AU2013289381A1 - Method for preparing substituted triazolopyridines - Google Patents
Method for preparing substituted triazolopyridines Download PDFInfo
- Publication number
- AU2013289381A1 AU2013289381A1 AU2013289381A AU2013289381A AU2013289381A1 AU 2013289381 A1 AU2013289381 A1 AU 2013289381A1 AU 2013289381 A AU2013289381 A AU 2013289381A AU 2013289381 A AU2013289381 A AU 2013289381A AU 2013289381 A1 AU2013289381 A1 AU 2013289381A1
- Authority
- AU
- Australia
- Prior art keywords
- pyridin
- triazolo
- amino
- benzamide
- phenyt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 169
- 150000008523 triazolopyridines Chemical class 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 358
- 238000002360 preparation method Methods 0.000 claims abstract description 54
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 294
- -1 hydroxy- Chemical class 0.000 claims description 244
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 233
- 239000000203 mixture Substances 0.000 claims description 230
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 117
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 114
- 125000005843 halogen group Chemical group 0.000 claims description 84
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 73
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 64
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 59
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 51
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 41
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 37
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 37
- 150000001412 amines Chemical class 0.000 claims description 28
- 238000005859 coupling reaction Methods 0.000 claims description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 claims description 18
- 150000002148 esters Chemical class 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 13
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 11
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 11
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 229910052763 palladium Inorganic materials 0.000 claims description 10
- 239000012634 fragment Substances 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 claims description 6
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 125000001475 halogen functional group Chemical group 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 2
- WUDPYZZMQYKTKW-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-[4-[2-[2-methoxy-4-(methylsulfonimidoyl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]acetamide Chemical compound COC1=CC(S(C)(=N)=O)=CC=C1NC1=NN2C=C(C=3C=CC(NC(=O)CC=4C=CC(F)=CC=4)=CC=3)C=CC2=N1 WUDPYZZMQYKTKW-UHFFFAOYSA-N 0.000 claims description 2
- UCFBXUOGFYVMQX-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-[4-[2-[4-(hydroxymethyl)-2-methoxyanilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]acetamide Chemical compound COC1=CC(CO)=CC=C1NC1=NN2C=C(C=3C=CC(NC(=O)CC=4C=CC(F)=CC=4)=CC=3)C=CC2=N1 UCFBXUOGFYVMQX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- RKHXDXIJRYGZDL-UHFFFAOYSA-N 4-[[6-[4-[(4-fluorophenyl)methylcarbamoyl]phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-(trifluoromethoxy)benzamide Chemical compound FC(F)(F)OC1=CC(C(=O)N)=CC=C1NC1=NN2C=C(C=3C=CC(=CC=3)C(=O)NCC=3C=CC(F)=CC=3)C=CC2=N1 RKHXDXIJRYGZDL-UHFFFAOYSA-N 0.000 claims description 2
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 claims description 2
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- XLAKONHZQDCIEH-UHFFFAOYSA-N n-(2-fluoroethyl)-4-[[6-[4-[(4-fluorophenyl)methylcarbamoyl]phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-(2,2,2-trifluoroethoxy)benzamide Chemical compound FC(F)(F)COC1=CC(C(=O)NCCF)=CC=C1NC1=NN2C=C(C=3C=CC(=CC=3)C(=O)NCC=3C=CC(F)=CC=3)C=CC2=N1 XLAKONHZQDCIEH-UHFFFAOYSA-N 0.000 claims description 2
- KDYHIHMVASSRMF-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-4-[2-[2-methoxy-4-(methylsulfonimidoyl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzamide Chemical compound COC1=CC(S(C)(=N)=O)=CC=C1NC1=NN2C=C(C=3C=CC(=CC=3)C(=O)NCC=3C=CC(F)=CC=3)C=CC2=N1 KDYHIHMVASSRMF-UHFFFAOYSA-N 0.000 claims description 2
- CRTOFESISWFZAU-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-4-[2-[4-(hydroxymethyl)-2-methoxyanilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzamide Chemical compound COC1=CC(CO)=CC=C1NC1=NN2C=C(C=3C=CC(=CC=3)C(=O)NCC=3C=CC(F)=CC=3)C=CC2=N1 CRTOFESISWFZAU-UHFFFAOYSA-N 0.000 claims description 2
- XEHCIJQQJFATFU-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]benzamide Chemical compound C1=CC(F)=CC=C1CNC(=O)C1=CC=CC=C1 XEHCIJQQJFATFU-UHFFFAOYSA-N 0.000 claims description 2
- 125000003262 carboxylic acid ester group Chemical class [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 claims 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 6
- 229910014033 C-OH Inorganic materials 0.000 claims 6
- 229910014570 C—OH Inorganic materials 0.000 claims 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- ZKSYUNLBFSOENV-UHFFFAOYSA-N N-benzoylethanolamine Natural products OCCNC(=O)C1=CC=CC=C1 ZKSYUNLBFSOENV-UHFFFAOYSA-N 0.000 claims 1
- 102220504163 Testis-specific XK-related protein, Y-linked 2_H31L_mutation Human genes 0.000 claims 1
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims 1
- AQWOIRBQLOOZGX-UHFFFAOYSA-N triazolo[1,5-a]pyridine Chemical compound C1=CC=CC2=CN=NN21 AQWOIRBQLOOZGX-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 160
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 151
- 239000002904 solvent Substances 0.000 description 134
- 239000000243 solution Substances 0.000 description 128
- 239000000543 intermediate Substances 0.000 description 127
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 88
- 238000005160 1H NMR spectroscopy Methods 0.000 description 87
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 72
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 65
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 56
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 52
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 50
- 239000007787 solid Substances 0.000 description 50
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 49
- 210000004027 cell Anatomy 0.000 description 48
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 48
- 238000010898 silica gel chromatography Methods 0.000 description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- 239000012074 organic phase Substances 0.000 description 45
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 44
- 229910052938 sodium sulfate Inorganic materials 0.000 description 44
- 235000011152 sodium sulphate Nutrition 0.000 description 44
- 239000000725 suspension Substances 0.000 description 43
- 230000015572 biosynthetic process Effects 0.000 description 42
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 37
