RU2600976C2 - Производные азаиндазола или диазаиндазола в качестве медикамента - Google Patents

Производные азаиндазола или диазаиндазола в качестве медикамента Download PDF

Info

Publication number: RU2600976C2
Authority: RU; Russia
Prior art keywords: compound; group; formula; pyrazolo; pyridin
Prior art date: 2011-01-27

Application number

RU2013138624/04A

Other languages

English (en)

Russian (ru)

Other versions

RU2013138624A (ru

Inventor

Эль Бахир КАЛУН

Карим БЕДЖЕГЕЛАЛЬ

Реми РАБО

Анна КРЮЗИНСКИ

Филипп ШМИТТ

Мишель ПЕРЕС

Николя РАЙЕ

Original Assignee

Пьер Фабр Медикамент

Priority date (The priority date 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 date listed.)

2011-01-27

Filing date

2012-01-27

Publication date

2016-10-27

2012-01-27 Application filed by Пьер Фабр Медикамент filed Critical Пьер Фабр Медикамент

2015-03-10 Publication of RU2013138624A publication Critical patent/RU2013138624A/ru

2016-10-27 Application granted granted Critical

2016-10-27 Publication of RU2600976C2 publication Critical patent/RU2600976C2/ru

Links

239000003814 drug Substances 0.000 title claims abstract description 9
VQNDBXJTIJKJPV-UHFFFAOYSA-N 2h-triazolo[4,5-b]pyridine Chemical class C1=CC=NC2=NNN=C21 VQNDBXJTIJKJPV-UHFFFAOYSA-N 0.000 title 1
QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 193
238000000034 method Methods 0.000 claims abstract description 153
206010028980 Neoplasm Diseases 0.000 claims abstract description 36
150000003839 salts Chemical class 0.000 claims abstract description 32
201000011510 cancer Diseases 0.000 claims abstract description 19
102000001332 SRC Human genes 0.000 claims abstract description 13
108060006706 SRC Proteins 0.000 claims abstract description 13
102000001253 Protein Kinase Human genes 0.000 claims abstract description 12
108060006633 protein kinase Proteins 0.000 claims abstract description 12
206010061218 Inflammation Diseases 0.000 claims abstract description 8
230000004054 inflammatory process Effects 0.000 claims abstract description 8
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
208000024827 Alzheimer disease Diseases 0.000 claims abstract description 7
230000004770 neurodegeneration Effects 0.000 claims abstract description 7
208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 7
239000003112 inhibitor Substances 0.000 claims abstract description 5
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 155
238000006243 chemical reaction Methods 0.000 claims description 69
229910052757 nitrogen Inorganic materials 0.000 claims description 48
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 37
229910052717 sulfur Inorganic materials 0.000 claims description 34
125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
125000000623 heterocyclic group Chemical group 0.000 claims description 18
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 16
125000005843 halogen group Chemical group 0.000 claims description 15
108091000080 Phosphotransferase Proteins 0.000 claims description 12
102000020233 phosphotransferase Human genes 0.000 claims description 12
238000011282 treatment Methods 0.000 claims description 12
125000004429 atom Chemical group 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
229910052770 Uranium Inorganic materials 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 5
125000004430 oxygen atom Chemical group O* 0.000 claims description 5
238000006268 reductive amination reaction Methods 0.000 claims description 4
230000002401 inhibitory effect Effects 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
230000000694 effects Effects 0.000 abstract description 11
238000004519 manufacturing process Methods 0.000 abstract description 8
239000000126 substance Substances 0.000 abstract description 7
229940043355 kinase inhibitor Drugs 0.000 abstract description 5
239000003757 phosphotransferase inhibitor Substances 0.000 abstract description 5
229940079593 drug Drugs 0.000 abstract 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 266
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 183
-1 Kit Proteins 0.000 description 177
239000000243 solution Substances 0.000 description 141
239000011541 reaction mixture Substances 0.000 description 119
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 101
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 94
238000005481 NMR spectroscopy Methods 0.000 description 94
239000007787 solid Substances 0.000 description 90
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 76
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 75
239000002904 solvent Substances 0.000 description 70
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 65
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 63
239000012074 organic phase Substances 0.000 description 56
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 52
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 51
239000000203 mixture Substances 0.000 description 48
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 40
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
229910052943 magnesium sulfate Inorganic materials 0.000 description 36
235000019341 magnesium sulphate Nutrition 0.000 description 36
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 34
238000003756 stirring Methods 0.000 description 28
125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
239000000047 product Substances 0.000 description 27
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 26
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 25
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 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
239000002798 polar solvent Substances 0.000 description 23
238000010898 silica gel chromatography Methods 0.000 description 23
229910052739 hydrogen Inorganic materials 0.000 description 22
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 22
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 21
239000002244 precipitate Substances 0.000 description 20
230000015572 biosynthetic process Effects 0.000 description 19
239000000843 powder Substances 0.000 description 19
102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 18
239000000543 intermediate Substances 0.000 description 18
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 description 17
239000007795 chemical reaction product Substances 0.000 description 17
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
150000007529 inorganic bases Chemical class 0.000 description 16
150000007530 organic bases Chemical class 0.000 description 16
125000003118 aryl group Chemical group 0.000 description 15
JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 14
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
239000002585 base Substances 0.000 description 14
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 13
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
238000000746 purification Methods 0.000 description 13
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
239000003795 chemical substances by application Substances 0.000 description 12
238000005755 formation reaction Methods 0.000 description 12
229910000027 potassium carbonate Inorganic materials 0.000 description 12
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 12
239000013078 crystal Substances 0.000 description 11
239000003480 eluent Substances 0.000 description 11
239000012429 reaction media Substances 0.000 description 11
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
238000003786 synthesis reaction Methods 0.000 description 11
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
239000008346 aqueous phase Substances 0.000 description 10
238000009835 boiling Methods 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
239000000460 chlorine Substances 0.000 description 10
239000012043 crude product Substances 0.000 description 10
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 10
AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
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 9
210000004027 cell Anatomy 0.000 description 9
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 9
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 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
206010073478 Anaplastic large-cell lymphoma Diseases 0.000 description 8
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
238000010511 deprotection reaction Methods 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
229910000041 hydrogen chloride Inorganic materials 0.000 description 8
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
238000007254 oxidation reaction Methods 0.000 description 8
229910052763 palladium Inorganic materials 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
229910000029 sodium carbonate Inorganic materials 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
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 7
XVIHGTRTKQZJAC-UHFFFAOYSA-N 6-chloro-3-nitropyridine-2-carbonitrile Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1C#N XVIHGTRTKQZJAC-UHFFFAOYSA-N 0.000 description 7
229910052786 argon Inorganic materials 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
230000003647 oxidation Effects 0.000 description 7
235000011181 potassium carbonates Nutrition 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
239000011734 sodium Substances 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
150000003462 sulfoxides Chemical class 0.000 description 7
FYHRQFFVACXNTB-UHFFFAOYSA-N 2-chloro-5-iodopyridine-3-carbonitrile Chemical class ClC1=NC=C(I)C=C1C#N FYHRQFFVACXNTB-UHFFFAOYSA-N 0.000 description 6
ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical compound O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
VOLMSPGWNYJHQQ-UHFFFAOYSA-N Pyranone Natural products CC1=C(O)C(=O)C(O)CO1 VOLMSPGWNYJHQQ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
230000002378 acidificating effect Effects 0.000 description 6
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical class [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
230000003197 catalytic effect Effects 0.000 description 6
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 6
230000003831 deregulation Effects 0.000 description 6
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 6
125000000524 functional group Chemical group 0.000 description 6
239000001257 hydrogen Substances 0.000 description 6
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
239000012038 nucleophile Substances 0.000 description 6
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
239000012453 solvate Substances 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
238000012360 testing method Methods 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 5
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
QDHZJXAAFQGWIY-UHFFFAOYSA-N 3-amino-6-iodopyrazine-2-carboxamide Chemical class NC(=O)C1=NC(I)=CN=C1N QDHZJXAAFQGWIY-UHFFFAOYSA-N 0.000 description 5
RVLCKYBNAYDRIJ-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfanyl-2h-pyrazolo[3,4-b]pyrazin-3-amine Chemical compound N1=C2C(N)=NNC2=NC=C1SC1=CC(F)=CC(F)=C1 RVLCKYBNAYDRIJ-UHFFFAOYSA-N 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 5
PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
230000009471 action Effects 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000000010 aprotic solvent Substances 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
239000012298 atmosphere Substances 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
208000002154 non-small cell lung carcinoma Diseases 0.000 description 5
230000003287 optical effect Effects 0.000 description 5
230000007170 pathology Effects 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
238000006722 reduction reaction Methods 0.000 description 5
235000010288 sodium nitrite Nutrition 0.000 description 5
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 5
