em um mamífero" |
| CN101903387B (zh) * | 2007-12-19 | 2014-05-21 | 健泰科生物技术公司 | 8-苯氨基咪唑并吡啶和它们在制备抗癌剂和/或抗炎剂中的用途 |
| WO2009093008A1 (en) | 2008-01-21 | 2009-07-30 | Ucb Pharma S.A. | Thieno-pyridine derivatives as mek inhibitors |
| GB0811304D0 (en) | 2008-06-19 | 2008-07-30 | Ucb Pharma Sa | Therapeutic agents |
| US8841462B2 (en) * | 2008-07-01 | 2014-09-23 | Robert A. Heald | Bicyclic heterocycles as MEK kinase inhibitors |
| JP5615274B2 (ja) * | 2008-07-01 | 2014-10-29 | ジェネンテック， インコーポレイテッド | Ｍｅｋキナーゼインヒビターとしてのイソインドロン誘導体及びその使用方法 |
| SG171993A1 (en) | 2008-12-08 | 2011-07-28 | Gilead Connecticut Inc | Imidazopyrazine syk inhibitors |
| WO2011054620A1 (en) * | 2009-10-12 | 2011-05-12 | F. Hoffmann-La Roche Ag | Combinations of a pi3k inhibitor and a mek inhibitor |
| BR112012022801B8 (pt) | 2010-03-09 | 2019-10-29 | Dana Farber Cancer Inst Inc | método de identificar um indivíduo que tem câncer que é provável beneficiar-se do tratamento com uma terapia de combinação com um inibidor de raf e um segundo inibidor e uso de um inibidor de raf e um segundo inibidor para a fabricação de um medicamento para tratar câncer |
| NZ602362A (en) | 2010-03-11 | 2014-11-28 | Gilead Connecticut Inc | Imidazopyridines syk inhibitors |
| CA2822357A1 (en) | 2010-12-22 | 2012-06-28 | Abbvie Inc. | Hepatitis c inhibitors and uses thereof |
| US8883819B2 (en) | 2011-09-01 | 2014-11-11 | Irm Llc | Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension |
| EP2578582A1 (en) | 2011-10-03 | 2013-04-10 | Respivert Limited | 1-Pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl)ureas as p38 MAP kinase inhibitors |
| CN103204822B (zh) | 2012-01-17 | 2014-12-03 | 上海科州药物研发有限公司 | 作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途 |
| JP6113828B2 (ja) | 2012-04-04 | 2017-04-12 | ライジェル ファーマシューティカルズ， インコーポレイテッド | プロテインキナーゼｃ阻害剤およびその使用 |
| CA2874905A1 (en) | 2012-05-31 | 2013-12-05 | Bayer Pharma Aktiengesellschaft | Biomarkers for determining effective response of treatments of hepatocellular carcinoma (hcc) patients |
| BR112015003418A2 (pt) | 2012-08-17 | 2017-07-04 | Hoffmann La Roche | produto farmacêutico, conjunto, métodos para estender a duração da resposta ao tratamento, de retardar ou prevenir o desenvolvimento de resistência ao tratamento, para a seleção de uma terapia e para otimizar a eficácia terapêutica. |
| EP2909188B1 (en) | 2012-10-12 | 2018-03-07 | Exelixis, Inc. | Novel process for making compounds for use in the treatment of cancer |
| UA111925C2 (uk) | 2012-12-11 | 2016-06-24 | Федора Фармасьютікалз Інк. | БІЦИКЛІЧНІ СПОЛУКИ ТА ЇХ ВИКОРИСТАННЯ ЯК АНТИБАКТЕРІАЛЬНИХ АГЕНТІВ ТА ІНГІБІТОРІВ β-ЛАКТАМАЗИ |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| CA2904610A1 (en) | 2013-03-14 | 2014-09-25 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
| UA118846C2 (uk) | 2013-03-21 | 2019-03-25 | Новартіс Аг | Комбінована терапія |
| AU2015206603B9 (en) | 2014-01-14 | 2019-07-18 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identification, assessment, prevention, and treatment of melanoma using PD-L1 isoforms |
| CN103980217B (zh) * | 2014-05-26 | 2015-12-30 | 南京林业大学 | 一类蒎烷基异噁唑类化合物及其合成方法和应用 |
| WO2016057367A1 (en) | 2014-10-06 | 2016-04-14 | Dana-Farber Cancer Institute, Inc. | Angiopoietin-2 biomarkers predictive of anti-immune checkpoint response |
| MA41866A (fr) | 2015-03-31 | 2018-02-06 | Massachusetts Gen Hospital | Molécules à auto-assemblage pour l'administration ciblée de médicaments |
| US20190008859A1 (en) | 2015-08-21 | 2019-01-10 | Acerta Pharma B.V. | Therapeutic Combinations of a MEK Inhibitor and a BTK Inhibitor |
| RU2638155C1 (ru) * | 2016-02-29 | 2017-12-12 | Общество С Ограниченной Ответственностью "Сай Фарма" | Производные бензо[d]изоксазола и их применение |
| CN107759532B (zh) * | 2017-11-23 | 2021-02-12 | 苏州大学 | 一种苯并噁唑-2-乙基肟衍生物、其制备方法及应用 |
| KR20210142154A (ko) | 2019-03-21 | 2021-11-24 | 옹쎄오 | 암 치료를 위한 키나제 억제제와 조합된 dbait 분자 |
| TWI817018B (zh) | 2019-06-28 | 2023-10-01 | 美商艾瑞生藥股份有限公司 | 用於治療ｂｒａｆ相關的疾病和失調症之化合物 |
| JP2023500906A (ja) | 2019-11-08 | 2023-01-11 | インサーム（インスティテュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシェ メディカル） | キナーゼ阻害剤に対する獲得抵抗性を有するがんの処置方法 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| CN116096710B (zh) | 2020-06-09 | 2025-07-25 | 阿雷生物药品公司 | 用于治疗braf相关疾病和障碍的4-氧代-3,4-二氢喹唑啉酮化合物 |
| JP2024521788A (ja) | 2021-05-27 | 2024-06-04 | ミラティ セラピューティクス， インコーポレイテッド | 併用療法 |
| WO2025073765A1 (en) | 2023-10-03 | 2025-04-10 | Institut National de la Santé et de la Recherche Médicale | Methods of prognosis and treatment of patients suffering from melanoma |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8607683D0 (en) | 1986-03-27 | 1986-04-30 | Ici Plc | Anti-tumor agents |
| GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| CA2116117A1 (en) | 1991-08-22 | 1993-03-04 | Hiroyuki Sueoka | Benzisoxazole compound and use thereof |
| US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| EP0710654A4 (en) | 1993-07-23 | 1996-08-28 | Green Cross Corp | TRIAZOLE DERIVATIVE AND ITS PHARMACEUTICAL USE |
| US5525625A (en) * | 1995-01-24 | 1996-06-11 | Warner-Lambert Company | 2-(2-Amino-3-methoxyphenyl)-4-oxo-4H-[1]benzopyran for treating proliferative disorders |
| US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| DK0821671T3 (da) | 1995-04-20 | 2001-04-23 | Pfizer | Arylsulfonylhydroxamsyrederivater som MMP- og TNF-inhibitorer |
| DE19517448A1 (de) * | 1995-05-12 | 1996-11-14 | Thomae Gmbh Dr K | Neue Benzothiazole und Benzoxazole, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung |
| JP3195756B2 (ja) | 1996-07-04 | 2001-08-06 | 公子 吉水 | 潤滑補助体 |
| YU1899A (sh) | 1996-07-18 | 2000-03-21 | Pfizer Inc. | Inhibitori matričnih metaloproteaza na bazi fosfinata |
| EA199900139A1 (ru) | 1996-08-23 | 1999-08-26 | Пфайзер, Инк. | Производные арилсульфониламиногидроксамовой кислоты |
| AU5131998A (en) | 1997-01-06 | 1998-08-03 | Pfizer Inc. | Cyclic sulfone derivatives |
| US6303636B1 (en) | 1997-02-03 | 2001-10-16 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| AU5493598A (en) | 1997-02-07 | 1998-08-26 | Pfizer Inc. | N-hydroxy-beta-sulfonyl-propionamide derivatives and their use as inhibitors of matrix metalloproteinases |
| CN1247531A (zh) | 1997-02-11 | 2000-03-15 | 辉瑞大药厂 | 芳基磺酰基异羟肟酸衍生物 |
| UA73073C2 (uk) | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
| US6821963B2 (en) * | 1997-07-01 | 2004-11-23 | Warner-Lambert Company | 4-Bromo or 4-iodo phenylamino benzhydroxamic acid derivatives and their use as MEK inhibitors |
| US6310060B1 (en) * | 1998-06-24 | 2001-10-30 | Warner-Lambert Company | 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives and their use as MEK inhibitors |
| DE69836378T2 (de) | 1997-07-01 | 2007-10-11 | Warner-Lambert Co. Llc | Benzoesäure- und Benzamid-Derivate von Anthranilsäure und ihre Anwendung als MEK-Inhibitoren |
| US6506798B1 (en) * | 1997-07-01 | 2003-01-14 | Warner-Lambert Company | 4-Arylamino, 4-aryloxy, and 4-arylthio diarylamines and derivatives thereof as selective MEK inhibitors |
| CA2290506C (en) | 1997-07-01 | 2005-12-27 | Warner-Lambert Company | 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives and their use as mek inhibitors |
| US5877309A (en) * | 1997-08-13 | 1999-03-02 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides against JNK |
| GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
| GB9801690D0 (en) | 1998-01-27 | 1998-03-25 | Pfizer Ltd | Therapeutic agents |
| PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
| PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
| HUP0104933A3 (en) | 1999-01-07 | 2003-12-29 | Warner Lambert Co | Antiviral method using mek inhibitors |
| BR9916785A (pt) | 1999-01-07 | 2001-10-23 | Warner Lambert Co | Tratamento de asma com inibidores mek |
| CA2348236A1 (en) | 1999-01-13 | 2000-07-20 | Stephen Douglas Barrett | 4-arylamino, 4-aryloxy, and 4-arylthio diarylamines and derivatives thereof as selective mek inhibitors |
| JP2000204079A (ja) * | 1999-01-13 | 2000-07-25 | Warner Lambert Co | ジアリ―ルアミン |
| AU2483400A (en) | 1999-01-13 | 2000-08-01 | Warner-Lambert Company | 4'heteroaryl diarylamines |
| BR9916894A (pt) * | 1999-01-13 | 2001-11-20 | Warner Lambert Co | ácidos sulfohidroxâmicos e sulfohidroxamatos eseu uso como inibidores de mek |
| ATE309205T1 (de) | 1999-01-13 | 2005-11-15 | Warner Lambert Co | Benzenesulfonamid-derivative und ihre verwendung als mek-inhibitoren |
| YU49401A (sh) | 1999-01-13 | 2004-07-15 | Warner-Lambert Company | Benzoheterocikli i njihova upotreba kao inhibitori mek |
| DE69926914T2 (de) | 1999-01-13 | 2006-06-29 | Warner-Lambert Co. Llc | 1-heterozyklus-substituierte diarylaminen |
| GB9910577D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
| CA2377100A1 (en) | 1999-07-16 | 2001-01-25 | Warner-Lambert Company | Method for treating chronic pain using mek inhibitors |
| ES2208364T3 (es) | 1999-07-16 | 2004-06-16 | Warner-Lambert Company Llc | Procedimiento para tratar dolor cronico usando inhibidores de mek. |
| PL352684A1 (pl) | 1999-07-16 | 2003-09-08 | Warner-Lambert Company | Sposób leczenia chronicznego bólu z użyciem inhibitorów MEK |
| IL147150A0 (en) | 1999-07-16 | 2002-08-14 | Warner Lambert Co | Method for treating chronic pain using mek inhibitors |
| US7030119B1 (en) * | 1999-07-16 | 2006-04-18 | Warner-Lambert Company | Method for treating chronic pain using MEK inhibitors |
| CA2403017A1 (en) | 2000-03-15 | 2001-09-20 | Warner-Lambert Company | 5-amide substituted diarylamines as mex inhibitors |
| NZ524120A (en) | 2000-07-19 | 2005-08-26 | Warner Lambert Co | Oxygenated esters of 4-iodo phenylamino benzhydroxamic acids |
| BR0113520A (pt) | 2000-08-25 | 2003-06-24 | Warner Lambert Co | Processo de preparação de ácidos n-aril-antranìlicos e seus derivados |
| US20020052373A1 (en) * | 2000-10-26 | 2002-05-02 | Zorn Stevin H. | Combination treatment for dementia or cognitive deficits associated with alzheimer's disease and parkinson's disease |
| WO2002044166A1 (en) | 2000-11-02 | 2002-06-06 | Astrazeneca Ab | Substituted quinolines as antitumor agents |
| US6748692B2 (en) * | 2001-10-23 | 2004-06-15 | Travis Sprouse | Spinner bait |
| JP2005526076A (ja) | 2002-03-13 | 2005-09-02 | アレイ バイオファーマ、インコーポレイテッド | Ｍｅｋ阻害剤としてのｎ３アルキル化ベンズイミダゾール誘導体 |
| US7235537B2 (en) * | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
| PL401638A1 (pl) * | 2002-03-13 | 2013-05-27 | Array Biopharma Inc. | N3 alkilowane pochodne benzimidazolu jako inhibitory MEK |
| US20050049276A1 (en) * | 2003-07-23 | 2005-03-03 | Warner-Lambert Company, Llc | Imidazopyridines and triazolopyridines |
| US7144907B2 (en) * | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
-
2003
- 2003-09-03 US US10/654,580 patent/US7144907B2/en not_active Expired - Fee Related
-
2004
- 2004-08-30 US US10/929,295 patent/US7230099B2/en not_active Expired - Fee Related
- 2004-09-01 CA CA002537321A patent/CA2537321A1/en not_active Abandoned
- 2004-09-01 EP EP04783028.6A patent/EP1673339B1/en not_active Expired - Lifetime
- 2004-09-01 RU RU2006109599/04A patent/RU2006109599A/ru not_active Application Discontinuation
- 2004-09-01 CN CNA2004800326551A patent/CN1874769A/zh active Pending
- 2004-09-01 MX MXPA06002466A patent/MXPA06002466A/es not_active Application Discontinuation
- 2004-09-01 AU AU2004270699A patent/AU2004270699B2/en not_active Ceased
- 2004-09-01 JP JP2006525449A patent/JP4131741B2/ja not_active Expired - Fee Related
- 2004-09-01 KR KR1020067004505A patent/KR20060070558A/ko not_active Withdrawn
- 2004-09-01 BR BRPI0414111-3A patent/BRPI0414111A/pt not_active IP Right Cessation
- 2004-09-01 ZA ZA200602581A patent/ZA200602581B/en unknown
- 2004-09-01 PT PT47830286T patent/PT1673339E/pt unknown
- 2004-09-01 WO PCT/US2004/028649 patent/WO2005023759A2/en not_active Ceased
- 2004-09-02 AR ARP040103151A patent/AR046081A1/es not_active Application Discontinuation
- 2004-09-02 TW TW093126520A patent/TW200526607A/zh unknown
-
2006
- 2006-02-26 IL IL173936A patent/IL173936A/en not_active IP Right Cessation
- 2006-03-31 IS IS8392A patent/IS8392A/is unknown
- 2006-04-03 NO NO20061506A patent/NO20061506L/no not_active Application Discontinuation
- 2006-04-24 US US11/410,344 patent/US20060189668A1/en not_active Abandoned
- 2006-04-24 US US11/410,336 patent/US7511058B2/en not_active Expired - Fee Related
- 2006-04-24 US US11/410,343 patent/US7271178B2/en not_active Expired - Fee Related
-
2012
- 2012-05-08 IL IL219670A patent/IL219670A/en not_active IP Right Cessation
- 2012-05-08 IL IL219671A patent/IL219671A0/en unknown
- 2012-05-08 IL IL219669A patent/IL219669A0/en unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010068738A1 (en) | 2008-12-10 | 2010-06-17 | Dana-Farber Cancer Institute, Inc. | Mek mutations conferring resistance to mek inhibitors |
| WO2011106298A1 (en) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| EP3028699A1 (en) | 2010-02-25 | 2016-06-08 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| WO2013169858A1 (en) | 2012-05-08 | 2013-11-14 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MXPA06002466A (es) | Inhibidores heterociclicos de mek y metodos de uso de los mismos. | |
| US7538120B2 (en) | Method of treating inflammatory diseases | |
| US7517994B2 (en) | Heterocyclic inhibitors of MEK and methods of use thereof | |
| EP2251327B1 (en) | Heterocyclic inhibitors of mek | |
| HK1150607B (en) | Heterocyclic inhibitors of mek | |
| HK1092684B (en) | Heterocyclic inhibitors of mek |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA | Abandonment or withdrawal |