- 238000006243 chemical reaction Methods 0.000 description 37
- 238000003786 synthesis reaction Methods 0.000 description 36
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 36
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 32
- 235000017557 sodium bicarbonate Nutrition 0.000 description 32
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 30
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 30
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 29
- 238000010992 reflux Methods 0.000 description 28
- 125000004432 carbon atom Chemical group C* 0.000 description 27
- 108091000080 Phosphotransferase Proteins 0.000 description 25
- 229910052786 argon Inorganic materials 0.000 description 25
- 102000020233 phosphotransferase Human genes 0.000 description 25
- 239000012047 saturated solution Substances 0.000 description 25
- 238000003556 assay Methods 0.000 description 24
- 229910000027 potassium carbonate Inorganic materials 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- 239000000741 silica gel Substances 0.000 description 24
- 229910002027 silica gel Inorganic materials 0.000 description 24
- 229960001866 silicon dioxide Drugs 0.000 description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 23
- 239000007821 HATU Substances 0.000 description 22
- 206010028980 Neoplasm Diseases 0.000 description 22
- 230000014759 maintenance of location Effects 0.000 description 21
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
- 125000006239 protecting group Chemical group 0.000 description 19
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 18
- 229910000160 potassium phosphate Inorganic materials 0.000 description 18
- 235000011009 potassium phosphates Nutrition 0.000 description 18
- 239000011877 solvent mixture Substances 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
- 238000000746 purification Methods 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- 238000001914 filtration Methods 0.000 description 16
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 16
- 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 15
- 150000001733 carboxylic acid esters Chemical class 0.000 description 15
- 235000019253 formic acid Nutrition 0.000 description 15
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- NMMPMZWIIQCZBA-UHFFFAOYSA-M chloropalladium(1+);dicyclohexyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane;2-phenylethanamine Chemical compound [Pd+]Cl.NCCC1=CC=CC=[C-]1.CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 NMMPMZWIIQCZBA-UHFFFAOYSA-M 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 10
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 description 10
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 10
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 10
- IXSCGBODJGIJNN-ZCFIWIBFSA-N (2r)-2-(4-fluorophenyl)propanoic acid Chemical compound OC(=O)[C@H](C)C1=CC=C(F)C=C1 IXSCGBODJGIJNN-ZCFIWIBFSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 9
- 101150003085 Pdcl gene Proteins 0.000 description 9
- 239000012317 TBTU Substances 0.000 description 9
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 125000000524 functional group Chemical group 0.000 description 9
- 125000001183 hydrocarbyl group Chemical group 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 102100033636 Histone H3.2 Human genes 0.000 description 8
- 108010033040 Histones Proteins 0.000 description 8
- 230000004663 cell proliferation Effects 0.000 description 8
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 8
- 229910052736 halogen Inorganic materials 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 8
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 7
- 150000001408 amides Chemical group 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 230000017205 mitotic cell cycle checkpoint Effects 0.000 description 7
- 230000000394 mitotic effect Effects 0.000 description 7
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 7
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 7
- QDZZDVQGBKTLHV-UHFFFAOYSA-N (2,4-difluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1F QDZZDVQGBKTLHV-UHFFFAOYSA-N 0.000 description 6
- 229940044613 1-propanol Drugs 0.000 description 6
- UEVXVBKBOFGKIN-UHFFFAOYSA-N 4-bromo-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1Br UEVXVBKBOFGKIN-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- 230000024932 T cell mediated immunity Effects 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical group NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- 230000010261 cell growth Effects 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 238000004296 chiral HPLC Methods 0.000 description 6
- 210000000349 chromosome Anatomy 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 238000000021 kinase assay Methods 0.000 description 6
- 230000011278 mitosis Effects 0.000 description 6
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- 238000000844 transformation Methods 0.000 description 6
- 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- KYRVNWMVYQXFEU-UHFFFAOYSA-N Nocodazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CS1 KYRVNWMVYQXFEU-UHFFFAOYSA-N 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000028709 inflammatory response Effects 0.000 description 5
- 230000000155 isotopic effect Effects 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 229950006344 nocodazole Drugs 0.000 description 5
- 239000011698 potassium fluoride Substances 0.000 description 5
- 235000003270 potassium fluoride Nutrition 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
- 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
- RMYYCPPLIIKPBI-UHFFFAOYSA-N 4-bromo-3-(2,2,2-trifluoroethoxy)benzoic acid Chemical compound OC(=O)C1=CC=C(Br)C(OCC(F)(F)F)=C1 RMYYCPPLIIKPBI-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 208000003174 Brain Neoplasms Diseases 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 150000001502 aryl halides Chemical class 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- 125000005605 benzo group Chemical group 0.000 description 4
- 235000010290 biphenyl Nutrition 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000003301 hydrolyzing effect Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 210000001853 liver microsome Anatomy 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 238000011321 prophylaxis Methods 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 230000024355 spindle assembly checkpoint Effects 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 3
- HUVAOAVBKOVPBZ-UHFFFAOYSA-N 2-bromo-5-fluorophenol Chemical compound OC1=CC(F)=CC=C1Br HUVAOAVBKOVPBZ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- 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 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 102100037236 Tyrosine-protein kinase receptor UFO Human genes 0.000 description 3
