DK2396307T3 - NOVEL AMINO-azaheterocyclic carboxamides - Google Patents

Info

Publication number

DK2396307T3

DK2396307T3 DK10705453.8T DK10705453T DK2396307T3 DK 2396307 T3 DK2396307 T3 DK 2396307T3 DK 10705453 T DK10705453 T DK 10705453T DK 2396307 T3 DK2396307 T3 DK 2396307T3

Authority

DK

Denmark

Prior art keywords

quinazoline

phenyl

carboxylic acid

amino

acid amide

Prior art date

2009-02-11

Links

• Espacenet
• Global Dossier
• Discuss

• 150000003857 carboxamides Chemical class 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims description 472
• 238000000034 method Methods 0.000 claims description 350
• -1 R 2 is H Chemical group 0.000 claims description 273
• 238000002360 preparation method Methods 0.000 claims description 155
• 229910052757 nitrogen Inorganic materials 0.000 claims description 89
• 229910052727 yttrium Inorganic materials 0.000 claims description 68
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 47
• 150000003839 salts Chemical class 0.000 claims description 47
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
• 239000012453 solvate Substances 0.000 claims description 30
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
• 206010028980 Neoplasm Diseases 0.000 claims description 26
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
• 201000011510 cancer Diseases 0.000 claims description 19
• 201000010099 disease Diseases 0.000 claims description 17
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 15
• 229910052739 hydrogen Inorganic materials 0.000 claims description 15
• 229920006395 saturated elastomer Polymers 0.000 claims description 15
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 13
• 150000002148 esters Chemical class 0.000 claims description 12
• 239000004480 active ingredient Substances 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 11
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 9
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 9
• DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 9
• 230000008569 process Effects 0.000 claims description 9
• 125000004434 sulfur atom Chemical group 0.000 claims description 9
• 229910052731 fluorine Inorganic materials 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 7
• 229910052801 chlorine Inorganic materials 0.000 claims description 7
• 230000003463 hyperproliferative effect Effects 0.000 claims description 7
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 7
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 6
• 229910052794 bromium Inorganic materials 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000003386 piperidinyl group Chemical group 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• 206010061218 Inflammation Diseases 0.000 claims description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 4
• 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
• 230000004054 inflammatory process Effects 0.000 claims description 4
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
• 125000000623 heterocyclic group Chemical group 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• 210000002307 prostate Anatomy 0.000 claims description 3
• 125000001424 substituent group Chemical group 0.000 claims description 3
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
• 201000004624 Dermatitis Diseases 0.000 claims description 2
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 2
• 208000032612 Glial tumor Diseases 0.000 claims description 2
• 206010018338 Glioma Diseases 0.000 claims description 2
• 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
• 125000000815 N-oxide group Chemical group 0.000 claims description 2
• 201000004681 Psoriasis Diseases 0.000 claims description 2
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 2
• 125000002947 alkylene group Chemical group 0.000 claims description 2
• 125000004429 atom Chemical group 0.000 claims description 2
• 208000010668 atopic eczema Diseases 0.000 claims description 2
• 208000002780 macular degeneration Diseases 0.000 claims description 2
• 201000001441 melanoma Diseases 0.000 claims description 2
• 125000002950 monocyclic group Chemical group 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• 125000006413 ring segment Chemical group 0.000 claims description 2
• 208000017520 skin disease Diseases 0.000 claims description 2
• 230000005747 tumor angiogenesis Effects 0.000 claims description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 3
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 2
• 125000000335 thiazolyl group Chemical group 0.000 claims 2
• YLKVXHWNIUCPAW-UHFFFAOYSA-N 2-[1-[3-(1,3-benzodioxole-5-carbonylamino)phenyl]ethylamino]quinazoline-8-carboxamide Chemical compound O1COC2=C1C=CC(=C2)C(=O)NC=1C=C(C=CC=1)C(C)NC1=NC2=C(C=CC=C2C=N1)C(=O)N YLKVXHWNIUCPAW-UHFFFAOYSA-N 0.000 claims 1
• QJJRFQQQVNALNE-UHFFFAOYSA-N 2-[[4-chloro-3-(trifluoromethyl)phenyl]methylamino]quinazoline-8-carboxamide Chemical compound ClC1=C(C=C(CNC2=NC3=C(C=CC=C3C=N2)C(=O)N)C=C1)C(F)(F)F QJJRFQQQVNALNE-UHFFFAOYSA-N 0.000 claims 1
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 1
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 claims 1
• IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical compound COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 claims 1
• KHBVDSUCIZIDBP-UHFFFAOYSA-N 4-[(3,4-dimethylphenyl)methylamino]quinazoline-8-carboxylic acid Chemical compound CC=1C=C(CNC2=NC=NC3=C(C=CC=C23)C(=O)O)C=CC1C KHBVDSUCIZIDBP-UHFFFAOYSA-N 0.000 claims 1
• SICPNVSSMIOAEC-UHFFFAOYSA-N 4-[1-[3-[(4-fluoro-3-hydroxybenzoyl)amino]phenyl]ethylamino]quinazoline-8-carboxamide Chemical compound N=1C=NC2=C(C(N)=O)C=CC=C2C=1NC(C)C(C=1)=CC=CC=1NC(=O)C1=CC=C(F)C(O)=C1 SICPNVSSMIOAEC-UHFFFAOYSA-N 0.000 claims 1
• WTFZIUTUHYCQSR-UHFFFAOYSA-N 4-[[1-[3-[(2,4-difluorobenzoyl)amino]phenyl]-3-(dimethylamino)propyl]amino]quinazoline-8-carboxylic acid Chemical compound N=1C=NC2=C(C(O)=O)C=CC=C2C=1NC(CCN(C)C)C(C=1)=CC=CC=1NC(=O)C1=CC=C(F)C=C1F WTFZIUTUHYCQSR-UHFFFAOYSA-N 0.000 claims 1
• CNFJGGPOIJUVKL-UHFFFAOYSA-N 4-[[1-[3-[(4-methoxybenzoyl)amino]phenyl]-2-(methylamino)ethyl]amino]quinazoline-8-carboxamide Chemical compound N=1C=NC2=C(C(N)=O)C=CC=C2C=1NC(CNC)C(C=1)=CC=CC=1NC(=O)C1=CC=C(OC)C=C1 CNFJGGPOIJUVKL-UHFFFAOYSA-N 0.000 claims 1
• PSRICGLSQBZSDR-UHFFFAOYSA-N 4-[[2-(dimethylamino)-1-[3-[(4-methoxybenzoyl)amino]phenyl]ethyl]amino]quinazoline-8-carboxylic acid Chemical compound COc1ccc(cc1)C(=O)Nc1cccc(c1)C(CN(C)C)Nc1ncnc2c(cccc12)C(O)=O PSRICGLSQBZSDR-UHFFFAOYSA-N 0.000 claims 1
• UALHJBCHHRMERK-UHFFFAOYSA-N 4-[[2-amino-1-(3,4-dichlorophenyl)ethyl]amino]quinazoline-8-carboxamide Chemical compound N=1C=NC2=C(C(N)=O)C=CC=C2C=1NC(CN)C1=CC=C(Cl)C(Cl)=C1 UALHJBCHHRMERK-UHFFFAOYSA-N 0.000 claims 1
• SGZFLJKVODZGJM-UHFFFAOYSA-N 4-[[2-amino-1-(3,4-dimethoxyphenyl)ethyl]amino]quinazoline-8-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(CN)NC1=NC=NC2=C(C(N)=O)C=CC=C12 SGZFLJKVODZGJM-UHFFFAOYSA-N 0.000 claims 1
• IKONXWFEIGCAGN-UHFFFAOYSA-N 4-[[2-amino-1-(3-fluorophenyl)ethyl]amino]quinazoline-8-carboxamide Chemical compound N=1C=NC2=C(C(N)=O)C=CC=C2C=1NC(CN)C1=CC=CC(F)=C1 IKONXWFEIGCAGN-UHFFFAOYSA-N 0.000 claims 1
• IKGIBXZTOLRYNB-UHFFFAOYSA-N 4-[[2-amino-1-(3-methoxyphenyl)ethyl]amino]quinazoline-8-carboxylic acid Chemical compound NCC(C1=CC(=CC=C1)OC)NC1=NC=NC2=C(C=CC=C12)C(=O)O IKGIBXZTOLRYNB-UHFFFAOYSA-N 0.000 claims 1
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims 1
• UVOCNINDPZNPIC-MRXNPFEDSA-N 6-methoxy-4-[[(1s)-2-(methylamino)-1-phenylethyl]amino]quinazoline-8-carboxamide Chemical compound C1([C@H](NC=2C3=CC(OC)=CC(=C3N=CN=2)C(N)=O)CNC)=CC=CC=C1 UVOCNINDPZNPIC-MRXNPFEDSA-N 0.000 claims 1
• UVOCNINDPZNPIC-UHFFFAOYSA-N 6-methoxy-4-[[2-(methylamino)-1-phenylethyl]amino]quinazoline-8-carboxamide Chemical compound N=1C=NC2=C(C(N)=O)C=C(OC)C=C2C=1NC(CNC)C1=CC=CC=C1 UVOCNINDPZNPIC-UHFFFAOYSA-N 0.000 claims 1
• TXAQHTLIDWWEHW-UHFFFAOYSA-N N1C=C(C2=CC=CC=C12)CCNC1=NC=NC2=C(C=CC=C12)C(=O)O Chemical compound N1C=C(C2=CC=CC=C12)CCNC1=NC=NC2=C(C=CC=C12)C(=O)O TXAQHTLIDWWEHW-UHFFFAOYSA-N 0.000 claims 1
• JEQDCZREFDAEQL-UHFFFAOYSA-N NCC(C1=CC(=CC=C1)Cl)NC1=NC=NC2=C(C=CC=C12)C(=O)O Chemical compound NCC(C1=CC(=CC=C1)Cl)NC1=NC=NC2=C(C=CC=C12)C(=O)O JEQDCZREFDAEQL-UHFFFAOYSA-N 0.000 claims 1
• SYJWMTJNRBOVBR-UHFFFAOYSA-N OCCN(C1=NC=CC(=C1)C(=O)NC=1C=C(CNC2=NC=NC3=C(C=CC=C23)C(=O)O)C=CC1)C Chemical compound OCCN(C1=NC=CC(=C1)C(=O)NC=1C=C(CNC2=NC=NC3=C(C=CC=C23)C(=O)O)C=CC1)C SYJWMTJNRBOVBR-UHFFFAOYSA-N 0.000 claims 1
• 208000002193 Pain Diseases 0.000 claims 1
• 206010033645 Pancreatitis Diseases 0.000 claims 1
• 208000017442 Retinal disease Diseases 0.000 claims 1
• 206010038923 Retinopathy Diseases 0.000 claims 1
• 229910006074 SO2NH2 Inorganic materials 0.000 claims 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 1
• 201000011066 hemangioma Diseases 0.000 claims 1
• 206010020718 hyperplasia Diseases 0.000 claims 1
• 208000017169 kidney disease Diseases 0.000 claims 1
• UPGZAERNNNZSPM-UHFFFAOYSA-N quinazoline-8-carboxylic acid Chemical compound N1=CN=C2C(C(=O)O)=CC=CC2=C1 UPGZAERNNNZSPM-UHFFFAOYSA-N 0.000 claims 1
• 208000037803 restenosis Diseases 0.000 claims 1
• 150000001408 amides Chemical class 0.000 description 345
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 273
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 271
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 243
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 213
