CA2573538C - Inhibitors of vegf receptor and hgf receptor signaling - Google Patents

Info

Publication number

CA2573538C

CA2573538C CA2573538A CA2573538A CA2573538C CA 2573538 C CA2573538 C CA 2573538C CA 2573538 A CA2573538 A CA 2573538A CA 2573538 A CA2573538 A CA 2573538A CA 2573538 C CA2573538 C CA 2573538C

Authority

CA

Canada

Prior art keywords

alkyl

group

heteroaryl

compound according

aryl

Prior art date

2004-07-30

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 230000011664 signaling Effects 0.000 title claims abstract description 57
• 108091008603 HGF receptors Proteins 0.000 title claims abstract description 30
• 108091008605 VEGF receptors Proteins 0.000 title claims abstract description 27
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 title claims abstract description 27
• 102000027430 HGF receptors Human genes 0.000 title claims abstract 12
• 239000003112 inhibitor Substances 0.000 title description 12
• 150000001875 compounds Chemical class 0.000 claims abstract description 575
• 239000000203 mixture Substances 0.000 claims abstract description 66
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 24
• 230000002062 proliferating effect Effects 0.000 claims abstract description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
• 201000010099 disease Diseases 0.000 claims abstract description 10
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 274
• 125000000623 heterocyclic group Chemical group 0.000 claims description 213
• 229910052739 hydrogen Inorganic materials 0.000 claims description 152
• 125000001072 heteroaryl group Chemical group 0.000 claims description 125
• 125000003118 aryl group Chemical group 0.000 claims description 118
• -1 nitro, tetrazolyl Chemical group 0.000 claims description 114
• 125000000217 alkyl group Chemical group 0.000 claims description 112
• 125000005843 halogen group Chemical group 0.000 claims description 97
• 229910052736 halogen Inorganic materials 0.000 claims description 87
• 150000002367 halogens Chemical class 0.000 claims description 87
• 229910052757 nitrogen Inorganic materials 0.000 claims description 85
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 81
• 125000001424 substituent group Chemical group 0.000 claims description 79
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 77
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 70
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 69
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 66
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 56
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 54
• 125000003545 alkoxy group Chemical group 0.000 claims description 47
• 125000004432 carbon atom Chemical group C* 0.000 claims description 44
• 239000001257 hydrogen Substances 0.000 claims description 41
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 39
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 36
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 31
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 30
• 229910052731 fluorine Inorganic materials 0.000 claims description 30
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 29
• 229910052717 sulfur Inorganic materials 0.000 claims description 29
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 23
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 22
• 150000003839 salts Chemical class 0.000 claims description 22
• 239000011737 fluorine Substances 0.000 claims description 21
• 229910052760 oxygen Inorganic materials 0.000 claims description 21
• 125000004429 atom Chemical group 0.000 claims description 19
• 125000001153 fluoro group Chemical group F* 0.000 claims description 19
• 229920006395 saturated elastomer Chemical group 0.000 claims description 15
• 239000000460 chlorine Chemical group 0.000 claims description 14
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
• 239000001301 oxygen Substances 0.000 claims description 13
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 12
• 125000004953 trihalomethyl group Chemical group 0.000 claims description 12
• 206010028980 Neoplasm Diseases 0.000 claims description 11
• 125000003342 alkenyl group Chemical group 0.000 claims description 11
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 11
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 11
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 11
• 229910052799 carbon Inorganic materials 0.000 claims description 10
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 9
• 125000006413 ring segment Chemical group 0.000 claims description 9
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 8
• 229910052801 chlorine Chemical group 0.000 claims description 8
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
• 125000000304 alkynyl group Chemical group 0.000 claims description 7
• 201000011510 cancer Diseases 0.000 claims description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
• 239000011593 sulfur Substances 0.000 claims description 7
• 125000004434 sulfur atom Chemical group 0.000 claims description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims description 6
• CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 230000004614 tumor growth Effects 0.000 claims description 6
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 5
• 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 5
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 3
• 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 3
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 3
• 150000004675 formic acid derivatives Chemical class 0.000 claims description 3
• 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 3
• VOZYTYSCFHSLCF-UHFFFAOYSA-N n-[[3-fluoro-4-(2-sulfamoylthieno[3,2-b]pyridin-7-yl)oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C=12SC(S(=O)(=O)N)=CC2=NC=CC=1OC(C(=C1)F)=CC=C1NC(=S)NC(=O)CC1=CC=CC=C1 VOZYTYSCFHSLCF-UHFFFAOYSA-N 0.000 claims description 3
• ZRISNUUUUNXNCA-UHFFFAOYSA-N sr17 Chemical compound C1=CC=C(C)N2C3=NC(C)=CC(Cl)=C3N=C21 ZRISNUUUUNXNCA-UHFFFAOYSA-N 0.000 claims description 3
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
• 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims 11
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 7
• 241001465754 Metazoa Species 0.000 claims 6
• 150000002431 hydrogen Chemical class 0.000 claims 6
• 101000599004 Homo sapiens Olfactory receptor 3A1 Proteins 0.000 claims 5
• 102100037784 Olfactory receptor 3A1 Human genes 0.000 claims 5
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
• ZOWLUHYYQGLSFQ-UHFFFAOYSA-N 2-[[4-[7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl]phenyl]methylamino]ethanol Chemical compound C1=CC(CNCCO)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(=CC=3)[N+]([O-])=O)F)=C2S1 ZOWLUHYYQGLSFQ-UHFFFAOYSA-N 0.000 claims 1
• ZLDCAGGBLTZUPU-UHFFFAOYSA-N 7-[2-fluoro-4-[(2-phenylacetyl)carbamothioylamino]phenoxy]-n,n-bis(2-methoxyethyl)thieno[3,2-b]pyridine-2-carboxamide Chemical compound C=12SC(C(=O)N(CCOC)CCOC)=CC2=NC=CC=1OC(C(=C1)F)=CC=C1NC(=S)NC(=O)CC1=CC=CC=C1 ZLDCAGGBLTZUPU-UHFFFAOYSA-N 0.000 claims 1
• FUWDWNBNVIAISB-UHFFFAOYSA-N 7-[2-fluoro-4-[(2-phenylacetyl)carbamothioylamino]phenoxy]-n-methoxy-n-methylthieno[3,2-b]pyridine-2-carboxamide Chemical compound C=12SC(C(=O)N(C)OC)=CC2=NC=CC=1OC(C(=C1)F)=CC=C1NC(=S)NC(=O)CC1=CC=CC=C1 FUWDWNBNVIAISB-UHFFFAOYSA-N 0.000 claims 1
• DPFPHZABJYXAMI-UHFFFAOYSA-N N-[[3-fluoro-4-[2-(2-hydroxyphenyl)thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound OC1=CC=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 DPFPHZABJYXAMI-UHFFFAOYSA-N 0.000 claims 1
• MNAUWXCQSPALPV-UHFFFAOYSA-N N-[[3-fluoro-4-[2-(4-hydroxyphenyl)thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C1=CC(O)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 MNAUWXCQSPALPV-UHFFFAOYSA-N 0.000 claims 1
• YGKVKDMFMDBGNS-UHFFFAOYSA-N N-[[4-[2-(4-hydroxyphenyl)thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C1=CC(O)=CC=C1C1=CC2=NC=CC(OC=3C=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)=C2S1 YGKVKDMFMDBGNS-UHFFFAOYSA-N 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• XWNFMPQSQLPOPP-UHFFFAOYSA-N n-(2-cyanoethyl)-7-[2-fluoro-4-[(2-phenylacetyl)carbamothioylamino]phenoxy]-n-phenylthieno[3,2-b]pyridine-2-carboxamide Chemical compound C=1C=C(OC=2C=3SC(=CC=3N=CC=2)C(=O)N(CCC#N)C=2C=CC=CC=2)C(F)=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 XWNFMPQSQLPOPP-UHFFFAOYSA-N 0.000 claims 1