- 150000008527 [1,2,4]triazolo-[1,5-a]pyridines Chemical class 0.000 description 3
- PHTMVIAGTMTVSK-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound C1=CC=CN2N=C(N)N=C21 PHTMVIAGTMTVSK-UHFFFAOYSA-N 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 230000031016 anaphase Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 108010023337 axl receptor tyrosine kinase Proteins 0.000 description 3
- 230000008033 biological extinction Effects 0.000 description 3
- 150000001642 boronic acid derivatives Chemical class 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000004202 carbamide Chemical group 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000001212 derivatisation Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- BDTDECDAHYOJRO-UHFFFAOYSA-N ethyl n-(sulfanylidenemethylidene)carbamate Chemical compound CCOC(=O)N=C=S BDTDECDAHYOJRO-UHFFFAOYSA-N 0.000 description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 229960004592 isopropanol Drugs 0.000 description 3
- 210000002415 kinetochore Anatomy 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 230000003228 microsomal effect Effects 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 3
- RMNIZOOYFMNEJJ-UHFFFAOYSA-K tripotassium;phosphate;hydrate Chemical compound O.[K+].[K+].[K+].[O-]P([O-])([O-])=O RMNIZOOYFMNEJJ-UHFFFAOYSA-K 0.000 description 3
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 2
- VYJXPBPEYOOMNE-GOSISDBHSA-N (2r)-2-(4-fluorophenyl)-n-[4-[2-[4-methylsulfonyl-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]propanamide Chemical compound O=C([C@H](C)C=1C=CC(F)=CC=1)NC(C=C1)=CC=C1C(=CN1N=2)C=CC1=NC=2NC1=CC=C(S(C)(=O)=O)C=C1OCC(F)(F)F VYJXPBPEYOOMNE-GOSISDBHSA-N 0.000 description 2
- KNFACTVCWZANEW-MUUNZHRXSA-N (2r)-2-amino-n-[4-[2-[4-(3-fluoroazetidine-1-carbonyl)-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]-2-(4-fluorophenyl)acetamide Chemical compound O=C([C@H](N)C=1C=CC(F)=CC=1)NC(C=C1)=CC=C1C(=CN1N=2)C=CC1=NC=2NC(C(=C1)OCC(F)(F)F)=CC=C1C(=O)N1CC(F)C1 KNFACTVCWZANEW-MUUNZHRXSA-N 0.000 description 2
- UKEXWLCGMBIZBE-SNVBAGLBSA-N (2r)-n-(4-bromophenyl)-2-(4-fluorophenyl)propanamide Chemical compound O=C([C@H](C)C=1C=CC(F)=CC=1)NC1=CC=C(Br)C=C1 UKEXWLCGMBIZBE-SNVBAGLBSA-N 0.000 description 2
- LLTWLOYZJCWIOT-PZLLXQLWSA-N (beta-D-mannosyl)methyl C32-phosphonomycoketide Chemical compound CCCCCCC[C@H](C)CCC[C@H](C)CCC[C@H](C)CCC[C@H](C)CCC[C@H](C)CCCOP(C[C@@H]([C@H]([C@H]1O)O)O[C@H](CO)[C@H]1O)(O)=O LLTWLOYZJCWIOT-PZLLXQLWSA-N 0.000 description 2
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- MCLBVTBTDQSOSY-UHFFFAOYSA-N 1-bromo-2-ethoxy-4-fluorobenzene Chemical compound CCOC1=CC(F)=CC=C1Br MCLBVTBTDQSOSY-UHFFFAOYSA-N 0.000 description 2
- XPBAUEMRAAGQAJ-UHFFFAOYSA-N 1-bromo-2-methoxy-4-methylsulfanylbenzene Chemical compound COC1=CC(SC)=CC=C1Br XPBAUEMRAAGQAJ-UHFFFAOYSA-N 0.000 description 2
- KGYXKRGMSUHYCY-UHFFFAOYSA-N 1-bromo-4-fluoro-2-methoxybenzene Chemical compound COC1=CC(F)=CC=C1Br KGYXKRGMSUHYCY-UHFFFAOYSA-N 0.000 description 2
- NLWCWEGVNJVLAX-UHFFFAOYSA-N 1-methoxy-2-phenylbenzene Chemical compound COC1=CC=CC=C1C1=CC=CC=C1 NLWCWEGVNJVLAX-UHFFFAOYSA-N 0.000 description 2
- RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 2
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- PXFUWRWCKSLCLS-UHFFFAOYSA-N 3-fluoroazetidine;hydron;chloride Chemical compound Cl.FC1CNC1 PXFUWRWCKSLCLS-UHFFFAOYSA-N 0.000 description 2
- ZANPJXNYBVVNSD-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N)C=C1 ZANPJXNYBVVNSD-UHFFFAOYSA-N 0.000 description 2
- YHMZDFBWPAFJOJ-UHFFFAOYSA-N 4-bromo-3-methoxybenzamide Chemical compound COC1=CC(C(N)=O)=CC=C1Br YHMZDFBWPAFJOJ-UHFFFAOYSA-N 0.000 description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 2
- VTLNRIWXFMEIAW-UHFFFAOYSA-N 6-chloro-n-(2-methoxy-4-methylsulfonylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound COC1=CC(S(C)(=O)=O)=CC=C1NC1=NN2C=C(Cl)C=CC2=N1 VTLNRIWXFMEIAW-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229910052693 Europium Inorganic materials 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 206010059282 Metastases to central nervous system Diseases 0.000 description 2
- 102000029749 Microtubule Human genes 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 206010029098 Neoplasm skin Diseases 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 101000953909 Streptomyces viridifaciens Isobutylamine N-hydroxylase Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QOLYAJSZHIJCTO-VQVTYTSYSA-N Thr-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(O)=O QOLYAJSZHIJCTO-VQVTYTSYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- DACWQSNZECJJGG-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=CC=CN2N=CN=C21 DACWQSNZECJJGG-UHFFFAOYSA-N 0.000 description 2
- JKRNJRAPYFXOHE-SNVBAGLBSA-N [4-[[(2r)-2-(4-fluorophenyl)propanoyl]amino]phenyl]boronic acid Chemical compound O=C([C@H](C)C=1C=CC(F)=CC=1)NC1=CC=C(B(O)O)C=C1 JKRNJRAPYFXOHE-SNVBAGLBSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229960001456 adenosine triphosphate Drugs 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 108010004469 allophycocyanin Proteins 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 150000001499 aryl bromides Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 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 2
- 239000004305 biphenyl Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 229910052794 bromium Inorganic materials 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
- 230000022131 cell cycle Effects 0.000 description 2
- 230000023359 cell cycle switching, meiotic to mitotic cell cycle Effects 0.000 description 2
- 208000019065 cervical carcinoma Diseases 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 229950006137 dexfosfoserine Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 238000003821 enantio-separation Methods 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- WCYJQVALWQMJGE-UHFFFAOYSA-M hydroxylammonium chloride Chemical compound [Cl-].O[NH3+] WCYJQVALWQMJGE-UHFFFAOYSA-M 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- 208000037841 lung tumor Diseases 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000006263 metalation reaction Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- AJPPKGMEHMXPMC-UHFFFAOYSA-N methyl 2-(4-fluorophenyl)acetate Chemical compound COC(=O)CC1=CC=C(F)C=C1 AJPPKGMEHMXPMC-UHFFFAOYSA-N 0.000 description 2
- VYOFPLOREOHCDP-UHFFFAOYSA-N methyl 4-bromo-3-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(Br)C(O)=C1 VYOFPLOREOHCDP-UHFFFAOYSA-N 0.000 description 2
- XLKDKHRGIJWOSN-UHFFFAOYSA-N methyl 4-bromo-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(Br)C(OC)=C1 XLKDKHRGIJWOSN-UHFFFAOYSA-N 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 2
- 150000003905 phosphatidylinositols Chemical class 0.000 description 2