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
IHWZCGMZILLKFD-UHFFFAOYSA-N 2-methoxypyridine-3-carbonitrile Chemical compound COC1=NC=CC=C1C#N IHWZCGMZILLKFD-UHFFFAOYSA-N 0.000 description 4
MOUURCSKHKVYPB-UHFFFAOYSA-N 2-methylsulfanyl-6-oxo-1h-pyridine-3-carbonitrile Chemical compound CSC1=NC(O)=CC=C1C#N MOUURCSKHKVYPB-UHFFFAOYSA-N 0.000 description 4
GPYNAAUDGBICPV-UHFFFAOYSA-N 3-amino-n-(3,5-difluorophenyl)-2h-pyrazolo[3,4-b]pyridine-5-sulfonamide Chemical compound C1=C2C(N)=NNC2=NC=C1S(=O)(=O)NC1=CC(F)=CC(F)=C1 GPYNAAUDGBICPV-UHFFFAOYSA-N 0.000 description 4
XNMSAEOZDVATJK-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfanyl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1=C2C(N)=NNC2=NC=C1SC1=CC(F)=CC(F)=C1 XNMSAEOZDVATJK-UHFFFAOYSA-N 0.000 description 4
KAXIYYPIORYZLB-UHFFFAOYSA-N 5-hydroxypyridine-3-carbonitrile Chemical class OC1=CN=CC(C#N)=C1 KAXIYYPIORYZLB-UHFFFAOYSA-N 0.000 description 4
BYEUNDASYOFKIW-UHFFFAOYSA-N 5-iodo-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical class C1=C(I)C=C2C(N)=NNC2=N1 BYEUNDASYOFKIW-UHFFFAOYSA-N 0.000 description 4
JWRYNLANQMKICK-UHFFFAOYSA-N 6-(2,4-difluoroanilino)-2-methylsulfanylpyridine-3-carbonitrile Chemical compound C1=C(C#N)C(SC)=NC(NC=2C(=CC(F)=CC=2)F)=C1 JWRYNLANQMKICK-UHFFFAOYSA-N 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
239000012223 aqueous fraction Substances 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
238000006555 catalytic reaction Methods 0.000 description 4
230000004663 cell proliferation Effects 0.000 description 4
229910052802 copper Inorganic materials 0.000 description 4
239000010949 copper Substances 0.000 description 4
MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 4
LYGPATUMODNSAM-ONEGZZNKSA-N ethyl (e)-3-(4-aminopyridin-3-yl)prop-2-enoate Chemical compound CCOC(=O)\C=C\C1=CN=CC=C1N LYGPATUMODNSAM-ONEGZZNKSA-N 0.000 description 4
239000002038 ethyl acetate fraction Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
238000007306 functionalization reaction Methods 0.000 description 4
125000001072 heteroaryl group Chemical group 0.000 description 4
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 4
229910052742 iron Inorganic materials 0.000 description 4
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 4
125000000896 monocarboxylic acid group Chemical group 0.000 description 4
238000010534 nucleophilic substitution reaction Methods 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
239000011591 potassium Substances 0.000 description 4
238000010992 reflux Methods 0.000 description 4
239000012047 saturated solution Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
150000003457 sulfones Chemical class 0.000 description 4
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
XMRKFDSPGSPFGE-UHFFFAOYSA-N (5-cyano-6-methylsulfanylpyridin-2-yl) trifluoromethanesulfonate Chemical compound CSC1=NC(OS(=O)(=O)C(F)(F)F)=CC=C1C#N XMRKFDSPGSPFGE-UHFFFAOYSA-N 0.000 description 3
UVKBAINRDCMDIE-UHFFFAOYSA-N 2,2,2-trichloro-1-[4-(4-methylpiperazin-1-yl)phenyl]ethanol Chemical compound C1CN(C)CCN1C1=CC=C(C(O)C(Cl)(Cl)Cl)C=C1 UVKBAINRDCMDIE-UHFFFAOYSA-N 0.000 description 3
LFCADBSUDWERJT-UHFFFAOYSA-N 2,6-dichloropyridine-3-carbonitrile Chemical compound ClC1=CC=C(C#N)C(Cl)=N1 LFCADBSUDWERJT-UHFFFAOYSA-N 0.000 description 3
JPGXJOYWNKSCGX-UHFFFAOYSA-N 2-[(4,4-difluorocyclohexyl)-(2,2,2-trifluoroacetyl)amino]-4-(4-methylpiperazin-1-yl)benzoic acid Chemical compound C1CN(C)CCN1C1=CC=C(C(O)=O)C(N(C2CCC(F)(F)CC2)C(=O)C(F)(F)F)=C1 JPGXJOYWNKSCGX-UHFFFAOYSA-N 0.000 description 3
UQNVAKOELHOJFN-UHFFFAOYSA-N 2-[4-(4-methylpiperazin-4-ium-1-yl)phenyl]acetate Chemical compound C1CN(C)CCN1C1=CC=C(CC(O)=O)C=C1 UQNVAKOELHOJFN-UHFFFAOYSA-N 0.000 description 3
UAFHMAWFIOXXQI-NSHDSACASA-N 2-[oxan-4-yl-(2,2,2-trifluoroacetyl)amino]-4-[(3s)-3-[(2,2,2-trifluoroacetyl)amino]pyrrolidin-1-yl]benzoic acid Chemical compound OC(=O)C1=CC=C(N2C[C@H](CC2)NC(=O)C(F)(F)F)C=C1N(C(=O)C(F)(F)F)C1CCOCC1 UAFHMAWFIOXXQI-NSHDSACASA-N 0.000 description 3
VVKFXPRMHQRBGL-UHFFFAOYSA-N 2-amino-5-cyano-6-methylsulfanylpyridine-3-carboxylic acid Chemical compound CSC1=NC(N)=C(C(O)=O)C=C1C#N VVKFXPRMHQRBGL-UHFFFAOYSA-N 0.000 description 3
YCNQPAVKQPLZRS-UHFFFAOYSA-N 2-benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical class O1C(C)(C)C(C)(C)OB1CC1=CC=CC=C1 YCNQPAVKQPLZRS-UHFFFAOYSA-N 0.000 description 3
PLERTPJDYXYVTI-UHFFFAOYSA-N 2-chloro-5-[(3,5-difluorophenyl)methoxy]pyridine-3-carbonitrile Chemical compound FC1=CC(F)=CC(COC=2C=C(C(Cl)=NC=2)C#N)=C1 PLERTPJDYXYVTI-UHFFFAOYSA-N 0.000 description 3
MCPVFSJAPYCXMS-UHFFFAOYSA-N 2-chloro-5-[(3,5-difluorophenyl)sulfamoyl]pyridine-3-carboxamide Chemical compound N1=C(Cl)C(C(=O)N)=CC(S(=O)(=O)NC=2C=C(F)C=C(F)C=2)=C1 MCPVFSJAPYCXMS-UHFFFAOYSA-N 0.000 description 3
PTDOCINOKMDHSU-UHFFFAOYSA-N 2-chloro-6-(2,4-difluorophenyl)sulfanylpyridine-3-carbonitrile Chemical compound FC1=CC(F)=CC=C1SC1=CC=C(C#N)C(Cl)=N1 PTDOCINOKMDHSU-UHFFFAOYSA-N 0.000 description 3
WUAWAZWIWVBBEM-UHFFFAOYSA-N 3-amino-6-iodopyrazine-2-carbonitrile Chemical compound NC1=NC=C(I)N=C1C#N WUAWAZWIWVBBEM-UHFFFAOYSA-N 0.000 description 3
UFTSPZWLJMPOKT-UHFFFAOYSA-N 3-chloro-6-iodopyrazine-2-carbonitrile Chemical compound ClC1=NC=C(I)N=C1C#N UFTSPZWLJMPOKT-UHFFFAOYSA-N 0.000 description 3
DYUMBFTYRJMAFK-UHFFFAOYSA-N 3-cyano-2-pyridone Chemical compound OC1=NC=CC=C1C#N DYUMBFTYRJMAFK-UHFFFAOYSA-N 0.000 description 3
FHHKMGLAIOHCQY-UHFFFAOYSA-N 3-nitro-6-sulfanylidene-1h-pyridine-2-carbonitrile Chemical compound [O-][N+](=O)C=1C=CC(=S)NC=1C#N FHHKMGLAIOHCQY-UHFFFAOYSA-N 0.000 description 3
UVSUWPMFLDLVMI-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzaldehyde Chemical compound C1CN(C)CCN1C1=CC=C(C=O)C(NC2CCOCC2)=C1 UVSUWPMFLDLVMI-UHFFFAOYSA-N 0.000 description 3
JVIGDQVFRFSUKJ-UHFFFAOYSA-N 5-[(3,5-difluorophenyl)methoxy]-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1=C2C(N)=NNC2=NC=C1OCC1=CC(F)=CC(F)=C1 JVIGDQVFRFSUKJ-UHFFFAOYSA-N 0.000 description 3
ABNOQRUXVJFBSN-UHFFFAOYSA-N 5-[(3,5-difluorophenyl)methoxy]pyridine-3-carbonitrile Chemical compound FC1=CC(F)=CC(COC=2C=C(C=NC=2)C#N)=C1 ABNOQRUXVJFBSN-UHFFFAOYSA-N 0.000 description 3
FRKLCMNRGGZZTQ-UHFFFAOYSA-N 5-bromo-2-methoxypyridine-3-carbonitrile Chemical compound COC1=NC=C(Br)C=C1C#N FRKLCMNRGGZZTQ-UHFFFAOYSA-N 0.000 description 3
SSNUTEUZXZIYTB-UHFFFAOYSA-N 5-bromo-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound N1=CC(Br)=CC2=C(N)NN=C21 SSNUTEUZXZIYTB-UHFFFAOYSA-N 0.000 description 3
DHWIFHCOMJIINQ-UHFFFAOYSA-N 5-cyano-6-methylsulfanyl-2-oxo-1h-pyridine-3-carboxylic acid Chemical compound CSC=1NC(=O)C(C(O)=O)=CC=1C#N DHWIFHCOMJIINQ-UHFFFAOYSA-N 0.000 description 3
VGWDPJMGTMXJIJ-UHFFFAOYSA-N 5-iodo-2-methylsulfanyl-6-oxo-1h-pyridine-3-carbonitrile Chemical compound CSC1=NC(O)=C(I)C=C1C#N VGWDPJMGTMXJIJ-UHFFFAOYSA-N 0.000 description 3
OYXUUECJEFKKLG-UHFFFAOYSA-N 5-iodo-2h-pyrazolo[3,4-b]pyridine-3,6-diamine Chemical compound NC1=C(I)C=C2C(N)=NNC2=N1 OYXUUECJEFKKLG-UHFFFAOYSA-N 0.000 description 3
CNTGLVVONIKHSF-UHFFFAOYSA-N 5-iodo-6-methoxy-2-methylsulfanylpyridine-3-carbonitrile Chemical compound COC1=NC(SC)=C(C#N)C=C1I CNTGLVVONIKHSF-UHFFFAOYSA-N 0.000 description 3
IOCCJZXMIMJYOD-UHFFFAOYSA-N 6-(2,4-difluorophenyl)sulfanyl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=1C=C2C(N)=NNC2=NC=1SC1=CC=C(F)C=C1F IOCCJZXMIMJYOD-UHFFFAOYSA-N 0.000 description 3
HSSNFLZQIPOZRO-UHFFFAOYSA-N 6-(3,5-dichlorophenyl)sulfanyl-3-nitropyridine-2-carbonitrile Chemical compound N1=C(C#N)C([N+](=O)[O-])=CC=C1SC1=CC(Cl)=CC(Cl)=C1 HSSNFLZQIPOZRO-UHFFFAOYSA-N 0.000 description 3
WDUYGQZRZXAAGJ-UHFFFAOYSA-N 6-amino-2-methylsulfanylpyridine-3-carbonitrile Chemical compound CSC1=NC(N)=CC=C1C#N WDUYGQZRZXAAGJ-UHFFFAOYSA-N 0.000 description 3
XHSOTQAXOCJEBS-UHFFFAOYSA-N 6-chloro-3-nitropyrazine-2-carbonitrile Chemical compound [O-][N+](=O)C1=NC=C(Cl)N=C1C#N XHSOTQAXOCJEBS-UHFFFAOYSA-N 0.000 description 3
JUVQPYNYLHZBKI-UHFFFAOYSA-N 6-n-(2,4-difluorophenyl)-2h-pyrazolo[3,4-b]pyridine-3,6-diamine Chemical compound C=1C=C2C(N)=NNC2=NC=1NC1=CC=C(F)C=C1F JUVQPYNYLHZBKI-UHFFFAOYSA-N 0.000 description 3
APASLXZZEDBGED-UHFFFAOYSA-N 6-n-(2,4-difluorophenyl)-6-n-methyl-2h-pyrazolo[3,4-b]pyridine-3,6-diamine Chemical compound C=1C=C2C(N)=NNC2=NC=1N(C)C1=CC=C(F)C=C1F APASLXZZEDBGED-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
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 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
0 C*C1CCN(C)CC1 Chemical compound C*C1CCN(C)CC1 0.000 description 3
241000282412 Homo Species 0.000 description 3
229910010082 LiAlH Inorganic materials 0.000 description 3
206010029260 Neuroblastoma Diseases 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
238000000297 Sandmeyer reaction Methods 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 3
VMMMYBOZMXKJMU-UHFFFAOYSA-N [4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)phenyl]methanol Chemical compound C1CN(C)CCN1C1=CC=C(CO)C(NC2CCOCC2)=C1 VMMMYBOZMXKJMU-UHFFFAOYSA-N 0.000 description 3
239000002246 antineoplastic agent Substances 0.000 description 3
239000012300 argon atmosphere Substances 0.000 description 3
229940098773 bovine serum albumin Drugs 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000000872 buffer Substances 0.000 description 3
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 3
230000008859 change Effects 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
150000001805 chlorine compounds Chemical class 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000007033 dehydrochlorination reaction Methods 0.000 description 3
239000012954 diazonium Substances 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 3
229940043279 diisopropylamine Drugs 0.000 description 3
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 3
PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 3
229910052736 halogen Inorganic materials 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
150000002429 hydrazines Chemical class 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 3
230000026045 iodination Effects 0.000 description 3
238000006192 iodination reaction Methods 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
239000011630 iodine Substances 0.000 description 3
239000012948 isocyanate Substances 0.000 description 3
150000002513 isocyanates Chemical class 0.000 description 3
150000002540 isothiocyanates Chemical class 0.000 description 3
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
229940040692 lithium hydroxide monohydrate Drugs 0.000 description 3
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
FDLARAKNPMCCKJ-UHFFFAOYSA-N methyl 3-amino-6-iodopyrazine-2-carboxylate Chemical compound COC(=O)C1=NC(I)=CN=C1N FDLARAKNPMCCKJ-UHFFFAOYSA-N 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
238000013508 migration Methods 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
FMLZEDJKDLHEAY-UHFFFAOYSA-N n-(3-amino-2h-pyrazolo[3,4-b]pyridin-5-yl)-3,5-difluorobenzenesulfonamide Chemical compound C1=C2C(N)=NNC2=NC=C1NS(=O)(=O)C1=CC(F)=CC(F)=C1 FMLZEDJKDLHEAY-UHFFFAOYSA-N 0.000 description 3
JDPQOPNYABKMJI-UHFFFAOYSA-N n-(6-chloro-5-cyanopyridin-3-yl)-3,5-difluorobenzenesulfonamide Chemical compound FC1=CC(F)=CC(S(=O)(=O)NC=2C=C(C(Cl)=NC=2)C#N)=C1 JDPQOPNYABKMJI-UHFFFAOYSA-N 0.000 description 3
ZGGJRARKGWGFIA-UHFFFAOYSA-N n-[5-(3,5-difluorophenyl)sulfanyl-2h-pyrazolo[3,4-b]pyridin-3-yl]-4-(4-methylpiperazin-1-yl)-2-[oxan-4-yl-(2,2,2-trifluoroacetyl)amino]benzamide Chemical compound C1CN(C)CCN1C(C=C1N(C2CCOCC2)C(=O)C(F)(F)F)=CC=C1C(=O)NC(C1=C2)=NNC1=NC=C2SC1=CC(F)=CC(F)=C1 ZGGJRARKGWGFIA-UHFFFAOYSA-N 0.000 description 3
229910052759 nickel Inorganic materials 0.000 description 3
231100000590 oncogenic Toxicity 0.000 description 3
230000002246 oncogenic effect Effects 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
229910052697 platinum Inorganic materials 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