• UXGDKBXMWTWQNG-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-7-[2-fluoro-4-[(2-phenylacetyl)carbamothioylamino]phenoxy]thieno[3,2-b]pyridine-2-carboxamide Chemical compound C=12SC(C(=O)NCCN(C)C)=CC2=NC=CC=1OC(C(=C1)F)=CC=C1NC(=S)NC(=O)CC1=CC=CC=C1 UXGDKBXMWTWQNG-UHFFFAOYSA-N 0.000 claims 1
• KTGNNIGYFOBZTH-UHFFFAOYSA-N n-[2-[di(propan-2-yl)amino]ethyl]-7-[2-fluoro-4-[(2-phenylacetyl)carbamothioylamino]phenoxy]thieno[3,2-b]pyridine-2-carboxamide Chemical compound C=12SC(C(=O)NCCN(C(C)C)C(C)C)=CC2=NC=CC=1OC(C(=C1)F)=CC=C1NC(=S)NC(=O)CC1=CC=CC=C1 KTGNNIGYFOBZTH-UHFFFAOYSA-N 0.000 claims 1
• ARXFOTZZRASPGF-UHFFFAOYSA-N n-[[3-fluoro-4-[2-(3-hydroxyazetidine-1-carbonyl)thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-(2-methoxyphenyl)acetamide Chemical compound COC1=CC=CC=C1CC(=O)NC(=S)NC(C=C1F)=CC=C1OC1=CC=NC2=C1SC(C(=O)N1CC(O)C1)=C2 ARXFOTZZRASPGF-UHFFFAOYSA-N 0.000 claims 1
• AFYSBIONGRVFNG-UHFFFAOYSA-N n-[[3-fluoro-4-[2-(3-hydroxyphenyl)thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound OC1=CC=CC(C=2SC3=C(OC=4C(=CC(NC(=S)NC(=O)CC=5C=CC=CC=5)=CC=4)F)C=CN=C3C=2)=C1 AFYSBIONGRVFNG-UHFFFAOYSA-N 0.000 claims 1
• HPXPIJLOAVKZSD-UHFFFAOYSA-N n-[[3-fluoro-4-[2-(3-morpholin-4-ylprop-1-ynyl)thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C=1C=C(OC=2C=3SC(=CC=3N=CC=2)C#CCN2CCOCC2)C(F)=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 HPXPIJLOAVKZSD-UHFFFAOYSA-N 0.000 claims 1
• YIZNEXNNUZRSHG-UHFFFAOYSA-N n-[[3-fluoro-4-[2-(4-methylsulfonylphenyl)thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 YIZNEXNNUZRSHG-UHFFFAOYSA-N 0.000 claims 1
• YUWZDWFVJHKFDE-GOSISDBHSA-N n-[[3-fluoro-4-[2-[(3r)-3-hydroxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C1[C@H](O)CCN1C(=O)C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 YUWZDWFVJHKFDE-GOSISDBHSA-N 0.000 claims 1
• YUWZDWFVJHKFDE-SFHVURJKSA-N n-[[3-fluoro-4-[2-[(3s)-3-hydroxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C1[C@@H](O)CCN1C(=O)C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 YUWZDWFVJHKFDE-SFHVURJKSA-N 0.000 claims 1
• QJTMLSMCPBDDMZ-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[1-[2-(methylamino)ethyl]pyrazol-4-yl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-(2-methoxyphenyl)acetamide Chemical compound C1=NN(CCNC)C=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C(=CC=CC=4)OC)=CC=3)F)=C2S1 QJTMLSMCPBDDMZ-UHFFFAOYSA-N 0.000 claims 1
• BROYWSBDHHGSQC-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[2-[(2-methoxyethylamino)methyl]phenyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound COCCNCC1=CC=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 BROYWSBDHHGSQC-UHFFFAOYSA-N 0.000 claims 1
• PPIMNKHWJJOGPR-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[3-[(2-methoxyethylamino)methyl]phenyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound COCCNCC1=CC=CC(C=2SC3=C(OC=4C(=CC(NC(=S)NC(=O)CC=5C=CC=CC=5)=CC=4)F)C=CN=C3C=2)=C1 PPIMNKHWJJOGPR-UHFFFAOYSA-N 0.000 claims 1
• VUCSJKJZTRXBNO-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[3-[(2-morpholin-4-ylethylamino)methyl]phenyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C=1C=C(OC=2C=3SC(=CC=3N=CC=2)C=2C=C(CNCCN3CCOCC3)C=CC=2)C(F)=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 VUCSJKJZTRXBNO-UHFFFAOYSA-N 0.000 claims 1
• HOYQZFVVGCECHL-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[4-[(2-methoxyethylamino)methyl]phenyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C1=CC(CNCCOC)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 HOYQZFVVGCECHL-UHFFFAOYSA-N 0.000 claims 1
• NOEFTGCRPQHAHC-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[4-[(oxolan-2-ylmethylamino)methyl]phenyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C=1C=C(OC=2C=3SC(=CC=3N=CC=2)C=2C=CC(CNCC3OCCC3)=CC=2)C(F)=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 NOEFTGCRPQHAHC-UHFFFAOYSA-N 0.000 claims 1
• RBJHNQJUFWRHPX-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[4-[[2-(methylamino)ethylamino]methyl]phenyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C1=CC(CNCCNC)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 RBJHNQJUFWRHPX-UHFFFAOYSA-N 0.000 claims 1
• LFMUBDLIDINQIJ-HXUWFJFHSA-N n-[[4-[2-[(3r)-3-(dimethylamino)pyrrolidine-1-carbonyl]thieno[3,2-b]pyridin-7-yl]oxy-3-fluorophenyl]carbamothioyl]-2-phenylacetamide Chemical compound C1[C@H](N(C)C)CCN1C(=O)C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 LFMUBDLIDINQIJ-HXUWFJFHSA-N 0.000 claims 1
• NVSWESAOIMKGNJ-UHFFFAOYSA-N n-[[4-[2-[4-(4-aminobutoxy)phenyl]thieno[3,2-b]pyridin-7-yl]oxy-3-fluorophenyl]carbamothioyl]-2-phenylacetamide;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCCCCN)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 NVSWESAOIMKGNJ-UHFFFAOYSA-N 0.000 claims 1
• WSRIWXGIDDENRS-UHFFFAOYSA-N n-[[4-[2-[4-(dimethylamino)phenyl]thieno[3,2-b]pyridin-7-yl]oxy-3-fluorophenyl]carbamothioyl]-2-phenylacetamide Chemical compound C1=CC(N(C)C)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC=CC=4)=CC=3)F)=C2S1 WSRIWXGIDDENRS-UHFFFAOYSA-N 0.000 claims 1
• 125000004430 oxygen atom Chemical group O* 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• 229910052698 phosphorus Inorganic materials 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 134
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 abstract description 14
• 102000003745 Hepatocyte Growth Factor Human genes 0.000 abstract description 13
• 108090000100 Hepatocyte Growth Factor Proteins 0.000 abstract description 13
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 12
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 12
• 102000005962 receptors Human genes 0.000 abstract description 10
• 108020003175 receptors Proteins 0.000 abstract description 10
• 230000005764 inhibitory process Effects 0.000 abstract description 9
• 210000004027 cell Anatomy 0.000 abstract description 8
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 332
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 262
• 239000007787 solid Substances 0.000 description 140
• VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 128
• 239000000243 solution Substances 0.000 description 127
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 122
• 238000012512 characterization method Methods 0.000 description 121
• 230000015572 biosynthetic process Effects 0.000 description 103
• 238000003786 synthesis reaction Methods 0.000 description 103
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 95
• 239000011541 reaction mixture Substances 0.000 description 95
• 238000005160 1H NMR spectroscopy Methods 0.000 description 92
• 238000005481 NMR spectroscopy Methods 0.000 description 80
• 230000002829 reductive effect Effects 0.000 description 80
• 150000001412 amines Chemical class 0.000 description 68
• 239000003480 eluent Substances 0.000 description 66
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 63
• LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 61
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
• 239000012279 sodium borohydride Substances 0.000 description 54
• 229910000033 sodium borohydride Inorganic materials 0.000 description 54
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 53
• 229910000027 potassium carbonate Inorganic materials 0.000 description 48
• 238000004440 column chromatography Methods 0.000 description 47
• 101150055528 SPAM1 gene Proteins 0.000 description 40
• 239000002904 solvent Substances 0.000 description 40
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 38
• 235000015320 potassium carbonate Nutrition 0.000 description 37
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 33
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 32
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 32
• 239000000725 suspension Substances 0.000 description 32
• 150000002828 nitro derivatives Chemical class 0.000 description 31
• 238000010992 reflux Methods 0.000 description 31
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 30
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 30
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 30