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 229920001992 poloxamer 407 Polymers 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000002165 resonance energy transfer Methods 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 201000004477 skin sarcoma Diseases 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- CZCCFXMNFXMDJU-UHFFFAOYSA-N tert-butyl n-[4-[2-(2-methoxy-4-methylsulfonylanilino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]carbamate Chemical compound COC1=CC(S(C)(=O)=O)=CC=C1NC1=NN2C=C(C=3C=CC(NC(=O)OC(C)(C)C)=CC=3)C=CC2=N1 CZCCFXMNFXMDJU-UHFFFAOYSA-N 0.000 description 2
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- 208000024719 uterine cervix neoplasm Diseases 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- FCYUPOCBNOAMHF-VGMFFHCQSA-N (1s)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1.C[C@H](N)C1=CC=CC=C1 FCYUPOCBNOAMHF-VGMFFHCQSA-N 0.000 description 1
- IEQBOUSLFRLKKX-SNVBAGLBSA-N (2r)-2-(4-fluorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)C1=CC=C(F)C=C1 IEQBOUSLFRLKKX-SNVBAGLBSA-N 0.000 description 1
- NRJKIOCCERLIDG-GOSISDBHSA-N (2r)-2-(4-fluorophenyl)-n-[4-[2-(2-methoxy-4-methylsulfonylanilino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]propanamide Chemical compound COC1=CC(S(C)(=O)=O)=CC=C1NC1=NN2C=C(C=3C=CC(NC(=O)[C@H](C)C=4C=CC(F)=CC=4)=CC=3)C=CC2=N1 NRJKIOCCERLIDG-GOSISDBHSA-N 0.000 description 1
- SHWCNYPROTZRQA-LJQANCHMSA-N (2r)-2-(4-fluorophenyl)-n-[4-[2-[2-methoxy-4-(2-oxo-1,3-oxazolidin-3-yl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]propanamide Chemical compound C1([C@@H](C)C(=O)NC2=CC=C(C=C2)C=2C=CC3=NC(=NN3C=2)NC2=CC=C(C=C2OC)N2C(OCC2)=O)=CC=C(F)C=C1 SHWCNYPROTZRQA-LJQANCHMSA-N 0.000 description 1
- ZHFPSWSGPIWZIU-OAQYLSRUSA-N (2r)-2-(4-fluorophenyl)-n-[4-[2-[2-methoxy-4-(pyrrolidine-1-carbonyl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]propanamide Chemical compound C1([C@@H](C)C(=O)NC2=CC=C(C=C2)C=2C=CC3=NC(=NN3C=2)NC2=CC=C(C=C2OC)C(=O)N2CCCC2)=CC=C(F)C=C1 ZHFPSWSGPIWZIU-OAQYLSRUSA-N 0.000 description 1
- VQHFHMPHSRDHRP-HHHXNRCGSA-N (2r)-2-amino-2-(4-fluorophenyl)-n-[4-[2-[2-methoxy-4-(2-oxo-1,3-oxazolidin-3-yl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]acetamide Chemical compound C1([C@@H](N)C(=O)NC2=CC=C(C=C2)C=2C=CC3=NC(=NN3C=2)NC2=CC=C(C=C2OC)N2C(OCC2)=O)=CC=C(F)C=C1 VQHFHMPHSRDHRP-HHHXNRCGSA-N 0.000 description 1
- NMFISVGDLHKOMF-GDLZYMKVSA-N (2r)-2-amino-2-(4-fluorophenyl)-n-[4-[2-[2-methoxy-4-(pyrrolidine-1-carbonyl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]acetamide Chemical compound C1([C@@H](N)C(=O)NC2=CC=C(C=C2)C=2C=CC3=NC(=NN3C=2)NC2=CC=C(C=C2OC)C(=O)N2CCCC2)=CC=C(F)C=C1 NMFISVGDLHKOMF-GDLZYMKVSA-N 0.000 description 1
- YYULTHOGCGGNNX-MUUNZHRXSA-N (2r)-2-amino-n-[4-[2-[4-(3-fluoroazetidine-1-carbonyl)-2-methoxyanilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]-2-(4-fluorophenyl)acetamide Chemical compound C1([C@@H](N)C(=O)NC2=CC=C(C=C2)C=2C=CC3=NC(=NN3C=2)NC2=CC=C(C=C2OC)C(=O)N2CC(F)C2)=CC=C(F)C=C1 YYULTHOGCGGNNX-MUUNZHRXSA-N 0.000 description 1
- VGYQVHKOWRKLRE-MUUNZHRXSA-N (2r)-2-amino-n-[4-[2-[4-(azetidine-1-carbonyl)-2-methoxyanilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]-2-(4-fluorophenyl)acetamide Chemical compound C1([C@@H](N)C(=O)NC2=CC=C(C=C2)C=2C=CC3=NC(=NN3C=2)NC2=CC=C(C=C2OC)C(=O)N2CCC2)=CC=C(F)C=C1 VGYQVHKOWRKLRE-MUUNZHRXSA-N 0.000 description 1
- IUWLUXOVMFUJBY-LJQANCHMSA-N (2r)-n-[4-[2-[4-(3-fluoroazetidine-1-carbonyl)-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]-2-(4-fluorophenyl)propanamide Chemical compound O=C([C@H](C)C=1C=CC(F)=CC=1)NC(C=C1)=CC=C1C(=CN1N=2)C=CC1=NC=2NC(C(=C1)OCC(F)(F)F)=CC=C1C(=O)N1CC(F)C1 IUWLUXOVMFUJBY-LJQANCHMSA-N 0.000 description 1
- BZJLXVMYVVLROC-XMMPIXPASA-N (2s)-2-(4-fluorophenyl)-3-hydroxy-n-[4-[2-(2-methoxy-4-methylsulfonylanilino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]propanamide Chemical compound COC1=CC(S(C)(=O)=O)=CC=C1NC1=NN2C=C(C=3C=CC(NC(=O)[C@H](CO)C=4C=CC(F)=CC=4)=CC=3)C=CC2=N1 BZJLXVMYVVLROC-XMMPIXPASA-N 0.000 description 1
- ZHKKTVQQLBWUBH-AREMUKBSSA-N (2s)-n-[4-[2-[4-(3-fluoroazetidine-1-carbonyl)-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]-2-(4-fluorophenyl)-3-hydroxypropanamide Chemical compound O=C([C@H](CO)C=1C=CC(F)=CC=1)NC(C=C1)=CC=C1C(=CN1N=2)C=CC1=NC=2NC(C(=C1)OCC(F)(F)F)=CC=C1C(=O)N1CC(F)C1 ZHKKTVQQLBWUBH-AREMUKBSSA-N 0.000 description 1
- QBYGJJSFMOVYOA-UHFFFAOYSA-N (4-boronophenyl)azanium;chloride Chemical compound Cl.NC1=CC=C(B(O)O)C=C1 QBYGJJSFMOVYOA-UHFFFAOYSA-N 0.000 description 1
- ROYMIBPTRHCVIB-UHFFFAOYSA-N (4-bromo-3-methoxyphenyl)-(3-fluoroazetidin-1-yl)methanone Chemical compound C1=C(Br)C(OC)=CC(C(=O)N2CC(F)C2)=C1 ROYMIBPTRHCVIB-UHFFFAOYSA-N 0.000 description 1
- ZXPZEXSSPDSBKD-UHFFFAOYSA-N (4-bromo-3-methoxyphenyl)-pyrrolidin-1-ylmethanone Chemical compound C1=C(Br)C(OC)=CC(C(=O)N2CCCC2)=C1 ZXPZEXSSPDSBKD-UHFFFAOYSA-N 0.000 description 1
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 description 1
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
- VUMCUSHVMYIRMB-UHFFFAOYSA-N 1,3,5-tri(propan-2-yl)benzene Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1 VUMCUSHVMYIRMB-UHFFFAOYSA-N 0.000 description 1
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 1
- DDWKPDDWQKXELH-UHFFFAOYSA-N 1-bromo-2-cyclopropyloxy-4-fluorobenzene Chemical compound FC1=CC=C(Br)C(OC2CC2)=C1 DDWKPDDWQKXELH-UHFFFAOYSA-N 0.000 description 1
- BNLMHIWPPSPPIQ-UHFFFAOYSA-N 1-bromo-2-cyclopropyloxy-4-methylsulfanylbenzene Chemical compound CSC1=CC=C(Br)C(OC2CC2)=C1 BNLMHIWPPSPPIQ-UHFFFAOYSA-N 0.000 description 1
- ADKYONRAMNWPKN-UHFFFAOYSA-N 1-bromo-2-cyclopropyloxy-4-methylsulfonylbenzene Chemical compound CS(=O)(=O)C1=CC=C(Br)C(OC2CC2)=C1 ADKYONRAMNWPKN-UHFFFAOYSA-N 0.000 description 1
- BQDVHQDTMHIRTO-UHFFFAOYSA-N 1-bromo-2-ethoxy-4-methylsulfanylbenzene Chemical compound CCOC1=CC(SC)=CC=C1Br BQDVHQDTMHIRTO-UHFFFAOYSA-N 0.000 description 1
- RIIPQBVKRKWNFS-UHFFFAOYSA-N 1-bromo-2-ethoxy-4-methylsulfonylbenzene Chemical compound CCOC1=CC(S(C)(=O)=O)=CC=C1Br RIIPQBVKRKWNFS-UHFFFAOYSA-N 0.000 description 1
- WTVKPGMTQBHSQS-UHFFFAOYSA-N 1-bromo-2-methoxy-4-methylsulfonylbenzene Chemical compound COC1=CC(S(C)(=O)=O)=CC=C1Br WTVKPGMTQBHSQS-UHFFFAOYSA-N 0.000 description 1
- BEJOCBPQBFEUNB-UHFFFAOYSA-N 1-bromo-4-fluoro-2-(2,2,2-trifluoroethoxy)benzene Chemical compound FC1=CC=C(Br)C(OCC(F)(F)F)=C1 BEJOCBPQBFEUNB-UHFFFAOYSA-N 0.000 description 1
- JKACTTARRNDIGL-UHFFFAOYSA-N 1-bromo-4-methylsulfanyl-2-(2,2,2-trifluoroethoxy)benzene Chemical compound CSC1=CC=C(Br)C(OCC(F)(F)F)=C1 JKACTTARRNDIGL-UHFFFAOYSA-N 0.000 description 1
- PLULOZSQQAESJA-UHFFFAOYSA-N 1-bromo-4-methylsulfonyl-2-(2,2,2-trifluoroethoxy)benzene Chemical compound CS(=O)(=O)C1=CC=C(Br)C(OCC(F)(F)F)=C1 PLULOZSQQAESJA-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 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
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