• 239000007787 solid Substances 0.000 description 211
• 239000000243 solution Substances 0.000 description 154
• 239000000047 product Substances 0.000 description 153
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 134
• 239000000203 mixture Substances 0.000 description 134
• 235000019439 ethyl acetate Nutrition 0.000 description 109
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 105
• 238000006243 chemical reaction Methods 0.000 description 101
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
• 238000005160 1H NMR spectroscopy Methods 0.000 description 84
• 239000011541 reaction mixture Substances 0.000 description 71
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 68
• 238000003756 stirring Methods 0.000 description 66
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 61
• 229940093499 ethyl acetate Drugs 0.000 description 53
• 239000002244 precipitate Substances 0.000 description 48
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 45
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 40
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 40
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 39
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
• 239000002904 solvent Substances 0.000 description 39
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 35
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
• 239000000463 material Substances 0.000 description 31
• 239000002253 acid Substances 0.000 description 27
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
• 238000004128 high performance liquid chromatography Methods 0.000 description 26
• 238000000746 purification Methods 0.000 description 24
• 230000015572 biosynthetic process Effects 0.000 description 23
• 239000003921 oil Substances 0.000 description 23
• 235000019198 oils Nutrition 0.000 description 23
• 238000002953 preparative HPLC Methods 0.000 description 23
• 239000000758 substrate Substances 0.000 description 23
• 238000003786 synthesis reaction Methods 0.000 description 23
• 230000000694 effects Effects 0.000 description 22
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
• 239000012267 brine Substances 0.000 description 21
• 230000002829 reductive effect Effects 0.000 description 21
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
• 239000000543 intermediate Substances 0.000 description 20
• 239000012071 phase Substances 0.000 description 19
• 239000000725 suspension Substances 0.000 description 19
• 102000001253 Protein Kinase Human genes 0.000 description 18
• 238000004440 column chromatography Methods 0.000 description 18
• 108060006633 protein kinase Proteins 0.000 description 18
• 108091000080 Phosphotransferase Proteins 0.000 description 17
• 238000001914 filtration Methods 0.000 description 17
• 239000003112 inhibitor Substances 0.000 description 17
• 102000020233 phosphotransferase Human genes 0.000 description 17
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
• 210000004027 cell Anatomy 0.000 description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
• MEMUNXSUKDSSRN-UHFFFAOYSA-N 4-[(3-aminophenyl)methylamino]quinazoline-8-carboxamide;hydrochloride Chemical compound Cl.N1=CN=C2C(C(=O)N)=CC=CC2=C1NCC1=CC=CC(N)=C1 MEMUNXSUKDSSRN-UHFFFAOYSA-N 0.000 description 14
• 241000124008 Mammalia Species 0.000 description 14
• 239000012043 crude product Substances 0.000 description 14
• GYBHRTQLUQOYID-UHFFFAOYSA-N quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1 GYBHRTQLUQOYID-UHFFFAOYSA-N 0.000 description 14
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
• 239000000706 filtrate Substances 0.000 description 13
• CAZALFALOKHBET-UHFFFAOYSA-N methyl 4-chloroquinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC=CC2=C1Cl CAZALFALOKHBET-UHFFFAOYSA-N 0.000 description 13
• 239000000651 prodrug Substances 0.000 description 13
• 229940002612 prodrug Drugs 0.000 description 13
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
• 238000001816 cooling Methods 0.000 description 12
• 150000004702 methyl esters Chemical class 0.000 description 12
• 229910052938 sodium sulfate Inorganic materials 0.000 description 12
• 235000011152 sodium sulphate Nutrition 0.000 description 12
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 11
• 108090000433 Aurora kinases Proteins 0.000 description 11
• 102000003989 Aurora kinases Human genes 0.000 description 11
• 102000004190 Enzymes Human genes 0.000 description 11
• 108090000790 Enzymes Proteins 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• 235000011114 ammonium hydroxide Nutrition 0.000 description 11
• 230000005764 inhibitory process Effects 0.000 description 11
• 239000012299 nitrogen atmosphere Substances 0.000 description 11
• 239000012044 organic layer Substances 0.000 description 11
• 230000026731 phosphorylation Effects 0.000 description 11
• 238000006366 phosphorylation reaction Methods 0.000 description 11
• ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 10
• 108091007960 PI3Ks Proteins 0.000 description 10
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 10
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 10
• 108091008611 Protein Kinase B Proteins 0.000 description 10
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
• 108090000765 processed proteins & peptides Proteins 0.000 description 10
• 239000000741 silica gel Substances 0.000 description 10
• 229910002027 silica gel Inorganic materials 0.000 description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 239000005441 aurora Substances 0.000 description 9
• 229910000024 caesium carbonate Inorganic materials 0.000 description 9
• 230000010261 cell growth Effects 0.000 description 9
• 239000007788 liquid Substances 0.000 description 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• 230000002159 abnormal effect Effects 0.000 description 8
• 239000000908 ammonium hydroxide Substances 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• 238000003818 flash chromatography Methods 0.000 description 8
• 230000006870 function Effects 0.000 description 8
• 230000002401 inhibitory effect Effects 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
• 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 8
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
• MCCOWFUKWQGOSO-UHFFFAOYSA-N 4-[[1-(3-aminophenyl)-3-pyrrolidin-1-ylpropyl]amino]quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1NC(C=1C=C(N)C=CC=1)CCN1CCCC1 MCCOWFUKWQGOSO-UHFFFAOYSA-N 0.000 description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
• 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 239000008346 aqueous phase Substances 0.000 description 7
• 239000000460 chlorine Substances 0.000 description 7
• 235000019441 ethanol Nutrition 0.000 description 7
• 239000001257 hydrogen Substances 0.000 description 7
• 230000001965 increasing effect Effects 0.000 description 7
• 238000004519 manufacturing process Methods 0.000 description 7
• WQWSKFSXFWLOHG-UHFFFAOYSA-N methyl 4-chloro-6-iodoquinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC(I)=CC2=C1Cl WQWSKFSXFWLOHG-UHFFFAOYSA-N 0.000 description 7
• FOIQBHSPCYEVGH-UHFFFAOYSA-N methyl 4-oxo-1h-quinazoline-8-carboxylate Chemical compound N1C=NC(=O)C2=C1C(C(=O)OC)=CC=C2 FOIQBHSPCYEVGH-UHFFFAOYSA-N 0.000 description 7
• 108090000623 proteins and genes Proteins 0.000 description 7
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• 238000005406 washing Methods 0.000 description 7
• 238000010626 work up procedure Methods 0.000 description 7
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
• 150000007513 acids Chemical class 0.000 description 6
• 230000003321 amplification Effects 0.000 description 6
• 230000006907 apoptotic process Effects 0.000 description 6
• 230000022131 cell cycle Effects 0.000 description 6
• 230000004663 cell proliferation Effects 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 238000003199 nucleic acid amplification method Methods 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• 230000019491 signal transduction Effects 0.000 description 6
• KDKUVYLMPJIGKA-UHFFFAOYSA-N 4-[[5-amino-1-[(2,6-difluorophenyl)-oxomethyl]-1,2,4-triazol-3-yl]amino]benzenesulfonamide Chemical compound N=1N(C(=O)C=2C(=CC=CC=2F)F)C(N)=NC=1NC1=CC=C(S(N)(=O)=O)C=C1 KDKUVYLMPJIGKA-UHFFFAOYSA-N 0.000 description 5
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
• 208000026310 Breast neoplasm Diseases 0.000 description 5
• 102100039872 Inner centromere protein Human genes 0.000 description 5
• 101710162819 Inner centromere protein Proteins 0.000 description 5
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 5
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 5
• 229960000583 acetic acid Drugs 0.000 description 5
• 230000004913 activation Effects 0.000 description 5
• 239000002246 antineoplastic agent Substances 0.000 description 5
• HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
• 230000000875 corresponding effect Effects 0.000 description 5
• 230000012010 growth Effects 0.000 description 5
• 208000013403 hyperactivity Diseases 0.000 description 5
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
• RMXSAKHTLYDYIP-UHFFFAOYSA-N methyl 6-iodo-4-oxo-1h-quinazoline-8-carboxylate Chemical compound N1C=NC(=O)C2=C1C(C(=O)OC)=CC(I)=C2 RMXSAKHTLYDYIP-UHFFFAOYSA-N 0.000 description 5
• 230000035772 mutation Effects 0.000 description 5
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 238000001556 precipitation Methods 0.000 description 5
• 230000035755 proliferation Effects 0.000 description 5
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
• WGGOYMCUJRCWRJ-UHFFFAOYSA-N 6-amino-4-[[4-chloro-3-(trifluoromethyl)phenyl]methylamino]quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC(N)=CC2=C1NCC1=CC=C(Cl)C(C(F)(F)F)=C1 WGGOYMCUJRCWRJ-UHFFFAOYSA-N 0.000 description 4
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
• 239000007821 HATU Substances 0.000 description 4
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 4
• 102000002278 Ribosomal Proteins Human genes 0.000 description 4
• 108010000605 Ribosomal Proteins Proteins 0.000 description 4
• 102100024908 Ribosomal protein S6 kinase beta-1 Human genes 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• 101710200273 Targeting protein for Xklp2 Proteins 0.000 description 4
• 102100024813 Targeting protein for Xklp2 Human genes 0.000 description 4
• 235000011054 acetic acid Nutrition 0.000 description 4
• 235000001014 amino acid Nutrition 0.000 description 4
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 4
• CELPHAGZKFMOMR-UHFFFAOYSA-N azanium;dichloromethane;methanol;hydroxide Chemical compound [NH4+].[OH-].OC.ClCCl CELPHAGZKFMOMR-UHFFFAOYSA-N 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 230000033228 biological regulation Effects 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
• 239000006185 dispersion Substances 0.000 description 4
• 239000003480 eluent Substances 0.000 description 4
• 230000014509 gene expression Effects 0.000 description 4
• 230000003993 interaction Effects 0.000 description 4
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
• 208000030159 metabolic disease Diseases 0.000 description 4
• ATIONWGROLCVEA-UHFFFAOYSA-N methyl 6-ethenyl-4-[[3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]methylamino]quinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC(C=C)=CC2=C1NCC1=CC=CC(NC(=O)OC(C)(C)C)=C1 ATIONWGROLCVEA-UHFFFAOYSA-N 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• 230000037361 pathway Effects 0.000 description 4
• 235000015108 pies Nutrition 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical class [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 230000001105 regulatory effect Effects 0.000 description 4
• 230000004044 response Effects 0.000 description 4
• 229960002930 sirolimus Drugs 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
• 238000006467 substitution reaction Methods 0.000 description 4
• 230000004083 survival effect Effects 0.000 description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• SSNBDGOCMUSQKH-UHFFFAOYSA-N tert-butyl n-[3-[[[8-carbamoyl-6-(1,2-dihydroxyethyl)quinazolin-4-yl]amino]methyl]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(CNC=2C3=CC(=CC(=C3N=CN=2)C(N)=O)C(O)CO)=C1 SSNBDGOCMUSQKH-UHFFFAOYSA-N 0.000 description 4
• 230000014616 translation Effects 0.000 description 4
• 239000003643 water by type Substances 0.000 description 4
• KRRWAASSBQOAHT-MRVPVSSYSA-N (1s)-2-azido-1-phenylethanamine Chemical compound [N-]=[N+]=NC[C@@H](N)C1=CC=CC=C1 KRRWAASSBQOAHT-MRVPVSSYSA-N 0.000 description 3
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
• IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 3
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
• NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 description 3
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
• HAWMGYVPJGGBFN-UHFFFAOYSA-N 4-[(3-aminophenyl)methylamino]quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1NCC1=CC=CC(N)=C1 HAWMGYVPJGGBFN-UHFFFAOYSA-N 0.000 description 3
• NPSTWKVVOHABJN-UHFFFAOYSA-N 4-[(4-aminophenyl)methylamino]quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1NCC1=CC=C(N)C=C1 NPSTWKVVOHABJN-UHFFFAOYSA-N 0.000 description 3
• YMZRVSIMAIQEJB-UHFFFAOYSA-N 4-oxo-1h-quinazoline-8-carboxylic acid Chemical compound N1=CNC(=O)C2=C1C(C(=O)O)=CC=C2 YMZRVSIMAIQEJB-UHFFFAOYSA-N 0.000 description 3
• 206010006187 Breast cancer Diseases 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• 108091007914 CDKs Proteins 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• 108090000266 Cyclin-dependent kinases Proteins 0.000 description 3
• 102000003903 Cyclin-dependent kinases Human genes 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 239000007995 HEPES buffer Substances 0.000 description 3
• 101001051706 Homo sapiens Ribosomal protein S6 kinase beta-1 Proteins 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 206010034764 Peutz-Jeghers syndrome Diseases 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 230000018199 S phase Effects 0.000 description 3
• 102100026715 Serine/threonine-protein kinase STK11 Human genes 0.000 description 3
• 101710181599 Serine/threonine-protein kinase STK11 Proteins 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• ARVVGPPODCHFPK-UHFFFAOYSA-N [3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(3-nitrophenyl)propyl] 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCC(NC(=O)OC(C)(C)C)C1=CC=CC([N+]([O-])=O)=C1 ARVVGPPODCHFPK-UHFFFAOYSA-N 0.000 description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 150000001413 amino acids Chemical class 0.000 description 3
• 229910021529 ammonia Inorganic materials 0.000 description 3
• 230000002547 anomalous effect Effects 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 230000021953 cytokinesis Effects 0.000 description 3
• 230000004069 differentiation Effects 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 238000001952 enzyme assay Methods 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 108020004999 messenger RNA Proteins 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 3
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
• WCYSVIMUYDWOPM-UHFFFAOYSA-N methyl 3-amino-3-(3-nitrophenyl)propanoate Chemical compound COC(=O)CC(N)C1=CC=CC([N+]([O-])=O)=C1 WCYSVIMUYDWOPM-UHFFFAOYSA-N 0.000 description 3
• JTSLALYXYSRPGW-UHFFFAOYSA-N n-[5-(4-cyanophenyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NC(C1=C2)=CNC1=NC=C2C1=CC=C(C#N)C=C1 JTSLALYXYSRPGW-UHFFFAOYSA-N 0.000 description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 3
• DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 230000005855 radiation Effects 0.000 description 3
• 238000001959 radiotherapy Methods 0.000 description 3
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
• 150000003384 small molecules Chemical class 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
• 238000013519 translation Methods 0.000 description 3
• 210000004881 tumor cell Anatomy 0.000 description 3
• 238000000825 ultraviolet detection Methods 0.000 description 3
• 238000011144 upstream manufacturing Methods 0.000 description 3
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
• DPXXYMQUWQIWCM-UHFFFAOYSA-N 1-(3-nitrophenyl)-3-pyrrolidin-1-ylpropan-1-amine Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C(N)CCN1CCCC1 DPXXYMQUWQIWCM-UHFFFAOYSA-N 0.000 description 2
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• RATSANVPHHXDCT-UHFFFAOYSA-N 4-(trifluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=C(OC(F)(F)F)C=C1 RATSANVPHHXDCT-UHFFFAOYSA-N 0.000 description 2
• UOYTTXGBPMYPLE-UHFFFAOYSA-N 4-[1-(3-aminophenyl)ethylamino]quinazoline-8-carboxamide Chemical compound N=1C=NC2=C(C(N)=O)C=CC=C2C=1NC(C)C1=CC=CC(N)=C1 UOYTTXGBPMYPLE-UHFFFAOYSA-N 0.000 description 2
• YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 2
• HITVHYHCWXALKZ-MRXNPFEDSA-N 4-[[(1s)-2-(ethylamino)-1-phenylethyl]amino]quinazoline-8-carboxamide Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=CN=2)C(N)=O)CNCC)=CC=CC=C1 HITVHYHCWXALKZ-MRXNPFEDSA-N 0.000 description 2
• MFPCXWBJHINRKG-QGZVFWFLSA-N 4-[[(1s)-2-hydroxy-1-phenylethyl]amino]quinoline-8-carbonitrile Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=CC=2)C#N)CO)=CC=CC=C1 MFPCXWBJHINRKG-QGZVFWFLSA-N 0.000 description 2
• DAJCKHCRJIXKHC-UHFFFAOYSA-N 4-[[1-(3-aminophenyl)-3-methoxypropyl]amino]quinazoline-8-carboxamide Chemical compound N=1C=NC2=C(C(N)=O)C=CC=C2C=1NC(CCOC)C1=CC=CC(N)=C1 DAJCKHCRJIXKHC-UHFFFAOYSA-N 0.000 description 2
• WEGBYDBCGCQGMC-UHFFFAOYSA-N 4-[[3-[(4-methoxybenzoyl)-methylamino]phenyl]methylamino]quinazoline-8-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)N(C)C1=CC=CC(CNC=2C3=CC=CC(=C3N=CN=2)C(N)=O)=C1 WEGBYDBCGCQGMC-UHFFFAOYSA-N 0.000 description 2
• MGAKKWGHIRKPMT-UHFFFAOYSA-N 4-[[3-methoxy-1-(3-nitrophenyl)propyl]amino]quinazoline-8-carboxamide Chemical compound N=1C=NC2=C(C(N)=O)C=CC=C2C=1NC(CCOC)C1=CC=CC([N+]([O-])=O)=C1 MGAKKWGHIRKPMT-UHFFFAOYSA-N 0.000 description 2
• CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 102000004228 Aurora kinase B Human genes 0.000 description 2
• 108090000749 Aurora kinase B Proteins 0.000 description 2
• JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 2
• 229940123587 Cell cycle inhibitor Drugs 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 241001137251 Corvidae Species 0.000 description 2
• 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 2
• 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 2
• PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 102000006947 Histones Human genes 0.000 description 2
• 108010033040 Histones Proteins 0.000 description 2
• 206010022489 Insulin Resistance Diseases 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 2
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
• 208000008589 Obesity Diseases 0.000 description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 102100037414 Rac GTPase-activating protein 1 Human genes 0.000 description 2