• ZFJOLNZPELDZNC-UHFFFAOYSA-N 2-phenylacetyl isothiocyanate Chemical class S=C=NC(=O)CC1=CC=CC=C1 ZFJOLNZPELDZNC-UHFFFAOYSA-N 0.000 description 29
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 29
• 238000000746 purification Methods 0.000 description 28
• 239000012074 organic phase Substances 0.000 description 26
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 25
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 25
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 25
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 24
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 22
• 235000011114 ammonium hydroxide Nutrition 0.000 description 22
• JQGGAELIYHNDQS-UHFFFAOYSA-N Nic 12 Natural products CC(C=CC(=O)C)c1ccc2C3C4OC4C5(O)CC=CC(=O)C5(C)C3CCc2c1 JQGGAELIYHNDQS-UHFFFAOYSA-N 0.000 description 21
• 239000000284 extract Substances 0.000 description 21
• 238000003756 stirring Methods 0.000 description 21
• 238000006243 chemical reaction Methods 0.000 description 20
• USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 20
• 125000001188 haloalkyl group Chemical group 0.000 description 20
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 19
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 19
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 18
• 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 18
• 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 18
• 239000000908 ammonium hydroxide Substances 0.000 description 18
• QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 18
• ORPHLVJBJOCHBR-UHFFFAOYSA-N 403-19-0 Chemical compound OC1=CC=C([N+]([O-])=O)C=C1F ORPHLVJBJOCHBR-UHFFFAOYSA-N 0.000 description 17
• XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Inorganic materials [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 16
• 238000003818 flash chromatography Methods 0.000 description 16
• 238000011282 treatment Methods 0.000 description 16
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 235000017557 sodium bicarbonate Nutrition 0.000 description 15
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 13
• BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical class OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 13
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 13
• 244000309464 bull Species 0.000 description 13
• QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 description 13
• 239000003921 oil Substances 0.000 description 13
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• 235000011181 potassium carbonates Nutrition 0.000 description 11
• 229910000104 sodium hydride Inorganic materials 0.000 description 11
• WCDLCPLAAKUJNY-UHFFFAOYSA-N 4-[4-[3-(1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C2=CNN=C2)C=C1 WCDLCPLAAKUJNY-UHFFFAOYSA-N 0.000 description 10
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
• MDKCFLQDBWCQCV-UHFFFAOYSA-N benzyl isothiocyanate Chemical compound S=C=NCC1=CC=CC=C1 MDKCFLQDBWCQCV-UHFFFAOYSA-N 0.000 description 10
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
• MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 9
• AUJJQNZIWOYGAN-UHFFFAOYSA-N 7-(2-fluoro-4-nitrophenoxy)-n,n-dimethylthieno[3,2-b]pyridine-2-carboxamide Chemical compound C=12SC(C(=O)N(C)C)=CC2=NC=CC=1OC1=CC=C([N+]([O-])=O)C=C1F AUJJQNZIWOYGAN-UHFFFAOYSA-N 0.000 description 9
• GYQUXKQLCNFKQT-UHFFFAOYSA-N 7-chlorothieno[3,2-b]pyridine Chemical compound ClC1=CC=NC2=C1SC=C2 GYQUXKQLCNFKQT-UHFFFAOYSA-N 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 101150041968 CDC13 gene Proteins 0.000 description 9
• 239000007832 Na2SO4 Substances 0.000 description 9
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
• 239000012267 brine Substances 0.000 description 9
• 229910002092 carbon dioxide Inorganic materials 0.000 description 9
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 239000000741 silica gel Substances 0.000 description 9
• 229910002027 silica gel Inorganic materials 0.000 description 9
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
• RKNQJPUYGVRWOW-UHFFFAOYSA-N 3-fluoro-4-thieno[3,2-b]pyridin-7-yloxyaniline Chemical compound FC1=CC(N)=CC=C1OC1=CC=NC2=C1SC=C2 RKNQJPUYGVRWOW-UHFFFAOYSA-N 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 8
• 239000000543 intermediate Substances 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 8
• GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 description 8
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 7
• RXNZFHIEDZEUQM-UHFFFAOYSA-N 2-bromo-1,3-thiazole Chemical compound BrC1=NC=CS1 RXNZFHIEDZEUQM-UHFFFAOYSA-N 0.000 description 7
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 7
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 7
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
• 125000002947 alkylene group Chemical group 0.000 description 7
• 229940125936 compound 42 Drugs 0.000 description 7
• 125000003386 piperidinyl group Chemical group 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• JNQMUUFBNQDWIE-UHFFFAOYSA-N 4-[7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(=CC=3)[N+]([O-])=O)F)=C2S1 JNQMUUFBNQDWIE-UHFFFAOYSA-N 0.000 description 6
• VLKFTMFLJYWQNK-UHFFFAOYSA-N 4-chlorothieno[3,2-d]pyrimidine-6-carbonyl chloride Chemical compound C1=NC(Cl)=C2SC(C(=O)Cl)=CC2=N1 VLKFTMFLJYWQNK-UHFFFAOYSA-N 0.000 description 6
• HNXKAHLDHQULJT-UHFFFAOYSA-N 7-(2-fluoro-4-nitrophenoxy)-2-(1h-imidazol-5-yl)thieno[3,2-b]pyridine Chemical compound FC1=CC([N+](=O)[O-])=CC=C1OC1=CC=NC2=C1SC(C=1N=CNC=1)=C2 HNXKAHLDHQULJT-UHFFFAOYSA-N 0.000 description 6
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
• 235000011089 carbon dioxide Nutrition 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 125000001183 hydrocarbyl group Chemical group 0.000 description 6
• KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 6
• 125000004193 piperazinyl group Chemical group 0.000 description 6
• 125000000714 pyrimidinyl group Chemical group 0.000 description 6
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 5
• PPZFUFKRHOBDAO-NSHDSACASA-N (3s)-1-[(4-bromophenyl)methyl]pyrrolidin-3-ol Chemical compound C1[C@@H](O)CCN1CC1=CC=C(Br)C=C1 PPZFUFKRHOBDAO-NSHDSACASA-N 0.000 description 5
• UVNPEUJXKZFWSJ-LMTQTHQJSA-N (R)-N-[(4S)-8-[6-amino-5-[(3,3-difluoro-2-oxo-1H-pyrrolo[2,3-b]pyridin-4-yl)sulfanyl]pyrazin-2-yl]-2-oxa-8-azaspiro[4.5]decan-4-yl]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](=O)N[C@@H]1COCC11CCN(CC1)c1cnc(Sc2ccnc3NC(=O)C(F)(F)c23)c(N)n1 UVNPEUJXKZFWSJ-LMTQTHQJSA-N 0.000 description 5
• QYZUILIYRXDFTH-UHFFFAOYSA-N 4-[2-[3-[7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl]phenoxy]ethyl]morpholine Chemical compound FC1=CC([N+](=O)[O-])=CC=C1OC1=CC=NC2=C1SC(C=1C=C(OCCN3CCOCC3)C=CC=1)=C2 QYZUILIYRXDFTH-UHFFFAOYSA-N 0.000 description 5
• JJPCHDAZZSJNRI-UHFFFAOYSA-N 7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine-2-carbonyl chloride Chemical compound FC1=CC([N+](=O)[O-])=CC=C1OC1=CC=NC2=C1SC(C(Cl)=O)=C2 JJPCHDAZZSJNRI-UHFFFAOYSA-N 0.000 description 5
• FFXSNKBFALEJLC-UHFFFAOYSA-N 7-[2-fluoro-4-[(2-phenylacetyl)carbamothioylamino]phenoxy]-n-[2-(methylamino)ethyl]thieno[3,2-b]pyridine-2-carboxamide;hydrochloride Chemical compound Cl.C=12SC(C(=O)NCCNC)=CC2=NC=CC=1OC(C(=C1)F)=CC=C1NC(=S)NC(=O)CC1=CC=CC=C1 FFXSNKBFALEJLC-UHFFFAOYSA-N 0.000 description 5
• GCOQDKNKQAPKGU-UHFFFAOYSA-N 7-chlorothieno[3,2-b]pyridine-2-carbaldehyde Chemical compound ClC1=CC=NC2=C1SC(C=O)=C2 GCOQDKNKQAPKGU-UHFFFAOYSA-N 0.000 description 5
• QAADZYUXQLUXFX-UHFFFAOYSA-N N-phenylmethylthioformamide Natural products S=CNCC1=CC=CC=C1 QAADZYUXQLUXFX-UHFFFAOYSA-N 0.000 description 5
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 5
• 239000003929 acidic solution Substances 0.000 description 5
• 150000001263 acyl chlorides Chemical class 0.000 description 5
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
• 229940125797 compound 12 Drugs 0.000 description 5
• 239000013058 crude material Substances 0.000 description 5
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 5
• JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• 125000002757 morpholinyl group Chemical group 0.000 description 5
• 125000004076 pyridyl group Chemical group 0.000 description 5
• LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 4