235000015320 potassium carbonate Nutrition 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
125000003226 pyrazolyl group Chemical group 0.000 description 3
ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 3
230000004044 response Effects 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
230000002194 synthesizing effect Effects 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
230000004614 tumor growth Effects 0.000 description 3
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 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 2
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
DXXKATNBNNUIAW-UHFFFAOYSA-N 1-(4-isothiocyanatophenyl)-4-methylpiperazine Chemical compound C1CN(C)CCN1C1=CC=C(N=C=S)C=C1 DXXKATNBNNUIAW-UHFFFAOYSA-N 0.000 description 2
ANHONFDXFZTKAC-UHFFFAOYSA-N 1-[5-(3,5-difluorophenyl)sulfanyl-2h-pyrazolo[3,4-b]pyridin-3-yl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC(C1=C2)=NNC1=NC=C2SC1=CC(F)=CC(F)=C1 ANHONFDXFZTKAC-UHFFFAOYSA-N 0.000 description 2
FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
NGTBLEBAODERFS-UHFFFAOYSA-N 1-tert-butyl-5-(3,5-difluorophenyl)sulfanylpyrazolo[3,4-b]pyridin-3-amine Chemical compound C=1N=C2N(C(C)(C)C)N=C(N)C2=CC=1SC1=CC(F)=CC(F)=C1 NGTBLEBAODERFS-UHFFFAOYSA-N 0.000 description 2
DDZGQYREBDXECY-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyrazine Chemical compound C1=CN=C2C=NNC2=N1 DDZGQYREBDXECY-UHFFFAOYSA-N 0.000 description 2
NMEPLWZDUIIAAC-UHFFFAOYSA-N 1h-pyrazolo[4,3-c]pyridazine Chemical class C1=NN=C2C=NNC2=C1 NMEPLWZDUIIAAC-UHFFFAOYSA-N 0.000 description 2
HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
SHCWQWRTKPNTEM-UHFFFAOYSA-N 2,6-dichloro-3-nitropyridine Chemical class [O-][N+](=O)C1=CC=C(Cl)N=C1Cl SHCWQWRTKPNTEM-UHFFFAOYSA-N 0.000 description 2
SIGRPFDCVORHOW-UHFFFAOYSA-N 2-(4-aminophenyl)-n-[5-(3,5-difluorophenyl)sulfanyl-2h-pyrazolo[3,4-b]pyridin-3-yl]acetamide Chemical compound C1=CC(N)=CC=C1CC(=O)NC(C1=C2)=NNC1=NC=C2SC1=CC(F)=CC(F)=C1 SIGRPFDCVORHOW-UHFFFAOYSA-N 0.000 description 2
JAUPUQRPBNDMDT-UHFFFAOYSA-N 2-chloropyridine-3-carbonitrile Chemical compound ClC1=NC=CC=C1C#N JAUPUQRPBNDMDT-UHFFFAOYSA-N 0.000 description 2
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 2
KQOIBXZRCYFZSO-UHFFFAOYSA-N 3,5-difluoroaniline Chemical compound NC1=CC(F)=CC(F)=C1 KQOIBXZRCYFZSO-UHFFFAOYSA-N 0.000 description 2
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
NUEYBFIIUBXAHT-UHFFFAOYSA-N 3-amino-6-(3,5-dichlorophenyl)sulfanylpyridine-2-carbonitrile Chemical compound N1=C(C#N)C(N)=CC=C1SC1=CC(Cl)=CC(Cl)=C1 NUEYBFIIUBXAHT-UHFFFAOYSA-N 0.000 description 2
PAUUZIXIERHUHC-UHFFFAOYSA-N 3-amino-6-(3,5-difluoroanilino)pyridine-2-carbonitrile Chemical compound N1=C(C#N)C(N)=CC=C1NC1=CC(F)=CC(F)=C1 PAUUZIXIERHUHC-UHFFFAOYSA-N 0.000 description 2
WRQYZMAMPGGLGG-UHFFFAOYSA-N 3-amino-6-[(3,5-difluorophenyl)methylsulfanyl]pyridine-2-carbonitrile Chemical compound N1=C(C#N)C(N)=CC=C1SCC1=CC(F)=CC(F)=C1 WRQYZMAMPGGLGG-UHFFFAOYSA-N 0.000 description 2
OXQLRGICXLDZGZ-UHFFFAOYSA-N 3-amino-6-[(3,5-difluorophenyl)methylsulfanyl]pyridine-2-carboxamide Chemical compound C1=C(N)C(C(=O)N)=NC(SCC=2C=C(F)C=C(F)C=2)=C1 OXQLRGICXLDZGZ-UHFFFAOYSA-N 0.000 description 2
WKPKXPORUZFLMM-UHFFFAOYSA-N 4-(1-methylpiperidin-4-yl)-2-[oxan-4-yl-(2,2,2-trifluoroacetyl)amino]benzoic acid Chemical compound C1CN(C)CCC1C1=CC=C(C(O)=O)C(N(C2CCOCC2)C(=O)C(F)(F)F)=C1 WKPKXPORUZFLMM-UHFFFAOYSA-N 0.000 description 2
PFODEVGLOVUVHS-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)benzaldehyde Chemical compound C1CN(C)CCN1C1=CC=C(C=O)C=C1 PFODEVGLOVUVHS-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
UXJJKFGTQCOPTI-NSHDSACASA-N 4-[(3s)-3-aminopyrrolidin-1-yl]-2-(oxan-4-ylamino)benzoic acid Chemical compound C1[C@@H](N)CCN1C1=CC=C(C(O)=O)C(NC2CCOCC2)=C1 UXJJKFGTQCOPTI-NSHDSACASA-N 0.000 description 2
XDBOLUQMQARCQO-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)sulfanyl-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1SC1=CC(Cl)=CC(Cl)=C1 XDBOLUQMQARCQO-UHFFFAOYSA-N 0.000 description 2
SIRWWTJTGFJUNU-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfanyl-n-[[4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)phenyl]methyl]-1h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1CN(C)CCN1C(C=C1NC2CCOCC2)=CC=C1CNC(C1=C2)=NNC1=NC=C2SC1=CC(F)=CC(F)=C1 SIRWWTJTGFJUNU-UHFFFAOYSA-N 0.000 description 2
KSAZYTFFRSXHLP-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfonyl-2h-pyrazolo[3,4-b]pyrazin-3-amine Chemical compound N1=C2C(N)=NNC2=NC=C1S(=O)(=O)C1=CC(F)=CC(F)=C1 KSAZYTFFRSXHLP-UHFFFAOYSA-N 0.000 description 2
RKJLJEWNXQZBIX-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfonyl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1=C2C(N)=NNC2=NC=C1S(=O)(=O)C1=CC(F)=CC(F)=C1 RKJLJEWNXQZBIX-UHFFFAOYSA-N 0.000 description 2
BMYJZWWKUPNCNN-UHFFFAOYSA-N 5-[(3,5-difluorophenyl)methoxy]-1-oxidopyridin-1-ium-3-carbonitrile Chemical compound N#CC1=C[N+]([O-])=CC(OCC=2C=C(F)C=C(F)C=2)=C1 BMYJZWWKUPNCNN-UHFFFAOYSA-N 0.000 description 2
DBKVEAQEKNGDAF-UHFFFAOYSA-N 5-[(3,5-difluorophenyl)methoxy]-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1OCC1=CC(F)=CC(F)=C1 DBKVEAQEKNGDAF-UHFFFAOYSA-N 0.000 description 2
BEWMMXCZNODTAZ-UHFFFAOYSA-N 5-[(3,5-difluorophenyl)methyl]-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1CC1=CC(F)=CC(F)=C1 BEWMMXCZNODTAZ-UHFFFAOYSA-N 0.000 description 2
YEFREPQOEYTXHU-UHFFFAOYSA-N 5-[(3,5-difluorophenyl)methyl]-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1=C2C(N)=NNC2=NC=C1CC1=CC(F)=CC(F)=C1 YEFREPQOEYTXHU-UHFFFAOYSA-N 0.000 description 2
VGYONHCACXTVFA-UHFFFAOYSA-N 5-[(3,5-difluorophenyl)methylsulfanyl]-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1SCC1=CC(F)=CC(F)=C1 VGYONHCACXTVFA-UHFFFAOYSA-N 0.000 description 2
RGFRMTNTNUBPQX-UHFFFAOYSA-N 5-[(3,5-difluorophenyl)sulfamoyl]pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC(S(=O)(=O)NC=2C=C(F)C=C(F)C=2)=C1 RGFRMTNTNUBPQX-UHFFFAOYSA-N 0.000 description 2
DHNUUSNUUZTHEN-UHFFFAOYSA-N 5-iodo-2-oxo-1h-pyridine-3-carbonitrile Chemical compound IC1=CNC(=O)C(C#N)=C1 DHNUUSNUUZTHEN-UHFFFAOYSA-N 0.000 description 2
XXMSBZGWGCYUDN-UHFFFAOYSA-N 5-iodo-2h-pyrazolo[3,4-b]pyrazin-3-amine Chemical compound C1=C(I)N=C2C(N)=NNC2=N1 XXMSBZGWGCYUDN-UHFFFAOYSA-N 0.000 description 2
DZGYLSFTOFCXFZ-UHFFFAOYSA-N 5-iodo-6-methoxy-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1=C(I)C(OC)=NC2=C1C(N)=NN2 DZGYLSFTOFCXFZ-UHFFFAOYSA-N 0.000 description 2
ZEXJVDQSKVHQKM-UHFFFAOYSA-N 5-n-(3,5-difluorophenyl)-1h-pyrazolo[4,3-b]pyridine-3,5-diamine Chemical compound N1=C2C(N)=NNC2=CC=C1NC1=CC(F)=CC(F)=C1 ZEXJVDQSKVHQKM-UHFFFAOYSA-N 0.000 description 2
YYBIEWNTHVYNHE-UHFFFAOYSA-N 6-(2,4-difluoro-n-methylanilino)-2-methylsulfanylpyridine-3-carbonitrile Chemical compound C1=C(C#N)C(SC)=NC(N(C)C=2C(=CC(F)=CC=2)F)=C1 YYBIEWNTHVYNHE-UHFFFAOYSA-N 0.000 description 2
PLRDSYYAKHJRON-UHFFFAOYSA-N 6-[(3,5-difluorophenyl)methyl]-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=1C=C2C(N)=NNC2=NC=1CC1=CC(F)=CC(F)=C1 PLRDSYYAKHJRON-UHFFFAOYSA-N 0.000 description 2
BJVTVMIGYUTGED-UHFFFAOYSA-N 6-[(3,5-difluorophenyl)methylsulfanyl]-3-nitropyridine-2-carbonitrile Chemical compound N1=C(C#N)C([N+](=O)[O-])=CC=C1SCC1=CC(F)=CC(F)=C1 BJVTVMIGYUTGED-UHFFFAOYSA-N 0.000 description 2
ONGQTMGRJGAOHG-UHFFFAOYSA-N 6-amino-5-iodo-2-methylsulfanylpyridine-3-carbonitrile Chemical compound CSC1=NC(N)=C(I)C=C1C#N ONGQTMGRJGAOHG-UHFFFAOYSA-N 0.000 description 2
ODCXTIKFDHBSQN-UHFFFAOYSA-N 6-amino-5-iodo-2-methylsulfinylpyridine-3-carbonitrile Chemical compound CS(=O)C1=NC(N)=C(I)C=C1C#N ODCXTIKFDHBSQN-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
208000003950 B-cell lymphoma Diseases 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
206010006187 Breast cancer Diseases 0.000 description 2
208000026310 Breast neoplasm Diseases 0.000 description 2
QGBPRGBGNLOROI-UHFFFAOYSA-N C(C)(C)(C)C=1C(=C(C(=O)O)C=CC=1N1CCN(CC1)C)N Chemical compound C(C)(C)(C)C=1C(=C(C(=O)O)C=CC=1N1CCN(CC1)C)N QGBPRGBGNLOROI-UHFFFAOYSA-N 0.000 description 2
CIFHABDFGKVJED-UHFFFAOYSA-N COCc1cc(F)cc(F)c1 Chemical compound COCc1cc(F)cc(F)c1 CIFHABDFGKVJED-UHFFFAOYSA-N 0.000 description 2
DYGCNLVHBDOEOE-UHFFFAOYSA-N CS(Cc1cc(F)cc(F)c1)(=O)=O Chemical compound CS(Cc1cc(F)cc(F)c1)(=O)=O DYGCNLVHBDOEOE-UHFFFAOYSA-N 0.000 description 2
206010009944 Colon cancer Diseases 0.000 description 2
229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-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
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
241000400611 Eucalyptus deanei Species 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
208000034951 Genetic Translocation Diseases 0.000 description 2
239000007821 HATU Substances 0.000 description 2
208000008839 Kidney Neoplasms Diseases 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
206010061902 Pancreatic neoplasm Diseases 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
229920001213 Polysorbate 20 Polymers 0.000 description 2
206010060862 Prostate cancer Diseases 0.000 description 2
208000000236 Prostatic Neoplasms Diseases 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 2
206010038389 Renal cancer Diseases 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
238000006069 Suzuki reaction reaction Methods 0.000 description 2
239000012317 TBTU Substances 0.000 description 2
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
KTFXBCVLEMBPGH-UHFFFAOYSA-M [Cl-].FC1=CC(F)=CC(C[Zn+])=C1 Chemical compound [Cl-].FC1=CC(F)=CC(C[Zn+])=C1 KTFXBCVLEMBPGH-UHFFFAOYSA-M 0.000 description 2
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 2
150000007513 acids Chemical class 0.000 description 2
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 2
230000006907 apoptotic process Effects 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
125000002618 bicyclic heterocycle group Chemical group 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
230000031709 bromination Effects 0.000 description 2
238000005893 bromination reaction Methods 0.000 description 2
229910000024 caesium carbonate Inorganic materials 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
208000029742 colonic neoplasm Diseases 0.000 description 2
238000001816 cooling Methods 0.000 description 2
150000001879 copper Chemical class 0.000 description 2
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
239000007822 coupling agent Substances 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
238000006297 dehydration reaction Methods 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
UCDROSIPSKGDQH-UHFFFAOYSA-N ethyl 5-cyano-6-methylsulfanyl-2-oxo-1h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC(C#N)=C(SC)N=C1O UCDROSIPSKGDQH-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
108020001507 fusion proteins Proteins 0.000 description 2
102000037865 fusion proteins Human genes 0.000 description 2
208000005017 glioblastoma Diseases 0.000 description 2
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
125000005842 heteroatom Chemical group 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
201000010982 kidney cancer Diseases 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
201000007270 liver cancer Diseases 0.000 description 2
208000014018 liver neoplasm Diseases 0.000 description 2
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
INCSQLZZXBPATR-UHFFFAOYSA-N methyl 3-aminopyrazine-2-carboxylate Chemical compound COC(=O)C1=NC=CN=C1N INCSQLZZXBPATR-UHFFFAOYSA-N 0.000 description 2
230000005012 migration Effects 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
238000002156 mixing Methods 0.000 description 2
QPQVPVSYRKEUAZ-UHFFFAOYSA-N n-[5-(3,5-difluorophenyl)sulfanyl-6-oxo-1,2-dihydropyrazolo[3,4-b]pyridin-3-yl]-4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzamide Chemical compound C1CN(C)CCN1C(C=C1NC2CCOCC2)=CC=C1C(=O)NC(C1=C2)=NNC1=NC(O)=C2SC1=CC(F)=CC(F)=C1 QPQVPVSYRKEUAZ-UHFFFAOYSA-N 0.000 description 2