• 101710196218 Rac GTPase-activating protein 1 Proteins 0.000 description 2
• 201000000582 Retinoblastoma Diseases 0.000 description 2
• 101710108924 Ribosomal protein S6 kinase beta-1 Proteins 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• 108010002687 Survivin Proteins 0.000 description 2
• 102000000763 Survivin Human genes 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 2
• 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 2
• YKNZTUQUXUXTLE-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=CC(C(F)(F)F)=C1 YKNZTUQUXUXTLE-UHFFFAOYSA-N 0.000 description 2
• 229940022663 acetate Drugs 0.000 description 2
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
• 235000019270 ammonium chloride Nutrition 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 230000033115 angiogenesis Effects 0.000 description 2
• 239000004037 angiogenesis inhibitor Substances 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 239000004305 biphenyl Substances 0.000 description 2
• 235000010290 biphenyl Nutrition 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 230000000973 chemotherapeutic effect Effects 0.000 description 2
• 238000004296 chiral HPLC Methods 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 210000001072 colon Anatomy 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 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 2
• 230000007423 decrease Effects 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 238000006911 enzymatic reaction Methods 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 239000002198 insoluble material Substances 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 229940043355 kinase inhibitor Drugs 0.000 description 2
• 239000004310 lactic acid Substances 0.000 description 2
• 235000014655 lactic acid Nutrition 0.000 description 2
• 125000005647 linker group Chemical group 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• 239000001630 malic acid Substances 0.000 description 2
• 235000011090 malic acid Nutrition 0.000 description 2
• 230000035800 maturation Effects 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• NJKAZVLZWRJRCF-UHFFFAOYSA-N methyl 4-[[3-methoxy-1-(3-nitrophenyl)propyl]amino]quinazoline-8-carboxylate Chemical compound N=1C=NC2=C(C(=O)OC)C=CC=C2C=1NC(CCOC)C1=CC=CC([N+]([O-])=O)=C1 NJKAZVLZWRJRCF-UHFFFAOYSA-N 0.000 description 2
• XPSLQEXRZDNOFZ-UHFFFAOYSA-N methyl 6-iodo-4-[[3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]methylamino]quinazoline-2-carboxylate Chemical compound C=12C=C(I)C=CC2=NC(C(=O)OC)=NC=1NCC1=CC=CC(NC(=O)OC(C)(C)C)=C1 XPSLQEXRZDNOFZ-UHFFFAOYSA-N 0.000 description 2
• LEGKDPRUXDCBCA-UHFFFAOYSA-N methyl 6-iodo-4-[[3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]methylamino]quinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC(I)=CC2=C1NCC1=CC=CC(NC(=O)OC(C)(C)C)=C1 LEGKDPRUXDCBCA-UHFFFAOYSA-N 0.000 description 2
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 2
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
• 244000005700 microbiome Species 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 230000011278 mitosis Effects 0.000 description 2
• 230000000394 mitotic effect Effects 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 235000020824 obesity Nutrition 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
• 239000012285 osmium tetroxide Substances 0.000 description 2
• 230000002018 overexpression Effects 0.000 description 2
• BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 2
• 201000002528 pancreatic cancer Diseases 0.000 description 2
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
• WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• 230000002062 proliferating effect Effects 0.000 description 2
• 230000002685 pulmonary effect Effects 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 230000001235 sensitizing effect Effects 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 2
• 239000012258 stirred mixture Substances 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• 230000008685 targeting Effects 0.000 description 2
• 239000011975 tartaric acid Substances 0.000 description 2
• 235000002906 tartaric acid Nutrition 0.000 description 2
• 238000003419 tautomerization reaction Methods 0.000 description 2
• LSOZALWRNWQPLK-UHFFFAOYSA-N tert-butyl n-[(3-aminophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC(N)=C1 LSOZALWRNWQPLK-UHFFFAOYSA-N 0.000 description 2
• IUBFAZSFGODJPA-UHFFFAOYSA-N tert-butyl n-[3-(1-aminoethyl)phenyl]carbamate Chemical compound CC(N)C1=CC=CC(NC(=O)OC(C)(C)C)=C1 IUBFAZSFGODJPA-UHFFFAOYSA-N 0.000 description 2
• JSSSBSWQIXUCLQ-UHFFFAOYSA-N tert-butyl n-[3-[1-[(8-carbamoylquinazolin-4-yl)amino]ethyl]phenyl]carbamate Chemical compound N=1C=NC2=C(C(N)=O)C=CC=C2C=1NC(C)C1=CC=CC(NC(=O)OC(C)(C)C)=C1 JSSSBSWQIXUCLQ-UHFFFAOYSA-N 0.000 description 2
• NQPCKXMZXDBUNY-UHFFFAOYSA-N tert-butyl n-[3-[[(8-carbamoyl-6-formylquinazolin-4-yl)amino]methyl]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(CNC=2C3=CC(C=O)=CC(=C3N=CN=2)C(N)=O)=C1 NQPCKXMZXDBUNY-UHFFFAOYSA-N 0.000 description 2
• BMXVHUJLRNUTPB-UHFFFAOYSA-N tert-butyl n-[3-[[[8-carbamoyl-6-(hydroxymethyl)quinazolin-4-yl]amino]methyl]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(CNC=2C3=CC(CO)=CC(=C3N=CN=2)C(N)=O)=C1 BMXVHUJLRNUTPB-UHFFFAOYSA-N 0.000 description 2
• HABQSOAEHLQKKG-UHFFFAOYSA-N tert-butyl n-[3-hydroxy-1-(3-nitrophenyl)propyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(CCO)C1=CC=CC([N+]([O-])=O)=C1 HABQSOAEHLQKKG-UHFFFAOYSA-N 0.000 description 2
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 2
• 238000001665 trituration Methods 0.000 description 2
• 230000004614 tumor growth Effects 0.000 description 2
• IKBMZMKEBCIDPD-FYZOBXCZSA-N (1r)-1-(3-nitrophenyl)ethanamine;hydrochloride Chemical compound Cl.C[C@@H](N)C1=CC=CC([N+]([O-])=O)=C1 IKBMZMKEBCIDPD-FYZOBXCZSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
• JUSWZYFYLXTMLJ-JTQLQIEISA-N (2s)-1-(benzenesulfonyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1S(=O)(=O)C1=CC=CC=C1 JUSWZYFYLXTMLJ-JTQLQIEISA-N 0.000 description 1
• RQYKQWFHJOBBAO-JTQLQIEISA-N (2s)-1-benzoylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)C1=CC=CC=C1 RQYKQWFHJOBBAO-JTQLQIEISA-N 0.000 description 1
• IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 1
• HGRWHBQLRXWSLV-DEOSSOPVSA-N (4s)-3'-(3,6-dihydro-2h-pyran-5-yl)-1'-fluoro-7'-(3-fluoropyridin-2-yl)spiro[5h-1,3-oxazole-4,5'-chromeno[2,3-c]pyridine]-2-amine Chemical compound C1OC(N)=N[C@]21C1=CC(C=3COCCC=3)=NC(F)=C1OC1=CC=C(C=3C(=CC=CN=3)F)C=C12 HGRWHBQLRXWSLV-DEOSSOPVSA-N 0.000 description 1
• 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
• 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
• FBQJSTRRHBTMMQ-UHFFFAOYSA-N 1-chloro-7-methylisoquinoline Chemical compound C1=CN=C(Cl)C2=CC(C)=CC=C21 FBQJSTRRHBTMMQ-UHFFFAOYSA-N 0.000 description 1
• 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000005808 2,4,6-trimethoxyphenyl group Chemical group [H][#6]-1=[#6](-[#8]C([H])([H])[H])-[#6](-*)=[#6](-[#8]C([H])([H])[H])-[#6]([H])=[#6]-1-[#8]C([H])([H])[H] 0.000 description 1
• JIZVMILRYBKPFN-UHFFFAOYSA-N 2,6-dibromo-4-methoxyaniline Chemical compound COC1=CC(Br)=C(N)C(Br)=C1 JIZVMILRYBKPFN-UHFFFAOYSA-N 0.000 description 1
• HNUJOYMRHWMPOM-UHFFFAOYSA-N 2-(3-fluorophenyl)-2-hydroxyacetic acid Chemical compound OC(=O)C(O)C1=CC=CC(F)=C1 HNUJOYMRHWMPOM-UHFFFAOYSA-N 0.000 description 1
• CTBARTMXUVSCRR-UHFFFAOYSA-N 2-(6-bromopyridin-3-yl)acetonitrile Chemical compound BrC1=CC=C(CC#N)C=N1 CTBARTMXUVSCRR-UHFFFAOYSA-N 0.000 description 1
• MOPFCAZSSMNDDE-UHFFFAOYSA-N 2-(dimethylamino)-1-(3-methoxyphenyl)ethanone Chemical compound COC1=CC=CC(C(=O)CN(C)C)=C1 MOPFCAZSSMNDDE-UHFFFAOYSA-N 0.000 description 1
• UZYQSNQJLWTICD-UHFFFAOYSA-N 2-(n-benzoylanilino)-2,2-dinitroacetic acid Chemical compound C=1C=CC=CC=1N(C(C(=O)O)([N+]([O-])=O)[N+]([O-])=O)C(=O)C1=CC=CC=C1 UZYQSNQJLWTICD-UHFFFAOYSA-N 0.000 description 1
• OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
• KQOFWDBENVYNSA-UHFFFAOYSA-N 2-amino-5-methoxybenzene-1,3-dicarbonitrile Chemical compound COC1=CC(C#N)=C(N)C(C#N)=C1 KQOFWDBENVYNSA-UHFFFAOYSA-N 0.000 description 1
• AGCMUJTYJYULPT-UHFFFAOYSA-N 2-amino-5-methoxybenzene-1,3-dicarboxylic acid Chemical compound COC1=CC(C(O)=O)=C(N)C(C(O)=O)=C1 AGCMUJTYJYULPT-UHFFFAOYSA-N 0.000 description 1
• DYZDIWNRWSNVPT-UHFFFAOYSA-N 2-amino-6-methoxybenzoic acid Chemical compound COC1=CC=CC(N)=C1C(O)=O DYZDIWNRWSNVPT-UHFFFAOYSA-N 0.000 description 1
• LDOMKUVUXZRECL-UHFFFAOYSA-N 2-aminobenzene-1,3-dicarboxylic acid Chemical compound NC1=C(C(O)=O)C=CC=C1C(O)=O LDOMKUVUXZRECL-UHFFFAOYSA-N 0.000 description 1
• KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
• IOOHBIFQNQQUFI-UHFFFAOYSA-N 2-bromo-1-(3-methoxyphenyl)ethanone Chemical compound COC1=CC=CC(C(=O)CBr)=C1 IOOHBIFQNQQUFI-UHFFFAOYSA-N 0.000 description 1
• LSZMVESSGLHDJE-UHFFFAOYSA-N 2-bromo-4-methylpyridine Chemical compound CC1=CC=NC(Br)=C1 LSZMVESSGLHDJE-UHFFFAOYSA-N 0.000 description 1
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
• IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
• BSQLQMLFTHJVKS-UHFFFAOYSA-N 2-chloro-1,3-benzothiazole Chemical compound C1=CC=C2SC(Cl)=NC2=C1 BSQLQMLFTHJVKS-UHFFFAOYSA-N 0.000 description 1
• GBNPVXZNWBWNEN-UHFFFAOYSA-N 2-chloro-4-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=NC(Cl)=C1 GBNPVXZNWBWNEN-UHFFFAOYSA-N 0.000 description 1
• CZQXWSPZVZKNRM-UHFFFAOYSA-N 2-chloro-6-(trifluoromethyl)-1h-benzimidazole Chemical compound FC(F)(F)C1=CC=C2N=C(Cl)NC2=C1 CZQXWSPZVZKNRM-UHFFFAOYSA-N 0.000 description 1
• FVUFTABOJFRHSU-UHFFFAOYSA-N 2-chloro-6-methoxy-1,3-benzothiazole Chemical compound COC1=CC=C2N=C(Cl)SC2=C1 FVUFTABOJFRHSU-UHFFFAOYSA-N 0.000 description 1
• QORVXCUHOOQAJL-UHFFFAOYSA-N 2-chloro-n-[3-[2-(dimethylamino)-1-(1,3-dioxoisoindol-2-yl)ethyl]phenyl]pyridine-4-carboxamide Chemical compound O=C1C2=CC=CC=C2C(=O)N1C(CN(C)C)C(C=1)=CC=CC=1NC(=O)C1=CC=NC(Cl)=C1 QORVXCUHOOQAJL-UHFFFAOYSA-N 0.000 description 1
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
• OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
• QRXBTPFMCTXCRD-UHFFFAOYSA-N 2-chloropyridine-4-carbonitrile Chemical compound ClC1=CC(C#N)=CC=N1 QRXBTPFMCTXCRD-UHFFFAOYSA-N 0.000 description 1
• UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
• OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 1
• LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
• ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• ONLRUXGFBWJVJE-UHFFFAOYSA-N 2-methoxy-1-(3-nitrophenyl)ethanamine Chemical compound COCC(N)C1=CC=CC([N+]([O-])=O)=C1 ONLRUXGFBWJVJE-UHFFFAOYSA-N 0.000 description 1
• HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• CESUXLKAADQNTB-SSDOTTSWSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@](N)=O CESUXLKAADQNTB-SSDOTTSWSA-N 0.000 description 1
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000004362 3,4,5-trichlorophenyl group Chemical group [H]C1=C(Cl)C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
• GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
• ZDBWYUOUYNQZBM-UHFFFAOYSA-N 3-(aminomethyl)aniline Chemical compound NCC1=CC=CC(N)=C1 ZDBWYUOUYNQZBM-UHFFFAOYSA-N 0.000 description 1
• KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 1
• BFGCKEHSFRPNRZ-UHFFFAOYSA-N 3-amino-2-fluorobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1F BFGCKEHSFRPNRZ-UHFFFAOYSA-N 0.000 description 1
• SJBFILRQMRECCK-UHFFFAOYSA-N 3-amino-3-(3-nitrophenyl)propanoic acid Chemical compound OC(=O)CC(N)C1=CC=CC([N+]([O-])=O)=C1 SJBFILRQMRECCK-UHFFFAOYSA-N 0.000 description 1
• HYNNNQDQEORWEU-UHFFFAOYSA-N 3-fluoro-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1F HYNNNQDQEORWEU-UHFFFAOYSA-N 0.000 description 1
• LOSBAHQDKBWMBY-UHFFFAOYSA-N 3-fluoro-4-methoxybenzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1F LOSBAHQDKBWMBY-UHFFFAOYSA-N 0.000 description 1
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• FAKWCPNASXXVJG-UHFFFAOYSA-N 3-methoxy-1-(3-nitrophenyl)propan-1-amine Chemical compound COCCC(N)C1=CC=CC([N+]([O-])=O)=C1 FAKWCPNASXXVJG-UHFFFAOYSA-N 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 1
• LWKVORKGASLSCM-UHFFFAOYSA-N 4-(benzylamino)-5-methoxyquinazoline-8-carbonitrile Chemical compound C=12C(OC)=CC=C(C#N)C2=NC=NC=1NCC1=CC=CC=C1 LWKVORKGASLSCM-UHFFFAOYSA-N 0.000 description 1
• SLZGHLVKUFSFBL-UHFFFAOYSA-N 4-(benzylamino)quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1NCC1=CC=CC=C1 SLZGHLVKUFSFBL-UHFFFAOYSA-N 0.000 description 1
• 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
• WKMQQUXWGSZFEY-UHFFFAOYSA-N 4-[(2-aminophenyl)methylamino]quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1NCC1=CC=CC=C1N WKMQQUXWGSZFEY-UHFFFAOYSA-N 0.000 description 1
• XVGWNXRXZBSCHZ-UHFFFAOYSA-N 4-[(3-aminophenyl)methylamino]-6-(hydroxymethyl)quinazoline-8-carboxamide;hydrochloride Chemical compound Cl.N1=CN=C2C(C(=O)N)=CC(CO)=CC2=C1NCC1=CC=CC(N)=C1 XVGWNXRXZBSCHZ-UHFFFAOYSA-N 0.000 description 1
• VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
• UOYTTXGBPMYPLE-SNVBAGLBSA-N 4-[[(1r)-1-(3-aminophenyl)ethyl]amino]quinazoline-8-carboxamide Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=CN=2)C(N)=O)C)=CC=CC(N)=C1 UOYTTXGBPMYPLE-SNVBAGLBSA-N 0.000 description 1
• QVKPUHCBABRGLM-JOCHJYFZSA-N 4-[[(1s)-2-[ethyl-(4-nitrophenyl)sulfonylamino]-1-phenylethyl]amino]quinazoline-8-carboxamide Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=CN=2)C(N)=O)CN(CC)S(=O)(=O)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=CC=C1 QVKPUHCBABRGLM-JOCHJYFZSA-N 0.000 description 1
• ZNBNDHNWIUYYAW-CQSZACIVSA-N 4-[[(1s)-2-azido-1-phenylethyl]amino]quinazoline-8-carboxamide Chemical compound C1([C@@H](CN=[N+]=[N-])NC2=C3C=CC=C(C3=NC=N2)C(=O)N)=CC=CC=C1 ZNBNDHNWIUYYAW-CQSZACIVSA-N 0.000 description 1
• LEZXTADOUHXXBO-QGZVFWFLSA-N 4-[[(1s)-2-azido-1-phenylethyl]amino]quinoline-8-carbonitrile Chemical compound C1([C@H](NC=2C3=CC=CC(=C3N=CC=2)C#N)CN=[N+]=[N-])=CC=CC=C1 LEZXTADOUHXXBO-QGZVFWFLSA-N 0.000 description 1
• FGCXCLHDTHADTE-UHFFFAOYSA-N 4-[[1-(3-aminophenyl)-2-hydroxyethyl]amino]quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1NC(CO)C1=CC=CC(N)=C1 FGCXCLHDTHADTE-UHFFFAOYSA-N 0.000 description 1
• VLEPKMISMIOUBK-UHFFFAOYSA-N 4-[[1-(3-chlorophenyl)-2-(dimethylamino)ethyl]amino]-6-phenylmethoxyquinazoline-8-carboxamide Chemical compound C=1C=CC(Cl)=CC=1C(CN(C)C)NC(C1=C2)=NC=NC1=C(C(N)=O)C=C2OCC1=CC=CC=C1 VLEPKMISMIOUBK-UHFFFAOYSA-N 0.000 description 1
• YCNIACHCKKBPGW-UHFFFAOYSA-N 4-[[1-(3-nitrophenyl)-3-pyrrolidin-1-ylpropyl]amino]quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1NC(C=1C=C(C=CC=1)[N+]([O-])=O)CCN1CCCC1 YCNIACHCKKBPGW-UHFFFAOYSA-N 0.000 description 1
• NERGHRXOVVUXNP-UHFFFAOYSA-N 4-[[1-[3-[(2-chloropyridine-4-carbonyl)amino]phenyl]-2-(dimethylamino)ethyl]amino]quinazoline-8-carboxamide Chemical compound N=1C=NC2=C(C(N)=O)C=CC=C2C=1NC(CN(C)C)C(C=1)=CC=CC=1NC(=O)C1=CC=NC(Cl)=C1 NERGHRXOVVUXNP-UHFFFAOYSA-N 0.000 description 1
• VPFYWPUBDHHVMD-UHFFFAOYSA-N 4-[[1-[3-[(5-cyclopropyl-1h-pyrazole-3-carbonyl)amino]phenyl]-3-hydroxypropyl]amino]quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1NC(CCO)C(C=1)=CC=CC=1NC(=O)C(NN=1)=CC=1C1CC1 VPFYWPUBDHHVMD-UHFFFAOYSA-N 0.000 description 1
• FKGMUZBYHNMNSM-UHFFFAOYSA-N 4-[[2-(dimethylamino)-1-(3-fluorophenyl)ethyl]amino]-6-hydroxyquinazoline-8-carboxamide Chemical compound N=1C=NC2=C(C(N)=O)C=C(O)C=C2C=1NC(CN(C)C)C1=CC=CC(F)=C1 FKGMUZBYHNMNSM-UHFFFAOYSA-N 0.000 description 1
• CXIHDFKIPQCBNU-UHFFFAOYSA-N 4-[[2-(dimethylamino)-1-(3-fluorophenyl)ethyl]amino]-6-phenylmethoxyquinazoline-8-carboxamide Chemical compound C=1C=CC(F)=CC=1C(CN(C)C)NC(C1=C2)=NC=NC1=C(C(N)=O)C=C2OCC1=CC=CC=C1 CXIHDFKIPQCBNU-UHFFFAOYSA-N 0.000 description 1
• FRCWIKMEVRFKBJ-UHFFFAOYSA-N 4-[[2-(methylamino)-1-phenylethyl]amino]-6-phenylmethoxyquinazoline-8-carboxamide Chemical compound C=1C=CC=CC=1C(CNC)NC(C1=C2)=NC=NC1=C(C(N)=O)C=C2OCC1=CC=CC=C1 FRCWIKMEVRFKBJ-UHFFFAOYSA-N 0.000 description 1
• QWMDXMFYSJOKEB-UHFFFAOYSA-N 4-[[2-fluoro-5-[(4-methoxybenzoyl)amino]phenyl]methylamino]quinazoline-8-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=C(F)C(CNC=2C3=CC=CC(=C3N=CN=2)C(N)=O)=C1 QWMDXMFYSJOKEB-UHFFFAOYSA-N 0.000 description 1
• SGOPVPGKQMBONR-UHFFFAOYSA-N 4-[[3-(trifluoromethyl)phenyl]methylamino]quinazoline-8-carboxylic acid Chemical compound N1=CN=C2C(C(=O)O)=CC=CC2=C1NCC1=CC=CC(C(F)(F)F)=C1 SGOPVPGKQMBONR-UHFFFAOYSA-N 0.000 description 1
• NCLXOZZMSLYBND-UHFFFAOYSA-N 4-[[3-(trifluoromethyl)phenyl]methylamino]quinoline-8-carbonitrile Chemical compound FC(F)(F)C1=CC=CC(CNC=2C3=CC=CC(=C3N=CC=2)C#N)=C1 NCLXOZZMSLYBND-UHFFFAOYSA-N 0.000 description 1
• CGRQRIYZFRKJTH-UHFFFAOYSA-N 4-[[3-[(3-hydroxybenzoyl)amino]phenyl]methylamino]quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1NCC(C=1)=CC=CC=1NC(=O)C1=CC=CC(O)=C1 CGRQRIYZFRKJTH-UHFFFAOYSA-N 0.000 description 1
• NWCVETNDCNXQME-UHFFFAOYSA-N 4-[[4-chloro-3-(trifluoromethyl)phenyl]methylamino]-6-nitroquinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC([N+]([O-])=O)=CC2=C1NCC1=CC=C(Cl)C(C(F)(F)F)=C1 NWCVETNDCNXQME-UHFFFAOYSA-N 0.000 description 1
• HLHJMHGNKSIYSU-UHFFFAOYSA-N 4-[[4-chloro-3-(trifluoromethyl)phenyl]methylamino]-6-nitroquinazoline-8-carboxylic acid Chemical compound N1=CN=C2C(C(=O)O)=CC([N+]([O-])=O)=CC2=C1NCC1=CC=C(Cl)C(C(F)(F)F)=C1 HLHJMHGNKSIYSU-UHFFFAOYSA-N 0.000 description 1
• CKSFNWDGZCXQON-UHFFFAOYSA-N 4-[[5-[(4-methoxybenzoyl)amino]-2-methylphenyl]methylamino]quinazoline-8-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=C(C)C(CNC=2C3=CC=CC(=C3N=CN=2)C(N)=O)=C1 CKSFNWDGZCXQON-UHFFFAOYSA-N 0.000 description 1
• NLSGLAZSZPWMLF-UHFFFAOYSA-N 4-amino-4-(3-nitrophenyl)butanoic acid Chemical compound OC(=O)CCC(N)C1=CC=CC([N+]([O-])=O)=C1 NLSGLAZSZPWMLF-UHFFFAOYSA-N 0.000 description 1
• 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
• MQKWVLSWSZHDGR-UHFFFAOYSA-N 4-bromoquinoline-8-carbonitrile Chemical compound C1=CC=C2C(Br)=CC=NC2=C1C#N MQKWVLSWSZHDGR-UHFFFAOYSA-N 0.000 description 1
• AFBRUNQKLYJRCA-UHFFFAOYSA-N 4-chloro-1-methylimidazo[4,5-c]pyridine Chemical compound N1=CC=C2N(C)C=NC2=C1Cl AFBRUNQKLYJRCA-UHFFFAOYSA-N 0.000 description 1
• GVRRXASZZAKBMN-UHFFFAOYSA-N 4-chloroquinazoline Chemical compound C1=CC=C2C(Cl)=NC=NC2=C1 GVRRXASZZAKBMN-UHFFFAOYSA-N 0.000 description 1
• OXKQMBHOOISBLS-UHFFFAOYSA-N 4-chloroquinoline-8-carbonitrile Chemical compound C1=CC=C2C(Cl)=CC=NC2=C1C#N OXKQMBHOOISBLS-UHFFFAOYSA-N 0.000 description 1
• 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
• GCHMJLGIJQKFDV-UHFFFAOYSA-N 4-morpholin-4-ylquinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC=CC2=C1N1CCOCC1 GCHMJLGIJQKFDV-UHFFFAOYSA-N 0.000 description 1
• JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
• 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 0.000 description 1
• HHTRAISBAAXRKZ-UHFFFAOYSA-N 5-amino-2-fluorobenzonitrile Chemical compound NC1=CC=C(F)C(C#N)=C1 HHTRAISBAAXRKZ-UHFFFAOYSA-N 0.000 description 1
• YDZVQWCVKXYGIU-UHFFFAOYSA-N 5-amino-2-methylbenzonitrile Chemical compound CC1=CC=C(N)C=C1C#N YDZVQWCVKXYGIU-UHFFFAOYSA-N 0.000 description 1
• 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 description 1
• GNWMHLBUCXEXPE-UHFFFAOYSA-N 5-cyclopropyl-1h-pyrazole-3-carboxylic acid Chemical compound N1N=C(C(=O)O)C=C1C1CC1 GNWMHLBUCXEXPE-UHFFFAOYSA-N 0.000 description 1
• YJEVNITWKNWUKX-UHFFFAOYSA-N 5-morpholin-4-ylpyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC(N2CCOCC2)=C1 YJEVNITWKNWUKX-UHFFFAOYSA-N 0.000 description 1
• SWYUPOALZWKXQY-UHFFFAOYSA-N 6-(hydroxymethyl)-4-[[3-[(4-methoxybenzoyl)amino]phenyl]methylamino]quinazoline-8-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=CC(CNC=2C3=CC(CO)=CC(=C3N=CN=2)C(N)=O)=C1 SWYUPOALZWKXQY-UHFFFAOYSA-N 0.000 description 1
• ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 1
• NVDJVEQITUWZDT-UHFFFAOYSA-N 6-Methoxy-pyridine-3-carboxylic acid Chemical compound COC1=CC=C(C(O)=O)C=N1 NVDJVEQITUWZDT-UHFFFAOYSA-N 0.000 description 1
• SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
• ORMLOSONIQIDBI-UHFFFAOYSA-N 6-hydroxy-4-[[4-(trifluoromethyl)phenyl]methylamino]quinazoline-8-carboxamide Chemical compound N1=CN=C2C(C(=O)N)=CC(O)=CC2=C1NCC1=CC=C(C(F)(F)F)C=C1 ORMLOSONIQIDBI-UHFFFAOYSA-N 0.000 description 1
• ZAUBVRZBSPZYHI-UHFFFAOYSA-N 6-methoxy-4-oxo-1h-quinazoline-8-carboxylic acid Chemical compound N1=CNC(=O)C2=CC(OC)=CC(C(O)=O)=C21 ZAUBVRZBSPZYHI-UHFFFAOYSA-N 0.000 description 1
• LFBFLVREWCTKLY-UHFFFAOYSA-N 6-nitro-4-oxo-1h-quinazoline-8-carboxylic acid Chemical compound N1=CNC(=O)C2=C1C(C(=O)O)=CC([N+]([O-])=O)=C2 LFBFLVREWCTKLY-UHFFFAOYSA-N 0.000 description 1
• BBRDYPDWYYISDZ-UHFFFAOYSA-N 6-phenylmethoxy-4-[[4-(trifluoromethyl)phenyl]methylamino]quinazoline-8-carbonitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1CNC(C1=C2)=NC=NC1=C(C#N)C=C2OCC1=CC=CC=C1 BBRDYPDWYYISDZ-UHFFFAOYSA-N 0.000 description 1
• UNQYAAAWKOOBFQ-UHFFFAOYSA-N 7-[(4-chlorophenyl)methyl]-8-[4-chloro-3-(trifluoromethoxy)phenoxy]-1-(3-hydroxypropyl)-3-methylpurine-2,6-dione Chemical compound C=1C=C(Cl)C=CC=1CN1C=2C(=O)N(CCCO)C(=O)N(C)C=2N=C1OC1=CC=C(Cl)C(OC(F)(F)F)=C1 UNQYAAAWKOOBFQ-UHFFFAOYSA-N 0.000 description 1
• 108010013238 70-kDa Ribosomal Protein S6 Kinases Proteins 0.000 description 1
• 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 1
• 101710168331 ALK tyrosine kinase receptor Proteins 0.000 description 1
• 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 102000042871 Aurora family Human genes 0.000 description 1
• 108091082291 Aurora family Proteins 0.000 description 1
• 108700020463 BRCA1 Proteins 0.000 description 1
• 102000036365 BRCA1 Human genes 0.000 description 1
• 101150072950 BRCA1 gene Proteins 0.000 description 1
• 108700020462 BRCA2 Proteins 0.000 description 1
• 102000052609 BRCA2 Human genes 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 241000167854 Bourreria succulenta Species 0.000 description 1
• 101150008921 Brca2 gene Proteins 0.000 description 1
• FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
• 101150013553 CD40 gene Proteins 0.000 description 1
• 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• 102100034484 DNA repair protein RAD51 homolog 3 Human genes 0.000 description 1
• 102100036912 Desmin Human genes 0.000 description 1
• 108010044052 Desmin Proteins 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 241000255925 Diptera Species 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 102100021238 Dynamin-2 Human genes 0.000 description 1
• 241000854350 Enicospilus group Species 0.000 description 1
• 108090000371 Esterases Proteins 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 101150025764 FGFR3 gene Proteins 0.000 description 1
• 101150009958 FLT4 gene Proteins 0.000 description 1
• GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
• 102100037813 Focal adhesion kinase 1 Human genes 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 230000005526 G1 to G0 transition Effects 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 1
• 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 description 1
• 101000768016 Homo sapiens AP-1 complex subunit sigma-2 Proteins 0.000 description 1
• 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 1
• 101001132271 Homo sapiens DNA repair protein RAD51 homolog 3 Proteins 0.000 description 1
• 101000817607 Homo sapiens Dynamin-2 Proteins 0.000 description 1
• 101000878536 Homo sapiens Focal adhesion kinase 1 Proteins 0.000 description 1
• 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
• 101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 description 1
• 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
• 101001106406 Homo sapiens Rho GTPase-activating protein 1 Proteins 0.000 description 1
• 101000944909 Homo sapiens Ribosomal protein S6 kinase alpha-1 Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 101000864800 Homo sapiens Serine/threonine-protein kinase Sgk1 Proteins 0.000 description 1
• 101000864342 Homo sapiens Tyrosine-protein kinase BTK Proteins 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 208000035888 Immune-mediated thrombotic thrombocytopenic purpura Diseases 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 102100021854 Inhibitor of nuclear factor kappa-B kinase subunit beta Human genes 0.000 description 1
• 101710205525 Inhibitor of nuclear factor kappa-B kinase subunit beta Proteins 0.000 description 1
• 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• 108090000862 Ion Channels Proteins 0.000 description 1
• 101150009057 JAK2 gene Proteins 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
• 101150081525 LIMK1 gene Proteins 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
• 208000001145 Metabolic Syndrome Diseases 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 102000029749 Microtubule Human genes 0.000 description 1
• 108091022875 Microtubule Proteins 0.000 description 1
• 102100026931 Mitogen-activated protein kinase 10 Human genes 0.000 description 1
• 102100026888 Mitogen-activated protein kinase kinase kinase 7 Human genes 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 1
• 101001094044 Mus musculus Solute carrier family 26 member 6 Proteins 0.000 description 1
• 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• 102000005640 Myosin Type II Human genes 0.000 description 1
• 108010045128 Myosin Type II Proteins 0.000 description 1
• FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 1
• 229910017912 NH2OH Inorganic materials 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 101150111783 NTRK1 gene Proteins 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
• 206010029719 Nonspecific reaction Diseases 0.000 description 1
• 101150073900 PTEN gene Proteins 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 108090000315 Protein Kinase C Proteins 0.000 description 1
• 102000003923 Protein Kinase C Human genes 0.000 description 1
• 102000005569 Protein Phosphatase 1 Human genes 0.000 description 1
• 108010059000 Protein Phosphatase 1 Proteins 0.000 description 1
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 101150111584 RHOA gene Proteins 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• 108050002653 Retinoblastoma protein Proteins 0.000 description 1
• 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
• 102100021433 Rho GTPase-activating protein 1 Human genes 0.000 description 1
• 108010034782 Ribosomal Protein S6 Kinases Proteins 0.000 description 1
• 102000009738 Ribosomal Protein S6 Kinases Human genes 0.000 description 1
• 102100033536 Ribosomal protein S6 kinase alpha-1 Human genes 0.000 description 1
• 101150001535 SRC gene Proteins 0.000 description 1
• 101001092180 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) RHO GTPase-activating protein RGD1 Proteins 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 102100030070 Serine/threonine-protein kinase Sgk1 Human genes 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
• 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 1
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
• 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
• 102000013127 Vimentin Human genes 0.000 description 1
• 108010065472 Vimentin Proteins 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• PRDBLLIPPDOICK-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=C(C(F)(F)F)C=C1 PRDBLLIPPDOICK-UHFFFAOYSA-N 0.000 description 1
• SRHQOQMNBVOXCF-UHFFFAOYSA-N [4-chloro-3-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=C(Cl)C(C(F)(F)F)=C1 SRHQOQMNBVOXCF-UHFFFAOYSA-N 0.000 description 1
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000001361 adipic acid Substances 0.000 description 1
• 235000011037 adipic acid Nutrition 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 230000007815 allergy Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 238000010640 amide synthesis reaction Methods 0.000 description 1
• 229960002684 aminocaproic acid Drugs 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
• 238000005349 anion exchange Methods 0.000 description 1
• MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
• 230000002280 anti-androgenic effect Effects 0.000 description 1
• 230000003388 anti-hormonal effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 125000000732 arylene group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• 238000002820 assay format Methods 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 230000015097 attachment of spindle microtubules to kinetochore Effects 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• XLAKSMRSDNVNKK-JOCHJYFZSA-N benzyl n-[(3r)-3-[(8-carbamoylquinazolin-4-yl)amino]-3-phenylpropyl]carbamate Chemical compound C([C@@H](NC1=C2C=CC=C(C2=NC=N1)C(=O)N)C=1C=CC=CC=1)CNC(=O)OCC1=CC=CC=C1 XLAKSMRSDNVNKK-JOCHJYFZSA-N 0.000 description 1
• 229960000397 bevacizumab Drugs 0.000 description 1
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 239000003560 cancer drug Substances 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 235000011089 carbon dioxide Nutrition 0.000 description 1
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 238000005341 cation exchange Methods 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000032823 cell division Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 210000003793 centrosome Anatomy 0.000 description 1
• 229960005395 cetuximab Drugs 0.000 description 1
• 150000001793 charged compounds Chemical class 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
• DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 235000019693 cherries Nutrition 0.000 description 1
• 239000007958 cherry flavor Substances 0.000 description 1
• 230000002759 chromosomal effect Effects 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 201000011024 colonic benign neoplasm Diseases 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 230000005757 colony formation Effects 0.000 description 1
• 238000005056 compaction Methods 0.000 description 1
• 238000010668 complexation reaction Methods 0.000 description 1
• 238000013329 compounding Methods 0.000 description 1
• 108010057108 condensin complexes Proteins 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000004966 cyanoalkyl group Chemical group 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 229960001251 denosumab Drugs 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000030609 dephosphorylation Effects 0.000 description 1
• 238000006209 dephosphorylation reaction Methods 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 210000005045 desmin Anatomy 0.000 description 1
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
• CDHICTNQMQYRSM-UHFFFAOYSA-N di(propan-2-yl)alumane Chemical compound CC(C)[AlH]C(C)C CDHICTNQMQYRSM-UHFFFAOYSA-N 0.000 description 1
• MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000002612 dispersion medium Substances 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
• 230000007783 downstream signaling Effects 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 229940125436 dual inhibitor Drugs 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 229960001776 edrecolomab Drugs 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 150000002085 enols Chemical group 0.000 description 1
• HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 229940088598 enzyme Drugs 0.000 description 1
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
• 230000014392 establishment of spindle localization Effects 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• ASCRXOPBUNVSNJ-UHFFFAOYSA-N ethyl 2-[3-[1-[(8-carbamoylquinazolin-4-yl)amino]ethyl]anilino]-1,3-oxazole-5-carboxylate Chemical compound O1C(C(=O)OCC)=CN=C1NC1=CC=CC(C(C)NC=2C3=CC=CC(=C3N=CN=2)C(N)=O)=C1 ASCRXOPBUNVSNJ-UHFFFAOYSA-N 0.000 description 1
• SYWQOPRAPDMWMC-UHFFFAOYSA-N ethyl 2-chloro-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC(Cl)=N1 SYWQOPRAPDMWMC-UHFFFAOYSA-N 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
• SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 238000001125 extrusion Methods 0.000 description 1
• 239000010685 fatty oil Substances 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 108091006104 gene-regulatory proteins Proteins 0.000 description 1
• 102000034356 gene-regulatory proteins Human genes 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
• 239000003979 granulating agent Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 239000008241 heterogeneous mixture Substances 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 235000014304 histidine Nutrition 0.000 description 1
• 150000002411 histidines Chemical class 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 238000013415 human tumor xenograft model Methods 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
• 201000001421 hyperglycemia Diseases 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 239000000367 immunologic factor Substances 0.000 description 1
• 230000000415 inactivating effect Effects 0.000 description 1
• 229940060367 inert ingredients Drugs 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
• 239000012444 intercalating antibiotic Substances 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 230000002147 killing effect Effects 0.000 description 1
• 238000000021 kinase assay Methods 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
• 229950002950 lintuzumab Drugs 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
• UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000021121 meiosis Effects 0.000 description 1
• 230000031864 metaphase Effects 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• JLITVWGQYVGHRZ-UHFFFAOYSA-N methyl 4,6-dichloroquinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC(Cl)=CC2=C1Cl JLITVWGQYVGHRZ-UHFFFAOYSA-N 0.000 description 1
• CNVFYELKJXIOFN-LLVKDONJSA-N methyl 4-[[(1r)-1-(3-nitrophenyl)ethyl]amino]quinazoline-8-carboxylate Chemical compound C1([C@@H](C)NC2=C3C=CC=C(C3=NC=N2)C(=O)OC)=CC=CC([N+]([O-])=O)=C1 CNVFYELKJXIOFN-LLVKDONJSA-N 0.000 description 1
• MXAFBADEGVDPJL-OAHLLOKOSA-N methyl 4-[[(1s)-2-azido-1-phenylethyl]amino]quinazoline-8-carboxylate Chemical compound C1([C@@H](CN=[N+]=[N-])NC2=C3C=CC=C(C3=NC=N2)C(=O)OC)=CC=CC=C1 MXAFBADEGVDPJL-OAHLLOKOSA-N 0.000 description 1
• QNVPUSHEFBLTBI-UHFFFAOYSA-N methyl 4-[[1-(3-nitrophenyl)-3-pyrrolidin-1-ylpropyl]amino]quinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC=CC2=C1NC(C=1C=C(C=CC=1)[N+]([O-])=O)CCN1CCCC1 QNVPUSHEFBLTBI-UHFFFAOYSA-N 0.000 description 1
• GEWKUMNCVZQXJP-UHFFFAOYSA-N methyl 4-[[3-(trifluoromethyl)phenyl]methylamino]quinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC=CC2=C1NCC1=CC=CC(C(F)(F)F)=C1 GEWKUMNCVZQXJP-UHFFFAOYSA-N 0.000 description 1
• KUAFHKVSEUQECY-UHFFFAOYSA-N methyl 4-[[3-[(4-methoxybenzoyl)-methylamino]phenyl]methylamino]quinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC=CC2=C1NCC(C=1)=CC=CC=1N(C)C(=O)C1=CC=C(OC)C=C1 KUAFHKVSEUQECY-UHFFFAOYSA-N 0.000 description 1
• QWYYFCOEHVYBKT-UHFFFAOYSA-N methyl 4-[[4-chloro-3-(trifluoromethyl)phenyl]methylamino]-6-nitroquinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC([N+]([O-])=O)=CC2=C1NCC1=CC=C(Cl)C(C(F)(F)F)=C1 QWYYFCOEHVYBKT-UHFFFAOYSA-N 0.000 description 1
• SFTIODPDUDDGCZ-UHFFFAOYSA-N methyl 4-amino-4-(3-nitrophenyl)butanoate Chemical compound COC(=O)CCC(N)C1=CC=CC([N+]([O-])=O)=C1 SFTIODPDUDDGCZ-UHFFFAOYSA-N 0.000 description 1
• AAJZXPWBILCHAW-UHFFFAOYSA-N methyl 5-bromopyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC(Br)=C1 AAJZXPWBILCHAW-UHFFFAOYSA-N 0.000 description 1
• JKKSUVYKLLZBOJ-UHFFFAOYSA-N methyl 5-morpholin-4-ylpyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC(N2CCOCC2)=C1 JKKSUVYKLLZBOJ-UHFFFAOYSA-N 0.000 description 1
• FHKUIGCQUJXPSI-UHFFFAOYSA-N methyl 6-chloro-4-[1-[3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]ethylamino]quinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC(Cl)=CC2=C1NC(C)C1=CC=CC(NC(=O)OC(C)(C)C)=C1 FHKUIGCQUJXPSI-UHFFFAOYSA-N 0.000 description 1
• KTBYZONFSIWERM-ZDUSSCGKSA-N methyl 6-iodo-4-[[(3s)-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-3-yl]amino]quinazoline-8-carboxylate Chemical compound N1=CN=C2C(C(=O)OC)=CC(I)=CC2=C1N[C@H]1CCCN(C(=O)OC(C)(C)C)C1 KTBYZONFSIWERM-ZDUSSCGKSA-N 0.000 description 1
• ZVJNIISINPNCPE-UHFFFAOYSA-N methyl 6-nitro-4-oxo-1h-quinazoline-8-carboxylate Chemical compound N1=CNC(=O)C2=C1C(C(=O)OC)=CC([N+]([O-])=O)=C2 ZVJNIISINPNCPE-UHFFFAOYSA-N 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 210000004688 microtubule Anatomy 0.000 description 1
• 239000003226 mitogen Substances 0.000 description 1
• 230000008747 mitogenic response Effects 0.000 description 1
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
• 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 230000004899 motility Effects 0.000 description 1
• 210000000066 myeloid cell Anatomy 0.000 description 1
• JFPYVWYSQXLONF-UHFFFAOYSA-N n-(3-cyanophenyl)-4-methoxy-n-methylbenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)N(C)C1=CC=CC(C#N)=C1 JFPYVWYSQXLONF-UHFFFAOYSA-N 0.000 description 1
• HXDBEVLWHUIGRV-UHFFFAOYSA-N n-(3-cyanophenyl)-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=CC(C#N)=C1 HXDBEVLWHUIGRV-UHFFFAOYSA-N 0.000 description 1
• FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
• HIFQSGLCAZLODB-UHFFFAOYSA-N n-(benzenesulfonyl)-n-(5-bromopyridin-3-yl)benzenesulfonamide Chemical compound BrC1=CN=CC(N(S(=O)(=O)C=2C=CC=CC=2)S(=O)(=O)C=2C=CC=CC=2)=C1 HIFQSGLCAZLODB-UHFFFAOYSA-N 0.000 description 1
• JQAQYRGSABEZBJ-UHFFFAOYSA-N n-[2-(dimethylamino)-1-(3-methoxyphenyl)ethylidene]hydroxylamine Chemical compound COC1=CC=CC(C(CN(C)C)=NO)=C1 JQAQYRGSABEZBJ-UHFFFAOYSA-N 0.000 description 1
• IKCLWFBBSBDUHC-UHFFFAOYSA-N n-[3-(aminomethyl)phenyl]-4-methoxy-n-methylbenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)N(C)C1=CC=CC(CN)=C1 IKCLWFBBSBDUHC-UHFFFAOYSA-N 0.000 description 1
• JMHLMDXDEGJECY-UHFFFAOYSA-N n-[3-(aminomethyl)phenyl]-6-methoxypyridine-3-carboxamide Chemical compound C1=NC(OC)=CC=C1C(=O)NC1=CC=CC(CN)=C1 JMHLMDXDEGJECY-UHFFFAOYSA-N 0.000 description 1
• SQLDPDURRFUEHG-UHFFFAOYSA-N n-[3-[1-amino-2-(dimethylamino)ethyl]phenyl]-2-chloropyridine-4-carboxamide Chemical compound CN(C)CC(N)C1=CC=CC(NC(=O)C=2C=C(Cl)N=CC=2)=C1 SQLDPDURRFUEHG-UHFFFAOYSA-N 0.000 description 1
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
• DOWVMJFBDGWVML-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-(1-oxidopyridin-1-ium-3-yl)imidazole-1-carboxamide Chemical compound C1=NC(C=2C=[N+]([O-])C=CC=2)=CN1C(=O)N(C)C1CCCCC1 DOWVMJFBDGWVML-UHFFFAOYSA-N 0.000 description 1
• GTUAWMBSCRFHKR-UHFFFAOYSA-N n-ethyl-4-nitrobenzenesulfonamide Chemical compound CCNS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 GTUAWMBSCRFHKR-UHFFFAOYSA-N 0.000 description 1
• YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 238000006386 neutralization reaction Methods 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 235000016709 nutrition Nutrition 0.000 description 1
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 210000000287 oocyte Anatomy 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 239000007968 orange flavor Substances 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 150000003906 phosphoinositides Chemical class 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 210000004508 polar body Anatomy 0.000 description 1
• 108010056274 polo-like kinase 1 Proteins 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 239000002157 polynucleotide Substances 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 238000010837 poor prognosis Methods 0.000 description 1
• LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 239000003909 protein kinase inhibitor Substances 0.000 description 1
• 230000009822 protein phosphorylation Effects 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 235000018102 proteins Nutrition 0.000 description 1
• 230000004850 protein–protein interaction Effects 0.000 description 1
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
• AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
• 125000005551 pyridylene group Chemical group 0.000 description 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
• 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• CIIFKVFOVFJZDM-UHFFFAOYSA-N quinoline-8-carbonitrile Chemical compound C1=CN=C2C(C#N)=CC=CC2=C1 CIIFKVFOVFJZDM-UHFFFAOYSA-N 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000022983 regulation of cell cycle Effects 0.000 description 1
• 230000024122 regulation of cell motility Effects 0.000 description 1
• 102000037983 regulatory factors Human genes 0.000 description 1
• 108091008025 regulatory factors Proteins 0.000 description 1
• 230000008844 regulatory mechanism Effects 0.000 description 1
• 201000010174 renal carcinoma Diseases 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 210000003705 ribosome Anatomy 0.000 description 1
• 229960004641 rituximab Drugs 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 230000004747 sister chromatid biorientation Effects 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 230000020347 spindle assembly Effects 0.000 description 1
• 230000024355 spindle assembly checkpoint Effects 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
• CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000000967 suction filtration Methods 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
• 125000001010 sulfinic acid amide group Chemical group 0.000 description 1
• 125000000565 sulfonamide group Chemical group 0.000 description 1
• 239000001117 sulphuric acid Substances 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 230000004654 survival pathway Effects 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229960000235 temsirolimus Drugs 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• ZURUVWIEMTVZTJ-LBPRGKRZSA-N tert-butyl (3s)-3-[(8-carbamoyl-6-iodoquinazolin-4-yl)amino]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC[C@@H]1NC1=NC=NC2=C(C(N)=O)C=C(I)C=C12 ZURUVWIEMTVZTJ-LBPRGKRZSA-N 0.000 description 1
• QZEQMEOSQLWVRN-SFHVURJKSA-N tert-butyl (3s)-3-[(8-carbamoyl-6-phenylquinazolin-4-yl)amino]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC[C@@H]1NC1=NC=NC2=C(C(N)=O)C=C(C=3C=CC=CC=3)C=C12 QZEQMEOSQLWVRN-SFHVURJKSA-N 0.000 description 1
• AKQXKEBCONUWCL-QMMMGPOBSA-N tert-butyl (3s)-3-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H](N)C1 AKQXKEBCONUWCL-QMMMGPOBSA-N 0.000 description 1
• ZKMVGXBRWLICLF-UHFFFAOYSA-N tert-butyl 3-[[3-[[(8-carbamoylquinazolin-4-yl)amino]methyl]phenyl]carbamoyl]-6,7-dihydro-4h-pyrazolo[1,5-a]pyrazine-5-carboxylate Chemical compound C1=CC=C2C(NCC=3C=CC=C(C=3)NC(=O)C=3C=NN4CCN(CC4=3)C(=O)OC(C)(C)C)=NC=NC2=C1C(N)=O ZKMVGXBRWLICLF-UHFFFAOYSA-N 0.000 description 1
• PXLWDYOUWTYABH-LLVKDONJSA-N tert-butyl n-[(1s)-1-(3-fluorophenyl)-2-hydroxyethyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CO)C1=CC=CC(F)=C1 PXLWDYOUWTYABH-LLVKDONJSA-N 0.000 description 1
• UGKAWIQUIOZIMD-UHFFFAOYSA-N tert-butyl n-[1-(3-aminophenyl)-3-hydroxypropyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(CCO)C1=CC=CC(N)=C1 UGKAWIQUIOZIMD-UHFFFAOYSA-N 0.000 description 1
• FPUJDBMWNXZNAV-UHFFFAOYSA-N tert-butyl n-[1-(3-nitrophenyl)-3-pyrrolidin-1-ylpropyl]carbamate Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C(NC(=O)OC(C)(C)C)CCN1CCCC1 FPUJDBMWNXZNAV-UHFFFAOYSA-N 0.000 description 1
• OMEIYNPFPKHQGY-UHFFFAOYSA-N tert-butyl n-[1-[3-[(5-cyclopropyl-1h-pyrazole-3-carbonyl)amino]phenyl]-3-hydroxypropyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(CCO)C1=CC=CC(NC(=O)C=2NN=C(C=2)C2CC2)=C1 OMEIYNPFPKHQGY-UHFFFAOYSA-N 0.000 description 1
• QCQLTRAUGWYUFV-UHFFFAOYSA-N tert-butyl n-[2-[(8-carbamoyl-6-hydroxyquinazolin-4-yl)amino]-2-phenylethyl]-n-methylcarbamate Chemical compound N=1C=NC2=C(C(N)=O)C=C(O)C=C2C=1NC(CN(C)C(=O)OC(C)(C)C)C1=CC=CC=C1 QCQLTRAUGWYUFV-UHFFFAOYSA-N 0.000 description 1
• FYEHHEDXJKWPIB-UHFFFAOYSA-N tert-butyl n-[2-[(8-carbamoyl-6-methoxyquinazolin-4-yl)amino]-2-phenylethyl]-n-methylcarbamate Chemical compound C12=CC(OC)=CC(C(N)=O)=C2N=CN=C1NC(CN(C)C(=O)OC(C)(C)C)C1=CC=CC=C1 FYEHHEDXJKWPIB-UHFFFAOYSA-N 0.000 description 1
• IIPQFFCDLPLTDA-UHFFFAOYSA-N tert-butyl n-[2-[(8-carbamoyl-6-phenylmethoxyquinazolin-4-yl)amino]-2-(3-chlorophenyl)ethyl]-n-methylcarbamate Chemical compound C=1C=CC(Cl)=CC=1C(CN(C)C(=O)OC(C)(C)C)NC(C1=C2)=NC=NC1=C(C(N)=O)C=C2OCC1=CC=CC=C1 IIPQFFCDLPLTDA-UHFFFAOYSA-N 0.000 description 1
• BZMFKCZBICAGJX-UHFFFAOYSA-N tert-butyl n-[2-[(8-carbamoyl-6-phenylmethoxyquinazolin-4-yl)amino]-2-phenylethyl]-n-methylcarbamate Chemical compound C=1C=CC=CC=1C(CN(C)C(=O)OC(C)(C)C)NC(C1=C2)=NC=NC1=C(C(N)=O)C=C2OCC1=CC=CC=C1 BZMFKCZBICAGJX-UHFFFAOYSA-N 0.000 description 1
• CNAHTFLEMVTQQC-UHFFFAOYSA-N tert-butyl n-[2-amino-2-(3-nitrophenyl)ethyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CC(N)C1=CC=CC([N+]([O-])=O)=C1 CNAHTFLEMVTQQC-UHFFFAOYSA-N 0.000 description 1
• NXQNEOIMZVWHQW-UHFFFAOYSA-N tert-butyl n-[3-(aminomethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(CN)=C1 NXQNEOIMZVWHQW-UHFFFAOYSA-N 0.000 description 1
• FUPDUVSANAQCMB-UHFFFAOYSA-N tert-butyl n-[3-[1-[(8-carbamoyl-6-chloroquinazolin-4-yl)amino]ethyl]phenyl]carbamate Chemical compound N=1C=NC2=C(C(N)=O)C=C(Cl)C=C2C=1NC(C)C1=CC=CC(NC(=O)OC(C)(C)C)=C1 FUPDUVSANAQCMB-UHFFFAOYSA-N 0.000 description 1
• AXWHGWQLVTVMQA-UHFFFAOYSA-N tert-butyl n-[3-[[(8-carbamoylquinazolin-4-yl)amino]methyl]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(CNC=2C3=CC=CC(=C3N=CN=2)C(N)=O)=C1 AXWHGWQLVTVMQA-UHFFFAOYSA-N 0.000 description 1
• VWOCYQBQLRGDCG-UHFFFAOYSA-N tert-butyl n-[3-[[3-[[(8-carbamoylquinazolin-4-yl)amino]methyl]phenyl]carbamoyl]phenyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C1=CC=CC(C(=O)NC=2C=C(CNC=3C4=CC=CC(=C4N=CN=3)C(N)=O)C=CC=2)=C1 VWOCYQBQLRGDCG-UHFFFAOYSA-N 0.000 description 1
• QXMOQSGCRNWKDY-UHFFFAOYSA-N tert-butyl n-[3-cyano-1-(3-nitrophenyl)propyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(CCC#N)C1=CC=CC([N+]([O-])=O)=C1 QXMOQSGCRNWKDY-UHFFFAOYSA-N 0.000 description 1
• SLJMTERFCITLKA-UHFFFAOYSA-N tert-butyl n-[4-[[(8-carbamoylquinazolin-4-yl)amino]methyl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1CNC1=NC=NC2=C(C(N)=O)C=CC=C12 SLJMTERFCITLKA-UHFFFAOYSA-N 0.000 description 1
• SFPKTHKAZYMGLV-UHFFFAOYSA-N tert-butyl n-[4-[[3-[[(8-carbamoylquinazolin-4-yl)amino]methyl]phenyl]carbamoyl]-1,3-thiazol-2-yl]carbamate Chemical compound S1C(NC(=O)OC(C)(C)C)=NC(C(=O)NC=2C=C(CNC=3C4=CC=CC(=C4N=CN=3)C(N)=O)C=CC=2)=C1 SFPKTHKAZYMGLV-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000002381 testicular Effects 0.000 description 1
• 108091008743 testicular receptors 4 Proteins 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 230000004797 therapeutic response Effects 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 230000017423 tissue regeneration Effects 0.000 description 1
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 229960000575 trastuzumab Drugs 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• 210000003556 vascular endothelial cell Anatomy 0.000 description 1
• 230000004862 vasculogenesis Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 210000005048 vimentin Anatomy 0.000 description 1
• QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 1
• QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 1
• 229950009002 zanolimumab Drugs 0.000 description 1
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1