• ZPCJPJQUVRIILS-UHFFFAOYSA-N 1-bromo-3-(bromomethyl)benzene Chemical compound BrCC1=CC=CC(Br)=C1 ZPCJPJQUVRIILS-UHFFFAOYSA-N 0.000 description 4
• FNVSWWVCCSKXMX-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetyl isothiocyanate Chemical compound COC1=CC=CC=C1CC(=O)N=C=S FNVSWWVCCSKXMX-UHFFFAOYSA-N 0.000 description 4
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 4
• HCLQARMRCPEALF-DNQXCXABSA-N 3-[[(2r)-2-[(1r)-2-[[1-(1-benzothiophen-2-yl)-2-methylpropan-2-yl]amino]-1-hydroxyethyl]pyrrolidin-1-yl]methyl]benzonitrile Chemical compound C([C@@H]1[C@H](O)CNC(C)(CC=2SC3=CC=CC=C3C=2)C)CCN1CC1=CC=CC(C#N)=C1 HCLQARMRCPEALF-DNQXCXABSA-N 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• CJZMRESPNIJBOX-UHFFFAOYSA-N 4-chloro-5-methylpyrrolo[3,2-d]pyrimidine Chemical compound C1=NC(Cl)=C2N(C)C=CC2=N1 CJZMRESPNIJBOX-UHFFFAOYSA-N 0.000 description 4
• BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 4
• HYXAWOCRWBRNJK-FERBBOLQSA-N 7-[2-fluoro-4-[(2-phenylacetyl)carbamothioylamino]phenoxy]-n-[[(3s)-pyrrolidin-3-yl]methyl]thieno[3,2-b]pyridine-2-carboxamide;hydrochloride Chemical compound Cl.C=1C=C(OC=2C=3SC(=CC=3N=CC=2)C(=O)NC[C@@H]2CNCC2)C(F)=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 HYXAWOCRWBRNJK-FERBBOLQSA-N 0.000 description 4
• SKXYCYORLNFXMD-UHFFFAOYSA-N N-[(7-chlorothieno[3,2-b]pyridin-2-yl)methylidene]hydroxylamine Chemical compound C1=CC(Cl)=C2SC(C=NO)=CC2=N1 SKXYCYORLNFXMD-UHFFFAOYSA-N 0.000 description 4
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
• 229910006074 SO2NH2 Inorganic materials 0.000 description 4
• 125000002252 acyl group Chemical group 0.000 description 4
• 125000004442 acylamino group Chemical group 0.000 description 4
• 150000001299 aldehydes Chemical class 0.000 description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
• 125000003277 amino group Chemical group 0.000 description 4
• 125000004103 aminoalkyl group Chemical group 0.000 description 4
• 235000019270 ammonium chloride Nutrition 0.000 description 4
• 239000008346 aqueous phase Substances 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
• 238000009835 boiling Methods 0.000 description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 4
• 150000007942 carboxylates Chemical class 0.000 description 4
• 125000001309 chloro group Chemical group Cl* 0.000 description 4
• 239000012230 colorless oil Substances 0.000 description 4
• 229940125773 compound 10 Drugs 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical group C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 4
• SURZCVYFPAXNGN-UHFFFAOYSA-N methyl-carbamic acid ethyl ester Chemical compound CCOC(=O)NC SURZCVYFPAXNGN-UHFFFAOYSA-N 0.000 description 4
• 230000007935 neutral effect Effects 0.000 description 4
• 125000004043 oxo group Chemical group O=* 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 238000006467 substitution reaction Methods 0.000 description 4
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 4
• 238000001665 trituration Methods 0.000 description 4
• 239000011592 zinc chloride Substances 0.000 description 4
• 235000005074 zinc chloride Nutrition 0.000 description 4
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
• YDMRDHQUQIVWBE-UHFFFAOYSA-N (2-hydroxyphenyl)boronic acid Chemical class OB(O)C1=CC=CC=C1O YDMRDHQUQIVWBE-UHFFFAOYSA-N 0.000 description 3
• UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 3
• UXUJWLDPUJVDPB-AWEZNQCLSA-N (3s)-1-[[4-(7-chlorothieno[3,2-b]pyridin-2-yl)phenyl]methyl]pyrrolidin-3-ol Chemical compound C1[C@@H](O)CCN1CC1=CC=C(C=2SC3=C(Cl)C=CN=C3C=2)C=C1 UXUJWLDPUJVDPB-AWEZNQCLSA-N 0.000 description 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 3
• PZMKGWRBZNOIPQ-UHFFFAOYSA-N 1h-thieno[3,2-d]pyrimidin-4-one Chemical compound OC1=NC=NC2=C1SC=C2 PZMKGWRBZNOIPQ-UHFFFAOYSA-N 0.000 description 3
• QTMAZYGAVHCKKX-UHFFFAOYSA-N 2-[(4-amino-5-bromopyrrolo[2,3-d]pyrimidin-7-yl)methoxy]propane-1,3-diol Chemical compound NC1=NC=NC2=C1C(Br)=CN2COC(CO)CO QTMAZYGAVHCKKX-UHFFFAOYSA-N 0.000 description 3
• XMZQZXNHMUDHNZ-UHFFFAOYSA-N 2-bromo-7-chlorothieno[3,2-b]pyridine Chemical compound ClC1=CC=NC2=C1SC(Br)=C2 XMZQZXNHMUDHNZ-UHFFFAOYSA-N 0.000 description 3
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 3
• AYFNMVPJAWSZEW-UHFFFAOYSA-N 2-phenyl-n-[[4-thieno[3,2-b]pyridin-7-yloxy-2-(trifluoromethyl)phenyl]carbamothioyl]acetamide Chemical compound FC(F)(F)C1=CC(OC=2C=3SC=CC=3N=CC=2)=CC=C1NC(=S)NC(=O)CC1=CC=CC=C1 AYFNMVPJAWSZEW-UHFFFAOYSA-N 0.000 description 3
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 3
• DKTRZBWXGOPYIX-UHFFFAOYSA-N 3-chloro-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C(Cl)=C1 DKTRZBWXGOPYIX-UHFFFAOYSA-N 0.000 description 3
• QCQGMJKWLDTWKS-UHFFFAOYSA-N 3-fluoro-4-[2-[1-(2-methoxyethyl)imidazol-4-yl]thieno[3,2-b]pyridin-7-yl]oxyaniline Chemical compound COCCN1C=NC(C=2SC3=C(OC=4C(=CC(N)=CC=4)F)C=CN=C3C=2)=C1 QCQGMJKWLDTWKS-UHFFFAOYSA-N 0.000 description 3
• BATKFFUMRUIAGN-UHFFFAOYSA-N 3-fluoro-4-[2-[3-(2-morpholin-4-ylethoxy)phenyl]thieno[3,2-b]pyridin-7-yl]oxyaniline Chemical compound FC1=CC(N)=CC=C1OC1=CC=NC2=C1SC(C=1C=C(OCCN3CCOCC3)C=CC=1)=C2 BATKFFUMRUIAGN-UHFFFAOYSA-N 0.000 description 3
• QJKZMSISXQFYSH-UHFFFAOYSA-N 4-(4-amino-2-fluorophenoxy)-n-(2-morpholin-4-ylethyl)thieno[3,2-d]pyrimidine-6-carboxamide Chemical compound FC1=CC(N)=CC=C1OC1=NC=NC2=C1SC(C(=O)NCCN1CCOCC1)=C2 QJKZMSISXQFYSH-UHFFFAOYSA-N 0.000 description 3
• NBBCGFZUDJBYJZ-UHFFFAOYSA-N 4-[2-[4-(2-morpholin-4-ylethoxy)phenyl]thieno[3,2-b]pyridin-7-yl]oxyaniline Chemical compound C1=CC(N)=CC=C1OC1=CC=NC2=C1SC(C=1C=CC(OCCN3CCOCC3)=CC=1)=C2 NBBCGFZUDJBYJZ-UHFFFAOYSA-N 0.000 description 3
• AMXUIMZQHUYUPY-UHFFFAOYSA-N 4-[7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl]phenol Chemical compound FC1=CC(N)=CC=C1OC1=CC=NC2=C1SC(C=1C=CC(O)=CC=1)=C2 AMXUIMZQHUYUPY-UHFFFAOYSA-N 0.000 description 3
• PAVSYEVRPSQXRF-UHFFFAOYSA-N 4-[7-(4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl]phenol Chemical compound C1=CC(O)=CC=C1C1=CC2=NC=CC(OC=3C=CC(=CC=3)[N+]([O-])=O)=C2S1 PAVSYEVRPSQXRF-UHFFFAOYSA-N 0.000 description 3
• BEHIXYZZEKJBNL-UHFFFAOYSA-N 7-(2-fluoro-4-nitrophenoxy)-2-(4-methylsulfonylphenyl)thieno[3,2-b]pyridine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(=CC=3)[N+]([O-])=O)F)=C2S1 BEHIXYZZEKJBNL-UHFFFAOYSA-N 0.000 description 3
• YNBNKPPQUGIDQH-UHFFFAOYSA-N 7-(2-fluoro-4-nitrophenoxy)-n-methoxy-n-methylthieno[3,2-b]pyridine-2-sulfonamide Chemical compound C=12SC(S(=O)(=O)N(C)OC)=CC2=NC=CC=1OC1=CC=C([N+]([O-])=O)C=C1F YNBNKPPQUGIDQH-UHFFFAOYSA-N 0.000 description 3
• CNUSLPFJBQVALY-UHFFFAOYSA-N 7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine-2-carbonitrile Chemical compound FC1=CC([N+](=O)[O-])=CC=C1OC1=CC=NC2=C1SC(C#N)=C2 CNUSLPFJBQVALY-UHFFFAOYSA-N 0.000 description 3
• VRDYVYLZAPTPQG-UHFFFAOYSA-N 7-[2-fluoro-4-[(2-phenylacetyl)carbamothioylamino]phenoxy]-n,n-bis(2-methylpropyl)thieno[3,2-b]pyridine-2-carboxamide Chemical compound C=12SC(C(=O)N(CC(C)C)CC(C)C)=CC2=NC=CC=1OC(C(=C1)F)=CC=C1NC(=S)NC(=O)CC1=CC=CC=C1 VRDYVYLZAPTPQG-UHFFFAOYSA-N 0.000 description 3
• ZFVBOLLDXJZHQP-UHFFFAOYSA-N 7-chloro-n,n-dimethylthieno[3,2-b]pyridine-2-carboxamide Chemical compound C1=CC(Cl)=C2SC(C(=O)N(C)C)=CC2=N1 ZFVBOLLDXJZHQP-UHFFFAOYSA-N 0.000 description 3
• VIFGWQPBWFCZSX-UHFFFAOYSA-N 7-chlorothieno[3,2-b]pyridine-2-carbonitrile Chemical compound ClC1=CC=NC2=C1SC(C#N)=C2 VIFGWQPBWFCZSX-UHFFFAOYSA-N 0.000 description 3
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 3
• 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 3
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
• 108091000080 Phosphotransferase Proteins 0.000 description 3
• 229910008066 SnC12 Inorganic materials 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 125000001931 aliphatic group Chemical group 0.000 description 3
• 125000003282 alkyl amino group Chemical group 0.000 description 3
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
• 125000003368 amide group Chemical group 0.000 description 3
• 230000033115 angiogenesis Effects 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 150000001499 aryl bromides Chemical class 0.000 description 3
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 3
• 229910052794 bromium Inorganic materials 0.000 description 3
• 125000001246 bromo group Chemical group Br* 0.000 description 3