BYDOOCPUDCJBNN-UHFFFAOYSA-N n-[5-[2-(3,5-difluorophenyl)ethynyl]-2h-pyrazolo[3,4-b]pyridin-3-yl]-4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzamide Chemical compound C1CN(C)CCN1C(C=C1NC2CCOCC2)=CC=C1C(=O)NC1=NNC2=NC=C(C#CC=3C=C(F)C=C(F)C=3)C=C12 BYDOOCPUDCJBNN-UHFFFAOYSA-N 0.000 description 2
125000002560 nitrile group Chemical group 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
239000012454 non-polar solvent Substances 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
201000002528 pancreatic cancer Diseases 0.000 description 2
208000008443 pancreatic carcinoma Diseases 0.000 description 2
230000036961 partial effect Effects 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
150000003141 primary amines Chemical class 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
230000002062 proliferating effect Effects 0.000 description 2
230000035755 proliferation Effects 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 2
150000005229 pyrazolopyridines Chemical class 0.000 description 2
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
238000011084 recovery Methods 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
238000007127 saponification reaction Methods 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
230000019491 signal transduction Effects 0.000 description 2
LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 2
229910001958 silver carbonate Inorganic materials 0.000 description 2
YPNVIBVEFVRZPJ-UHFFFAOYSA-L silver sulfate Chemical compound [Ag+].[Ag+].[O-]S([O-])(=O)=O YPNVIBVEFVRZPJ-UHFFFAOYSA-L 0.000 description 2
229910000367 silver sulfate Inorganic materials 0.000 description 2
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
235000011150 stannous chloride Nutrition 0.000 description 2
125000000565 sulfonamide group Chemical group 0.000 description 2
150000003459 sulfonic acid esters Chemical class 0.000 description 2
HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
239000011593 sulfur Substances 0.000 description 2
125000004434 sulfur atom Chemical group 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
231100001274 therapeutic index Toxicity 0.000 description 2
125000005309 thioalkoxy group Chemical group 0.000 description 2
150000003568 thioethers Chemical class 0.000 description 2
150000003573 thiols Chemical class 0.000 description 2
229910052718 tin Inorganic materials 0.000 description 2
239000011135 tin Substances 0.000 description 2
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
210000004881 tumor cell Anatomy 0.000 description 2
230000005748 tumor development Effects 0.000 description 2
AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 2
239000008096 xylene Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
239000011701 zinc Substances 0.000 description 2
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 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
HYAVEDMFTNAZQE-UHFFFAOYSA-N (benzyldiselanyl)methylbenzene Chemical compound C=1C=CC=CC=1C[Se][Se]CC1=CC=CC=C1 HYAVEDMFTNAZQE-UHFFFAOYSA-N 0.000 description 1
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
POXVFBFTIHUAOP-UHFFFAOYSA-N 1-(3,5-difluorophenyl)sulfanylpyrazolo[3,4-b]pyridin-3-amine Chemical compound C12=NC=CC=C2C(N)=NN1SC1=CC(F)=CC(F)=C1 POXVFBFTIHUAOP-UHFFFAOYSA-N 0.000 description 1
HUJDWVCICJKNQJ-UHFFFAOYSA-N 1-(4-isocyanatophenyl)-4-methylpiperazine Chemical compound C1CN(C)CCN1C1=CC=C(N=C=O)C=C1 HUJDWVCICJKNQJ-UHFFFAOYSA-N 0.000 description 1
KVSVNRFSKRFPIL-UHFFFAOYSA-N 1-(bromomethyl)-3,5-difluorobenzene Chemical compound FC1=CC(F)=CC(CBr)=C1 KVSVNRFSKRFPIL-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
CNWXPGJFPGBHRD-UHFFFAOYSA-N 1-[1-tert-butyl-5-(3,5-difluorophenyl)sulfanylpyrazolo[3,4-b]pyridin-3-yl]-3-[4-(4-methylpiperazin-1-yl)phenyl]thiourea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=S)NC(C1=C2)=NN(C(C)(C)C)C1=NC=C2SC1=CC(F)=CC(F)=C1 CNWXPGJFPGBHRD-UHFFFAOYSA-N 0.000 description 1
JKEWHRKMGKQITN-UHFFFAOYSA-N 1-[1-tert-butyl-5-(3,5-difluorophenyl)sulfanylpyrazolo[3,4-b]pyridin-3-yl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC(C1=C2)=NN(C(C)(C)C)C1=NC=C2SC1=CC(F)=CC(F)=C1 JKEWHRKMGKQITN-UHFFFAOYSA-N 0.000 description 1
UPWYHLSNQUXQOS-UHFFFAOYSA-N 1-[5-(3,5-difluorophenyl)sulfanyl-2h-pyrazolo[3,4-b]pyridin-3-yl]-3-[4-(4-methylpiperazin-1-yl)phenyl]thiourea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=S)NC(C1=C2)=NNC1=NC=C2SC1=CC(F)=CC(F)=C1 UPWYHLSNQUXQOS-UHFFFAOYSA-N 0.000 description 1
AWNXKZVIZARMME-UHFFFAOYSA-N 1-[[5-[2-[(2-chloropyridin-4-yl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol Chemical compound N=1C(NCC(C)(O)C)=NC=C(C=2N=C(NC=3C=C(Cl)N=CC=3)N=CC=2)C=1CC1CC1 AWNXKZVIZARMME-UHFFFAOYSA-N 0.000 description 1
OTDGZDMGSFBZLI-UHFFFAOYSA-N 1-ethynyl-3,5-difluorobenzene Chemical compound FC1=CC(F)=CC(C#C)=C1 OTDGZDMGSFBZLI-UHFFFAOYSA-N 0.000 description 1
SRXBBUOEOULGKN-UHFFFAOYSA-N 1-tert-butyl-5-[(3,5-difluorophenyl)methylsulfanyl]pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=1N=C2N(C(C)(C)C)N=C(N)C2=CC=1SCC1=CC(F)=CC(F)=C1 SRXBBUOEOULGKN-UHFFFAOYSA-N 0.000 description 1
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
MJEPPEQNLZSPAP-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridin-3-amine Chemical class C1=CN=C2C(N)=NNC2=C1 MJEPPEQNLZSPAP-UHFFFAOYSA-N 0.000 description 1
FVJBHWZOURTPME-UHFFFAOYSA-N 1h-pyrazolo[4,3-c]pyridazin-3-amine Chemical class C1=NN=C2C(N)=NNC2=C1 FVJBHWZOURTPME-UHFFFAOYSA-N 0.000 description 1
HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical class CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 description 1
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
FJRPOHLDJUJARI-UHFFFAOYSA-N 2,3-dihydro-1,2-oxazole Chemical compound C1NOC=C1 FJRPOHLDJUJARI-UHFFFAOYSA-N 0.000 description 1
GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 description 1
OUHBWOIKQHDTAD-UHFFFAOYSA-N 2-(2-fluoroethoxy)-4-(4-methylpiperazin-1-yl)benzoic acid Chemical compound C1CN(C)CCN1C1=CC=C(C(O)=O)C(OCCF)=C1 OUHBWOIKQHDTAD-UHFFFAOYSA-N 0.000 description 1
IXJUKNQCZOUQQC-UHFFFAOYSA-N 2-(2-fluoroethoxy)-4-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]benzoic acid Chemical compound C1CN(C)CCC1N1CCN(C=2C=C(OCCF)C(C(O)=O)=CC=2)CC1 IXJUKNQCZOUQQC-UHFFFAOYSA-N 0.000 description 1
WKGFDTBUUBBWJZ-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)benzoic acid Chemical compound C1CN(C)CCN1C1=CC=CC=C1C(O)=O WKGFDTBUUBBWJZ-UHFFFAOYSA-N 0.000 description 1
JXVVPESTVKNKAG-UHFFFAOYSA-N 2-(oxan-4-ylamino)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NC1CCOCC1 JXVVPESTVKNKAG-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
LGJSPTFUIMJKTA-UHFFFAOYSA-N 2-[(3,5-difluorophenyl)methyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1CC1=CC(F)=CC(F)=C1 LGJSPTFUIMJKTA-UHFFFAOYSA-N 0.000 description 1
QKYVZDRYXYVJBZ-UHFFFAOYSA-N 2-[2-fluoroethyl-(2,2,2-trifluoroacetyl)amino]-4-(4-methylpiperazin-1-yl)benzoic acid Chemical compound C1CN(C)CCN1C1=CC=C(C(O)=O)C(N(CCF)C(=O)C(F)(F)F)=C1 QKYVZDRYXYVJBZ-UHFFFAOYSA-N 0.000 description 1
WBWGUECQZSTJSY-UHFFFAOYSA-N 2-[4-(4-methylpiperazin-1-yl)-2-nitrophenyl]acetic acid Chemical compound C1CN(C)CCN1C1=CC=C(CC(O)=O)C([N+]([O-])=O)=C1 WBWGUECQZSTJSY-UHFFFAOYSA-N 0.000 description 1
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
CJMKBNLIAVFWJM-UHFFFAOYSA-N 2-chloro-5-(phenylsulfamoyl)pyridine-3-carboxylic acid Chemical class N1=C(Cl)C(C(=O)O)=CC(S(=O)(=O)NC=2C=CC=CC=2)=C1 CJMKBNLIAVFWJM-UHFFFAOYSA-N 0.000 description 1
LPZQFYVQHSUQNF-UHFFFAOYSA-N 2-chloro-5-[(3,5-difluorophenyl)sulfamoyl]pyridine-3-carboxylic acid Chemical compound N1=C(Cl)C(C(=O)O)=CC(S(=O)(=O)NC=2C=C(F)C=C(F)C=2)=C1 LPZQFYVQHSUQNF-UHFFFAOYSA-N 0.000 description 1
BHPYMZQTCPRLNR-UHFFFAOYSA-N 2-cyanoethanethioamide Chemical compound NC(=S)CC#N BHPYMZQTCPRLNR-UHFFFAOYSA-N 0.000 description 1
LUAQTQAFUORQHV-UHFFFAOYSA-N 2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1=CC=C2C(N)=NNC2=N1 LUAQTQAFUORQHV-UHFFFAOYSA-N 0.000 description 1
OFQGDWQZEWDVGY-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-2h-1,4-benzoxazine Chemical compound C1=CCC2NCCOC2=C1 OFQGDWQZEWDVGY-UHFFFAOYSA-N 0.000 description 1
AOCSJJIMCMXDDG-UHFFFAOYSA-N 3,5-dichloro-2-nitropyrazine Chemical class [O-][N+](=O)C1=NC=C(Cl)N=C1Cl AOCSJJIMCMXDDG-UHFFFAOYSA-N 0.000 description 1
WRXIPCQPHZMXOO-UHFFFAOYSA-N 3,5-dichlorobenzenethiol Chemical compound SC1=CC(Cl)=CC(Cl)=C1 WRXIPCQPHZMXOO-UHFFFAOYSA-N 0.000 description 1
IIQKIICAOXAXEJ-UHFFFAOYSA-N 3,5-difluorobenzenesulfonyl chloride Chemical compound FC1=CC(F)=CC(S(Cl)(=O)=O)=C1 IIQKIICAOXAXEJ-UHFFFAOYSA-N 0.000 description 1
LFYVNHDFVIPZHV-UHFFFAOYSA-N 3,5-difluorobenzenethiol Chemical compound FC1=CC(F)=CC(S)=C1 LFYVNHDFVIPZHV-UHFFFAOYSA-N 0.000 description 1
NZBQURHUOCWMNQ-UHFFFAOYSA-N 3-amino-6-[(3,5-difluorophenyl)methyl]pyridine-2-carbonitrile Chemical compound N1=C(C#N)C(N)=CC=C1CC1=CC(F)=CC(F)=C1 NZBQURHUOCWMNQ-UHFFFAOYSA-N 0.000 description 1
CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 1
KMHCTFSFWQRZTR-UHFFFAOYSA-N 3-aminopyridine-2-carbonitrile Chemical compound NC1=CC=CN=C1C#N KMHCTFSFWQRZTR-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
JDXQWYKOKYUQDN-UHFFFAOYSA-N 3-hydroxypyrrolidine-2,5-dione Chemical compound OC1CC(=O)NC1=O JDXQWYKOKYUQDN-UHFFFAOYSA-N 0.000 description 1
DFCXLZADIHRIBI-UHFFFAOYSA-N 3-n-(2,5-dichlorophenyl)-1h-pyrazolo[4,3-b]pyridine-3,5-diamine Chemical compound C12=NC(N)=CC=C2NN=C1NC1=CC(Cl)=CC=C1Cl DFCXLZADIHRIBI-UHFFFAOYSA-N 0.000 description 1
BWGXRTLLVXQMCC-UHFFFAOYSA-N 3-n-(2,5-difluorophenyl)-1h-pyrazolo[4,3-b]pyridine-3,5-diamine Chemical compound C12=NC(N)=CC=C2NN=C1NC1=CC(F)=CC=C1F BWGXRTLLVXQMCC-UHFFFAOYSA-N 0.000 description 1
SXJDZYIIHRCJGR-UHFFFAOYSA-N 3-nitro-6-sulfanylidene-1h-pyrazine-2-carbonitrile Chemical compound [O-][N+](=O)C=1N=CC(=S)NC=1C#N SXJDZYIIHRCJGR-UHFFFAOYSA-N 0.000 description 1
GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
JHVKFHDSZWQIFF-UHFFFAOYSA-N 4,4,5,5-tetramethyl-3-(4,4,5,5-tetramethyldioxaborolan-3-yl)dioxaborolane Chemical compound CC1(C)C(C)(C)OOB1B1C(C)(C)C(C)(C)OO1 JHVKFHDSZWQIFF-UHFFFAOYSA-N 0.000 description 1
NYYSPVRERVXMLJ-UHFFFAOYSA-N 4,4-difluorocyclohexan-1-one Chemical compound FC1(F)CCC(=O)CC1 NYYSPVRERVXMLJ-UHFFFAOYSA-N 0.000 description 1
FDNXQCAFVGNIPT-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)-2-[oxan-4-yl-(2,2,2-trifluoroacetyl)amino]benzoic acid Chemical compound C1CN(C)CCN1C1=CC=C(C(O)=O)C(N(C2CCOCC2)C(=O)C(F)(F)F)=C1 FDNXQCAFVGNIPT-UHFFFAOYSA-N 0.000 description 1
FKERHSPGYLZIDP-UHFFFAOYSA-N 4-[3-(dimethylamino)propyl-methylamino]-2-[2-fluoroethyl-(2,2,2-trifluoroacetyl)amino]benzoic acid Chemical compound CN(C)CCCN(C)C1=CC=C(C(O)=O)C(N(CCF)C(=O)C(F)(F)F)=C1 FKERHSPGYLZIDP-UHFFFAOYSA-N 0.000 description 1
LPTRHISTMVJAGX-UHFFFAOYSA-N 4-[3-(dimethylamino)propyl-methylamino]-2-[oxan-4-yl-(2,2,2-trifluoroacetyl)amino]benzoic acid Chemical compound CN(C)CCCN(C)C1=CC=C(C(O)=O)C(N(C2CCOCC2)C(=O)C(F)(F)F)=C1 LPTRHISTMVJAGX-UHFFFAOYSA-N 0.000 description 1
SJRJJKPEHAURKC-UHFFFAOYSA-O 4-methylmorpholin-4-ium Chemical compound C[NH+]1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-O 0.000 description 1
JZUHRPMBVSKAQQ-UHFFFAOYSA-N 4-methylsulfanyl-6-oxo-1h-pyridazine-3-carbonitrile Chemical compound CSC1=CC(O)=NN=C1C#N JZUHRPMBVSKAQQ-UHFFFAOYSA-N 0.000 description 1
SVSBNSLUTSGNME-UHFFFAOYSA-N 4-methylsulfanyl-6-oxo-1h-pyridine-3-carbonitrile Chemical class CSC1=CC(O)=NC=C1C#N SVSBNSLUTSGNME-UHFFFAOYSA-N 0.000 description 1
WTGQNAVNDYUULG-UHFFFAOYSA-N 5-(2,4-dichlorophenyl)sulfanyl-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1SC1=CC=C(Cl)C=C1Cl WTGQNAVNDYUULG-UHFFFAOYSA-N 0.000 description 1
GBVQVUAMLXURFK-UHFFFAOYSA-N 5-(2,4-dichlorophenyl)sulfanyl-2h-pyrazolo[3,4-b]pyrazin-3-amine Chemical compound N1=C2C(N)=NNC2=NC=C1SC1=CC=C(Cl)C=C1Cl GBVQVUAMLXURFK-UHFFFAOYSA-N 0.000 description 1