- OSBDFWJQDYDRLR-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetamide Chemical compound O1C(C)(C)C(C)(C)OB1C(C=C1)=CC=C1NC(=O)CC1=CC=C(F)C=C1 OSBDFWJQDYDRLR-UHFFFAOYSA-N 0.000 description 1
- VYJXPBPEYOOMNE-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-[4-[2-[4-methylsulfonyl-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]propanamide Chemical compound C=1C=C(F)C=CC=1C(C)C(=O)NC(C=C1)=CC=C1C(=CN1N=2)C=CC1=NC=2NC1=CC=C(S(C)(=O)=O)C=C1OCC(F)(F)F VYJXPBPEYOOMNE-UHFFFAOYSA-N 0.000 description 1
- MGKPFALCNDRSQD-UHFFFAOYSA-N 2-(4-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(F)C=C1 MGKPFALCNDRSQD-UHFFFAOYSA-N 0.000 description 1
- IXSCGBODJGIJNN-UHFFFAOYSA-N 2-(4-fluorophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(F)C=C1 IXSCGBODJGIJNN-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- IVZSPJZYISIMBV-UHFFFAOYSA-N 2-anilinopurin-8-one Chemical class N=1C2=NC(=O)N=C2C=NC=1NC1=CC=CC=C1 IVZSPJZYISIMBV-UHFFFAOYSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- SVDDJQGVOFZBNX-UHFFFAOYSA-N 2-chloroethyl carbonochloridate Chemical compound ClCCOC(Cl)=O SVDDJQGVOFZBNX-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
- 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
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- ZVQIKYMMLMYCJW-UHFFFAOYSA-N 3-(4-bromo-3-methoxyphenyl)-1,3-oxazolidin-2-one Chemical compound C1=C(Br)C(OC)=CC(N2C(OCC2)=O)=C1 ZVQIKYMMLMYCJW-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- BXLCENGNDVFRAZ-UHFFFAOYSA-N 3-hydroxyazetidine-1-carbaldehyde Chemical compound OC1CN(C=O)C1 BXLCENGNDVFRAZ-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- YELMWJNXDALKFE-UHFFFAOYSA-N 3h-imidazo[4,5-f]quinoxaline Chemical class N1=CC=NC2=C(NC=N3)C3=CC=C21 YELMWJNXDALKFE-UHFFFAOYSA-N 0.000 description 1
- 125000001963 4 membered heterocyclic group Chemical group 0.000 description 1
- JEWASFLDFPTRFC-UHFFFAOYSA-N 4-[(6-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)amino]-3-methoxy-n,n-dimethylbenzamide Chemical compound COC1=CC(C(=O)N(C)C)=CC=C1NC1=NN2C=C(Cl)C=CC2=N1 JEWASFLDFPTRFC-UHFFFAOYSA-N 0.000 description 1
- KVLRLNPRTWQZJA-UHFFFAOYSA-N 4-[2-(2-methoxy-4-methylsulfonylanilino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzoic acid Chemical compound COC1=CC(S(C)(=O)=O)=CC=C1NC1=NN2C=C(C=3C=CC(=CC=3)C(O)=O)C=CC2=N1 KVLRLNPRTWQZJA-UHFFFAOYSA-N 0.000 description 1
- WSGQWOKMSGHCBI-UHFFFAOYSA-N 4-[[6-(4-aminophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-(2,2,2-trifluoroethoxy)benzamide Chemical compound FC(F)(F)COC1=CC(C(=O)N)=CC=C1NC1=NN2C=C(C=3C=CC(N)=CC=3)C=CC2=N1 WSGQWOKMSGHCBI-UHFFFAOYSA-N 0.000 description 1
- COTYDDKFHDTHNA-UHFFFAOYSA-N 4-[[6-(4-aminophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-methoxy-n,n-dimethylbenzamide Chemical compound COC1=CC(C(=O)N(C)C)=CC=C1NC1=NN2C=C(C=3C=CC(N)=CC=3)C=CC2=N1 COTYDDKFHDTHNA-UHFFFAOYSA-N 0.000 description 1
- ROOOBBXOIJFCPC-UHFFFAOYSA-N 4-[[6-(4-aminophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-methoxy-n-(2,2,2-trifluoroethyl)benzamide Chemical compound COC1=CC(C(=O)NCC(F)(F)F)=CC=C1NC1=NN2C=C(C=3C=CC(N)=CC=3)C=CC2=N1 ROOOBBXOIJFCPC-UHFFFAOYSA-N 0.000 description 1
- QOCBTXYGFBJPAY-UHFFFAOYSA-N 4-[[6-(4-aminophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-methoxybenzamide Chemical compound COC1=CC(C(N)=O)=CC=C1NC1=NN2C=C(C=3C=CC(N)=CC=3)C=CC2=N1 QOCBTXYGFBJPAY-UHFFFAOYSA-N 0.000 description 1
- CFRDJNOBCVXNRR-UHFFFAOYSA-N 4-bromo-3-(2,2,2-trifluoroethoxy)benzamide Chemical compound NC(=O)C1=CC=C(Br)C(OCC(F)(F)F)=C1 CFRDJNOBCVXNRR-UHFFFAOYSA-N 0.000 description 1
- RIDSVLNSIKUVKR-UHFFFAOYSA-N 4-bromo-3-methoxy-n,n-dimethylbenzamide Chemical compound COC1=CC(C(=O)N(C)C)=CC=C1Br RIDSVLNSIKUVKR-UHFFFAOYSA-N 0.000 description 1
- ATGDJNLVHPJVDZ-UHFFFAOYSA-N 4-bromo-3-methoxy-n-(2,2,2-trifluoroethyl)benzamide Chemical compound COC1=CC(C(=O)NCC(F)(F)F)=CC=C1Br ATGDJNLVHPJVDZ-UHFFFAOYSA-N 0.000 description 1
- RUTNWXBHRAIQSP-UHFFFAOYSA-N 4-bromo-3-methoxyaniline Chemical compound COC1=CC(N)=CC=C1Br RUTNWXBHRAIQSP-UHFFFAOYSA-N 0.000 description 1
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 1
- SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 1
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
- WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 1
- MAXBVGJEFDMHNV-UHFFFAOYSA-N 5-chloropyridin-2-amine Chemical compound NC1=CC=C(Cl)C=N1 MAXBVGJEFDMHNV-UHFFFAOYSA-N 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- MOKRVGLBQJHEJC-UHFFFAOYSA-N 6-(4-aminophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound C=1N2N=C(N)N=C2C=CC=1C1=CC=C(N)C=C1 MOKRVGLBQJHEJC-UHFFFAOYSA-N 0.000 description 1
- PUYRZKONYPDTBA-UHFFFAOYSA-N 6-(4-aminophenyl)-n-[4-methylsulfonyl-2-(2,2,2-trifluoroethoxy)phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound FC(F)(F)COC1=CC(S(=O)(=O)C)=CC=C1NC1=NN2C=C(C=3C=CC(N)=CC=3)C=CC2=N1 PUYRZKONYPDTBA-UHFFFAOYSA-N 0.000 description 1
- XHBQNLHFUPSZNL-UHFFFAOYSA-N 6-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound C1=CC(Br)=CN2N=C(N)N=C21 XHBQNLHFUPSZNL-UHFFFAOYSA-N 0.000 description 1
- LXNPYPUQZKXAIW-UHFFFAOYSA-N 6-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound C1=CC(Cl)=CN2N=C(N)N=C21 LXNPYPUQZKXAIW-UHFFFAOYSA-N 0.000 description 1
- XVYWTOXDYLKBNU-UHFFFAOYSA-N 6-chloro-n-[4-methylsulfonyl-2-(2,2,2-trifluoroethoxy)phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound FC(F)(F)COC1=CC(S(=O)(=O)C)=CC=C1NC1=NN2C=C(Cl)C=CC2=N1 XVYWTOXDYLKBNU-UHFFFAOYSA-N 0.000 description 1
- 102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
- 108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- GXGJIOMUZAGVEH-UHFFFAOYSA-N Chamazulene Chemical group CCC1=CC=C(C)C2=CC=C(C)C2=C1 GXGJIOMUZAGVEH-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 230000004668 G2/M phase Effects 0.000 description 1
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 101100521345 Mus musculus Prop1 gene Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
- 108700017836 Prophet of Pit-1 Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- QLOWGDIISXJREF-UHFFFAOYSA-N [1,2,4]triazolo[1,5-c]pyrimidine Chemical class C1=CN=CN2N=CN=C21 QLOWGDIISXJREF-UHFFFAOYSA-N 0.000 description 1
- UJQAHAANAPEYLR-UHFFFAOYSA-N [2-chloro-6-[2,4,6-tri(propan-2-yl)phenyl]phenyl]-dicyclohexylphosphane Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC(Cl)=C1P(C1CCCCC1)C1CCCCC1 UJQAHAANAPEYLR-UHFFFAOYSA-N 0.000 description 1
- ICWADCIRKVJQJW-UHFFFAOYSA-N [4-[(6-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)amino]-3-methoxyphenyl]-(3-fluoroazetidin-1-yl)methanone Chemical compound C=1C=C(NC2=NN3C=C(Cl)C=CC3=N2)C(OC)=CC=1C(=O)N1CC(F)C1 ICWADCIRKVJQJW-UHFFFAOYSA-N 0.000 description 1
- HKDLJWHVTCVVOC-UHFFFAOYSA-N [4-[[6-(4-aminophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-(2,2,2-trifluoroethoxy)phenyl]-(3-fluoroazetidin-1-yl)methanone Chemical compound C1=CC(N)=CC=C1C1=CN2N=C(NC=3C(=CC(=CC=3)C(=O)N3CC(F)C3)OCC(F)(F)F)N=C2C=C1 HKDLJWHVTCVVOC-UHFFFAOYSA-N 0.000 description 1
