ES2650312T3 - Derivados de quinazolinona útiles como moduladores FGFR quinasa - Google Patents
Derivados de quinazolinona útiles como moduladores FGFR quinasa Download PDFInfo
- Publication number
- ES2650312T3 ES2650312T3 ES14725756.2T ES14725756T ES2650312T3 ES 2650312 T3 ES2650312 T3 ES 2650312T3 ES 14725756 T ES14725756 T ES 14725756T ES 2650312 T3 ES2650312 T3 ES 2650312T3
- Authority
- ES
- Spain
- Prior art keywords
- 6alkyl
- substituted
- 4alkyl
- nr14r15
- haloc1
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108091008794 FGF receptors Proteins 0.000 title description 32
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 title description 31
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 260
- 150000001875 compounds Chemical class 0.000 abstract description 224
- -1 -NR4R5 Chemical group 0.000 abstract description 152
- 125000005842 heteroatom Chemical group 0.000 abstract description 55
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 54
- 150000003839 salts Chemical class 0.000 abstract description 47
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 42
- 229910052760 oxygen Inorganic materials 0.000 abstract description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 35
- 229910052717 sulfur Inorganic materials 0.000 abstract description 33
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 32
- 239000001257 hydrogen Substances 0.000 abstract description 32
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 32
- 125000005843 halogen group Chemical group 0.000 abstract description 26
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract description 20
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 18
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 17
- 125000001424 substituent group Chemical group 0.000 abstract description 16
- 125000000217 alkyl group Chemical group 0.000 abstract description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 15
- 125000004452 carbocyclyl group Chemical group 0.000 abstract description 14
- 125000002950 monocyclic group Chemical group 0.000 abstract description 14
- 239000012453 solvate Substances 0.000 abstract description 14
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract description 13
- 125000002618 bicyclic heterocycle group Chemical group 0.000 abstract description 12
- 229910052736 halogen Inorganic materials 0.000 abstract description 12
- 150000002367 halogens Chemical class 0.000 abstract description 12
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract description 10
- 150000001204 N-oxides Chemical class 0.000 abstract description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 6
- 229910052799 carbon Inorganic materials 0.000 abstract description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 abstract description 5
- 125000001624 naphthyl group Chemical group 0.000 abstract description 4
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 abstract description 3
- 125000004429 atom Chemical group 0.000 abstract description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract 1
- 229910052731 fluorine Chemical group 0.000 abstract 1
- 239000011737 fluorine Chemical group 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 120
- 238000006243 chemical reaction Methods 0.000 description 98
- 239000002904 solvent Substances 0.000 description 97
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 85
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 81
- 238000011282 treatment Methods 0.000 description 69
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- 238000000034 method Methods 0.000 description 63
- 238000002360 preparation method Methods 0.000 description 63
- 206010028980 Neoplasm Diseases 0.000 description 60
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- 239000002585 base Substances 0.000 description 51
- 230000015572 biosynthetic process Effects 0.000 description 51
- 238000003786 synthesis reaction Methods 0.000 description 49
- 239000007858 starting material Substances 0.000 description 46
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 33
- 201000010099 disease Diseases 0.000 description 30
- 201000011510 cancer Diseases 0.000 description 29
- 239000000203 mixture Substances 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
- 125000003226 pyrazolyl group Chemical group 0.000 description 28
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 26
- 239000002253 acid Substances 0.000 description 26
- 229910000104 sodium hydride Inorganic materials 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 18
- 239000003814 drug Substances 0.000 description 18
- 239000012312 sodium hydride Substances 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 239000000047 product Substances 0.000 description 15
- 108091008605 VEGF receptors Proteins 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- 238000011321 prophylaxis Methods 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- 235000015320 potassium carbonate Nutrition 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 229940125846 compound 25 Drugs 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 11
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 11
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 230000001404 mediated effect Effects 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 230000033115 angiogenesis Effects 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 150000002431 hydrogen Chemical group 0.000 description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 8
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
- 125000001072 heteroaryl group Chemical group 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 7
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 7
- 230000002159 abnormal effect Effects 0.000 description 7
- 239000002246 antineoplastic agent Substances 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- 201000010028 Acrocephalosyndactylia Diseases 0.000 description 6
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 6
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 6
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 6
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 6
- 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 description 6
- 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 5
- 206010021143 Hypoxia Diseases 0.000 description 5
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 5
- 208000034578 Multiple myelomas Diseases 0.000 description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 5
- 229910020175 SiOH Inorganic materials 0.000 description 5
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 230000010261 cell growth Effects 0.000 description 5
- 230000003034 chemosensitisation Effects 0.000 description 5
- 239000006114 chemosensitizer Substances 0.000 description 5
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 5
- 230000001788 irregular Effects 0.000 description 5
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 5
- 230000002018 overexpression Effects 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 235000017550 sodium carbonate Nutrition 0.000 description 5