BRSZWFONSHJECR-UHFFFAOYSA-N 5-(2,4-difluorophenyl)sulfanyl-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1SC1=CC=C(F)C=C1F BRSZWFONSHJECR-UHFFFAOYSA-N 0.000 description 1
KEFKWGUNMWAUEM-UHFFFAOYSA-N 5-(2,5-dichlorophenyl)sulfanyl-2h-pyrazolo[3,4-b]pyridine-3,6-diamine Chemical compound C1=C2C(N)=NNC2=NC(N)=C1SC1=CC(Cl)=CC=C1Cl KEFKWGUNMWAUEM-UHFFFAOYSA-N 0.000 description 1
IXSPOEXJANGDAP-UHFFFAOYSA-N 5-(2,5-dichlorophenyl)sulfanyl-6-methoxy-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound COC1=NC=2NN=C(N)C=2C=C1SC1=CC(Cl)=CC=C1Cl IXSPOEXJANGDAP-UHFFFAOYSA-N 0.000 description 1
YYKDSDMDAXDCGV-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfanyl-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1SC1=CC(F)=CC(F)=C1 YYKDSDMDAXDCGV-UHFFFAOYSA-N 0.000 description 1
BQRRVRKINAUAFW-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfanyl-6-methoxy-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound COC1=NC=2NN=C(N)C=2C=C1SC1=CC(F)=CC(F)=C1 BQRRVRKINAUAFW-UHFFFAOYSA-N 0.000 description 1
OYUFUIGBJNCRJZ-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfanyl-6-methyl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound CC1=NC=2NN=C(N)C=2C=C1SC1=CC(F)=CC(F)=C1 OYUFUIGBJNCRJZ-UHFFFAOYSA-N 0.000 description 1
RUGMMSFOZYAUSA-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfanyl-n-[[4-(4-methylpiperazin-1-yl)-2-nitrophenyl]methyl]-1h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1CN(C)CCN1C(C=C1[N+]([O-])=O)=CC=C1CNC(C1=C2)=NNC1=NC=C2SC1=CC(F)=CC(F)=C1 RUGMMSFOZYAUSA-UHFFFAOYSA-N 0.000 description 1
LJYGALOYSVFZBF-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfanyl-n-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1CNC(C1=C2)=NNC1=NC=C2SC1=CC(F)=CC(F)=C1 LJYGALOYSVFZBF-UHFFFAOYSA-N 0.000 description 1
ANCBPIWGSUPBAJ-UHFFFAOYSA-N 5-(3,5-difluorophenyl)sulfinyl-2h-pyrazolo[3,4-b]pyrazin-3-amine Chemical compound N1=C2C(N)=NNC2=NC=C1S(=O)C1=CC(F)=CC(F)=C1 ANCBPIWGSUPBAJ-UHFFFAOYSA-N 0.000 description 1
WRUANGUKBYQKJR-UHFFFAOYSA-N 5-(pyridin-3-ylmethoxy)-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1OCC1=CC=CN=C1 WRUANGUKBYQKJR-UHFFFAOYSA-N 0.000 description 1
IQTNKFWXBWLUNW-UHFFFAOYSA-N 5-[(2,5-dichlorophenyl)methoxy]-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1OCC1=CC(Cl)=CC=C1Cl IQTNKFWXBWLUNW-UHFFFAOYSA-N 0.000 description 1
BJBWVVWNWOSAAS-UHFFFAOYSA-N 5-[(2,5-dichlorophenyl)methylsulfanyl]-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1SCC1=CC(Cl)=CC=C1Cl BJBWVVWNWOSAAS-UHFFFAOYSA-N 0.000 description 1
FKCVWIPUNLTOQD-UHFFFAOYSA-N 5-[(2,5-difluorophenyl)methoxy]-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1OCC1=CC(F)=CC=C1F FKCVWIPUNLTOQD-UHFFFAOYSA-N 0.000 description 1
VKHNSESVUJWVNQ-UHFFFAOYSA-N 5-[(2,5-difluorophenyl)methylsulfanyl]-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1SCC1=CC(F)=CC=C1F VKHNSESVUJWVNQ-UHFFFAOYSA-N 0.000 description 1
VDZUDESFMBBNGW-UHFFFAOYSA-N 5-[(3,5-difluorophenyl)methyl]-2h-pyrazolo[3,4-b]pyrazin-3-amine Chemical compound N1=C2C(N)=NNC2=NC=C1CC1=CC(F)=CC(F)=C1 VDZUDESFMBBNGW-UHFFFAOYSA-N 0.000 description 1
YQCDGMYQMQMZAS-UHFFFAOYSA-N 5-[2-(trifluoromethyl)phenyl]sulfanyl-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1SC1=CC=CC=C1C(F)(F)F YQCDGMYQMQMZAS-UHFFFAOYSA-N 0.000 description 1
CCSZPLOMAACBRP-UHFFFAOYSA-N 5-[2-(trifluoromethyl)phenyl]sulfanyl-2h-pyrazolo[3,4-b]pyrazin-3-amine Chemical compound N1=C2C(N)=NNC2=NC=C1SC1=CC=CC=C1C(F)(F)F CCSZPLOMAACBRP-UHFFFAOYSA-N 0.000 description 1
NDVXHUASBHLXER-UHFFFAOYSA-N 5-[[5-chloro-2-(trifluoromethyl)phenyl]methoxy]-1h-pyrazolo[4,3-b]pyridin-3-amine Chemical compound N1=C2C(N)=NNC2=CC=C1OCC1=CC(Cl)=CC=C1C(F)(F)F NDVXHUASBHLXER-UHFFFAOYSA-N 0.000 description 1
AEJWPGFVMYKWCQ-UHFFFAOYSA-N 5-amino-2-chloropyridine-3-carbonitrile Chemical compound NC1=CN=C(Cl)C(C#N)=C1 AEJWPGFVMYKWCQ-UHFFFAOYSA-N 0.000 description 1
YXWLEUCOZAOKNX-UHFFFAOYSA-N 5-benzyl-2-nitropyridine-3-carbonitrile Chemical class C1=C(C#N)C([N+](=O)[O-])=NC=C1CC1=CC=CC=C1 YXWLEUCOZAOKNX-UHFFFAOYSA-N 0.000 description 1
CAPUQSWTJRCRPV-UHFFFAOYSA-N 5-chloro-2-nitro-1h-pyridine-2-carbonitrile Chemical compound [O-][N+](=O)C1(C#N)NC=C(Cl)C=C1 CAPUQSWTJRCRPV-UHFFFAOYSA-N 0.000 description 1
DMQTXELGRVDQPY-UHFFFAOYSA-N 5-cyano-6-methylsulfanylpyridine-3-carboxylic acid Chemical group CSC1=NC=C(C(O)=O)C=C1C#N DMQTXELGRVDQPY-UHFFFAOYSA-N 0.000 description 1
KSGXFRBLXNHRNM-UHFFFAOYSA-N 5-iodo-6-methoxy-2-methylsulfinylpyridine-3-carbonitrile Chemical compound COC1=NC(S(C)=O)=C(C#N)C=C1I KSGXFRBLXNHRNM-UHFFFAOYSA-N 0.000 description 1
DVNQWINEMXGMIB-UHFFFAOYSA-N 5-iodo-6-methyl-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C1=C(I)C(C)=NC2=C1C(N)=NN2 DVNQWINEMXGMIB-UHFFFAOYSA-N 0.000 description 1
DMLPQTWDFZCDTJ-UHFFFAOYSA-N 5-methoxypyridine-3-carbonitrile Chemical compound COC1=CN=CC(C#N)=C1 DMLPQTWDFZCDTJ-UHFFFAOYSA-N 0.000 description 1
MZRUFMBFIKGOAL-UHFFFAOYSA-N 5-nitro-1h-pyrazole Chemical class [O-][N+](=O)C1=CC=NN1 MZRUFMBFIKGOAL-UHFFFAOYSA-N 0.000 description 1
YDHMCUQZBSUAMP-UHFFFAOYSA-N 6-(2,4-difluorophenoxy)-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical compound C=1C=C2C(N)=NNC2=NC=1OC1=CC=C(F)C=C1F YDHMCUQZBSUAMP-UHFFFAOYSA-N 0.000 description 1
YRFSPIXYUZDAAR-UHFFFAOYSA-N 6-(3,5-difluoro-n-methylanilino)-2-methylsulfanylpyridine-3-carbonitrile Chemical compound C1=C(C#N)C(SC)=NC(N(C)C=2C=C(F)C=C(F)C=2)=C1 YRFSPIXYUZDAAR-UHFFFAOYSA-N 0.000 description 1
IQPPCENBKPZGQL-UHFFFAOYSA-N 6-(3,5-difluoroanilino)-3-nitropyridine-2-carbonitrile Chemical compound N1=C(C#N)C([N+](=O)[O-])=CC=C1NC1=CC(F)=CC(F)=C1 IQPPCENBKPZGQL-UHFFFAOYSA-N 0.000 description 1
WGUBQNSZEHNKFH-UHFFFAOYSA-N 6-[(3,5-difluorophenyl)methyl]-3-nitropyridine-2-carbonitrile Chemical compound N1=C(C#N)C([N+](=O)[O-])=CC=C1CC1=CC(F)=CC(F)=C1 WGUBQNSZEHNKFH-UHFFFAOYSA-N 0.000 description 1
LMRYVMLKXMJWNL-UHFFFAOYSA-N 6-amino-5-iodo-2-methylsulfonylpyridine-3-carbonitrile Chemical compound CS(=O)(=O)C1=NC(N)=C(I)C=C1C#N LMRYVMLKXMJWNL-UHFFFAOYSA-N 0.000 description 1
AOMBSGDJMMMUNI-UHFFFAOYSA-N 6-benzyl-3-nitropyrazine-2-carbonitrile Chemical class N1=C(C#N)C([N+](=O)[O-])=NC=C1CC1=CC=CC=C1 AOMBSGDJMMMUNI-UHFFFAOYSA-N 0.000 description 1
SCZZEMIFQWCCGY-UHFFFAOYSA-N 6-benzyl-3-nitropyridine-2-carbonitrile Chemical class N1=C(C#N)C([N+](=O)[O-])=CC=C1CC1=CC=CC=C1 SCZZEMIFQWCCGY-UHFFFAOYSA-N 0.000 description 1
MJPKMVITEZGZAY-UHFFFAOYSA-N 6-chloro-1h-pyrazolo[4,3-c]pyridazin-3-amine Chemical class ClC1=NN=C2C(N)=NNC2=C1 MJPKMVITEZGZAY-UHFFFAOYSA-N 0.000 description 1
ZGCFHYKQHHBJJZ-UHFFFAOYSA-N 6-chloro-1h-pyrazolo[4,3-c]pyridin-3-amine Chemical class ClC1=NC=C2C(N)=NNC2=C1 ZGCFHYKQHHBJJZ-UHFFFAOYSA-N 0.000 description 1
QCZHYDWXQYPQKI-UHFFFAOYSA-N 6-n-[(3,5-difluorophenyl)methyl]-2h-pyrazolo[3,4-b]pyridine-3,6-diamine Chemical compound C=1C=C2C(N)=NNC2=NC=1NCC1=CC(F)=CC(F)=C1 QCZHYDWXQYPQKI-UHFFFAOYSA-N 0.000 description 1
101710168331 ALK tyrosine kinase receptor Proteins 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
ZUFDBHBZSUTYLM-UHFFFAOYSA-N C(C)(C)(C)C=1C(=C(C(=O)O)C=CC=1F)[N+](=O)[O-] Chemical compound C(C)(C)(C)C=1C(=C(C(=O)O)C=CC=1F)[N+](=O)[O-] ZUFDBHBZSUTYLM-UHFFFAOYSA-N 0.000 description 1
HGBWDLZNNKBURE-UHFFFAOYSA-N C(C)C1=NC(=C(C(=O)O)C=C1S(=O)(=O)Cl)Cl Chemical compound C(C)C1=NC(=C(C(=O)O)C=C1S(=O)(=O)Cl)Cl HGBWDLZNNKBURE-UHFFFAOYSA-N 0.000 description 1
IGAQXKSSGUOCTJ-UHFFFAOYSA-N CC(C)(C)OC(C(C=CC(C1=CCN(C)C=C1)=C1)=C1[N+]([O-])=O)=O.I Chemical compound CC(C)(C)OC(C(C=CC(C1=CCN(C)C=C1)=C1)=C1[N+]([O-])=O)=O.I IGAQXKSSGUOCTJ-UHFFFAOYSA-N 0.000 description 1
UJWGSVACAOPXEK-UHFFFAOYSA-N CCN(C1CCOCC1)C(C(F)(F)F)=O Chemical compound CCN(C1CCOCC1)C(C(F)(F)F)=O UJWGSVACAOPXEK-UHFFFAOYSA-N 0.000 description 1
DXUZVZJYUPSEOR-UHFFFAOYSA-N CN(C1CCOCC1)C(C(F)(F)F)=O Chemical compound CN(C1CCOCC1)C(C(F)(F)F)=O DXUZVZJYUPSEOR-UHFFFAOYSA-N 0.000 description 1
JKUXYOXGKFFNHX-UHFFFAOYSA-N CN(CC1)CCC1c1ccc(C(NC(c2cc(Sc3cc(F)cc(F)c3)cnc2N)=N)=O)c(NC2CCOCC2)c1 Chemical compound CN(CC1)CCC1c1ccc(C(NC(c2cc(Sc3cc(F)cc(F)c3)cnc2N)=N)=O)c(NC2CCOCC2)c1 JKUXYOXGKFFNHX-UHFFFAOYSA-N 0.000 description 1
XHASBBQIAZWFMC-UHFFFAOYSA-N CN(CC1)CCN1c(cc1)ccc1NC(NC(c1cc(Sc2cc(F)cc(F)c2)cnc1N)=N)=O Chemical compound CN(CC1)CCN1c(cc1)ccc1NC(NC(c1cc(Sc2cc(F)cc(F)c2)cnc1N)=N)=O XHASBBQIAZWFMC-UHFFFAOYSA-N 0.000 description 1
XLYXVMNVBCGDDX-UHFFFAOYSA-N CN(CC1)CCN1c1ccc(C(NC(c2cc(Sc3cc(F)cc(F)c3)cnc2N)=N)=O)c(NC(CC2)CCC2(F)F)c1 Chemical compound CN(CC1)CCN1c1ccc(C(NC(c2cc(Sc3cc(F)cc(F)c3)cnc2N)=N)=O)c(NC(CC2)CCC2(F)F)c1 XLYXVMNVBCGDDX-UHFFFAOYSA-N 0.000 description 1
IPZSJHGCVXRHHJ-UHFFFAOYSA-O CN(CC1)CCN1c1ccc(C(NC(c2ccc(Cc3cc(F)cc(F)c3)nc2[NH3+])=N)=O)c(NC2CCOCC2)c1 Chemical compound CN(CC1)CCN1c1ccc(C(NC(c2ccc(Cc3cc(F)cc(F)c3)nc2[NH3+])=N)=O)c(NC2CCOCC2)c1 IPZSJHGCVXRHHJ-UHFFFAOYSA-O 0.000 description 1
VBWOIPSGMMWLFM-UHFFFAOYSA-N CN(CC1)CCN1c1ccc(CNC(c2c(N)ncc(Sc3cc(F)cc(F)c3)c2)=N)c(NC2CCOCC2)c1 Chemical compound CN(CC1)CCN1c1ccc(CNC(c2c(N)ncc(Sc3cc(F)cc(F)c3)c2)=N)c(NC2CCOCC2)c1 VBWOIPSGMMWLFM-UHFFFAOYSA-N 0.000 description 1
LREVWSPAJVDCOB-UHFFFAOYSA-N CN(CC1)CCN1c1ccc(CNC(c2cc(Sc3cc(F)cc(F)c3)cnc2N)=N)cc1 Chemical compound CN(CC1)CCN1c1ccc(CNC(c2cc(Sc3cc(F)cc(F)c3)cnc2N)=N)cc1 LREVWSPAJVDCOB-UHFFFAOYSA-N 0.000 description 1
UVTZXPAIODZEMK-UHFFFAOYSA-N CN(CC1)CCN1c1ccc(CNC(c2nc(Sc3cc(F)cc(F)c3)cnc2N)=N)c(NC2CCOCC2)c1 Chemical compound CN(CC1)CCN1c1ccc(CNC(c2nc(Sc3cc(F)cc(F)c3)cnc2N)=N)c(NC2CCOCC2)c1 UVTZXPAIODZEMK-UHFFFAOYSA-N 0.000 description 1
RPGDVPAENGWKAO-UHFFFAOYSA-N CNc(ccc(F)c1)c1F Chemical compound CNc(ccc(F)c1)c1F RPGDVPAENGWKAO-UHFFFAOYSA-N 0.000 description 1
SAGAEZGLJJTKRE-UHFFFAOYSA-N CNc1cc(F)ccc1F Chemical compound CNc1cc(F)ccc1F SAGAEZGLJJTKRE-UHFFFAOYSA-N 0.000 description 1
CKMPGOWDZWCYMI-UHFFFAOYSA-N COc(nc(c(C(N)=N)c1)N)c1I Chemical compound COc(nc(c(C(N)=N)c1)N)c1I CKMPGOWDZWCYMI-UHFFFAOYSA-N 0.000 description 1
FEVDSYDQNXTMPT-UHFFFAOYSA-N CS(c1cc(F)cc(F)c1)(=O)=O Chemical compound CS(c1cc(F)cc(F)c1)(=O)=O FEVDSYDQNXTMPT-UHFFFAOYSA-N 0.000 description 1
NPJIKKXEAPKKFT-UHFFFAOYSA-N CSc(c(Cl)c1)ccc1Cl Chemical compound CSc(c(Cl)c1)ccc1Cl NPJIKKXEAPKKFT-UHFFFAOYSA-N 0.000 description 1
NEUFJYUCEJEKET-UHFFFAOYSA-N CSc(cc(cc1)Cl)c1Cl Chemical compound CSc(cc(cc1)Cl)c1Cl NEUFJYUCEJEKET-UHFFFAOYSA-N 0.000 description 1
PSSCMQMQOXVMFG-UHFFFAOYSA-N CSc1cc(Cl)cc(Cl)c1 Chemical compound CSc1cc(Cl)cc(Cl)c1 PSSCMQMQOXVMFG-UHFFFAOYSA-N 0.000 description 1
FUXPOXBGHMSQSK-UHFFFAOYSA-N CSc1cc(F)cc(F)c1 Chemical compound CSc1cc(F)cc(F)c1 FUXPOXBGHMSQSK-UHFFFAOYSA-N 0.000 description 1
SKFJFYDRJQXZHI-GFCCVEGCSA-N C[S@](Cc(cc(cc1)F)c1F)=O Chemical compound C[S@](Cc(cc(cc1)F)c1F)=O SKFJFYDRJQXZHI-GFCCVEGCSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
108091026890 Coding region Proteins 0.000 description 1
ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
101100261976 Drosophila melanogaster trk gene Proteins 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
101150029707 ERBB2 gene Proteins 0.000 description 1
108091008794 FGF receptors Proteins 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
201000003803 Inflammatory myofibroblastic tumor Diseases 0.000 description 1
206010067917 Inflammatory myofibroblastic tumour Diseases 0.000 description 1
102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 1
LNQCUTNLHUQZLR-VNPYQEQNSA-N Iridin Natural products O(C)c1c(O)c2C(=O)C(c3cc(OC)c(OC)c(O)c3)=COc2cc1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 LNQCUTNLHUQZLR-VNPYQEQNSA-N 0.000 description 1
229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
101100262697 Mus musculus Axl gene Proteins 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
ADYZSQLZFHWUEN-UHFFFAOYSA-N NC(c1c(N)ncc(S(c2cc(F)cc(F)c2)=O)n1)=N Chemical compound NC(c1c(N)ncc(S(c2cc(F)cc(F)c2)=O)n1)=N ADYZSQLZFHWUEN-UHFFFAOYSA-N 0.000 description 1