- XEZWXSBGKPXYQO-UHFFFAOYSA-N [4-[[6-(4-aminophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-(2,2,2-trifluoroethoxy)phenyl]-pyrrolidin-1-ylmethanone Chemical compound C1=CC(N)=CC=C1C1=CN2N=C(NC=3C(=CC(=CC=3)C(=O)N3CCCC3)OCC(F)(F)F)N=C2C=C1 XEZWXSBGKPXYQO-UHFFFAOYSA-N 0.000 description 1
- KXKWPFABOBXHMD-UHFFFAOYSA-N [4-[[6-(4-aminophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-methoxyphenyl]-(3-fluoroazetidin-1-yl)methanone Chemical compound COC1=CC(C(=O)N2CC(F)C2)=CC=C1NC(=NN1C=2)N=C1C=CC=2C1=CC=C(N)C=C1 KXKWPFABOBXHMD-UHFFFAOYSA-N 0.000 description 1
- FSVGIGLZXCPZLR-UHFFFAOYSA-N [4-[[6-(4-aminophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-methoxyphenyl]-(azetidin-1-yl)methanone Chemical compound COC1=CC(C(=O)N2CCC2)=CC=C1NC(=NN1C=2)N=C1C=CC=2C1=CC=C(N)C=C1 FSVGIGLZXCPZLR-UHFFFAOYSA-N 0.000 description 1
- JBOIOUITDDGUEP-UHFFFAOYSA-N [4-[[6-(4-aminophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]-3-methoxyphenyl]-pyrrolidin-1-ylmethanone Chemical compound COC1=CC(C(=O)N2CCCC2)=CC=C1NC(=NN1C=2)N=C1C=CC=2C1=CC=C(N)C=C1 JBOIOUITDDGUEP-UHFFFAOYSA-N 0.000 description 1
- QQZKRNFQLGYWJR-UHFFFAOYSA-N [4-bromo-3-(2,2,2-trifluoroethoxy)phenyl]-(3-fluoroazetidin-1-yl)methanone Chemical compound C1C(F)CN1C(=O)C1=CC=C(Br)C(OCC(F)(F)F)=C1 QQZKRNFQLGYWJR-UHFFFAOYSA-N 0.000 description 1
- VZSJTPYRZCDTSZ-UHFFFAOYSA-N [4-bromo-3-(2,2,2-trifluoroethoxy)phenyl]-(3-hydroxyazetidin-1-yl)methanone Chemical compound C1C(O)CN1C(=O)C1=CC=C(Br)C(OCC(F)(F)F)=C1 VZSJTPYRZCDTSZ-UHFFFAOYSA-N 0.000 description 1
- WCQIXDALKPDGFT-UHFFFAOYSA-N [4-bromo-3-(2,2,2-trifluoroethoxy)phenyl]-pyrrolidin-1-ylmethanone Chemical compound C1=C(Br)C(OCC(F)(F)F)=CC(C(=O)N2CCCC2)=C1 WCQIXDALKPDGFT-UHFFFAOYSA-N 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 208000036878 aneuploidy Diseases 0.000 description 1
- 231100001075 aneuploidy Toxicity 0.000 description 1
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
- 125000005427 anthranyl group Chemical group 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- UQUPQEUNHVVNKW-UHFFFAOYSA-N azetidin-1-ium-3-ol;chloride Chemical compound Cl.OC1CNC1 UQUPQEUNHVVNKW-UHFFFAOYSA-N 0.000 description 1
- AQAYYJFLJZKWCR-UHFFFAOYSA-N azetidin-1-yl-(4-bromo-3-methoxyphenyl)methanone Chemical compound C1=C(Br)C(OC)=CC(C(=O)N2CCC2)=C1 AQAYYJFLJZKWCR-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- HTJWUNNIRKDDIV-UHFFFAOYSA-N bis(1-adamantyl)-butylphosphane Chemical compound C1C(C2)CC(C3)CC2CC13P(CCCC)C1(C2)CC(C3)CC2CC3C1 HTJWUNNIRKDDIV-UHFFFAOYSA-N 0.000 description 1
- XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
- LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 description 1
- DLIJPAHLBJIQHE-UHFFFAOYSA-N butylphosphane Chemical compound CCCCP DLIJPAHLBJIQHE-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000034303 cell budding Effects 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013000 chemical inhibitor Substances 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000024321 chromosome segregation Effects 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 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
- 230000000368 destabilizing effect Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical group OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 1
- SACNIGZYDTUHKB-UHFFFAOYSA-N ditert-butyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C(C)(C)C)C(C)(C)C SACNIGZYDTUHKB-UHFFFAOYSA-N 0.000 description 1
- 125000005883 dithianyl group Chemical group 0.000 description 1
- UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- CWUSWANRIVVXCI-UHFFFAOYSA-N ethyl n-[(5-bromopyridin-2-yl)carbamothioyl]carbamate Chemical compound CCOC(=O)NC(=S)NC1=CC=C(Br)C=N1 CWUSWANRIVVXCI-UHFFFAOYSA-N 0.000 description 1
- SUDFDUAHBQUCKX-UHFFFAOYSA-N ethyl n-[(5-chloropyridin-2-yl)carbamothioyl]carbamate Chemical compound CCOC(=O)NC(=S)NC1=CC=C(Cl)C=N1 SUDFDUAHBQUCKX-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 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 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000002489 hematologic effect Effects 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
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 238000002955 isolation Methods 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
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- VBUWXVKWJPKNEK-UHFFFAOYSA-N isothiocyanato n-(sulfanylidenemethylidene)carbamate Chemical compound S=C=NC(=O)ON=C=S VBUWXVKWJPKNEK-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000007477 logistic regression Methods 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- CJGWNNKCEBLFSR-UHFFFAOYSA-N methyl 2-(4-fluorophenyl)-3-hydroxypropanoate Chemical compound COC(=O)C(CO)C1=CC=C(F)C=C1 CJGWNNKCEBLFSR-UHFFFAOYSA-N 0.000 description 1
- HRSNKYJSOMIHNH-UHFFFAOYSA-N methyl 2-(4-fluorophenyl)propanoate Chemical compound COC(=O)C(C)C1=CC=C(F)C=C1 HRSNKYJSOMIHNH-UHFFFAOYSA-N 0.000 description 1
- KIUAWNHTCCQVBP-UHFFFAOYSA-N methyl 4-bromo-3-(2,2,2-trifluoroethoxy)benzoate Chemical compound COC(=O)C1=CC=C(Br)C(OCC(F)(F)F)=C1 KIUAWNHTCCQVBP-UHFFFAOYSA-N 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 230000008880 microtubule cytoskeleton organization Effects 0.000 description 1
- 230000036456 mitotic arrest Effects 0.000 description 1
- 230000008600 mitotic progression Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- AFYZKBPZMUOPIG-UHFFFAOYSA-N n-[4-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl]-2-(4-fluorophenyl)propanamide Chemical compound C=1C=C(C2=CN3N=C(N)N=C3C=C2)C=CC=1NC(=O)C(C)C1=CC=C(F)C=C1 AFYZKBPZMUOPIG-UHFFFAOYSA-N 0.000 description 1
- HJSXMBIWAUULQQ-UHFFFAOYSA-N n-[4-[2-(2-ethoxy-4-fluoroanilino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]-2-(4-fluorophenyl)acetamide Chemical compound CCOC1=CC(F)=CC=C1NC1=NN2C=C(C=3C=CC(NC(=O)CC=4C=CC(F)=CC=4)=CC=3)C=CC2=N1 HJSXMBIWAUULQQ-UHFFFAOYSA-N 0.000 description 1
- GIJBGFMZYQQSPA-UHFFFAOYSA-N n-[4-[2-(2-ethoxy-4-methylsulfonylanilino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]-2-(4-fluorophenyl)propanamide Chemical compound CCOC1=CC(S(C)(=O)=O)=CC=C1NC1=NN2C=C(C=3C=CC(NC(=O)C(C)C=4C=CC(F)=CC=4)=CC=3)C=CC2=N1 GIJBGFMZYQQSPA-UHFFFAOYSA-N 0.000 description 1
- DMAJORPFXLBYCW-UHFFFAOYSA-N n-[4-[2-(4-cyano-2-methoxyanilino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]-2-(4-fluorophenyl)acetamide Chemical compound COC1=CC(C#N)=CC=C1NC1=NN2C=C(C=3C=CC(NC(=O)CC=4C=CC(F)=CC=4)=CC=3)C=CC2=N1 DMAJORPFXLBYCW-UHFFFAOYSA-N 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 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
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 101150061302 och1 gene Proteins 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003585 oxepinyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 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