• 125000006278 bromobenzyl group Chemical group 0.000 description 3
• 239000001569 carbon dioxide Substances 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 239000002027 dichloromethane extract Substances 0.000 description 3
• ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 3
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
• ZUAFSRDYQVCEPE-UHFFFAOYSA-N n-carbamothioyl-2-phenylacetamide Chemical compound NC(=S)NC(=O)CC1=CC=CC=C1 ZUAFSRDYQVCEPE-UHFFFAOYSA-N 0.000 description 3
• 239000012044 organic layer Substances 0.000 description 3
• 125000000160 oxazolidinyl group Chemical group 0.000 description 3
• 230000037361 pathway Effects 0.000 description 3
• 102000020233 phosphotransferase Human genes 0.000 description 3
• 150000003254 radicals Chemical class 0.000 description 3
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 3
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 239000011369 resultant mixture Substances 0.000 description 3
• 239000011343 solid material Substances 0.000 description 3
• QIRIZLYNEIXQTA-UHFFFAOYSA-N tert-butyl 4-[4-[7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl]phenyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(C=2SC3=C(OC=4C(=CC(=CC=4)[N+]([O-])=O)F)C=CN=C3C=2)C=C1 QIRIZLYNEIXQTA-UHFFFAOYSA-N 0.000 description 3
• YGALLNHOJFJALM-UHFFFAOYSA-N tert-butyl n-[(3-bromophenyl)methyl]-n-(2-methoxyethyl)carbamate Chemical compound COCCN(C(=O)OC(C)(C)C)CC1=CC=CC(Br)=C1 YGALLNHOJFJALM-UHFFFAOYSA-N 0.000 description 3
• BCEGCQOVJQKQIS-UHFFFAOYSA-N tert-butyl n-[[3-[7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl]phenyl]methyl]-n-(2-methoxyethyl)carbamate Chemical compound COCCN(C(=O)OC(C)(C)C)CC1=CC=CC(C=2SC3=C(OC=4C(=CC(=CC=4)[N+]([O-])=O)F)C=CN=C3C=2)=C1 BCEGCQOVJQKQIS-UHFFFAOYSA-N 0.000 description 3
• 125000001544 thienyl group Chemical group 0.000 description 3
• XVCDIZWEKFUGJW-UHFFFAOYSA-N tributyl-(4-chlorothieno[3,2-d]pyrimidin-6-yl)stannane Chemical compound C1=NC(Cl)=C2SC([Sn](CCCC)(CCCC)CCCC)=CC2=N1 XVCDIZWEKFUGJW-UHFFFAOYSA-N 0.000 description 3
• 210000004881 tumor cell Anatomy 0.000 description 3
• YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 2
• WFWQWTPAPNEOFE-UHFFFAOYSA-N (3-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(O)=C1 WFWQWTPAPNEOFE-UHFFFAOYSA-N 0.000 description 2
• OIIOPWHTJZYKIL-PMACEKPBSA-N (5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one Chemical compound C1(=C(N=C(C2=C(C(C3=CC=CC(=C3Cl)C3=NC(OC)=C(N=C3)CNC[C@H]3NC(=O)CC3)=CC=C2)Cl)C=N1)OC)CNC[C@H]1NC(=O)CC1 OIIOPWHTJZYKIL-PMACEKPBSA-N 0.000 description 2
• MTMHBQNHFZUJPE-UHFFFAOYSA-N (7-chlorothieno[3,2-b]pyridin-2-yl)-trimethylstannane Chemical compound C1=CC(Cl)=C2SC([Sn](C)(C)C)=CC2=N1 MTMHBQNHFZUJPE-UHFFFAOYSA-N 0.000 description 2
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 2
• 125000006643 (C2-C6) haloalkenyl group Chemical group 0.000 description 2
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
• AGRIQBHIKABLPJ-UHFFFAOYSA-N 1-Pyrrolidinecarboxaldehyde Chemical compound O=CN1CCCC1 AGRIQBHIKABLPJ-UHFFFAOYSA-N 0.000 description 2
• SZCBDIVMCGFVPW-UHFFFAOYSA-N 1-[4-(aminomethyl)-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,8-naphthyridin-3-yl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=C(CN)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OC)=C1 SZCBDIVMCGFVPW-UHFFFAOYSA-N 0.000 description 2
• RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-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
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 2
• 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 2
• PAYROHWFGZADBR-UHFFFAOYSA-N 2-[[4-amino-5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidin-2-yl]amino]propane-1,3-diol Chemical compound C1=C(I)C(OC)=CC(C(C)C)=C1OC1=CN=C(NC(CO)CO)N=C1N PAYROHWFGZADBR-UHFFFAOYSA-N 0.000 description 2
• GDGQQZPCVJQVTQ-UHFFFAOYSA-N 2-bromo-3-methyl-n-(2-morpholin-4-ylethyl)imidazole-4-carboxamide Chemical compound CN1C(Br)=NC=C1C(=O)NCCN1CCOCC1 GDGQQZPCVJQVTQ-UHFFFAOYSA-N 0.000 description 2
• YQQZFSUEBYGNCO-UHFFFAOYSA-N 2-bromo-7-(4-nitrophenoxy)thieno[3,2-b]pyridine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=NC2=C1SC(Br)=C2 YQQZFSUEBYGNCO-UHFFFAOYSA-N 0.000 description 2
• ACTOYGYVZCDQEN-UHFFFAOYSA-N 2-chloro-4-thieno[3,2-d]pyrimidin-4-yloxyaniline Chemical compound C1=C(Cl)C(N)=CC=C1OC1=NC=NC2=C1SC=C2 ACTOYGYVZCDQEN-UHFFFAOYSA-N 0.000 description 2
• TZQYYEHERBEFAP-UHFFFAOYSA-N 2-phenyl-n-[[4-[2-(pyrrolidine-1-carbonyl)thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]acetamide Chemical compound C=1C=C(OC=2C=3SC(=CC=3N=CC=2)C(=O)N2CCCC2)C=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 TZQYYEHERBEFAP-UHFFFAOYSA-N 0.000 description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• VDQSACYMBGQMFC-UHFFFAOYSA-N 3-methoxy-4-nitrophenol Chemical compound COC1=CC(O)=CC=C1[N+]([O-])=O VDQSACYMBGQMFC-UHFFFAOYSA-N 0.000 description 2
• WPHJRNVULINVHW-UHFFFAOYSA-N 3-methyl-n-(2-morpholin-4-ylethyl)imidazole-4-carboxamide Chemical compound CN1C=NC=C1C(=O)NCCN1CCOCC1 WPHJRNVULINVHW-UHFFFAOYSA-N 0.000 description 2
• JEDVKUHCDPPWNR-UHFFFAOYSA-N 3h-thieno[2,3-d]pyrimidin-4-one Chemical compound O=C1NC=NC2=C1C=CS2 JEDVKUHCDPPWNR-UHFFFAOYSA-N 0.000 description 2
• RPRBUNJJEGCHBL-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)-n-(2-morpholin-4-ylethyl)thieno[3,2-d]pyrimidine-6-carboxamide Chemical compound FC1=CC([N+](=O)[O-])=CC=C1OC1=NC=NC2=C1SC(C(=O)NCCN1CCOCC1)=C2 RPRBUNJJEGCHBL-UHFFFAOYSA-N 0.000 description 2
• DEWRDFPURUJUOG-UHFFFAOYSA-N 4-[2-[4-[7-(4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl]phenoxy]ethyl]morpholine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=NC2=C1SC(C=1C=CC(OCCN3CCOCC3)=CC=1)=C2 DEWRDFPURUJUOG-UHFFFAOYSA-N 0.000 description 2
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
• GSDQYSSLIKJJOG-UHFFFAOYSA-N 4-chloro-2-(3-chloroanilino)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1NC1=CC=CC(Cl)=C1 GSDQYSSLIKJJOG-UHFFFAOYSA-N 0.000 description 2
• ZGJDDWOXVGDTSP-UHFFFAOYSA-N 4-chloro-5h-pyrrolo[3,2-d]pyrimidine Chemical compound ClC1=NC=NC2=C1NC=C2 ZGJDDWOXVGDTSP-UHFFFAOYSA-N 0.000 description 2
• NZCRUBBNZGVREM-UHFFFAOYSA-N 4-chlorothieno[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CS2 NZCRUBBNZGVREM-UHFFFAOYSA-N 0.000 description 2
• TWTODSLDHCDLDR-UHFFFAOYSA-N 4-chlorothieno[3,2-d]pyrimidine Chemical compound ClC1=NC=NC2=C1SC=C2 TWTODSLDHCDLDR-UHFFFAOYSA-N 0.000 description 2
• AIKAEOONESRENG-UHFFFAOYSA-N 4-chlorothieno[3,2-d]pyrimidine-6-carbaldehyde Chemical compound ClC1=NC=NC2=C1SC(C=O)=C2 AIKAEOONESRENG-UHFFFAOYSA-N 0.000 description 2
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
• AACVULYSNJAKEQ-UHFFFAOYSA-N 4h-thieno[3,2-b]pyridin-7-one Chemical compound OC1=CC=NC2=C1SC=C2 AACVULYSNJAKEQ-UHFFFAOYSA-N 0.000 description 2
• IJRKLHTZAIFUTB-UHFFFAOYSA-N 5-nitro-2-(2-phenylethylamino)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NCCC1=CC=CC=C1 IJRKLHTZAIFUTB-UHFFFAOYSA-N 0.000 description 2
• WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 2
• KMFQJCZBJFJJAV-UHFFFAOYSA-N 7-(2-fluoro-4-nitrophenoxy)-2-(1-methylimidazol-4-yl)thieno[3,2-b]pyridine Chemical compound CN1C=NC(C=2SC3=C(OC=4C(=CC(=CC=4)[N+]([O-])=O)F)C=CN=C3C=2)=C1 KMFQJCZBJFJJAV-UHFFFAOYSA-N 0.000 description 2
• BWGRCYDBPFQWCD-UHFFFAOYSA-N 7-(2-fluoro-4-nitrophenoxy)-2-(6-methoxypyridin-3-yl)thieno[3,2-b]pyridine Chemical compound C1=NC(OC)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(=CC=3)[N+]([O-])=O)F)=C2S1 BWGRCYDBPFQWCD-UHFFFAOYSA-N 0.000 description 2
• YWIZJSODCFXCBY-UHFFFAOYSA-N 7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine Chemical compound FC1=CC([N+](=O)[O-])=CC=C1OC1=CC=NC2=C1SC=C2 YWIZJSODCFXCBY-UHFFFAOYSA-N 0.000 description 2
• YJWLZQUFCCNKKY-UHFFFAOYSA-N 7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine-2-carboxylic acid Chemical compound C=12SC(C(=O)O)=CC2=NC=CC=1OC1=CC=C([N+]([O-])=O)C=C1F YJWLZQUFCCNKKY-UHFFFAOYSA-N 0.000 description 2
• MPVXDDQQQXLJQV-UHFFFAOYSA-N 7-(4-nitrophenoxy)thieno[3,2-b]pyridine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=NC2=C1SC=C2 MPVXDDQQQXLJQV-UHFFFAOYSA-N 0.000 description 2
• SXJYEIKOISIVAK-UHFFFAOYSA-N 7-chloro-n-methoxy-n-methylthieno[3,2-b]pyridine-2-sulfonamide Chemical compound C1=CC(Cl)=C2SC(S(=O)(=O)N(C)OC)=CC2=N1 SXJYEIKOISIVAK-UHFFFAOYSA-N 0.000 description 2
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• 229910015845 BBr3 Inorganic materials 0.000 description 2
• IYHHRZBKXXKDDY-UHFFFAOYSA-N BI-605906 Chemical compound N=1C=2SC(C(N)=O)=C(N)C=2C(C(F)(F)CC)=CC=1N1CCC(S(C)(=O)=O)CC1 IYHHRZBKXXKDDY-UHFFFAOYSA-N 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
• 102000043136 MAP kinase family Human genes 0.000 description 2
• 108091054455 MAP kinase family Proteins 0.000 description 2
• 206010027476 Metastases Diseases 0.000 description 2
• POFVJRKJJBFPII-UHFFFAOYSA-N N-cyclopentyl-5-[2-[[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1(CCCC1)NC=1SC(=C(N=1)C)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)CC POFVJRKJJBFPII-UHFFFAOYSA-N 0.000 description 2
• 229910017912 NH2OH Inorganic materials 0.000 description 2
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
• 229910021120 PdC12 Inorganic materials 0.000 description 2
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
• GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 2
• 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 2
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
• QUSMSKPJZOZSLW-UHFFFAOYSA-N [4-[7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl]phenyl]methanol Chemical compound C1=CC(CO)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(=CC=3)[N+]([O-])=O)F)=C2S1 QUSMSKPJZOZSLW-UHFFFAOYSA-N 0.000 description 2
• WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 2
• VITFJKNVGRZRKB-UHFFFAOYSA-N acetyl isothiocyanate Chemical compound CC(=O)N=C=S VITFJKNVGRZRKB-UHFFFAOYSA-N 0.000 description 2
• 125000004450 alkenylene group Chemical group 0.000 description 2
• 125000002877 alkyl aryl group Chemical group 0.000 description 2
• 125000004419 alkynylene group Chemical group 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• 125000005140 aralkylsulfonyl group Chemical group 0.000 description 2
• 125000003435 aroyl group Chemical group 0.000 description 2
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
• 125000000732 arylene group Chemical group 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
• KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 2
• 125000005621 boronate group Chemical class 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• 230000009400 cancer invasion Effects 0.000 description 2
• 239000012830 cancer therapeutic Substances 0.000 description 2
• 125000002837 carbocyclic group Chemical group 0.000 description 2
• 150000003857 carboxamides Chemical class 0.000 description 2
• 125000005518 carboxamido group Chemical group 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 125000003636 chemical group Chemical group 0.000 description 2
• KWTSZCJMWHGPOS-UHFFFAOYSA-M chloro(trimethyl)stannane Chemical group C[Sn](C)(C)Cl KWTSZCJMWHGPOS-UHFFFAOYSA-M 0.000 description 2
• 239000013065 commercial product Substances 0.000 description 2
• 229940125810 compound 20 Drugs 0.000 description 2
• 229940125833 compound 23 Drugs 0.000 description 2
• 229940125961 compound 24 Drugs 0.000 description 2
• 229940126540 compound 41 Drugs 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• 238000006471 dimerization reaction Methods 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 2
• 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 2
• 125000004464 hydroxyphenyl group Chemical group 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
• 150000002540 isothiocyanates Chemical class 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• ANYSGBYRTLOUPO-UHFFFAOYSA-N lithium tetramethylpiperidide Chemical compound [Li]N1C(C)(C)CCCC1(C)C ANYSGBYRTLOUPO-UHFFFAOYSA-N 0.000 description 2
• RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
• JYCSHDAKFVICIB-UHFFFAOYSA-N methyl 7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine-2-carboxylate Chemical compound C=12SC(C(=O)OC)=CC2=NC=CC=1OC1=CC=C([N+]([O-])=O)C=C1F JYCSHDAKFVICIB-UHFFFAOYSA-N 0.000 description 2
• WYMRMHKAXXQOMO-UHFFFAOYSA-N methyl 7-chlorothieno[3,2-b]pyridine-2-carboxylate Chemical compound C1=CC(Cl)=C2SC(C(=O)OC)=CC2=N1 WYMRMHKAXXQOMO-UHFFFAOYSA-N 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 239000003226 mitogen Substances 0.000 description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
• IHCHOVVAJBADAH-UHFFFAOYSA-N n-[2-hydroxy-4-(1h-pyrazol-4-yl)phenyl]-6-methoxy-3,4-dihydro-2h-chromene-3-carboxamide Chemical compound C1C2=CC(OC)=CC=C2OCC1C(=O)NC(C(=C1)O)=CC=C1C=1C=NNC=1 IHCHOVVAJBADAH-UHFFFAOYSA-N 0.000 description 2
• RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 2
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 2
• 150000002989 phenols Chemical class 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 238000002360 preparation method Methods 0.000 description 2
• 150000003140 primary amides Chemical class 0.000 description 2
• 150000003141 primary amines Chemical class 0.000 description 2
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 2
• MVILWLLYYQVYNH-UHFFFAOYSA-N pyridine-2-carboxamide Chemical compound NC(=O)C1=CC=CC=N1.NC(=O)C1=CC=CC=N1 MVILWLLYYQVYNH-UHFFFAOYSA-N 0.000 description 2
• KNXKVYCVGXFLES-UHFFFAOYSA-N pyridine-2-carboximidamide Chemical compound NC(=N)C1=CC=CC=N1 KNXKVYCVGXFLES-UHFFFAOYSA-N 0.000 description 2
• 150000003334 secondary amides Chemical class 0.000 description 2
• 150000003335 secondary amines Chemical class 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• PRFKXUANUQECJP-UHFFFAOYSA-M sodium;hydrogen carbonate;oxolane Chemical compound [Na+].OC([O-])=O.C1CCOC1 PRFKXUANUQECJP-UHFFFAOYSA-M 0.000 description 2
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• FBUVZUHGXCYTMP-UHFFFAOYSA-N thieno[3,2-d]pyrimidin-7-ol Chemical compound N1=CN=C2C(O)=CSC2=C1 FBUVZUHGXCYTMP-UHFFFAOYSA-N 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• 230000029663 wound healing Effects 0.000 description 2
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
• GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
• IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
• VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
• FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 1
• HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
• JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical compound O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 1
• UZFBWSFTHSYXCN-UHFFFAOYSA-N (4-hydroxy-3-methoxyphenyl)boronic acid Chemical compound COC1=CC(B(O)O)=CC=C1O UZFBWSFTHSYXCN-UHFFFAOYSA-N 0.000 description 1
• COIQUVGFTILYGA-UHFFFAOYSA-N (4-hydroxyphenyl)boronic acid Chemical group OB(O)C1=CC=C(O)C=C1 COIQUVGFTILYGA-UHFFFAOYSA-N 0.000 description 1
• DHADXDMPEUWEAS-UHFFFAOYSA-N (6-methoxypyridin-3-yl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=N1 DHADXDMPEUWEAS-UHFFFAOYSA-N 0.000 description 1
• 125000006699 (C1-C3) hydroxyalkyl group Chemical group 0.000 description 1
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
• 125000006644 (C2-C6) haloalkynyl group Chemical group 0.000 description 1
• SRKGZXIJDGWVAI-GVAVTCRGSA-M (e,3r)-7-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)C1=NC(C(C)(C)C)=CC(C=2C=CC(F)=CC=2)=C1\C=C\C(O)C[C@@H](O)CC([O-])=O SRKGZXIJDGWVAI-GVAVTCRGSA-M 0.000 description 1
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
• SEZHLKZEWYFCRB-UHFFFAOYSA-N 1,2-dimethoxyethane;oxolane Chemical compound C1CCOC1.COCCOC SEZHLKZEWYFCRB-UHFFFAOYSA-N 0.000 description 1
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
• KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
• DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
• SRJBKVJKZBNVOV-UHFFFAOYSA-N 1-phenylcyclopropane-1-carbonyl isothiocyanate Chemical compound C=1C=CC=CC=1C1(C(N=C=S)=O)CC1 SRJBKVJKZBNVOV-UHFFFAOYSA-N 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000005955 1H-indazolyl group Chemical group 0.000 description 1
• HVLREKCWOGNXDT-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)acetyl isothiocyanate Chemical compound ClC1=CC=CC(Cl)=C1CC(=O)N=C=S HVLREKCWOGNXDT-UHFFFAOYSA-N 0.000 description 1
• VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 1
• QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 1
• OMVUOLRLHMJRAV-UHFFFAOYSA-N 2-(2-fluorophenyl)acetyl isothiocyanate Chemical compound FC1=CC=CC=C1CC(=O)N=C=S OMVUOLRLHMJRAV-UHFFFAOYSA-N 0.000 description 1
• GIPHGNKBBBAPHD-UHFFFAOYSA-N 2-(2-oxopyrrolidin-1-yl)acetyl isothiocyanate Chemical compound S=C=NC(=O)CN1CCCC1=O GIPHGNKBBBAPHD-UHFFFAOYSA-N 0.000 description 1
• OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 1
• BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
• KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
• NAIQFHKIRUMXEX-UHFFFAOYSA-N 2-(oxan-4-yl)acetyl isothiocyanate Chemical compound S=C=NC(=O)CC1CCOCC1 NAIQFHKIRUMXEX-UHFFFAOYSA-N 0.000 description 1
• BVOHFHIEDQSTKD-UHFFFAOYSA-N 2-[(4-iodoimidazol-1-yl)methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCN1C=NC(I)=C1 BVOHFHIEDQSTKD-UHFFFAOYSA-N 0.000 description 1
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
• VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
• ZTUKRGQWDZCKQG-UHFFFAOYSA-N 2-bromo-7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine Chemical compound FC1=CC([N+](=O)[O-])=CC=C1OC1=CC=NC2=C1SC(Br)=C2 ZTUKRGQWDZCKQG-UHFFFAOYSA-N 0.000 description 1
• AVDJRZSRUGHQHN-UHFFFAOYSA-N 2-cyclohexylacetyl isothiocyanate Chemical compound S=C=NC(=O)CC1CCCCC1 AVDJRZSRUGHQHN-UHFFFAOYSA-N 0.000 description 1
• IJJIFRMFKUTURO-UHFFFAOYSA-N 2-cyclopentylacetyl isothiocyanate Chemical compound S=C=NC(=O)CC1CCCC1 IJJIFRMFKUTURO-UHFFFAOYSA-N 0.000 description 1
• IBZKBSXREAQDTO-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)ethanamine Chemical compound COCCNCCOC IBZKBSXREAQDTO-UHFFFAOYSA-N 0.000 description 1
• NJBCRXCAPCODGX-UHFFFAOYSA-N 2-methyl-n-(2-methylpropyl)propan-1-amine Chemical compound CC(C)CNCC(C)C NJBCRXCAPCODGX-UHFFFAOYSA-N 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• QYPXPTWCADLXTP-UHFFFAOYSA-N 2-thiophen-2-ylacetyl isothiocyanate Chemical compound S=C=NC(=O)CC1=CC=CS1 QYPXPTWCADLXTP-UHFFFAOYSA-N 0.000 description 1
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
• OZHWHTICSNFGBZ-UHFFFAOYSA-N 3-(cyclopropylamino)propanenitrile Chemical compound N#CCCNC1CC1 OZHWHTICSNFGBZ-UHFFFAOYSA-N 0.000 description 1
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
• WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 1
• UNSHMXUHOHBLIQ-UHFFFAOYSA-N 3-[4-chloro-3-(2-methylphenoxy)naphthalen-1-yl]-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione Chemical compound ClC1=C(C=C(C2=CC=CC=C12)N1C(NC(=CC1=O)C(F)(F)F)=O)OC1=C(C=CC=C1)C UNSHMXUHOHBLIQ-UHFFFAOYSA-N 0.000 description 1
• CVVVPJNNKHUMEN-UHFFFAOYSA-N 3-fluoro-4-[6-(1,3-thiazol-2-yl)thieno[3,2-d]pyrimidin-4-yl]oxyaniline Chemical compound FC1=CC(N)=CC=C1OC1=NC=NC2=C1SC(C=1SC=CN=1)=C2 CVVVPJNNKHUMEN-UHFFFAOYSA-N 0.000 description 1
• JUVHGEBZWCDKPL-UHFFFAOYSA-N 3-methyl-2-phenylbutanoyl isothiocyanate Chemical compound S=C=NC(=O)C(C(C)C)C1=CC=CC=C1 JUVHGEBZWCDKPL-UHFFFAOYSA-N 0.000 description 1
• VYIBCOSBNVFEIW-UHFFFAOYSA-N 3-phenylpropanamide Chemical compound NC(=O)CCC1=CC=CC=C1 VYIBCOSBNVFEIW-UHFFFAOYSA-N 0.000 description 1
• YVIWODWWGFHTIU-UHFFFAOYSA-N 3-phenylpropanoyl isothiocyanate Chemical compound S=C=NC(=O)CCC1=CC=CC=C1 YVIWODWWGFHTIU-UHFFFAOYSA-N 0.000 description 1
• WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 1
• YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
• WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
• MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 1
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
• ZEFMBAFMCSYJOO-UHFFFAOYSA-N 4-nitro-3-(trifluoromethyl)phenol Chemical compound OC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 ZEFMBAFMCSYJOO-UHFFFAOYSA-N 0.000 description 1
• TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 1
• AXBVSRMHOPMXBA-UHFFFAOYSA-N 4-nitrothiophenol Chemical compound [O-][N+](=O)C1=CC=C(S)C=C1 AXBVSRMHOPMXBA-UHFFFAOYSA-N 0.000 description 1
• 125000005986 4-piperidonyl group Chemical group 0.000 description 1
• OKDZHAQIKCVKFE-UHFFFAOYSA-N 4-prop-2-ynylmorpholine Chemical compound C#CCN1CCOCC1 OKDZHAQIKCVKFE-UHFFFAOYSA-N 0.000 description 1
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
• VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
• XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
• SSHFCFRJYJIJDV-UHFFFAOYSA-N 5-nitropyrimidin-2-amine Chemical compound NC1=NC=C([N+]([O-])=O)C=N1 SSHFCFRJYJIJDV-UHFFFAOYSA-N 0.000 description 1
• GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
• VYQPOEUGLZHRSA-UHFFFAOYSA-N 6-fluoro-6-nitrocyclohexa-2,4-dien-1-ol Chemical compound OC1C=CC=CC1(F)[N+]([O-])=O VYQPOEUGLZHRSA-UHFFFAOYSA-N 0.000 description 1
• PXSGFTWBZNPNIC-UHFFFAOYSA-N 618-80-4 Chemical compound OC1=C(Cl)C=C([N+]([O-])=O)C=C1Cl PXSGFTWBZNPNIC-UHFFFAOYSA-N 0.000 description 1
• HCCNBKFJYUWLEX-UHFFFAOYSA-N 7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one Chemical compound O=C1N(CCOCCC)C2=CC(C=3C=NC(OC)=CC=3)=NC=C2N=C1NCC1=CN=CC=N1 HCCNBKFJYUWLEX-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 1
• XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
• IRBAWVGZNJIROV-SFHVURJKSA-N 9-(2-cyclopropylethynyl)-2-[[(2s)-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=C2C3=CC=C(C#CC4CC4)C=C3CCN2C(=O)N=C1OC[C@@H]1COCCO1 IRBAWVGZNJIROV-SFHVURJKSA-N 0.000 description 1
• JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
• UHNRLQRZRNKOKU-UHFFFAOYSA-N CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O Chemical compound CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O UHNRLQRZRNKOKU-UHFFFAOYSA-N 0.000 description 1
• PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 1
• 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
• 101100459912 Caenorhabditis elegans ncs-1 gene Proteins 0.000 description 1
• 101100293720 Caenorhabditis elegans ncs-2 gene Proteins 0.000 description 1
• 229940127007 Compound 39 Drugs 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• 239000004593 Epoxy Substances 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 101000637977 Homo sapiens Neuronal calcium sensor 1 Proteins 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 101001083117 Microbacterium liquefaciens Hydantoin permease Proteins 0.000 description 1
• 241001024304 Mino Species 0.000 description 1
• 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
• 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
• 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
• 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 1
• 238000006751 Mitsunobu reaction Methods 0.000 description 1
• 241000907681 Morpho Species 0.000 description 1
• 101500025412 Mus musculus Processed cyclic AMP-responsive element-binding protein 3-like protein 1 Proteins 0.000 description 1
• LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
• LIMFPAAAIVQRRD-BCGVJQADSA-N N-[2-[(3S,4R)-3-fluoro-4-methoxypiperidin-1-yl]pyrimidin-4-yl]-8-[(2R,3S)-2-methyl-3-(methylsulfonylmethyl)azetidin-1-yl]-5-propan-2-ylisoquinolin-3-amine Chemical compound F[C@H]1CN(CC[C@H]1OC)C1=NC=CC(=N1)NC=1N=CC2=C(C=CC(=C2C=1)C(C)C)N1[C@@H]([C@H](C1)CS(=O)(=O)C)C LIMFPAAAIVQRRD-BCGVJQADSA-N 0.000 description 1
• AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 1
• FVRDBYUAEAZBTN-UHFFFAOYSA-N N-benzylthieno[3,2-b]pyridine-2-carboxamide Chemical compound C(C1=CC=CC=C1)NC(=O)C1=CC2=NC=CC=C2S1 FVRDBYUAEAZBTN-UHFFFAOYSA-N 0.000 description 1
• 229910017974 NH40H Inorganic materials 0.000 description 1
• 229910004068 NO2Cl Inorganic materials 0.000 description 1
• QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
• 206010029113 Neovascularisation Diseases 0.000 description 1
• 102100032077 Neuronal calcium sensor 1 Human genes 0.000 description 1
• 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
• IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
• 206010064390 Tumour invasion Diseases 0.000 description 1
• LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
• SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 1
• PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
• BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 1
• PZRPBPMLSSNFOM-UHFFFAOYSA-N [4-(hydroxymethyl)phenyl]boronic acid Chemical compound OCC1=CC=C(B(O)O)C=C1 PZRPBPMLSSNFOM-UHFFFAOYSA-N 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
• 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 150000001414 amino alcohols Chemical class 0.000 description 1
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 230000002491 angiogenic effect Effects 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000001772 anti-angiogenic effect Effects 0.000 description 1
• 238000011122 anti-angiogenic therapy Methods 0.000 description 1
• 230000000692 anti-sense effect Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 239000012223 aqueous fraction Substances 0.000 description 1
• 125000004659 aryl alkyl thio group Chemical group 0.000 description 1
• 125000001769 aryl amino group Chemical group 0.000 description 1
• 150000001543 aryl boronic acids Chemical class 0.000 description 1
• 125000005116 aryl carbamoyl group Chemical group 0.000 description 1
• 125000005129 aryl carbonyl group Chemical group 0.000 description 1
• 125000005135 aryl sulfinyl group Chemical group 0.000 description 1
• 125000005110 aryl thio group Chemical group 0.000 description 1
• 238000010533 azeotropic distillation Methods 0.000 description 1
• 125000004069 aziridinyl group Chemical group 0.000 description 1
• 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
• 238000006664 bond formation reaction Methods 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 238000005893 bromination reaction Methods 0.000 description 1
• AOJDZKCUAATBGE-UHFFFAOYSA-N bromomethane Chemical compound Br[CH2] AOJDZKCUAATBGE-UHFFFAOYSA-N 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000005569 butenylene group Chemical group 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
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 125000005622 butynylene group Chemical group 0.000 description 1
• 230000005907 cancer growth Effects 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 125000004623 carbolinyl group Chemical group 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000012292 cell migration Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 229940126142 compound 16 Drugs 0.000 description 1
• 229940126208 compound 22 Drugs 0.000 description 1
• 229940125846 compound 25 Drugs 0.000 description 1
• 229940127204 compound 29 Drugs 0.000 description 1
• 229940125807 compound 37 Drugs 0.000 description 1
• 229940127271 compound 49 Drugs 0.000 description 1
• 229940126545 compound 53 Drugs 0.000 description 1
• 229940125900 compound 59 Drugs 0.000 description 1
• 229940126179 compound 72 Drugs 0.000 description 1
• 229920001577 copolymer Chemical group 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• VFSFCYAQBIPUSL-UHFFFAOYSA-N cyclopropylbenzene Chemical compound C1CC1C1=CC=CC=C1 VFSFCYAQBIPUSL-UHFFFAOYSA-N 0.000 description 1
• 108091007930 cytoplasmic receptors Proteins 0.000 description 1
• 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 230000013020 embryo development Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 210000003038 endothelium Anatomy 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
• 230000029578 entry into host Effects 0.000 description 1
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 210000003494 hepatocyte Anatomy 0.000 description 1
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
• 125000005549 heteroarylene group Chemical group 0.000 description 1
• 125000006038 hexenyl group Chemical group 0.000 description 1
• 125000005980 hexynyl group Chemical group 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 239000000710 homodimer Substances 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 230000001146 hypoxic effect Effects 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 125000004926 indolenyl group Chemical group 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 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
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
• 125000005438 isoindazolyl group Chemical group 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 125000005647 linker group Chemical group 0.000 description 1
• 238000006138 lithiation reaction Methods 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• AFCCDDWKHLHPDF-UHFFFAOYSA-M metam-sodium Chemical compound [Na+].CNC([S-])=S AFCCDDWKHLHPDF-UHFFFAOYSA-M 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
• UFEJKYYYVXYMMS-UHFFFAOYSA-N methylcarbamic acid Chemical compound CNC(O)=O UFEJKYYYVXYMMS-UHFFFAOYSA-N 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 230000008747 mitogenic response Effects 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 1
• 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
• 230000004899 motility Effects 0.000 description 1
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
• YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
• LPOIGVZLNWEGJG-UHFFFAOYSA-N n-benzyl-5-(4-methylpiperazin-1-yl)-2-nitroaniline Chemical compound C1CN(C)CCN1C1=CC=C([N+]([O-])=O)C(NCC=2C=CC=CC=2)=C1 LPOIGVZLNWEGJG-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 238000006386 neutralization reaction Methods 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• 230000020477 pH reduction Effects 0.000 description 1
• 230000003076 paracrine Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 125000005981 pentynyl group Chemical group 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
• 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
• 125000005954 phenoxathiinyl group Chemical group 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 1
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
• 125000004928 piperidonyl group Chemical group 0.000 description 1
• 229960005235 piperonyl butoxide Drugs 0.000 description 1
• 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 125000006410 propenylene group Chemical group 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 210000004994 reproductive system Anatomy 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 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
• 239000000377 silicon dioxide Substances 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 235000011150 stannous chloride Nutrition 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 210000002536 stromal cell Anatomy 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 125000000565 sulfonamide group Chemical group 0.000 description 1
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• XJJBXZIKXFOMLP-ZETCQYMHSA-N tert-butyl (2s)-pyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCN1 XJJBXZIKXFOMLP-ZETCQYMHSA-N 0.000 description 1
• CTEDVGRUGMPBHE-UHFFFAOYSA-N tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CO)CC1 CTEDVGRUGMPBHE-UHFFFAOYSA-N 0.000 description 1
• QQWYQAQQADNEIC-RVDMUPIBSA-N tert-butyl [(z)-[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)O\N=C(/C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-RVDMUPIBSA-N 0.000 description 1
• QYJVBVKFXDHFPQ-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)-n-methylcarbamate Chemical compound NCCN(C)C(=O)OC(C)(C)C QYJVBVKFXDHFPQ-UHFFFAOYSA-N 0.000 description 1
• LIYMTLVBAVHPBU-UHFFFAOYSA-N tert-butyl n-(4-hydroxybutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCO LIYMTLVBAVHPBU-UHFFFAOYSA-N 0.000 description 1
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 description 1
• RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical compound C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 description 1
• VFWVWPWWZVTJDG-UHFFFAOYSA-N thieno[3,2-d]pyrimidine-6-carboxamide Chemical compound C1=NC=C2SC(C(=O)N)=CC2=N1 VFWVWPWWZVTJDG-UHFFFAOYSA-N 0.000 description 1
• 229940125670 thienopyridine Drugs 0.000 description 1
• 239000002175 thienopyridine Substances 0.000 description 1
• YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• OQLOAKBBORZGFN-UHFFFAOYSA-N tributyl-(7-chlorothieno[3,2-b]pyridin-2-yl)stannane Chemical compound C1=CC(Cl)=C2SC([Sn](CCCC)(CCCC)CCCC)=CC2=N1 OQLOAKBBORZGFN-UHFFFAOYSA-N 0.000 description 1
• PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
• 125000001680 trimethoxyphenyl group Chemical group 0.000 description 1
• LYRCQNDYYRPFMF-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C LYRCQNDYYRPFMF-UHFFFAOYSA-N 0.000 description 1
• 230000005747 tumor angiogenesis Effects 0.000 description 1
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 150000003672 ureas Chemical group 0.000 description 1
• 239000002525 vasculotropin inhibitor Substances 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1