ZKONTMISXJRFAG-UHFFFAOYSA-N NC(c1ccc(Cc2cc(F)cc(F)c2)nc1N)=N Chemical compound NC(c1ccc(Cc2cc(F)cc(F)c2)nc1N)=N ZKONTMISXJRFAG-UHFFFAOYSA-N 0.000 description 1
GIGBKGWKOXMFCA-UHFFFAOYSA-N NC(c1ccc(Nc(c(F)c2)ccc2F)nc1N)=N Chemical compound NC(c1ccc(Nc(c(F)c2)ccc2F)nc1N)=N GIGBKGWKOXMFCA-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
102000043276 Oncogene Human genes 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
229910019213 POCl3 Inorganic materials 0.000 description 1
101150003085 Pdcl gene Proteins 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
102000052575 Proto-Oncogene Human genes 0.000 description 1
108700020978 Proto-Oncogene Proteins 0.000 description 1
229910019020 PtO2 Inorganic materials 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
101100517381 Rattus norvegicus Ntrk1 gene Proteins 0.000 description 1
101100537955 Schizosaccharomyces pombe (strain 972 / ATCC 24843) trk1 gene Proteins 0.000 description 1
238000003436 Schotten-Baumann reaction Methods 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
229940122924 Src inhibitor Drugs 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
238000006619 Stille reaction Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
108091008605 VEGF receptors Proteins 0.000 description 1
102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
150000000475 acetylene derivatives Chemical class 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
239000000853 adhesive Substances 0.000 description 1
230000001070 adhesive effect Effects 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
230000003698 anagen phase Effects 0.000 description 1
150000001448 anilines Chemical class 0.000 description 1
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
230000001028 anti-proliverative effect Effects 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
150000001499 aryl bromides Chemical class 0.000 description 1
150000001502 aryl halides Chemical class 0.000 description 1
150000001503 aryl iodides Chemical class 0.000 description 1
125000004421 aryl sulphonamide group Chemical group 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
150000003938 benzyl alcohols Chemical class 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical class BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
229940073608 benzyl chloride Drugs 0.000 description 1
UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 1
150000003939 benzylamines Chemical class 0.000 description 1
HBWDWGMBZIFBQE-UHFFFAOYSA-N benzylboronic acid Chemical compound OB(O)CC1=CC=CC=C1 HBWDWGMBZIFBQE-UHFFFAOYSA-N 0.000 description 1
RRIWSQXXBIFKQM-UHFFFAOYSA-N benzylcarbamic acid Chemical class OC(=O)NCC1=CC=CC=C1 RRIWSQXXBIFKQM-UHFFFAOYSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-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
230000000903 blocking effect Effects 0.000 description 1
239000012267 brine Substances 0.000 description 1
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 1
244000309464 bull Species 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
150000004657 carbamic acid derivatives Chemical class 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
150000003857 carboxamides Chemical class 0.000 description 1
230000021164 cell adhesion Effects 0.000 description 1
230000006369 cell cycle progression Effects 0.000 description 1
230000004709 cell invasion Effects 0.000 description 1
230000012292 cell migration Effects 0.000 description 1
230000003833 cell viability Effects 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
125000003636 chemical group Chemical group 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
KGLYSXGHNGYWSL-UHFFFAOYSA-N chloromethylbenzene;zinc Chemical compound [Zn].ClCC1=CC=CC=C1 KGLYSXGHNGYWSL-UHFFFAOYSA-N 0.000 description 1
LIQBAAKGMWRWPS-UHFFFAOYSA-M chlorozinc(1+);methanidylbenzene Chemical compound [Zn+]Cl.[CH2-]C1=CC=CC=C1 LIQBAAKGMWRWPS-UHFFFAOYSA-M 0.000 description 1
VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
230000006378 damage Effects 0.000 description 1
229960002448 dasatinib Drugs 0.000 description 1
238000006114 decarboxylation reaction Methods 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
230000017858 demethylation Effects 0.000 description 1
238000010520 demethylation reaction Methods 0.000 description 1
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical group C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
XEDHNTPQPKCZSF-UHFFFAOYSA-N diethyl 2-(4-fluoro-2-nitrophenyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C1=CC=C(F)C=C1[N+]([O-])=O XEDHNTPQPKCZSF-UHFFFAOYSA-N 0.000 description 1
LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
PGFWCWVVIAJUKT-UHFFFAOYSA-N diethyl 2-[4-(4-methylpiperazin-1-yl)-2-nitrophenyl]propanedioate Chemical compound C1=C([N+]([O-])=O)C(C(C(=O)OCC)C(=O)OCC)=CC=C1N1CCN(C)CC1 PGFWCWVVIAJUKT-UHFFFAOYSA-N 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 description 1
SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
VTIIJXUACCWYHX-UHFFFAOYSA-L disodium;carboxylatooxy carbonate Chemical compound [Na+].[Na+].[O-]C(=O)OOC([O-])=O VTIIJXUACCWYHX-UHFFFAOYSA-L 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000009826 distribution Methods 0.000 description 1
CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
PFNXTASHNOUFCN-UHFFFAOYSA-N ethyl 2-amino-5-cyano-6-methylsulfanylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC(C#N)=C(SC)N=C1N PFNXTASHNOUFCN-UHFFFAOYSA-N 0.000 description 1
KEXGUJMBPOYKBG-UHFFFAOYSA-N ethyl 2-chloro-5-chlorosulfonylpyridine-3-carboxylate Chemical class CCOC(=O)C1=CC(S(Cl)(=O)=O)=CN=C1Cl KEXGUJMBPOYKBG-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
UEXCJVNBTNXOEH-OUBTZVSYSA-N ethynylbenzene Chemical class [13CH]#CC1=CC=CC=C1 UEXCJVNBTNXOEH-OUBTZVSYSA-N 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
ZYXBIOIYWUIXSM-UHFFFAOYSA-N furo[2,3-c]pyridine Chemical compound C1=NC=C2OC=CC2=C1 ZYXBIOIYWUIXSM-UHFFFAOYSA-N 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
230000005917 in vivo anti-tumor Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
230000009545 invasion Effects 0.000 description 1
LNQCUTNLHUQZLR-OZJWLQQPSA-N iridin Chemical compound OC1=C(OC)C(OC)=CC(C=2C(C3=C(O)C(OC)=C(O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)C=C3OC=2)=O)=C1 LNQCUTNLHUQZLR-OZJWLQQPSA-N 0.000 description 1
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000004492 methyl ester group Chemical group 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
230000011278 mitosis Effects 0.000 description 1
230000000394 mitotic effect Effects 0.000 description 1
230000037230 mobility Effects 0.000 description 1
210000000651 myofibroblast Anatomy 0.000 description 1
DDDZNRSTGCSUJP-UHFFFAOYSA-N n'-(3-cyano-5-iodopyrazin-2-yl)-n,n-dimethylmethanimidamide Chemical compound CN(C)C=NC1=NC=C(I)N=C1C#N DDDZNRSTGCSUJP-UHFFFAOYSA-N 0.000 description 1
IMCCZKHIPVEUEI-UHFFFAOYSA-N n,n-difluoroaniline Chemical compound FN(F)C1=CC=CC=C1 IMCCZKHIPVEUEI-UHFFFAOYSA-N 0.000 description 1
YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
JGPJNEQDNBDCOJ-UHFFFAOYSA-N n-[5-(3,5-difluorophenyl)sulfanyl-2h-pyrazolo[3,4-b]pyridin-3-yl]-2-(4-nitrophenyl)acetamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1CC(=O)NC(C1=C2)=NNC1=NC=C2SC1=CC(F)=CC(F)=C1 JGPJNEQDNBDCOJ-UHFFFAOYSA-N 0.000 description 1
RUAZKOVTMSAJDH-UHFFFAOYSA-N n-[5-[(3,5-difluorophenyl)sulfamoyl]-2h-pyrazolo[3,4-b]pyridin-3-yl]-4-(4-methylpiperazin-1-yl)-2-[oxan-4-yl-(2,2,2-trifluoroacetyl)amino]benzamide Chemical compound C1CN(C)CCN1C(C=C1N(C2CCOCC2)C(=O)C(F)(F)F)=CC=C1C(=O)NC1=NNC2=NC=C(S(=O)(=O)NC=3C=C(F)C=C(F)C=3)C=C12 RUAZKOVTMSAJDH-UHFFFAOYSA-N 0.000 description 1
GTJRZXUZLSBJFN-UHFFFAOYSA-N n-[5-[2-(3,5-difluorophenyl)ethyl]-2h-pyrazolo[3,4-b]pyridin-3-yl]-4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzamide Chemical compound C1CN(C)CCN1C(C=C1NC2CCOCC2)=CC=C1C(=O)NC(C1=C2)=NNC1=NC=C2CCC1=CC(F)=CC(F)=C1 GTJRZXUZLSBJFN-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000006501 nitrophenyl group Chemical group 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
239000012434 nucleophilic reagent Substances 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
238000011369 optimal treatment Methods 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
108700009251 p80(NPM-ALK) Proteins 0.000 description 1
150000002940 palladium Chemical class 0.000 description 1
MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
UEXCJVNBTNXOEH-UHFFFAOYSA-N phenyl acethylene Natural products C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
230000008288 physiological mechanism Effects 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229940072033 potash Drugs 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
239000004323 potassium nitrate Substances 0.000 description 1
235000010333 potassium nitrate Nutrition 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000008569 process Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
JBDKAABFESSFMV-UHFFFAOYSA-N pyrrolo[1,2-a]pyrimidine Chemical compound N1=CC=CN2C=CC=C21 JBDKAABFESSFMV-UHFFFAOYSA-N 0.000 description 1
RIEKLTCRUGDAPM-UHFFFAOYSA-N pyrrolo[1,2-c]pyrimidine Chemical compound C1=CN=CN2C=CC=C21 RIEKLTCRUGDAPM-UHFFFAOYSA-N 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000011535 reaction buffer Substances 0.000 description 1
229910052702 rhenium Inorganic materials 0.000 description 1
WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
SAQSTQBVENFSKT-UHFFFAOYSA-N sodium 2,2,2-trichloroacetic acid Chemical compound [Na+].OC(=O)C(Cl)(Cl)Cl SAQSTQBVENFSKT-UHFFFAOYSA-N 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
AVPCPPOOQICIRJ-UHFFFAOYSA-L sodium glycerol 2-phosphate Chemical compound [Na+].[Na+].OCC(CO)OP([O-])([O-])=O AVPCPPOOQICIRJ-UHFFFAOYSA-L 0.000 description 1
229960001922 sodium perborate Drugs 0.000 description 1
229940045872 sodium percarbonate Drugs 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 0.000 description 1
YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000000725 suspension Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
GHERUNYLCLILIJ-UHFFFAOYSA-N tert-butyl 2-[(4,4-difluorocyclohexyl)amino]-4-(4-methylpiperazin-1-yl)benzoate Chemical compound C1CN(C)CCN1C1=CC=C(C(=O)OC(C)(C)C)C(NC2CCC(F)(F)CC2)=C1 GHERUNYLCLILIJ-UHFFFAOYSA-N 0.000 description 1
FEWNHXSFBOSNBZ-UHFFFAOYSA-M tert-butyl 4-(1-methylpyridin-1-ium-4-yl)-2-nitrobenzoate;iodide Chemical compound [I-].C1=C[N+](C)=CC=C1C1=CC=C(C(=O)OC(C)(C)C)C([N+]([O-])=O)=C1 FEWNHXSFBOSNBZ-UHFFFAOYSA-M 0.000 description 1
PNTUIHOIJCQTSU-UHFFFAOYSA-N tert-butyl 4-(4-methylpiperazin-1-yl)-2-nitrobenzoate Chemical compound C1CN(C)CCN1C1=CC=C(C(=O)OC(C)(C)C)C([N+]([O-])=O)=C1 PNTUIHOIJCQTSU-UHFFFAOYSA-N 0.000 description 1
PERCTFQKRUVUOS-SFHVURJKSA-N tert-butyl 4-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]-2-(oxan-4-ylamino)benzoate Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)CCN1C1=CC=C(C(=O)OC(C)(C)C)C(NC2CCOCC2)=C1 PERCTFQKRUVUOS-SFHVURJKSA-N 0.000 description 1
WFQHGCOHRFRRHU-UHFFFAOYSA-N tert-butyl 4-bromo-2-nitrobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(Br)C=C1[N+]([O-])=O WFQHGCOHRFRRHU-UHFFFAOYSA-N 0.000 description 1
DQQJBEAXSOOCPG-ZETCQYMHSA-N tert-butyl n-[(3s)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCNC1 DQQJBEAXSOOCPG-ZETCQYMHSA-N 0.000 description 1
NAYIMYIHMQMARV-UHFFFAOYSA-N tert-butyl n-[5-(4-methylpiperazin-1-yl)-2-nitrophenyl]carbamate Chemical compound C1CN(C)CCN1C1=CC=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=C1 NAYIMYIHMQMARV-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
210000001519 tissue Anatomy 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
125000005490 tosylate group Chemical group 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
150000008648 triflates Chemical class 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical class FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)

RU2013138624/04A 2011-01-27 2012-01-27 Производные азаиндазола или диазаиндазола в качестве медикамента RU2600976C2 (ru)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
FR1150651A FR2970967B1 (fr)	2011-01-27	2011-01-27	Derives de type azaindazole ou diazaindazole comme medicament
FR1150651		2011-01-27
PCT/EP2012/051283 WO2012101239A1 (en)	2011-01-27	2012-01-27	Derivatives of azaindazole or diazaindazole type as medicament

Publications (2)

Publication Number	Publication Date
RU2013138624A RU2013138624A (ru)	2015-03-10
RU2600976C2 true RU2600976C2 (ru)	2016-10-27

Family

ID=44318089

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
RU2013138624/04A RU2600976C2 (ru)	2011-01-27	2012-01-27	Производные азаиндазола или диазаиндазола в качестве медикамента

Country Status (30)

Country	Link
US (2)	US20130172360A1 (2)
EP (1)	EP2668184B1 (2)
JP (1)	JP5931926B2 (2)
KR (2)	KR20180122028A (2)
CN (1)	CN103339129B (2)
AR (1)	AR084935A1 (2)
AU (1)	AU2012210467B2 (2)
BR (1)	BR112013018852B1 (2)
CA (1)	CA2823824C (2)
CY (1)	CY1120088T1 (2)
DK (1)	DK2668184T3 (2)
ES (1)	ES2661695T3 (2)
FR (1)	FR2970967B1 (2)
HR (1)	HRP20180524T1 (2)
HU (1)	HUE037153T2 (2)
IL (2)	IL227496B (2)
LT (1)	LT2668184T (2)
MA (1)	MA34903B1 (2)
MX (1)	MX356411B (2)
MY (1)	MY180666A (2)
PL (1)	PL2668184T3 (2)
PT (1)	PT2668184T (2)
RS (1)	RS57101B1 (2)
RU (1)	RU2600976C2 (2)
SI (1)	SI2668184T1 (2)
TN (1)	TN2013000293A1 (2)
TR (1)	TR201802944T4 (2)
TW (1)	TWI546303B (2)
UA (1)	UA109698C2 (2)
WO (1)	WO2012101239A1 (2)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2640046C2 (ru) *	2012-07-27	2017-12-26	Пьер Фабр Медикамент	Производные типа азаиндазола или диазаиндазола для лечения боли
RU2792163C2 (ru) *	2018-05-02	2023-03-17	ДжейВ ФАРМАСЬЮТИКАЛ КОРПОРЕЙШН	Новое гетероциклическое производное
US12583852B2 (en)	2018-05-02	2026-03-24	Jw Pharmaceutical Corporation	Heterocycle derivative

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US8754114B2 (en)	2010-12-22	2014-06-17	Incyte Corporation	Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3
FR2970967B1 (fr) *	2011-01-27	2013-02-15	Pf Medicament	Derives de type azaindazole ou diazaindazole comme medicament
EP2817292B1 (en)	2012-02-22	2019-12-18	Sanford-Burnham Medical Research Institute	Sulfonamide compounds and uses as tnap inhibitors
ES2704744T3 (es)	2012-06-13	2019-03-19	Incyte Holdings Corp	Compuestos tricíclicos sustituidos como inhibidores de FGFR
EP2689779A1 (en) *	2012-07-27	2014-01-29	Pierre Fabre Medicament	Derivatives of azaindazole or diazaindazole type for treating a cancer overexpressing trk
US9388185B2 (en)	2012-08-10	2016-07-12	Incyte Holdings Corporation	Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors
US9266892B2 (en)	2012-12-19	2016-02-23	Incyte Holdings Corporation	Fused pyrazoles as FGFR inhibitors
EA035095B1 (ru)	2013-04-19	2020-04-27	Инсайт Холдингс Корпорейшн	Бициклические гетероциклы в качестве ингибиторов fgfr
US10851105B2 (en)	2014-10-22	2020-12-01	Incyte Corporation	Bicyclic heterocycles as FGFR4 inhibitors
US10336707B2 (en)	2014-12-16	2019-07-02	Eudendron S.R.L.	Heterocyclic derivatives modulating activity of certain protein kinases
MX373169B (es)	2015-02-20	2020-04-24	Incyte Holdings Corp	Heterociclos bicíclicos como inhibidores de receptores del factor de crecimiento fibroblástico (fgfr).
WO2016134294A1 (en)	2015-02-20	2016-08-25	Incyte Corporation	Bicyclic heterocycles as fgfr4 inhibitors
MA41551A (fr)	2015-02-20	2017-12-26	Incyte Corp	Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4
US10211205B2 (en) *	2016-04-27	2019-02-19	International Business Machines Corporation	Field effect transistor structure for reducing contact resistance
CN108570052A (zh) *	2017-03-13	2018-09-25	中国科学院上海药物研究所	五元杂环并吡嗪化合物、制备方法、中间体、组合和应用
AR111960A1 (es)	2017-05-26	2019-09-04	Incyte Corp	Formas cristalinas de un inhibidor de fgfr y procesos para su preparación
MA52493A (fr)	2018-05-04	2021-03-10	Incyte Corp	Sels d'un inhibiteur de fgfr
CR20200590A (es)	2018-05-04	2021-04-26	Incyte Corp	Formas sólidas de un inhibidor de fgfr y procesos para prepararlas
WO2020185532A1 (en)	2019-03-08	2020-09-17	Incyte Corporation	Methods of treating cancer with an fgfr inhibitor
EP3725777A1 (en) *	2019-04-17	2020-10-21	Rottapharm Biotech S.r.l.	Benzo- and pyrido-pyrazoles as protein kinase inhibitors
WO2021007269A1 (en)	2019-07-09	2021-01-14	Incyte Corporation	Bicyclic heterocycles as fgfr inhibitors
WO2021009568A1 (en)	2019-07-17	2021-01-21	2692372 Ontario, Inc.	Benzenesulfonamide derivatives and uses thereof
WO2021067374A1 (en)	2019-10-01	2021-04-08	Incyte Corporation	Bicyclic heterocycles as fgfr inhibitors
TWI891666B (zh)	2019-10-14	2025-08-01	美商英塞特公司	作為ｆｇｆｒ抑制劑之雙環雜環
WO2021076728A1 (en)	2019-10-16	2021-04-22	Incyte Corporation	Bicyclic heterocycles as fgfr inhibitors
EP4069696A1 (en)	2019-12-04	2022-10-12	Incyte Corporation	Tricyclic heterocycles as fgfr inhibitors
BR112022010664A2 (pt)	2019-12-04	2022-08-16	Incyte Corp	Derivados de um inibidor de fgfr
EP4085061A1 (en) *	2019-12-31	2022-11-09	IFM Due, Inc.	Compounds and compositions for treating conditions associated with sting activity
WO2021146424A1 (en)	2020-01-15	2021-07-22	Incyte Corporation	Bicyclic heterocycles as fgfr inhibitors
WO2021197467A1 (zh) *	2020-04-02	2021-10-07	上海华汇拓医药科技有限公司	多靶点的抗肿瘤化合物及其制备方法和应用
GB2617477A (en) *	2020-11-20	2023-10-11	2692372 Ontario Inc	Benzenesulfonamide derivatives and uses thereof
TW202304459A (zh)	2021-04-12	2023-02-01	美商英塞特公司	包含ｆｇｆｒ抑制劑及ｎｅｃｔｉｎ－４靶向劑之組合療法
EP4352059A1 (en)	2021-06-09	2024-04-17	Incyte Corporation	Tricyclic heterocycles as fgfr inhibitors
WO2022261159A1 (en)	2021-06-09	2022-12-15	Incyte Corporation	Tricyclic heterocycles as fgfr inhibitors

Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE102004061288A1 (de) *	2004-12-14	2006-06-29	Schering Ag	3-Amino-Pyrazolo[3,4b]pyridine als Inhibitoren von Proteintyrosinkinasen, deren Herstellung und Verwendung als Arzneimittel

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK0970084T3 (da) *	1997-03-19	2003-09-29	Abbott Gmbh & Co Kg	Pyrrolo[2,3-d]pyrimidiner og deres anvendelse som inhibitorer for tyrosinkinase
EP1215208B1 (en)	1997-10-27	2006-07-12	Agouron Pharmaceuticals, Inc.	4-Aminothiazole derivatives, their preparation and their use as inhibitors of cyclin-dependent kinases
AU2001262597B2 (en)	2000-06-22	2005-10-20	Pfizer Inc.	Process for the preparation of pyrazolopyrimidinones
AU2003245700A1 (en) *	2002-02-12	2003-09-04	Glaxo Group Limited	Pyrazolopyridine derivatives
RU2008110941A (ru) *	2005-08-25	2009-09-27	Ф.Хоффманн-Ля Рош Аг (Ch)	ИНГИБИТОРЫ КИНАЗЫ p38 МАР И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
US20100056516A1 (en)	2006-07-17	2010-03-04	Williams Peter D	1-hydroxy naphthyridine compounds as anti-hiv agents
EP2120932B1 (en)	2006-12-20	2014-07-09	Nerviano Medical Sciences S.r.l.	Indazole derivatives as kinase inhibitors for the treatment of cancer
PH12013501594A1 (en)	2007-07-20	2014-05-12	Nerviano Medical Sciences Srl	Substituted indazole derivatives active as kinase inhibitors
EP2373626B1 (en)	2008-12-18	2016-08-24	Nerviano Medical Sciences S.r.l.	Substituted indazole derivatives active as kinase inhibitors
FR2970967B1 (fr) *	2011-01-27	2013-02-15	Pf Medicament	Derives de type azaindazole ou diazaindazole comme medicament

2011
- 2011-01-27 FR FR1150651A patent/FR2970967B1/fr active Active
2012
- 2012-01-20 TW TW101102531A patent/TWI546303B/zh active
- 2012-01-27 KR KR1020187031264A patent/KR20180122028A/ko not_active Ceased
- 2012-01-27 HR HRP20180524TT patent/HRP20180524T1/hr unknown
- 2012-01-27 PT PT127018844T patent/PT2668184T/pt unknown
- 2012-01-27 RS RS20180418A patent/RS57101B1/sr unknown
- 2012-01-27 KR KR1020137022330A patent/KR101923751B1/ko not_active Expired - Fee Related
- 2012-01-27 PL PL12701884T patent/PL2668184T3/pl unknown
- 2012-01-27 HU HUE12701884A patent/HUE037153T2/hu unknown
- 2012-01-27 MY MYPI2013002799A patent/MY180666A/en unknown
- 2012-01-27 MA MA36177A patent/MA34903B1/fr unknown
- 2012-01-27 TR TR2018/02944T patent/TR201802944T4/tr unknown
- 2012-01-27 JP JP2013550886A patent/JP5931926B2/ja active Active
- 2012-01-27 WO PCT/EP2012/051283 patent/WO2012101239A1/en not_active Ceased
- 2012-01-27 ES ES12701884.4T patent/ES2661695T3/es active Active
- 2012-01-27 US US13/823,658 patent/US20130172360A1/en not_active Abandoned
- 2012-01-27 CA CA2823824A patent/CA2823824C/en active Active
- 2012-01-27 AR ARP120100272A patent/AR084935A1/es active IP Right Grant
- 2012-01-27 RU RU2013138624/04A patent/RU2600976C2/ru active
- 2012-01-27 UA UAA201310425A patent/UA109698C2/ru unknown
- 2012-01-27 AU AU2012210467A patent/AU2012210467B2/en not_active Ceased
- 2012-01-27 CN CN201280006671.8A patent/CN103339129B/zh not_active Expired - Fee Related
- 2012-01-27 SI SI201231273T patent/SI2668184T1/en unknown
- 2012-01-27 LT LTEP12701884.4T patent/LT2668184T/lt unknown
- 2012-01-27 MX MX2013008673A patent/MX356411B/es active IP Right Grant
- 2012-01-27 BR BR112013018852-9A patent/BR112013018852B1/pt not_active IP Right Cessation
- 2012-01-27 EP EP12701884.4A patent/EP2668184B1/en active Active
- 2012-01-27 DK DK12701884.4T patent/DK2668184T3/en active
- 2012-11-27 US US13/686,334 patent/US8883821B2/en active Active
2013
- 2013-07-11 TN TNP2013000293A patent/TN2013000293A1/fr unknown
- 2013-07-16 IL IL227496A patent/IL227496B/en active IP Right Grant
2018
- 2018-02-26 IL IL257748A patent/IL257748B/en active IP Right Grant
- 2018-03-26 CY CY20181100338T patent/CY1120088T1/el unknown

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE102004061288A1 (de) *	2004-12-14	2006-06-29	Schering Ag	3-Amino-Pyrazolo[3,4b]pyridine als Inhibitoren von Proteintyrosinkinasen, deren Herstellung und Verwendung als Arzneimittel

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KOCEVAR M. ET AL "Neighbouring Group Participation in Formation of Condensed Azines. Formation of Pyrazolo(3,4-b)pyrazines, Isoxazolo(4,5-b)pyrazines and Isothiazolo(5,4-b)pyridine", Monatshefte fur Chemie, vol. 113, N 5, 1982,pages 731-744, exsample 10. KORBONITS D. ET AL "Ring Transformation of 3-(2-Aminoaryl)-1,2,4-oxadiazoles into 3-Acyl-aminoindazoles; 1 Extension of the Boulton-Katritzky Scheme", Journal of The Chemical Society, Perkin Trasactions I, vol.1, N 3, pages 759-766, Scheme 3, example 6.1. *
WO 98/41525 A1? 24.09.1998. *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2640046C2 (ru) *	2012-07-27	2017-12-26	Пьер Фабр Медикамент	Производные типа азаиндазола или диазаиндазола для лечения боли
RU2792163C2 (ru) *	2018-05-02	2023-03-17	ДжейВ ФАРМАСЬЮТИКАЛ КОРПОРЕЙШН	Новое гетероциклическое производное
US12583852B2 (en)	2018-05-02	2026-03-24	Jw Pharmaceutical Corporation	Heterocycle derivative

Also Published As

Publication number	Publication date
HRP20180524T1 (hr)	2018-05-04
HUE037153T2 (hu)	2018-08-28
TWI546303B (zh)	2016-08-21
FR2970967B1 (fr)	2013-02-15
CY1120088T1 (el)	2018-12-12
TN2013000293A1 (en)	2015-01-20
BR112013018852B1 (pt)	2021-12-21
CA2823824A1 (en)	2012-08-02
ES2661695T3 (es)	2018-04-03
IL257748A (en)	2018-04-30
HK1186737A1 (en)	2014-03-21
AU2012210467A1 (en)	2013-09-12
IL257748B (en)	2020-06-30
RU2013138624A (ru)	2015-03-10
MX356411B (es)	2018-05-24
SI2668184T1 (en)	2018-06-29
NZ614432A (en)	2015-03-27
MY180666A (en)	2020-12-04
DK2668184T3 (en)	2018-03-12
EP2668184B1 (en)	2018-01-10
TR201802944T4 (tr)	2018-03-21
KR20140014147A (ko)	2014-02-05
UA109698C2 (xx)	2015-09-25
US8883821B2 (en)	2014-11-11
BR112013018852A2 (pt)	2017-08-15
KR20180122028A (ko)	2018-11-09
MX2013008673A (es)	2013-12-02
US20130172360A1 (en)	2013-07-04
PT2668184T (pt)	2018-03-13
US20130085144A1 (en)	2013-04-04
CN103339129A (zh)	2013-10-02
PL2668184T3 (pl)	2018-06-29
EP2668184A1 (en)	2013-12-04
KR101923751B1 (ko)	2018-11-29
AU2012210467B2 (en)	2016-07-07
IL227496A0 (en)	2013-09-30
FR2970967A1 (fr)	2012-08-03
CN103339129B (zh)	2015-07-29
MA34903B1 (fr)	2014-02-01
JP5931926B2 (ja)	2016-06-08
LT2668184T (lt)	2018-04-10
CA2823824C (en)	2018-12-11
JP2014503574A (ja)	2014-02-13
TW201247664A (en)	2012-12-01
WO2012101239A1 (en)	2012-08-02
AR084935A1 (es)	2013-07-10
RS57101B1 (sr)	2018-06-29
IL227496B (en)	2019-02-28

Publication	Publication Date	Title
RU2600976C2 (ru)	2016-10-27	Производные азаиндазола или диазаиндазола в качестве медикамента
CN104684554B (zh)	2017-05-10	用于治疗疼痛的氮杂吲唑或二氮杂吲唑型衍生物
US9428510B2 (en)	2016-08-30	Derivatives of azaindazole or diazaindazole type for treating a cancer overexpressing Trk
HK1186737B (en)	2016-03-24	Derivatives of azaindazole or diazaindazole type as medicament
HK1207302B (en)	2018-04-13	Derivatives of azaindazole or diazaindazole type for treating pain
OA16493A (en)	2015-10-21	Derivatives of azaindazole or diazaindazole type as medicament.
NZ614432B2 (en)	2015-06-30	Derivatives of azaindazole or diazaindazole type as medicament

RU2600976C2 - Производные азаиндазола или диазаиндазола в качестве медикамента - Google Patents

Info

Links

Classifications

Landscapes

Applications Claiming Priority (3)

Publications (2)

Family

ID=44318089

Family Applications (1)

Country Status (30)

Cited By (3)

Families Citing this family (34)

Citations (1)

Family Cites Families (10)

Patent Citations (1)

Non-Patent Citations (2)

Cited By (3)

Also Published As

Similar Documents