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 229960005335 propanol Drugs 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- MVILWLLYYQVYNH-UHFFFAOYSA-N pyridine-2-carboxamide Chemical compound NC(=O)C1=CC=CC=N1.NC(=O)C1=CC=CC=N1 MVILWLLYYQVYNH-UHFFFAOYSA-N 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- YOWAEZWWQFSEJD-UHFFFAOYSA-N quinoxalin-2-amine Chemical class C1=CC=CC2=NC(N)=CN=C21 YOWAEZWWQFSEJD-UHFFFAOYSA-N 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000006413 ring segment Chemical group 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
- 238000005204 segregation Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000019130 spindle checkpoint Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000016853 telophase Effects 0.000 description 1
- UWOPGNRQXQFXOS-JGCGQSQUSA-N tert-butyl N-[(1R)-1-(4-fluorophenyl)-2-oxo-2-[4-[2-[4-(pyrrolidine-1-carbonyl)-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]anilino]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C(=O)Nc1ccc(cc1)-c1ccc2nc(Nc3ccc(cc3OCC(F)(F)F)C(=O)N3CCCC3)nn2c1)c1ccc(F)cc1 UWOPGNRQXQFXOS-JGCGQSQUSA-N 0.000 description 1
- KLFNBBPRYVIGPC-WJOKGBTCSA-N tert-butyl n-[(1r)-2-[4-[2-[4-(3-fluoroazetidine-1-carbonyl)-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]anilino]-1-(4-fluorophenyl)-2-oxoethyl]carbamate Chemical compound O=C([C@H](NC(=O)OC(C)(C)C)C=1C=CC(F)=CC=1)NC(C=C1)=CC=C1C(=CN1N=2)C=CC1=NC=2NC(C(=C1)OCC(F)(F)F)=CC=C1C(=O)N1CC(F)C1 KLFNBBPRYVIGPC-WJOKGBTCSA-N 0.000 description 1
- GNMSUFRNBBLZAK-WJOKGBTCSA-N tert-butyl n-[(1r)-2-[4-[2-[4-(azetidine-1-carbonyl)-2-methoxyanilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]anilino]-1-(4-fluorophenyl)-2-oxoethyl]carbamate Chemical compound C1([C@@H](NC(=O)OC(C)(C)C)C(=O)NC2=CC=C(C=C2)C=2C=CC3=NC(=NN3C=2)NC2=CC=C(C=C2OC)C(=O)N2CCC2)=CC=C(F)C=C1 GNMSUFRNBBLZAK-WJOKGBTCSA-N 0.000 description 1
- HNUHNECIEYXPJH-UHFFFAOYSA-N tert-butyl n-[4-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CN2N=C(N)N=C2C=C1 HNUHNECIEYXPJH-UHFFFAOYSA-N 0.000 description 1
- GDDJAERCAZQRRB-UHFFFAOYSA-N tert-butyl n-[4-[2-[2-methoxy-4-(2,2,2-trifluoroethylcarbamoyl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]carbamate Chemical compound COC1=CC(C(=O)NCC(F)(F)F)=CC=C1NC1=NN2C=C(C=3C=CC(NC(=O)OC(C)(C)C)=CC=3)C=CC2=N1 GDDJAERCAZQRRB-UHFFFAOYSA-N 0.000 description 1
- ODSIOLXOOVBDBL-UHFFFAOYSA-N tert-butyl n-[4-[2-[2-methoxy-4-(2-oxo-1,3-oxazolidin-3-yl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]carbamate Chemical compound COC1=CC(N2C(OCC2)=O)=CC=C1NC(=NN1C=2)N=C1C=CC=2C1=CC=C(NC(=O)OC(C)(C)C)C=C1 ODSIOLXOOVBDBL-UHFFFAOYSA-N 0.000 description 1
- KYAYQXFXFHQECD-UHFFFAOYSA-N tert-butyl n-[4-[2-[2-methoxy-4-(pyrrolidine-1-carbonyl)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]carbamate Chemical compound COC1=CC(C(=O)N2CCCC2)=CC=C1NC(=NN1C=2)N=C1C=CC=2C1=CC=C(NC(=O)OC(C)(C)C)C=C1 KYAYQXFXFHQECD-UHFFFAOYSA-N 0.000 description 1
- VGNHHHIYUJDPRV-UHFFFAOYSA-N tert-butyl n-[4-[2-[4-(3-fluoroazetidine-1-carbonyl)-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CN2N=C(NC=3C(=CC(=CC=3)C(=O)N3CC(F)C3)OCC(F)(F)F)N=C2C=C1 VGNHHHIYUJDPRV-UHFFFAOYSA-N 0.000 description 1
- JIROXBIIIGAPTK-UHFFFAOYSA-N tert-butyl n-[4-[2-[4-(3-fluoroazetidine-1-carbonyl)-2-methoxyanilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]carbamate Chemical compound COC1=CC(C(=O)N2CC(F)C2)=CC=C1NC(=NN1C=2)N=C1C=CC=2C1=CC=C(NC(=O)OC(C)(C)C)C=C1 JIROXBIIIGAPTK-UHFFFAOYSA-N 0.000 description 1
- MTWWIWFGMXCGPD-UHFFFAOYSA-N tert-butyl n-[4-[2-[4-(3-hydroxyazetidine-1-carbonyl)-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CN2N=C(NC=3C(=CC(=CC=3)C(=O)N3CC(O)C3)OCC(F)(F)F)N=C2C=C1 MTWWIWFGMXCGPD-UHFFFAOYSA-N 0.000 description 1
- GBZKCHSSUDPDNZ-UHFFFAOYSA-N tert-butyl n-[4-[2-[4-(azetidine-1-carbonyl)-2-methoxyanilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]carbamate Chemical compound COC1=CC(C(=O)N2CCC2)=CC=C1NC(=NN1C=2)N=C1C=CC=2C1=CC=C(NC(=O)OC(C)(C)C)C=C1 GBZKCHSSUDPDNZ-UHFFFAOYSA-N 0.000 description 1
- WUIGILVBCQZZBM-UHFFFAOYSA-N tert-butyl n-[4-[2-[4-carbamoyl-2-(2,2,2-trifluoroethoxy)anilino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CN2N=C(NC=3C(=CC(=CC=3)C(N)=O)OCC(F)(F)F)N=C2C=C1 WUIGILVBCQZZBM-UHFFFAOYSA-N 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- MHNHYTDAOYJUEZ-UHFFFAOYSA-N triphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 MHNHYTDAOYJUEZ-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12175640 | 2012-07-10 | ||
| EP12175640.7 | 2012-07-10 | ||
| EP12185590 | 2012-09-24 | ||
| EP12185590.2 | 2012-09-24 | ||
| EP13170585 | 2013-06-05 | ||
| EP13170585.7 | 2013-06-05 | ||
| PCT/EP2013/064017 WO2014009219A1 (en) | 2012-07-10 | 2013-07-03 | Method for preparing substituted triazolopyridines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2013289381A1 true AU2013289381A1 (en) | 2015-01-22 |
Family
ID=48793197
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013289381A Abandoned AU2013289381A1 (en) | 2012-07-10 | 2013-07-03 | Method for preparing substituted triazolopyridines |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US9388177B2 (enExample) |
| EP (1) | EP2872506A1 (enExample) |
| JP (1) | JP6238979B2 (enExample) |
| KR (1) | KR20150040845A (enExample) |
| CN (1) | CN104603136B (enExample) |
| AP (1) | AP3778A (enExample) |
| AU (1) | AU2013289381A1 (enExample) |
| BR (1) | BR112015000308A2 (enExample) |
| CA (1) | CA2878481A1 (enExample) |
| CL (1) | CL2015000038A1 (enExample) |
| CO (1) | CO7160002A2 (enExample) |
| CR (1) | CR20150006A (enExample) |
| DO (1) | DOP2015000007A (enExample) |
| EA (1) | EA027544B1 (enExample) |
| HK (1) | HK1206731A1 (enExample) |
| IL (1) | IL236265A (enExample) |
| IN (1) | IN2015DN00085A (enExample) |
| MX (1) | MX2015000348A (enExample) |
| NZ (1) | NZ703020A (enExample) |
| PE (1) | PE20150354A1 (enExample) |
| PH (1) | PH12015500061A1 (enExample) |
| SG (1) | SG11201408419QA (enExample) |
| TN (1) | TN2015000008A1 (enExample) |
| WO (1) | WO2014009219A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014195276A1 (en) * | 2013-06-07 | 2014-12-11 | Bayer Pharma Aktiengesellschaft | Substituted triazolopyridines having activity as mps-1 inhibitors |
| PT3008062T (pt) * | 2013-06-11 | 2017-06-07 | Bayer Pharma AG | Derivados de profármaco de triazolopiridinas substituídas |
| MA38656A1 (fr) | 2013-06-11 | 2018-05-31 | Bayer Pharma AG | Combinaisons pour le traitement du cancer comprenant un inhibiteur de la kinase mps-1 et un inhibiteur de la mitose |
| CN107567503B (zh) | 2015-04-17 | 2022-03-22 | 荷兰转化研究中心有限责任公司 | 用于ttk抑制剂化疗的预后生物标记 |
| TW201800408A (zh) | 2016-06-15 | 2018-01-01 | 拜耳製藥公司 | Mps-1抑制劑 |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2003030937A1 (ja) * | 2001-10-05 | 2005-01-20 | 小野薬品工業株式会社 | ミトコンドリアルベンゾジアゼピン受容体アンタゴニストからなるストレス疾患の治療剤 |