- SUXITUVUFUOAGT-UHFFFAOYSA-N 2,6-difluoro-3,5-dimethoxyaniline Chemical compound COC1=CC(OC)=C(F)C(N)=C1F SUXITUVUFUOAGT-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 208000025490 Apert syndrome Diseases 0.000 description 4
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 4
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
- 208000014767 Myeloproliferative disease Diseases 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 230000002491 angiogenic effect Effects 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 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 4
- 239000002775 capsule Substances 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 208000015122 neurodegenerative disease Diseases 0.000 description 4
- 125000006574 non-aromatic ring group Chemical group 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
- 210000005166 vasculature Anatomy 0.000 description 4
- 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 3
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-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
- 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 3
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 3
- CUKXRHLWPSBCTI-UHFFFAOYSA-N 2-amino-5-bromobenzoic acid Chemical compound NC1=CC=C(Br)C=C1C(O)=O CUKXRHLWPSBCTI-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
- 229930024421 Adenine Natural products 0.000 description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 3
- 206010018364 Glomerulonephritis Diseases 0.000 description 3
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 3
- 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 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 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 3
- 229960001467 bortezomib Drugs 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 229940125810 compound 20 Drugs 0.000 description 3
- 229940127204 compound 29 Drugs 0.000 description 3
- 229940125877 compound 31 Drugs 0.000 description 3
- 229940127113 compound 57 Drugs 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 230000004077 genetic alteration Effects 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 208000014951 hematologic disease Diseases 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 230000007954 hypoxia Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- FSUMZUVANZAHBW-UHFFFAOYSA-N n,n-dimethoxyaniline Chemical compound CON(OC)C1=CC=CC=C1 FSUMZUVANZAHBW-UHFFFAOYSA-N 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 229940127084 other anti-cancer agent Drugs 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000001023 pro-angiogenic effect Effects 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 239000002534 radiation-sensitizing agent Substances 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 102200143304 rs351855 Human genes 0.000 description 3
- 230000012488 skeletal system development Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 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 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
- 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 2
- VUEGYUOUAAVYAS-JGGQBBKZSA-N (6ar,9s,10ar)-9-(dimethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(C)C)=C3C2=CNC3=C1 VUEGYUOUAAVYAS-JGGQBBKZSA-N 0.000 description 2
- SRKGZXIJDGWVAI-GVAVTCRGSA-M (e,3r)-7-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)C1=NC(C(C)(C)C)=CC(C=2C=CC(F)=CC=2)=C1\C=C\C(O)C[C@@H](O)CC([O-])=O SRKGZXIJDGWVAI-GVAVTCRGSA-M 0.000 description 2
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 2
- WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
- JBKINHFZTVLNEM-UHFFFAOYSA-N 2-bromoethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCBr JBKINHFZTVLNEM-UHFFFAOYSA-N 0.000 description 2
- ZHUWTVUANDGPRC-UHFFFAOYSA-N 2-fluoro-3,5-dimethoxyaniline Chemical compound COC1=CC(N)=C(F)C(OC)=C1 ZHUWTVUANDGPRC-UHFFFAOYSA-N 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 2
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 206010008723 Chondrodystrophy Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 229940127007 Compound 39 Drugs 0.000 description 2
- 206010066946 Craniofacial dysostosis Diseases 0.000 description 2
- 208000009283 Craniosynostoses Diseases 0.000 description 2
- 206010049889 Craniosynostosis Diseases 0.000 description 2
- 201000006526 Crouzon syndrome Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 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
- 206010013883 Dwarfism Diseases 0.000 description 2
- 206010058314 Dysplasia Diseases 0.000 description 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 206010016935 Follicular thyroid cancer Diseases 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 102000003964 Histone deacetylase Human genes 0.000 description 2
- 108090000353 Histone deacetylase Proteins 0.000 description 2
- 108010078049 Interferon alpha-2 Proteins 0.000 description 2
- 208000009289 Jackson-Weiss syndrome Diseases 0.000 description 2
- 238000003749 KINOMEscan Methods 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 229910003849 O-Si Inorganic materials 0.000 description 2
- 229910003872 O—Si Inorganic materials 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 201000004014 Pfeiffer syndrome Diseases 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 239000007983 Tris buffer Substances 0.000 description 2
- IOSLINNLJFQMFF-XMMPIXPASA-N [(2R)-1-[[4-[[3-[(4-fluorophenyl)methylsulfanyl]phenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound FC1=CC=C(CSC=2C=C(OCC3=CC=C(CN4[C@H](CCC4)CO)C=C3)C=CC=2)C=C1 IOSLINNLJFQMFF-XMMPIXPASA-N 0.000 description 2
- 208000008919 achondroplasia Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000002870 angiogenesis inducing agent Substances 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 2
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 229940126086 compound 21 Drugs 0.000 description 2
- 229940125807 compound 37 Drugs 0.000 description 2
- 229940127573 compound 38 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 229940125900 compound 59 Drugs 0.000 description 2
- 210000004714 cranial suture Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- WDVGNXKCFBOKDF-UHFFFAOYSA-N dicyclohexyl-[3,6-dimethoxy-2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical compound COC1=CC=C(OC)C(C=2C(=CC(=CC=2C(C)C)C(C)C)C(C)C)=C1P(C1CCCCC1)C1CCCCC1 WDVGNXKCFBOKDF-UHFFFAOYSA-N 0.000 description 2
- IWMMXPNBCHCFCY-UHFFFAOYSA-M dicyclohexyl-[3,6-dimethoxy-2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane;palladium(2+);2-phenylethanamine;chloride Chemical compound [Pd+]Cl.NCCC1=CC=CC=[C-]1.COC1=CC=C(OC)C(C=2C(=CC(=CC=2C(C)C)C(C)C)C(C)C)=C1P(C1CCCCC1)C1CCCCC1 IWMMXPNBCHCFCY-UHFFFAOYSA-M 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 2
- 210000002196 fr. b Anatomy 0.000 description 2
- 210000003918 fraction a Anatomy 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 230000001146 hypoxic effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 230000005865 ionizing radiation Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 235000015097 nutrients Nutrition 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
- 230000011164 ossification Effects 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 201000002511 pituitary cancer Diseases 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 125000005017 substituted alkenyl group Chemical group 0.000 description 2
- 125000004426 substituted alkynyl group Chemical group 0.000 description 2
- 238000004808 supercritical fluid chromatography Methods 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
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 230000005747 tumor angiogenesis Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 2
- 235000012431 wafers Nutrition 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 2
- 229960004276 zoledronic acid Drugs 0.000 description 2
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- BWDQBBCUWLSASG-MDZDMXLPSA-N (e)-n-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1h-indol-3-yl)ethyl]amino]methyl]phenyl]prop-2-enamide Chemical compound C=1NC2=CC=CC=C2C=1CCN(CCO)CC1=CC=C(\C=C\C(=O)NO)C=C1 BWDQBBCUWLSASG-MDZDMXLPSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 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 1
- OWQPOVKKUWUEKE-UHFFFAOYSA-N 1,2,3-benzotriazine Chemical compound N1=NN=CC2=CC=CC=C21 OWQPOVKKUWUEKE-UHFFFAOYSA-N 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 description 1
- VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical group C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- WVWOOAYQYLJEFD-UHFFFAOYSA-N 1-(2-nitroimidazol-1-yl)-3-piperidin-1-ylpropan-2-ol Chemical compound C1=CN=C([N+]([O-])=O)N1CC(O)CN1CCCCC1 WVWOOAYQYLJEFD-UHFFFAOYSA-N 0.000 description 1
- OEWYWFJWBZNJJG-UHFFFAOYSA-N 1-(aziridin-1-yl)-3-(2-nitroimidazol-1-yl)propan-2-ol Chemical compound C1=CN=C([N+]([O-])=O)N1CC(O)CN1CC1 OEWYWFJWBZNJJG-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 1
- LBGSWBJURUFGLR-UHFFFAOYSA-N 1-methylpyrazol-4-amine Chemical compound CN1C=C(N)C=N1 LBGSWBJURUFGLR-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- 229940122124 17,20 lyase inhibitor Drugs 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- MFJCPDOGFAYSTF-UHFFFAOYSA-N 1H-isochromene Chemical compound C1=CC=C2COC=CC2=C1 MFJCPDOGFAYSTF-UHFFFAOYSA-N 0.000 description 1
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 description 1
- MXILHVKNAYIRPJ-UHFFFAOYSA-N 2,3,7,7a-tetrahydro-1h-triazolo[4,5-b]pyrazine Chemical compound N1C=CN=C2NNNC21 MXILHVKNAYIRPJ-UHFFFAOYSA-N 0.000 description 1
- LCQFHEIDCMPNAN-UHFFFAOYSA-N 2,6-dichloro-3,5-dimethoxyaniline Chemical compound COC1=CC(OC)=C(Cl)C(N)=C1Cl LCQFHEIDCMPNAN-UHFFFAOYSA-N 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 1
- 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 1
- LDHYTBAFXANWKM-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one Chemical compound O=C1NC(N)=NC2=C1NC=N2.O=C1NC(N)=NC2=C1N=CN2 LDHYTBAFXANWKM-UHFFFAOYSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
- XPBJPGMCFKYBBV-UHFFFAOYSA-N 2-bromoethyl-[2-hydroxy-3-(2-nitroimidazol-1-yl)propyl]azanium;bromide Chemical compound Br.BrCCNCC(O)CN1C=CN=C1[N+]([O-])=O XPBJPGMCFKYBBV-UHFFFAOYSA-N 0.000 description 1
- JSAAXJFDFKYJRJ-UHFFFAOYSA-N 2-ethylpyridine Chemical compound [CH2]CC1=CC=CC=N1 JSAAXJFDFKYJRJ-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- 150000004959 2-nitroimidazoles Chemical class 0.000 description 1
- MHIITNFQDPFSES-UHFFFAOYSA-N 25,26,27,28-tetrazahexacyclo[16.6.1.13,6.18,11.113,16.019,24]octacosa-1(25),2,4,6,8(27),9,11,13,15,17,19,21,23-tridecaene Chemical class N1C(C=C2C3=CC=CC=C3C(C=C3NC(=C4)C=C3)=N2)=CC=C1C=C1C=CC4=N1 MHIITNFQDPFSES-UHFFFAOYSA-N 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 description 1
- UMZCLZPXPCNKML-UHFFFAOYSA-N 2h-imidazo[4,5-d][1,3]thiazole Chemical compound C1=NC2=NCSC2=N1 UMZCLZPXPCNKML-UHFFFAOYSA-N 0.000 description 1
- HEYGLTRAXBZNAD-UHFFFAOYSA-N 3,3-dimethylmorpholine Chemical group CC1(C)COCCN1 HEYGLTRAXBZNAD-UHFFFAOYSA-N 0.000 description 1
- WPWNEKFMGCWNPR-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromene Chemical compound C1=CC=C2CCCSC2=C1 WPWNEKFMGCWNPR-UHFFFAOYSA-N 0.000 description 1
- NUGLIYXAARVRPQ-UHFFFAOYSA-N 3-(2-nitroimidazol-1-yl)propane-1,2-diol Chemical compound OCC(O)CN1C=CN=C1[N+]([O-])=O NUGLIYXAARVRPQ-UHFFFAOYSA-N 0.000 description 1
- XDADYJOYIMVXTH-UHFFFAOYSA-N 3h-imidazo[1,2-a]imidazole Chemical compound C1=CN2CC=NC2=N1 XDADYJOYIMVXTH-UHFFFAOYSA-N 0.000 description 1
- YCVAGNVTZICLNM-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzofuran Chemical compound C1CCCC2=C1C=CO2 YCVAGNVTZICLNM-UHFFFAOYSA-N 0.000 description 1
- XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 1
- KISUPFXQEHWGAR-RRKCRQDMSA-N 4-amino-5-bromo-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(Br)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 KISUPFXQEHWGAR-RRKCRQDMSA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
- UMEIYBJBGZKZOS-UHFFFAOYSA-N 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1NCCN2C=NN=C21 UMEIYBJBGZKZOS-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-ZVCIMWCZSA-N 9-cis-retinoic acid Chemical compound OC(=O)/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-ZVCIMWCZSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 108010000239 Aequorin Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 102100022987 Angiogenin Human genes 0.000 description 1
- 102400000068 Angiostatin Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- MXPOCMVWFLDDLZ-NSCUHMNNSA-N Apaziquone Chemical compound CN1C(\C=C\CO)=C(CO)C(C2=O)=C1C(=O)C=C2N1CC1 MXPOCMVWFLDDLZ-NSCUHMNNSA-N 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- UJKPHYRXOLRVJJ-MLSVHJFASA-N CC(O)C1=C(C)/C2=C/C3=N/C(=C\C4=C(CCC(O)=O)C(C)=C(N4)/C=C4\N=C(\C=C\1/N\2)C(C)=C4C(C)O)/C(CCC(O)=O)=C3C Chemical class CC(O)C1=C(C)/C2=C/C3=N/C(=C\C4=C(CCC(O)=O)C(C)=C(N4)/C=C4\N=C(\C=C\1/N\2)C(C)=C4C(C)O)/C(CCC(O)=O)=C3C UJKPHYRXOLRVJJ-MLSVHJFASA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- OQZDGJJWLGXCJH-UHFFFAOYSA-N ClCC1(NC=CN1)S(=O)(=O)N(C)C Chemical compound ClCC1(NC=CN1)S(=O)(=O)N(C)C OQZDGJJWLGXCJH-UHFFFAOYSA-N 0.000 description 1
- 206010048832 Colon adenoma Diseases 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- 230000008265 DNA repair mechanism Effects 0.000 description 1
- 108010019673 Darbepoetin alfa Proteins 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 208000008334 Dermatofibrosarcoma Diseases 0.000 description 1
- 206010057070 Dermatofibrosarcoma protuberans Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- XXPXYPLPSDPERN-UHFFFAOYSA-N Ecteinascidin 743 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(O)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C XXPXYPLPSDPERN-UHFFFAOYSA-N 0.000 description 1
- 102100037241 Endoglin Human genes 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 102400001047 Endostatin Human genes 0.000 description 1
- 108010079505 Endostatins Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 208000032027 Essential Thrombocythemia Diseases 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- RADBETBHIRGHDX-UHFFFAOYSA-N FCC.[I] Chemical compound FCC.[I] RADBETBHIRGHDX-UHFFFAOYSA-N 0.000 description 1
- 101150081124 FGFR gene Proteins 0.000 description 1
- 102000003972 Fibroblast growth factor 7 Human genes 0.000 description 1
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 108010029961 Filgrastim Proteins 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010048643 Hypereosinophilic syndrome Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000003815 Interleukin-11 Human genes 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 150000000996 L-ascorbic acids Chemical class 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000013460 Malate Dehydrogenase Human genes 0.000 description 1
- 108010026217 Malate Dehydrogenase Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- PAWIYAYFNXQGAP-UHFFFAOYSA-N N-hydroxy-2-[4-[[(1-methyl-3-indolyl)methylamino]methyl]-1-piperidinyl]-5-pyrimidinecarboxamide Chemical compound C12=CC=CC=C2N(C)C=C1CNCC(CC1)CCN1C1=NC=C(C(=O)NO)C=N1 PAWIYAYFNXQGAP-UHFFFAOYSA-N 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 102000001854 Steroid 17-alpha-Hydroxylase Human genes 0.000 description 1
- 108010015330 Steroid 17-alpha-Hydroxylase Proteins 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- NAVMQTYZDKMPEU-UHFFFAOYSA-N Targretin Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C(=C)C1=CC=C(C(O)=O)C=C1 NAVMQTYZDKMPEU-UHFFFAOYSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 108091033399 Telomestatin Proteins 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-NWVFGJFESA-N Tretinoin Chemical compound OC(=O)/C=C(\C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NWVFGJFESA-N 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 229940091171 VEGFR-2 tyrosine kinase inhibitor Drugs 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 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
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 206010048218 Xeroderma Diseases 0.000 description 1
- MXZNUGFCDVAXLG-CHWSQXEVSA-N [(2S)-1-[(2R)-3-methyl-2-(pyridine-4-carbonylamino)butanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@@H](NC(=O)c1ccncc1)C(=O)N1CCC[C@@H]1B(O)O MXZNUGFCDVAXLG-CHWSQXEVSA-N 0.000 description 1
- SRNKZYRMFBGSGE-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CN=C21 SRNKZYRMFBGSGE-UHFFFAOYSA-N 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 1
- 229960002184 abarelix Drugs 0.000 description 1
- AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 description 1
- 108010023617 abarelix Proteins 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- GZOSMCIZMLWJML-VJLLXTKPSA-N abiraterone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CC[C@H](O)CC3=CC2)C)CC[C@@]11C)C=C1C1=CC=CN=C1 GZOSMCIZMLWJML-VJLLXTKPSA-N 0.000 description 1
- 229960000853 abiraterone Drugs 0.000 description 1
- UVIQSJCZCSLXRZ-UBUQANBQSA-N abiraterone acetate Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CC[C@@H](CC4=CC[C@H]31)OC(=O)C)C=C2C1=CC=CN=C1 UVIQSJCZCSLXRZ-UBUQANBQSA-N 0.000 description 1
- 229960004103 abiraterone acetate Drugs 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000017733 acquired polycythemia vera Diseases 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229960001445 alitretinoin Drugs 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 108010072788 angiogenin Proteins 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- AAMATCKFMHVIDO-UHFFFAOYSA-N azane;1h-pyrrole Chemical compound N.C=1C=CNC=1 AAMATCKFMHVIDO-UHFFFAOYSA-N 0.000 description 1
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 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
- XFILPEOLDIKJHX-QYZOEREBSA-N batimastat Chemical compound C([C@@H](C(=O)NC)NC(=O)[C@H](CC(C)C)[C@H](CSC=1SC=CC=1)C(=O)NO)C1=CC=CC=C1 XFILPEOLDIKJHX-QYZOEREBSA-N 0.000 description 1
- 229950001858 batimastat Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 description 1
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 102000006995 beta-Glucosidase Human genes 0.000 description 1
- 108010047754 beta-Glucosidase Proteins 0.000 description 1
- 229960002938 bexarotene Drugs 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 208000015322 bone marrow disease Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 1
- 229950004398 broxuridine Drugs 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- 150000001767 cationic compounds Chemical class 0.000 description 1
- 229960002412 cediranib Drugs 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000025434 cerebellar degeneration Diseases 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical compound C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 1
- ZXFCRFYULUUSDW-OWXODZSWSA-N chembl2104970 Chemical compound C([C@H]1C2)C3=CC=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2CC(O)=C(C(=O)N)C1=O ZXFCRFYULUUSDW-OWXODZSWSA-N 0.000 description 1
- 230000035572 chemosensitivity Effects 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 208000013044 corticobasal degeneration disease Diseases 0.000 description 1
- 125000004122 cyclic group Chemical group 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
- 229960005029 darbepoetin alfa Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 238000005828 desilylation reaction Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 239000003085 diluting agent Substances 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
- 230000005750 disease progression Effects 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229950004203 droloxifene Drugs 0.000 description 1
- NOTIQUSPUUHHEH-UXOVVSIBSA-N dromostanolone propionate Chemical compound C([C@@H]1CC2)C(=O)[C@H](C)C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](OC(=O)CC)[C@@]2(C)CC1 NOTIQUSPUUHHEH-UXOVVSIBSA-N 0.000 description 1
- 229950004683 drostanolone propionate Drugs 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- WCDWBPCFGJXFJZ-UHFFFAOYSA-N etanidazole Chemical compound OCCNC(=O)CN1C=CN=C1[N+]([O-])=O WCDWBPCFGJXFJZ-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- ZTWTYVWXUKTLCP-UHFFFAOYSA-L ethenyl-dioxido-oxo-$l^{5}-phosphane Chemical compound [O-]P([O-])(=O)C=C ZTWTYVWXUKTLCP-UHFFFAOYSA-L 0.000 description 1
- HVJJYOAPXBPQQV-UHFFFAOYSA-N ethyl 2-azidoacetate Chemical compound CCOC(=O)CN=[N+]=[N-] HVJJYOAPXBPQQV-UHFFFAOYSA-N 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960000255 exemestane Drugs 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 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
- 230000003176 fibrotic effect Effects 0.000 description 1
- 229960004177 filgrastim Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical group C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 231100000118 genetic alteration Toxicity 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
- 229960003690 goserelin acetate Drugs 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 229960003911 histrelin acetate Drugs 0.000 description 1
- BKEMVGVBBDMHKL-VYFXDUNUSA-N histrelin acetate Chemical compound CC(O)=O.CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC(N=C1)=CN1CC1=CC=CC=C1 BKEMVGVBBDMHKL-VYFXDUNUSA-N 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 206010021198 ichthyosis Diseases 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- UFBBWLWUIISIPW-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole Chemical compound C1=CSC2=NC=CN21 UFBBWLWUIISIPW-UHFFFAOYSA-N 0.000 description 1
- CQQJSOXDEFZGFG-UHFFFAOYSA-N imidazo[4,5-d]imidazole Chemical compound C1=NC2=NC=NC2=N1 CQQJSOXDEFZGFG-UHFFFAOYSA-N 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000000338 in vitro 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
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 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
- 230000006698 induction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910001411 inorganic cation Inorganic materials 0.000 description 1
- 229960003521 interferon alfa-2a Drugs 0.000 description 1
- 229960003507 interferon alfa-2b Drugs 0.000 description 1
- 229940074383 interleukin-11 Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical compound C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl 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
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229960004942 lenalidomide Drugs 0.000 description 1
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000011981 lindlar catalyst Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
- OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
- 229950008959 marimastat Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 description 1
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- OBBCSXFCDPPXOL-UHFFFAOYSA-N misonidazole Chemical compound COCC(O)CN1C=CN=C1[N+]([O-])=O OBBCSXFCDPPXOL-UHFFFAOYSA-N 0.000 description 1
- 229950010514 misonidazole Drugs 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229960000350 mitotane Drugs 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000002346 musculoskeletal system Anatomy 0.000 description 1
- 206010028537 myelofibrosis Diseases 0.000 description 1
- 230000002071 myeloproliferative effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- QOSWSNDWUATJBJ-UHFFFAOYSA-N n,n'-diphenyloctanediamide Chemical compound C=1C=CC=CC=1NC(=O)CCCCCCC(=O)NC1=CC=CC=C1 QOSWSNDWUATJBJ-UHFFFAOYSA-N 0.000 description 1
- BLCLNMBMMGCOAS-UHFFFAOYSA-N n-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amin Chemical compound C1CCC(C(=O)NNC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(COC(C)(C)C)NC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 BLCLNMBMMGCOAS-UHFFFAOYSA-N 0.000 description 1
- MUTBJZVSRNUIHA-UHFFFAOYSA-N n-hydroxy-2-(4-naphthalen-2-ylsulfonylpiperazin-1-yl)pyrimidine-5-carboxamide Chemical compound N1=CC(C(=O)NO)=CN=C1N1CCN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CC1 MUTBJZVSRNUIHA-UHFFFAOYSA-N 0.000 description 1
- 229960004719 nandrolone Drugs 0.000 description 1
- REACBNMPQDINOF-YBBIQVIJSA-N nandrolone cyclotate Chemical compound C1CC(C)(C=C2)CCC12C(=O)O[C@H]1CC[C@H]2[C@H](CCC=3[C@@H]4CCC(=O)C=3)[C@@H]4CC[C@@]21C REACBNMPQDINOF-YBBIQVIJSA-N 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- MDJFHRLTPRPZLY-UHFFFAOYSA-N nimorazole Chemical compound [O-][N+](=O)C1=CN=CN1CCN1CCOCC1 MDJFHRLTPRPZLY-UHFFFAOYSA-N 0.000 description 1
- 229960004918 nimorazole Drugs 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 210000003254 palate Anatomy 0.000 description 1
- 229960002404 palifermin Drugs 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
- 229940046231 pamidronate Drugs 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- HQQSBEDKMRHYME-UHFFFAOYSA-N pefloxacin mesylate Chemical compound [H+].CS([O-])(=O)=O.C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN(C)CC1 HQQSBEDKMRHYME-UHFFFAOYSA-N 0.000 description 1
- 229960001373 pegfilgrastim Drugs 0.000 description 1
- 108010044644 pegfilgrastim Proteins 0.000 description 1
- 229960003931 peginterferon alfa-2b Drugs 0.000 description 1
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229950010456 pimonidazole Drugs 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical class COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
- 239000003600 podophyllotoxin derivative Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 208000037244 polycythemia vera Diseases 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 208000003476 primary myelofibrosis Diseases 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 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
- DVUBDHRTVYLIPA-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine Chemical compound C1=CC=CN2N=CC=C21 DVUBDHRTVYLIPA-UHFFFAOYSA-N 0.000 description 1
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 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
- 229950010654 quisinostat Drugs 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 229960000424 rasburicase Drugs 0.000 description 1
- 108010084837 rasburicase Proteins 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 229960002530 sargramostim Drugs 0.000 description 1
- 108010038379 sargramostim Proteins 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- MIXCUJKCXRNYFM-UHFFFAOYSA-M sodium;diiodomethanesulfonate;n-propyl-n-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboxamide Chemical compound [Na+].[O-]S(=O)(=O)C(I)I.C1=CN=CN1C(=O)N(CCC)CCOC1=C(Cl)C=C(Cl)C=C1Cl MIXCUJKCXRNYFM-UHFFFAOYSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 208000002320 spinal muscular atrophy Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 150000003444 succinic acids Chemical class 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 239000003277 telomerase inhibitor Substances 0.000 description 1
- YVSQVYZBDXIXCC-INIZCTEOSA-N telomestatin Chemical compound N=1C2=COC=1C(N=1)=COC=1C(N=1)=COC=1C(N=1)=COC=1C(N=1)=COC=1C(=C(O1)C)N=C1C(=C(O1)C)N=C1[C@@]1([H])N=C2SC1 YVSQVYZBDXIXCC-INIZCTEOSA-N 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- PLHJCIYEEKOWNM-HHHXNRCGSA-N tipifarnib Chemical compound CN1C=NC=C1[C@](N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(C)C2=CC=1)C1=CC=C(Cl)C=C1 PLHJCIYEEKOWNM-HHHXNRCGSA-N 0.000 description 1
- 229950009158 tipifarnib Drugs 0.000 description 1
- QVMPZNRFXAKISM-UHFFFAOYSA-N tirapazamine Chemical compound C1=CC=C2[N+]([O-])=NC(=N)N(O)C2=C1 QVMPZNRFXAKISM-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical compound BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 description 1
- RTKIYFITIVXBLE-QEQCGCAPSA-N trichostatin A Chemical compound ONC(=O)/C=C/C(/C)=C/[C@@H](C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-QEQCGCAPSA-N 0.000 description 1
- INQOMBQAUSQDDS-FIBGUPNXSA-N trideuterio(iodo)methane Chemical compound [2H]C([2H])([2H])I INQOMBQAUSQDDS-FIBGUPNXSA-N 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 230000006663 ubiquitin-proteasome pathway Effects 0.000 description 1
- 208000011479 upper respiratory tract disease Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000003741 urothelium Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine 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=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 1
- 229960000237 vorinostat Drugs 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940004212 yondelis Drugs 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
- C07D239/82—Oxygen atoms with an aryl radical attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Toys (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB201307577 | 2013-04-26 | ||
| GBGB1307577.5A GB201307577D0 (en) | 2013-04-26 | 2013-04-26 | New compounds |
| PCT/GB2014/051288 WO2014174307A1 (en) | 2013-04-26 | 2014-04-25 | Quinazolinone derivatives useful as fgfr kinase modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2650312T3 true ES2650312T3 (es) | 2018-01-17 |
Family
ID=48626899
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14725756.2T Active ES2650312T3 (es) | 2013-04-26 | 2014-04-25 | Derivados de quinazolinona útiles como moduladores FGFR quinasa |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US9493426B2 (enExample) |
| EP (1) | EP2989092B1 (enExample) |
| JP (1) | JP6419784B2 (enExample) |
| KR (1) | KR102341202B1 (enExample) |
| CN (1) | CN105324378B (enExample) |
| AU (1) | AU2014259151B2 (enExample) |
| BR (1) | BR112015026830B1 (enExample) |
| CA (1) | CA2910142C (enExample) |
| DK (1) | DK2989092T3 (enExample) |
| ES (1) | ES2650312T3 (enExample) |
| GB (1) | GB201307577D0 (enExample) |
| MX (1) | MX366166B (enExample) |
| RU (1) | RU2701517C2 (enExample) |
| WO (1) | WO2014174307A1 (enExample) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201007286D0 (en) | 2010-04-30 | 2010-06-16 | Astex Therapeutics Ltd | New compounds |
| GB201020179D0 (en) | 2010-11-29 | 2011-01-12 | Astex Therapeutics Ltd | New compounds |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| GB201118656D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| GB201118675D0 (en) | 2011-10-28 | 2011-12-14 | Astex Therapeutics Ltd | New compounds |
| GB201118654D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| GB201118652D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| GB201209609D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
| GB201209613D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
| SI2861595T1 (sl) | 2012-06-13 | 2017-04-26 | Incyte Holdings Corporation | Substituirane triciklične spojine kot inhibitorji fgfr |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| LT2986610T (lt) | 2013-04-19 | 2018-04-10 | Incyte Holdings Corporation | Bicikliniai heterociklai, kaip fgfr inhibitoriai |
| GB201307577D0 (en) | 2013-04-26 | 2013-06-12 | Astex Therapeutics Ltd | New compounds |
| EP3060563B1 (en) | 2013-10-25 | 2018-05-02 | Novartis AG | Ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors |
| JO3512B1 (ar) | 2014-03-26 | 2020-07-05 | Astex Therapeutics Ltd | مشتقات كينوكسالين مفيدة كمعدلات لإنزيم fgfr كيناز |
| MX370099B (es) | 2014-03-26 | 2019-12-02 | Astex Therapeutics Ltd | Combinación que comprende un inhibidor de fgfr y un inhibidor de cmet para el tratamiento del cáncer. |
| HUE053653T2 (hu) | 2014-03-26 | 2021-07-28 | Astex Therapeutics Ltd | FGFR inhibitor és IGF1R inhibitor kombinációi |
| PL3200786T3 (pl) | 2014-10-03 | 2020-03-31 | Novartis Ag | Zastosowanie pochodnych pirydylowych o skondensowanym układzie bicyklicznym jako inhibitorów fgfr4 |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| JOP20200201A1 (ar) | 2015-02-10 | 2017-06-16 | Astex Therapeutics Ltd | تركيبات صيدلانية تشتمل على n-(3.5- ثنائي ميثوكسي فينيل)-n'-(1-ميثيل إيثيل)-n-[3-(ميثيل-1h-بيرازول-4-يل) كينوكسالين-6-يل]إيثان-1.2-ثنائي الأمين |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| SG10201913036RA (en) | 2015-02-20 | 2020-02-27 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| US9802917B2 (en) | 2015-03-25 | 2017-10-31 | Novartis Ag | Particles of N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide |
| US10478494B2 (en) | 2015-04-03 | 2019-11-19 | Astex Therapeutics Ltd | FGFR/PD-1 combination therapy for the treatment of cancer |
| JP6898919B2 (ja) * | 2015-09-23 | 2021-07-07 | ヤンセン ファーマシューティカ エヌ.ベー. | 新規化合物 |
| WO2017050865A1 (en) * | 2015-09-23 | 2017-03-30 | Janssen Pharmaceutica Nv | Bi-heteroaryl substituted 1,4-benzodiazepines and uses thereof for the treatment of cancer |
| RU2732127C1 (ru) * | 2016-09-01 | 2020-09-11 | Наньцзин Транстера Биосайенсиз Ко. Лтд. | Ингибиторы рецептора фактора роста фибробластов и их применение |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| PL3788047T3 (pl) | 2018-05-04 | 2025-04-14 | Incyte Corporation | Stałe postacie inhibitora fgfr i sposoby ich otrzymywania |
| KR20210018264A (ko) | 2018-05-04 | 2021-02-17 | 인사이트 코포레이션 | Fgfr 억제제의 염 |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| CR20220169A (es) | 2019-10-14 | 2022-10-27 | Incyte Corp | Heterociclos bicíclicos como inhibidores de fgfr |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| AU2020395185A1 (en) | 2019-12-04 | 2022-06-02 | Incyte Corporation | Derivatives of an FGFR inhibitor |
| JP7720840B2 (ja) | 2019-12-04 | 2025-08-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
| CN110903253B (zh) * | 2019-12-13 | 2020-12-25 | 西安交通大学医学院第一附属医院 | 一种喹唑啉酮类化合物及其制备方法和应用 |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| JP7630801B2 (ja) * | 2020-07-13 | 2025-02-18 | 国立大学法人富山大学 | Nr4a1拮抗薬を用いた鎮痛薬 |
| CN112279834B (zh) * | 2020-12-29 | 2021-04-09 | 北京鑫开元医药科技有限公司 | 一种fgfr4抑制剂、制备方法、药物组合物及其应用 |
| TW202304459A (zh) | 2021-04-12 | 2023-02-01 | 美商英塞特公司 | 包含fgfr抑制劑及nectin-4靶向劑之組合療法 |
| CN115260164B (zh) * | 2021-05-01 | 2024-03-26 | 杭州星鳌生物科技有限公司 | 新型4(3h)-喹唑啉酮类似物的制备方法、结构组成及其在抗肿瘤药物中的应用 |
| US11939331B2 (en) | 2021-06-09 | 2024-03-26 | Incyte Corporation | Tricyclic heterocycles as FGFR inhibitors |
| EP4352060A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| KR102862736B1 (ko) | 2022-12-07 | 2025-09-22 | 부산대학교 산학협력단 | 신규 2-((트랜스-4-(4-아릴옥시)사이클로헥실)아미노)퀴나졸리논 유도체 및 이의 제조방법 |
Family Cites Families (104)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2940972A (en) | 1957-06-27 | 1960-06-14 | Thomae Gmbh Dr K | Tri-and tetra-substituted pteridine derivatives |
| US4666828A (en) | 1984-08-15 | 1987-05-19 | The General Hospital Corporation | Test for Huntington's disease |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4801531A (en) | 1985-04-17 | 1989-01-31 | Biotechnology Research Partners, Ltd. | Apo AI/CIII genomic polymorphisms predictive of atherosclerosis |
| US5272057A (en) | 1988-10-14 | 1993-12-21 | Georgetown University | Method of detecting a predisposition to cancer by the use of restriction fragment length polymorphism of the gene for human poly (ADP-ribose) polymerase |
| US5192659A (en) | 1989-08-25 | 1993-03-09 | Genetype Ag | Intron sequence analysis method for detection of adjacent and remote locus alleles as haplotypes |
| GB9125001D0 (en) | 1991-11-25 | 1992-01-22 | Ici Plc | Heterocyclic compounds |
| US5700823A (en) | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
| US6331555B1 (en) | 1995-06-01 | 2001-12-18 | University Of California | Treatment of platelet derived growth factor related disorders such as cancers |
| US6218529B1 (en) | 1995-07-31 | 2001-04-17 | Urocor, Inc. | Biomarkers and targets for diagnosis, prognosis and management of prostate, breast and bladder cancer |
| CA2744096C (en) | 1996-07-31 | 2013-07-30 | Laboratory Corporation Of America Holdings | Biomarkers and targets for diagnosis, prognosis and management of prostate disease |
| TW472045B (en) | 1996-09-25 | 2002-01-11 | Astra Ab | Protein kinase C inhibitor compounds, method for their preparation, pharmaceutical composition thereof and intermediate used for their preparation |
| CZ296845B6 (cs) | 1997-05-28 | 2006-07-12 | Aventis Pharmaceuticals Inc. | Derivát chinolinu a chinoxalinu, farmaceutický prostredek obsahující tento derivát a pouzití |
| UA71555C2 (en) | 1997-10-06 | 2004-12-15 | Zentaris Gmbh | Methods for modulating function of serine/threonine protein kinases by 5-azaquinoline derivatives |
| JP2002534512A (ja) | 1999-01-15 | 2002-10-15 | ノボ ノルディスク アクティーゼルスカブ | 非ペプチドglp−1アゴニスト |
| CA2393896A1 (en) | 1999-09-15 | 2001-03-22 | Warner-Lambert Company | Pteridinones as kinase inhibitors |
| DE10013318A1 (de) | 2000-03-17 | 2001-09-20 | Merck Patent Gmbh | Formulierung enthaltend Chinoxalinderivate |
| WO2002076985A1 (en) | 2001-03-23 | 2002-10-03 | Smithkline Beecham Corporation | Compounds useful as kinase inhibitors for the treatment of hyperproliferative diseases |
| AU2002359714B2 (en) | 2001-12-18 | 2006-12-21 | Merck Sharp & Dohme Corp. | Heteroaryl substituted pyrazole modulators of metabotropic glutamate receptor-5 |
| ES2333702T3 (es) | 2001-12-24 | 2010-02-26 | Astrazeneca Ab | Derivados de quinazolina sustituidos que actuan como unhibidores de cinasas aurora. |
| JP2003213463A (ja) | 2002-01-17 | 2003-07-30 | Sumitomo Chem Co Ltd | 金属腐食防止剤および洗浄液 |
| US7265378B2 (en) | 2002-07-10 | 2007-09-04 | E. I. Du Pont De Nemours And Company | Electronic devices made with electron transport and/or anti-quenching layers |
| US7825132B2 (en) | 2002-08-23 | 2010-11-02 | Novartis Vaccines And Diagnostics, Inc. | Inhibition of FGFR3 and treatment of multiple myeloma |
| KR20050056227A (ko) | 2002-10-03 | 2005-06-14 | 탈자진 인코포레이티드 | 혈관항상성 유지제 및 그의 사용 방법 |
| AR043059A1 (es) | 2002-11-12 | 2005-07-13 | Bayer Pharmaceuticals Corp | Derivados de indolil pirazinona utiles para el tratamiento de trastornos hiper-proliferativos |
| MXPA05007503A (es) | 2003-01-17 | 2005-09-21 | Warner Lambert Co | Heterociclicos 2-aminopiridina sustituidos como inhibidores de proliferacion celular. |
| EP1620413A2 (en) | 2003-04-30 | 2006-02-01 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| MXPA05012281A (es) | 2003-05-14 | 2006-05-19 | Torreypines Therapeutics Inc | Compuestos y uso de los mismos en la modulacion beta amiloide. |
| RU2330851C9 (ru) | 2003-05-23 | 2008-10-20 | Центарис Гмбх | ПИРИДО[2,3-b]ПИРАЗИНОВЫЕ ПРОИЗВОДНЫЕ, ЛЕКАРСТВЕННОЕ СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ ИЛИ НАРУШЕНИЯ, КОТОРЫЕ ОБУСЛОВЛЕНЫ НЕПРАВИЛЬНО НАПРАВЛЕННЫМИ ПРОЦЕССАМИ КЛЕТОЧНОЙ СИГНАЛЬНОЙ ТРАНСДУКЦИИ, СПОСОБ ПОЛУЧЕНИЯ ЛЕКАРСТВЕННОГО СРЕДСТВА |
| DE10323345A1 (de) | 2003-05-23 | 2004-12-16 | Zentaris Gmbh | Neue Pyridopyrazine und deren Verwendung als Kinase-Inhibitoren |
| WO2005007099A2 (en) | 2003-07-10 | 2005-01-27 | Imclone Systems Incorporated | Pkb inhibitors as anti-tumor agents |
| EP1646383A4 (en) | 2003-07-21 | 2009-03-25 | Bethesda Pharmaceuticals Inc | DESIGN AND SYNTHESIS OF OPTIMIZED LIGANDS FOR PPAR |
| JP4890255B2 (ja) | 2003-11-07 | 2012-03-07 | ノバルティス バクシンズ アンド ダイアグノスティックス,インコーポレーテッド | 改良された薬物特性を有するキノリノン化合物の薬学的に受容可能な塩 |
| MXPA06005687A (es) | 2003-11-20 | 2006-08-17 | Janssen Pharmaceutica Nv | 2-quinolinonas y 2-quinoxalinonas sustituidas con 6-alquenilo y 6-fenilalquilo como inhibidores de la poli(adenosin fosfato-ribosa)polimerasa. |
| JP2007512275A (ja) | 2003-11-24 | 2007-05-17 | エフ.ホフマン−ラ ロシュ アーゲー | ピラゾリルおよびイミダゾリルピリミジン |
| MXPA06007326A (es) | 2003-12-23 | 2007-01-26 | Astex Therapeutics Ltd | Derivados de pirazol como moduladores de proteina cinasa. |
| US7098222B2 (en) | 2004-05-12 | 2006-08-29 | Abbott Laboratories | Bicyclic-substituted amines having cyclic-substituted monocyclic substituents |
| US7205316B2 (en) | 2004-05-12 | 2007-04-17 | Abbott Laboratories | Tri- and bi-cyclic heteroaryl histamine-3 receptor ligands |
| BRPI0514691A (pt) * | 2004-08-31 | 2008-06-17 | Astrazeneca Ab | composto ou um sal farmaceuticamente aceitável do mesmo, processo para preparar o mesmo, composição farmacêutica, e, uso de um composto ou um sal farmaceuticamente aceitável do mesmo |
| EP1830869B1 (en) | 2004-12-24 | 2013-05-22 | Spinifex Pharmaceuticals Pty Ltd | Method of treatment or prophylaxis |
| CA2597447C (en) | 2005-02-14 | 2014-03-25 | Bionomics Limited | Novel tubulin polymerisation inhibitors |
| EP1853261B1 (de) | 2005-03-03 | 2017-01-11 | Universität des Saarlandes | Selektive hemmstoffe humaner corticoidsynthasen |
| CA2606017A1 (en) | 2005-05-12 | 2006-11-23 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| GB0513692D0 (en) | 2005-07-04 | 2005-08-10 | Karobio Ab | Novel pharmaceutical compositions |
| EP1957487A1 (de) | 2005-11-11 | 2008-08-20 | AEterna Zentaris GmbH | Neue pyridopyrazine und deren verwendung als modulatoren von kinasen |
| US8217042B2 (en) | 2005-11-11 | 2012-07-10 | Zentaris Gmbh | Pyridopyrazines and their use as modulators of kinases |
| EP1790342A1 (de) | 2005-11-11 | 2007-05-30 | Zentaris GmbH | Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege |
| EP1966214B9 (en) | 2005-12-21 | 2017-09-13 | Janssen Pharmaceutica N.V. | Triazolopyridazines as tyrosine kinase modulators |
| JP2009535393A (ja) | 2006-05-01 | 2009-10-01 | ファイザー・プロダクツ・インク | 置換2−アミノ縮合複素環式化合物 |
| GB0609621D0 (en) | 2006-05-16 | 2006-06-21 | Astrazeneca Ab | Novel co-crystal |
| CA2653117A1 (en) | 2006-05-24 | 2007-11-29 | Boehringer Ingelheim International Gmbh | Substituted pteridines substituted with a four-membered heterocycle |
| JP2009541460A (ja) | 2006-07-03 | 2009-11-26 | ベレナギング ヴォー クリスタラク ホガー オンダーヴェイル ヴェーテンザパーリク オンダージーク エン パシェンテンゾーク | ヒスタミンh4受容体と相互作用する縮合二環式化合物 |
| JP2008127446A (ja) | 2006-11-20 | 2008-06-05 | Canon Inc | 1,5−ナフチリジン化合物及び有機発光素子 |
| WO2008076278A2 (en) | 2006-12-13 | 2008-06-26 | Schering Corporation | Methods of cancer treatment with igf1r inhibitors |
| JP2010514695A (ja) | 2006-12-21 | 2010-05-06 | プレキシコン,インコーポレーテッド | キナーゼ調節のための化合物および方法およびそのための適応症 |
| CA2673003A1 (en) | 2006-12-22 | 2008-07-03 | Novartis Ag | Quinazolines for pdk1 inhibition |
| AU2007337886C1 (en) | 2006-12-22 | 2014-10-16 | Astex Therapeutics Limited | Bicyclic heterocyclic compounds as FGFR inhibitors |
| KR20080062876A (ko) | 2006-12-29 | 2008-07-03 | 주식회사 대웅제약 | 신규한 항진균성 트리아졸 유도체 |
| EP2150255A4 (en) | 2007-05-10 | 2011-10-05 | Glaxosmithkline Llc | CHINOXALINE DERIVATIVES AS P13 KINASE INHIBITORS |
| EP1990342A1 (en) | 2007-05-10 | 2008-11-12 | AEterna Zentaris GmbH | Pyridopyrazine Derivatives, Process of Manufacturing and Uses thereof |
| JP2010529031A (ja) | 2007-05-29 | 2010-08-26 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | Pi3キナーゼ阻害剤としてのナフチリジン誘導体 |
| AR066879A1 (es) | 2007-06-08 | 2009-09-16 | Novartis Ag | Derivados de quinoxalina como inhibidores de la actividad de cinasa de tirosina de las cinasas janus |
| EP2172450B9 (en) * | 2007-06-20 | 2014-10-08 | Mitsubishi Tanabe Pharma Corporation | Novel malonic acid sulfonamide derivative and pharmaceutical use thereof |
| WO2008155378A1 (en) | 2007-06-21 | 2008-12-24 | Janssen Pharmaceutica Nv | Polymorphic and hydrate forms, salts and process for preparing 6-{difluoro[6-(1-methyl-1h-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}quinoline |
| EP2173354A4 (en) | 2007-08-09 | 2011-10-05 | Glaxosmithkline Llc | CHINOXALIN DERIVATIVES AS PI3 KINASE INHIBITORS |
| WO2009019518A1 (en) | 2007-08-09 | 2009-02-12 | Astrazeneca Ab | Pyrimidine compounds having a fgfr inhibitory effect |
| US20090054304A1 (en) | 2007-08-23 | 2009-02-26 | Kalypsys, Inc. | Heterocyclic modulators of tgr5 for treatment of disease |
| WO2009064835A1 (en) | 2007-11-16 | 2009-05-22 | Incyte Corporation | 4-pyrazolyl-n-arylpyrimidin-2-amines and 4-pyrazolyl-n-heteroarylpyrimidin-2-amines as janus kinase inhibitors |
| EP2282995B1 (en) | 2008-05-23 | 2015-08-26 | Novartis AG | Derivatives of quinolines and quinoxalines as protein tyrosine kinase inhibitors |
| JP2012509342A (ja) | 2008-11-20 | 2012-04-19 | オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド | 置換ピロロ[2,3−b]−ピリジンおよび−ピラジン |
| CA2750047A1 (en) | 2009-01-21 | 2010-07-29 | Basilea Pharmaceutica Ag | Novel bicyclic antibiotics |
| EP2391623A4 (en) | 2009-02-02 | 2012-09-05 | Merck Sharp & Dohme | HAMMER OF ACT ACTIVITY |
| TW201041888A (en) | 2009-05-06 | 2010-12-01 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| HRP20230248T1 (hr) | 2009-06-12 | 2023-04-14 | Abivax | Spojevi korisni za liječenje preranog starenja, te naročito progerije |
| CA2772714C (en) | 2009-09-03 | 2017-09-26 | Bioenergenix | Heterocyclic compounds for the inhibition of pask |
| WO2011026579A1 (en) | 2009-09-04 | 2011-03-10 | Bayer Schering Pharma Aktiengesellschaft | Substituted aminoquinoxalines as tyrosine threonine kinase inhibitors |
| EP2332939A1 (en) | 2009-11-26 | 2011-06-15 | Æterna Zentaris GmbH | Novel Naphthyridine derivatives and the use thereof as kinase inhibitors |
| RU2017144535A (ru) | 2010-03-30 | 2019-02-18 | Версеон Корпорейшн | Мультизамещенные ароматические соединения в качестве ингибиторов тромбина |
| GB201007286D0 (en) | 2010-04-30 | 2010-06-16 | Astex Therapeutics Ltd | New compounds |
| US8513421B2 (en) | 2010-05-19 | 2013-08-20 | Millennium Pharmaceuticals, Inc. | Substituted hydroxamic acids and uses thereof |
| WO2011149937A1 (en) | 2010-05-24 | 2011-12-01 | Intellikine, Inc. | Heterocyclic compounds and uses thereof |
| GB201020179D0 (en) * | 2010-11-29 | 2011-01-12 | Astex Therapeutics Ltd | New compounds |
| CN102532141A (zh) | 2010-12-08 | 2012-07-04 | 中国科学院上海药物研究所 | [1,2,4]三唑并[4,3-b][1,2,4]三嗪类化合物、其制备方法和用途 |
| EP2670753B1 (en) | 2011-01-31 | 2016-10-19 | Novartis AG | Novel heterocyclic derivatives |
| TWI592411B (zh) | 2011-02-23 | 2017-07-21 | 英特爾立秦有限責任公司 | 激酶抑制劑之組合及其用途 |
| WO2012118492A1 (en) * | 2011-03-01 | 2012-09-07 | Array Biopharma Inc. | Heterocyclic sulfonamides as raf inhibitors |
| JP6002223B2 (ja) | 2011-08-26 | 2016-10-05 | ニューファーマ, インコーポレイテッド | 特定の化学的実体、組成物、および方法 |
| EP3332785B1 (en) | 2011-09-14 | 2020-05-06 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| US9249110B2 (en) | 2011-09-21 | 2016-02-02 | Neupharma, Inc. | Substituted quinoxalines as B-raf kinase inhibitors |
| EP2763994A4 (en) | 2011-10-04 | 2015-08-26 | Gilead Calistoga Llc | NEW QUINOXALINE INHIBITORS OF THE PI3K PATH |
| GB201118656D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| GB201118654D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| PH12014500912A1 (en) | 2011-10-28 | 2014-06-09 | Novartis Ag | Novel purine derivatives and their use in the treatment of disease |
| GB201118675D0 (en) | 2011-10-28 | 2011-12-14 | Astex Therapeutics Ltd | New compounds |
| JO3210B1 (ar) | 2011-10-28 | 2018-03-08 | Merck Sharp & Dohme | مثبط منصهر لبروتين نقل الكوليسترليستير اوكسازوليدينون ثمائي الحلقة |
| GB201118652D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
| GB201209609D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
| GB201209613D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
| GB201307577D0 (en) | 2013-04-26 | 2013-06-12 | Astex Therapeutics Ltd | New compounds |
| US9221804B2 (en) | 2013-10-15 | 2015-12-29 | Janssen Pharmaceutica Nv | Secondary alcohol quinolinyl modulators of RORγt |
| MX370099B (es) | 2014-03-26 | 2019-12-02 | Astex Therapeutics Ltd | Combinación que comprende un inhibidor de fgfr y un inhibidor de cmet para el tratamiento del cáncer. |
| JO3512B1 (ar) | 2014-03-26 | 2020-07-05 | Astex Therapeutics Ltd | مشتقات كينوكسالين مفيدة كمعدلات لإنزيم fgfr كيناز |
| HUE053653T2 (hu) | 2014-03-26 | 2021-07-28 | Astex Therapeutics Ltd | FGFR inhibitor és IGF1R inhibitor kombinációi |
| JOP20200201A1 (ar) | 2015-02-10 | 2017-06-16 | Astex Therapeutics Ltd | تركيبات صيدلانية تشتمل على n-(3.5- ثنائي ميثوكسي فينيل)-n'-(1-ميثيل إيثيل)-n-[3-(ميثيل-1h-بيرازول-4-يل) كينوكسالين-6-يل]إيثان-1.2-ثنائي الأمين |
-
2013
- 2013-04-26 GB GBGB1307577.5A patent/GB201307577D0/en not_active Ceased
-
2014
- 2014-04-25 AU AU2014259151A patent/AU2014259151B2/en active Active
- 2014-04-25 CN CN201480036664.1A patent/CN105324378B/zh active Active
- 2014-04-25 WO PCT/GB2014/051288 patent/WO2014174307A1/en not_active Ceased
- 2014-04-25 BR BR112015026830-7A patent/BR112015026830B1/pt active IP Right Grant
- 2014-04-25 KR KR1020157033349A patent/KR102341202B1/ko active Active
- 2014-04-25 US US14/787,089 patent/US9493426B2/en active Active
- 2014-04-25 EP EP14725756.2A patent/EP2989092B1/en active Active
- 2014-04-25 DK DK14725756.2T patent/DK2989092T3/da active
- 2014-04-25 MX MX2015014471A patent/MX366166B/es active IP Right Grant
- 2014-04-25 RU RU2015150417A patent/RU2701517C2/ru active
- 2014-04-25 JP JP2016509551A patent/JP6419784B2/ja active Active
- 2014-04-25 ES ES14725756.2T patent/ES2650312T3/es active Active
- 2014-04-25 CA CA2910142A patent/CA2910142C/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| BR112015026830A2 (pt) | 2017-07-25 |
| MX366166B (es) | 2019-07-01 |
| EP2989092A1 (en) | 2016-03-02 |
| GB201307577D0 (en) | 2013-06-12 |
| BR112015026830B1 (pt) | 2022-11-16 |
| US20160075666A1 (en) | 2016-03-17 |
| EP2989092B1 (en) | 2017-08-30 |
| CA2910142C (en) | 2021-08-10 |
| CN105324378A (zh) | 2016-02-10 |
| US9493426B2 (en) | 2016-11-15 |
| CA2910142A1 (en) | 2014-10-30 |
| JP2016521276A (ja) | 2016-07-21 |
| BR112015026830A8 (pt) | 2019-12-24 |
| CN105324378B (zh) | 2017-10-24 |
| AU2014259151B2 (en) | 2018-03-15 |
| WO2014174307A1 (en) | 2014-10-30 |
| AU2014259151A1 (en) | 2015-11-26 |
| MX2015014471A (es) | 2016-06-28 |
| KR102341202B1 (ko) | 2021-12-20 |
| RU2015150417A3 (enExample) | 2018-03-29 |
| RU2015150417A (ru) | 2017-06-06 |
| DK2989092T3 (da) | 2017-11-13 |
| JP6419784B2 (ja) | 2018-11-07 |
| KR20160003035A (ko) | 2016-01-08 |
| RU2701517C2 (ru) | 2019-09-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2650312T3 (es) | Derivados de quinazolinona útiles como moduladores FGFR quinasa | |
| ES2765031T3 (es) | Benzopirazinas anticancerígenas a través de la inhibición de las fgfr quinasas | |
| CN104011052B (zh) | 化合物 | |
| JP6363068B2 (ja) | Fgfr阻害剤としてのプテリジン | |
| CA2796204C (en) | Pyrazolyl quinoxaline kinase inhibitors | |
| ES2791179T3 (es) | Derivados de piridopirazina y naftiridina para el tratamiento del cáncer | |
| DK2776397T3 (en) | QUINOLINES AS FGFR CHINA MODULATORS | |
| ES2541493T3 (es) | Derivados de benzopirazina sustituida como inhibidores de FGFR quinasa para el tratamiento de enfermedades cancerígenas | |
| ES2688868T3 (es) | Piridopirazinas anticáncer a través de la inhibición de FGFR quinasas | |
| HK1187916B (en) | Substituted benzopyrazin derivatives as fgfr kinase inhibitors for the treatment of cancer diseases |