| WO2005110410A2 (en) * | 2004-05-14 | 2005-11-24 | Abbott Laboratories | Kinase inhibitors as therapeutic agents |
| UA89503C2 (uk) * | 2004-09-13 | 2010-02-10 | Х. Луннбек А/С | Заміщені похідні аніліну |
| US7524860B2 (en) * | 2004-10-07 | 2009-04-28 | Pfizer Inc. | Antibacterial agents |
| US20060194823A1 (en) * | 2004-12-22 | 2006-08-31 | Georg Kettschau | Sulfonamido-macrocycles as Tie2 inhibitors and the salts thereof, a pharmaceutical composition comprising these compounds, the method of preparing and the use thereof |
| MX2008015747A (es) * | 2006-06-06 | 2008-12-19 | Schering Corp | Imidazopirazinas como inhibidores de la proteina quinasa. |
| EP1870416A1 (en) * | 2006-06-21 | 2007-12-26 | Bayer Schering Pharma Aktiengesellschaft | Sulphonamido-macrocycles as tie2 inhibitors |
| SG174086A1 (en) | 2006-08-30 | 2011-09-29 | Cellzome Ltd | Triazole derivatives as kinase inhibitors |
| JO3598B1 (ar) * | 2006-10-10 | 2020-07-05 | Infinity Discovery Inc | الاحماض والاسترات البورونية كمثبطات اميد هيدروليز الحامض الدهني |
| KR20100049073A (ko) | 2007-07-18 | 2010-05-11 | 노파르티스 아게 | 비시클릭 헤테로아릴 화합물 및 키나제 억제제로서의 그의 용도 |
| JP2010536841A (ja) | 2007-08-23 | 2010-12-02 | アストラゼネカ アクチボラグ | 増殖性疾患治療のためのｔｔｋ／ｍｐｓ１阻害剤としての２−アニリノプリン−８−オン類 |
| JP2010536917A (ja) | 2007-08-31 | 2010-12-02 | メルク セローノ ソシエテ アノニム | トリアゾロピリジン化合物と、ａｓｋ阻害剤としてのその化合物の利用法 |
| GB0719803D0 (en) | 2007-10-10 | 2007-11-21 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| GB0724342D0 (en) * | 2007-12-13 | 2008-01-30 | Prolysis Ltd | Anitbacterial compositions |
| WO2009137322A2 (en) * | 2008-05-05 | 2009-11-12 | The Trustees Of The University Of Pennsylvania | Processes for the preparation of biphenyl compounds |
| WO2009155527A2 (en) * | 2008-06-19 | 2009-12-23 | Progenics Pharmaceuticals, Inc. | Phosphatidylinositol 3 kinase inhibitors |
| KR20110116160A (ko) | 2009-02-13 | 2011-10-25 | 포비어 파마수티칼스 | 카이네이스 저해제로서의 〔1,2,4〕트리아졸로〔1,5-ａ〕피리딘 |
| CN102413831B (zh) | 2009-04-29 | 2014-06-04 | 拜耳知识产权有限责任公司 | 取代的咪唑并喹喔啉 |
| WO2010141360A1 (en) * | 2009-06-05 | 2010-12-09 | Merck Sharp & Dohme Corp. | Biaryl benzotriazole derivatives |
| MX2011012961A (es) * | 2009-06-05 | 2012-01-30 | Cephalon Inc | Preparacion y usos de derivados de 1,2,4-triazolo[1,5a]-piridina. |
| CA2772790C (en) | 2009-09-04 | 2017-06-27 | Benjamin Bader | Substituted aminoquinoxalines as tyrosine threonine kinase inhibitors |
| EP2343294A1 (en) * | 2009-11-30 | 2011-07-13 | Bayer Schering Pharma AG | Substituted triazolopyridines |
| EP2343295A1 (en) * | 2009-11-30 | 2011-07-13 | Bayer Schering Pharma AG | Triazolopyridine derivates |
| EP2343297A1 (en) * | 2009-11-30 | 2011-07-13 | Bayer Schering Pharma AG | Triazolopyridines |
| UY33452A (es) | 2010-06-16 | 2012-01-31 | Bayer Schering Pharma Ag | Triazolopiridinas sustituidas |
| WO2012044567A2 (en) * | 2010-09-30 | 2012-04-05 | Merck Sharp & Dohme Corp. | Imidazole derivatives |
| PL2699575T3 (pl) * | 2011-04-21 | 2015-08-31 | Bayer Ip Gmbh | Triazolopirydyny |
| WO2012160029A1 (en) * | 2011-05-23 | 2012-11-29 | Bayer Intellectual Property Gmbh | Substituted triazolopyridines |
| UA112096C2 (uk) * | 2011-12-12 | 2016-07-25 | Байєр Інтеллектуал Проперті Гмбх | Заміщені триазолопіридини та їх застосування як інгібіторів ttk |
-
2013
- 2013-07-03 NZ NZ703020A patent/NZ703020A/en not_active IP Right Cessation
- 2013-07-03 US US14/414,164 patent/US9388177B2/en not_active Expired - Fee Related
- 2013-07-03 BR BR112015000308A patent/BR112015000308A2/pt not_active IP Right Cessation
- 2013-07-03 WO PCT/EP2013/064017 patent/WO2014009219A1/en not_active Ceased
- 2013-07-03 HK HK15107242.4A patent/HK1206731A1/xx unknown
- 2013-07-03 MX MX2015000348A patent/MX2015000348A/es unknown
- 2013-07-03 IN IN85DEN2015 patent/IN2015DN00085A/en unknown
- 2013-07-03 EP EP13737181.1A patent/EP2872506A1/en not_active Withdrawn
- 2013-07-03 SG SG11201408419QA patent/SG11201408419QA/en unknown
- 2013-07-03 EA EA201590116A patent/EA027544B1/ru not_active IP Right Cessation
- 2013-07-03 JP JP2015520907A patent/JP6238979B2/ja not_active Expired - Fee Related
- 2013-07-03 KR KR20157000338A patent/KR20150040845A/ko not_active Withdrawn
- 2013-07-03 AU AU2013289381A patent/AU2013289381A1/en not_active Abandoned
- 2013-07-03 CA CA2878481A patent/CA2878481A1/en not_active Abandoned
- 2013-07-03 PE PE2015000017A patent/PE20150354A1/es not_active Application Discontinuation
- 2013-07-03 AP AP2014008177A patent/AP3778A/en active
- 2013-07-03 CN CN201380045913.9A patent/CN104603136B/zh not_active Expired - Fee Related
-
2014
- 2014-12-15 IL IL236265A patent/IL236265A/en not_active IP Right Cessation
-
2015
- 2015-01-07 TN TNP2015000008A patent/TN2015000008A1/fr unknown
- 2015-01-08 CL CL2015000038A patent/CL2015000038A1/es unknown
- 2015-01-09 CO CO15004251A patent/CO7160002A2/es unknown
- 2015-01-09 DO DO2015000007A patent/DOP2015000007A/es unknown
- 2015-01-09 CR CR20150006A patent/CR20150006A/es unknown
- 2015-01-09 PH PH12015500061A patent/PH12015500061A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2878481A1 (en) | 2014-01-16 |
| AP2014008177A0 (en) | 2014-12-31 |
| PH12015500061A1 (en) | 2015-03-02 |
| CN104603136B (zh) | 2017-06-27 |
| JP2015523372A (ja) | 2015-08-13 |
| US9388177B2 (en) | 2016-07-12 |
| CR20150006A (es) | 2015-02-16 |
| SG11201408419QA (en) | 2015-01-29 |
| AP3778A (en) | 2016-08-31 |
| DOP2015000007A (es) | 2015-02-15 |
| CL2015000038A1 (es) | 2015-03-13 |
| PE20150354A1 (es) | 2015-03-21 |
| CN104603136A (zh) | 2015-05-06 |
| WO2014009219A1 (en) | 2014-01-16 |
| US20150148542A1 (en) | 2015-05-28 |
| HK1206731A1 (en) | 2016-01-15 |
| CO7160002A2 (es) | 2015-01-15 |
| KR20150040845A (ko) | 2015-04-15 |
| IL236265A0 (en) | 2015-02-26 |
| TN2015000008A1 (en) | 2016-06-29 |
| JP6238979B2 (ja) | 2017-11-29 |
| BR112015000308A2 (pt) | 2017-06-27 |
| EP2872506A1 (en) | 2015-05-20 |
| IL236265A (en) | 2017-07-31 |
| MX2015000348A (es) | 2015-04-14 |
| NZ703020A (en) | 2017-08-25 |
| EA201590116A1 (ru) | 2015-07-30 |
| EA027544B1 (ru) | 2017-08-31 |
| IN2015DN00085A (enExample) | 2015-05-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2632464C1 (ru) | Замещенные триазолопиридины и их применение в качестве ингибиторов тирозин треонин киназы (ттк) | |
| RU2560153C2 (ru) | Триазолпиридиновые соединения, ингибирующие jak, и способы | |
| ES2545541T3 (es) | Compuestos de pirazolopirimidina inhibidores de JAK y métodos | |
| AU2014280395A1 (en) | Novel compounds for the treatment of cancer | |
| US9388177B2 (en) | Method for preparing substituted triazolopyridines | |
| EP3008062B1 (en) | Prodrug derivatives of substituted triazolopyridines | |
| WO2014195276A1 (en) | Substituted triazolopyridines having activity as mps-1 inhibitors | |
| EP3004092B1 (en) | Substituted triazolopyridines | |
| HK1222652B (en) | Substituted triazolopyridines | |
| HK1161529B (en) | Pyrazolopyrimidine jak inhibitor compounds and methods |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |