BG63162B1 - 6-АРИЛ ПИРИДО[2,3-d]ПИРИМИДИНИ И НАФТИРИДИНИ ЗА ИНХИБИРАНЕ НА КЛЕТЪЧНА ПРОЛИФЕРАЦИЯ, МЕДИИРАНА ОТ ПРОТЕИНОВА ТИРОЗИНКИНАЗА - Google Patents

Info

Publication number

BG63162B1

BG63162B1 BG101326A BG10132697A BG63162B1 BG 63162 B1 BG63162 B1 BG 63162B1 BG 101326 A BG101326 A BG 101326A BG 10132697 A BG10132697 A BG 10132697A BG 63162 B1 BG63162 B1 BG 63162B1

Authority

BG

Bulgaria

Prior art keywords

pyrido

pyrimidin

dichlorophenyl

urea

compound

Prior art date

1994-11-14

Links

• Espacenet
• Global Dossier
• Discuss

• 230000004663 cell proliferation Effects 0.000 title claims abstract description 7
• 102000004169 proteins and genes Human genes 0.000 title description 10
• 108090000623 proteins and genes Proteins 0.000 title description 9
• 230000005764 inhibitory process Effects 0.000 title description 8
• 150000001875 compounds Chemical class 0.000 claims abstract description 230
• 238000011282 treatment Methods 0.000 claims abstract description 20
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 18
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 18
• 208000037803 restenosis Diseases 0.000 claims abstract description 16
• 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 10
• 208000035143 Bacterial infection Diseases 0.000 claims abstract description 3
• 201000004681 Psoriasis Diseases 0.000 claims abstract description 3
• 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 3
• -1 Ar ' Chemical group 0.000 claims description 247
• 238000000034 method Methods 0.000 claims description 91
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 55
• 239000001257 hydrogen Substances 0.000 claims description 39
• 229910052739 hydrogen Inorganic materials 0.000 claims description 39
• 229910052757 nitrogen Inorganic materials 0.000 claims description 39
• 239000004202 carbamide Substances 0.000 claims description 38
• 235000013877 carbamide Nutrition 0.000 claims description 38
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 31
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 31
• 125000003118 aryl group Chemical group 0.000 claims description 25
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
• 125000000217 alkyl group Chemical group 0.000 claims description 24
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 23
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 23
• 239000002253 acid Substances 0.000 claims description 23
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 23
• 150000003839 salts Chemical class 0.000 claims description 23
• 150000002431 hydrogen Chemical class 0.000 claims description 22
• 230000002401 inhibitory effect Effects 0.000 claims description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
• 125000002971 oxazolyl group Chemical group 0.000 claims description 15
• 229910052760 oxygen Inorganic materials 0.000 claims description 15
• 239000001301 oxygen Chemical group 0.000 claims description 14
• 229910052717 sulfur Chemical group 0.000 claims description 14
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims description 14
• 101800003838 Epidermal growth factor Proteins 0.000 claims description 13
• 229940116977 epidermal growth factor Drugs 0.000 claims description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
• 125000000304 alkynyl group Chemical group 0.000 claims description 11
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
• 239000011593 sulfur Chemical group 0.000 claims description 11
• 125000003342 alkenyl group Chemical group 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 125000006308 propyl amino group Chemical group 0.000 claims description 10
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 9
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 7
• 238000002399 angioplasty Methods 0.000 claims description 7
• 239000002552 dosage form Substances 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 230000002062 proliferating effect Effects 0.000 claims description 7
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 claims description 6
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 claims description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
• 125000002252 acyl group Chemical group 0.000 claims description 5
• UMGDCJDMYOKAJW-UHFFFAOYSA-N aminothiocarboxamide Natural products NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 5
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
• 125000000623 heterocyclic group Chemical group 0.000 claims description 5
• 238000013508 migration Methods 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 5
• RKLBPUIJSDPKOA-UHFFFAOYSA-N 1-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]imidazolidin-2-one Chemical compound N=1C2=NC(N)=NC=C2C=C(C=2C(=CC=CC=2Cl)Cl)C=1N1CCNC1=O RKLBPUIJSDPKOA-UHFFFAOYSA-N 0.000 claims description 4
• WEMVXACYHSUWDL-UHFFFAOYSA-N 3-(2-chlorophenyl)-1,6-naphthyridine-2,7-diamine Chemical compound C1=C2C=NC(N)=CC2=NC(N)=C1C1=CC=CC=C1Cl WEMVXACYHSUWDL-UHFFFAOYSA-N 0.000 claims description 4
• 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 4
• 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 4
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
• 239000003795 chemical substances by application Substances 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 125000001072 heteroaryl group Chemical group 0.000 claims description 4
• 210000002464 muscle smooth vascular Anatomy 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 4
• 125000001424 substituent group Chemical group 0.000 claims description 4
• 125000000335 thiazolyl group Chemical group 0.000 claims description 4
• PSGCJFMDGKOFIG-UHFFFAOYSA-N 1-(1-adamantyl)-3-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NC23CC4CC(CC(C4)C2)C3)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 PSGCJFMDGKOFIG-UHFFFAOYSA-N 0.000 claims description 3
• QRWYSOZFHKXHIF-UHFFFAOYSA-N 1-[2-amino-6-(2,3,6-trichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=C(Cl)C=CC(Cl)=C1Cl QRWYSOZFHKXHIF-UHFFFAOYSA-N 0.000 claims description 3
• CMOQWRCLKYBEOS-UHFFFAOYSA-N 1-[2-amino-6-(2-methylphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC1=CC=CC=C1C1=CC2=CN=C(N)N=C2N=C1NC(=O)NC(C)(C)C CMOQWRCLKYBEOS-UHFFFAOYSA-N 0.000 claims description 3
• ZZEVABBPVKGWBW-UHFFFAOYSA-N 1-tert-butyl-3-[2-(tert-butylcarbamoylamino)-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(NC(=O)NC(C)(C)C)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl ZZEVABBPVKGWBW-UHFFFAOYSA-N 0.000 claims description 3
• QJIICVSRCKDXPF-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-(3-morpholin-4-ylpropylamino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C=C2C=C(C=3C(=CC=CC=3Cl)Cl)C(NC(=O)NC(C)(C)C)=NC2=NC=1NCCCN1CCOCC1 QJIICVSRCKDXPF-UHFFFAOYSA-N 0.000 claims description 3
• ULIJLYCJYRQKBG-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[3-(diethylamino)propylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(NCCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl ULIJLYCJYRQKBG-UHFFFAOYSA-N 0.000 claims description 3
• UGBGMQHBTSWQBW-UHFFFAOYSA-N 2-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-4,5-dihydro-1,3-oxazol-4-amine Chemical compound NC1COC(C=2C(=CC3=CN=C(N)N=C3N=2)C=2C(=CC=CC=2Cl)Cl)=N1 UGBGMQHBTSWQBW-UHFFFAOYSA-N 0.000 claims description 3
• YTZQWPMNWREPRP-UHFFFAOYSA-N 3-(2-methylphenyl)-1,6-naphthyridine-2,7-diamine Chemical compound CC1=CC=CC=C1C1=CC2=CN=C(N)C=C2N=C1N YTZQWPMNWREPRP-UHFFFAOYSA-N 0.000 claims description 3
• SFCDDCGMFLBTSE-UHFFFAOYSA-N 3-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-1,1-diethylurea Chemical compound N=1C=C2C=C(C=3C(=CC=CC=3Cl)Cl)C(NC(=O)N(CC)CC)=NC2=NC=1NCCCN1CCN(C)CC1 SFCDDCGMFLBTSE-UHFFFAOYSA-N 0.000 claims description 3
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
• 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 claims description 3
• 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 claims description 3
• 125000004423 acyloxy group Chemical group 0.000 claims description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000001041 indolyl group Chemical group 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
• PTLBTVSQIPIRSE-UHFFFAOYSA-N 1-(2-amino-6-pyridin-4-ylpyrido[2,3-d]pyrimidin-7-yl)-3-tert-butylurea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=CC=NC=C1 PTLBTVSQIPIRSE-UHFFFAOYSA-N 0.000 claims description 2
• JEPFUEYLCGNLKG-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NC=2C=CC(Cl)=CC=2)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 JEPFUEYLCGNLKG-UHFFFAOYSA-N 0.000 claims description 2
• ZAPMLUQRTGRJST-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea Chemical compound N=1C=C2C=C(C=3C(=CC=CC=3Cl)Cl)C(NC(=O)NCC)=NC2=NC=1NCCCN1CCN(C)CC1 ZAPMLUQRTGRJST-UHFFFAOYSA-N 0.000 claims description 2
• RYUBQHSXZNDWIH-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[4-(diethylamino)butylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea hydrochloride Chemical compound Cl.CCNC(=O)Nc1nc2nc(NCCCCN(CC)CC)ncc2cc1-c1c(Cl)cccc1Cl RYUBQHSXZNDWIH-UHFFFAOYSA-N 0.000 claims description 2
• LYJIVFCOOJRVBF-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[4-(diethylamino)butylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-phenylurea Chemical compound N=1C2=NC(NCCCCN(CC)CC)=NC=C2C=C(C=2C(=CC=CC=2Cl)Cl)C=1NC(=O)NC1=CC=CC=C1 LYJIVFCOOJRVBF-UHFFFAOYSA-N 0.000 claims description 2
• TWRMMAAINFMTFO-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[3-(2-methylpiperidin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC1CCCCN1CCCNC1=NC=C(C=C(C(NC(=O)NC(C)(C)C)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 TWRMMAAINFMTFO-UHFFFAOYSA-N 0.000 claims description 2
• PAZDFSJAERQBCY-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NC(C)(C)C)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 PAZDFSJAERQBCY-UHFFFAOYSA-N 0.000 claims description 2
• BUUXCZKMEAGSSK-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[4-(4-methylpiperazin-1-yl)butylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C1CN(C)CCN1CCCCNC1=NC=C(C=C(C(NC(=O)NC(C)(C)C)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 BUUXCZKMEAGSSK-UHFFFAOYSA-N 0.000 claims description 2
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
• IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical class CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 claims description 2
• 125000002541 furyl group Chemical group 0.000 claims description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
• DEKZYFFYBHIKGO-UHFFFAOYSA-N n-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl DEKZYFFYBHIKGO-UHFFFAOYSA-N 0.000 claims description 2
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 125000004434 sulfur atom Chemical group 0.000 claims description 2
• 241000124008 Mammalia Species 0.000 claims 9
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 3
• 208000031481 Pathologic Constriction Diseases 0.000 claims 3
• 208000037804 stenosis Diseases 0.000 claims 3
• 230000036262 stenosis Effects 0.000 claims 3
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
• 238000002054 transplantation Methods 0.000 claims 2
• UPXKTBHZBYXIDT-UHFFFAOYSA-N 1-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-propan-2-ylurea Chemical compound CC(C)NC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl UPXKTBHZBYXIDT-UHFFFAOYSA-N 0.000 claims 1
• GFSGJXPPDLRFGJ-UHFFFAOYSA-N 1-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-propylurea Chemical compound CCCNC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl GFSGJXPPDLRFGJ-UHFFFAOYSA-N 0.000 claims 1
• PFCYMLKAPXNHFU-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-[4-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NC=2C=CC(=CC=2)C(F)(F)F)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 PFCYMLKAPXNHFU-UHFFFAOYSA-N 0.000 claims 1
• ASYJZVHCOILIEE-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-prop-2-enylurea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NCC=C)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 ASYJZVHCOILIEE-UHFFFAOYSA-N 0.000 claims 1
• CRQMGAADPYRSGJ-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(diethylamino)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-propan-2-ylurea Chemical compound CC(C)NC(=O)NC1=NC2=NC(NCCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl CRQMGAADPYRSGJ-UHFFFAOYSA-N 0.000 claims 1
• YWOCRLCDMOSBLX-UHFFFAOYSA-N 1-butyl-3-[2-(butylcarbamoylamino)-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CCCCNC(=O)NC1=NC2=NC(NC(=O)NCCCC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl YWOCRLCDMOSBLX-UHFFFAOYSA-N 0.000 claims 1
• UKIASJDTPIGRRQ-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-(dimethylaminomethylideneamino)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(N=CN(C)C)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl UKIASJDTPIGRRQ-UHFFFAOYSA-N 0.000 claims 1
• BWRWVDQRWYBUIX-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[2-(diethylamino)ethylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(NCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl BWRWVDQRWYBUIX-UHFFFAOYSA-N 0.000 claims 1
• NEADWQYKOBKUBP-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[[3-(dimethylamino)-2,2-dimethylpropyl]amino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(NCC(C)(C)CN(C)C)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl NEADWQYKOBKUBP-UHFFFAOYSA-N 0.000 claims 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
• XFWVHYHJBWTAIV-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-7-n-(5,6-dihydro-4h-1,3-oxazin-2-yl)-2-n-[3-(4-methylpiperazin-1-yl)propyl]pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC=2OCCCN=2)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 XFWVHYHJBWTAIV-UHFFFAOYSA-N 0.000 claims 1
• NCFMPDJYEAYDBR-UHFFFAOYSA-N 6-(4-methoxyphenyl)-7-n-methylpyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound CNC1=NC2=NC(N)=NC=C2C=C1C1=CC=C(OC)C=C1 NCFMPDJYEAYDBR-UHFFFAOYSA-N 0.000 claims 1
• 102000029330 CSK Tyrosine-Protein Kinase Human genes 0.000 claims 1
• 108010069682 CSK Tyrosine-Protein Kinase Proteins 0.000 claims 1
• 102000009024 Epidermal Growth Factor Human genes 0.000 claims 1
• 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims 1
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims 1
• 208000029578 Muscle disease Diseases 0.000 claims 1
• 125000003282 alkyl amino group Chemical group 0.000 claims 1
• 230000012292 cell migration Effects 0.000 claims 1
• 210000004351 coronary vessel Anatomy 0.000 claims 1
• 238000001990 intravenous administration Methods 0.000 claims 1
• 125000000842 isoxazolyl group Chemical group 0.000 claims 1
• MJVMCMVSWBHPMD-UHFFFAOYSA-N n'-[6-(2,6-dichlorophenyl)-2-[3-(diethylamino)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-n,n-dimethylmethanimidamide Chemical compound CN(C)C=NC1=NC2=NC(NCCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl MJVMCMVSWBHPMD-UHFFFAOYSA-N 0.000 claims 1
• 210000000056 organ Anatomy 0.000 claims 1
• 230000002093 peripheral effect Effects 0.000 claims 1
• 102000027426 receptor tyrosine kinases Human genes 0.000 claims 1
• 108091008598 receptor tyrosine kinases Proteins 0.000 claims 1
• 125000001544 thienyl group Chemical group 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 abstract description 7
• 230000001404 mediated effect Effects 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 263
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 153
• 235000019439 ethyl acetate Nutrition 0.000 description 93
• 238000004458 analytical method Methods 0.000 description 88
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 86
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 84
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 75
• 239000000047 product Substances 0.000 description 73
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
• 239000000243 solution Substances 0.000 description 63
• 239000000203 mixture Substances 0.000 description 62
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 46
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
• 239000000460 chlorine Substances 0.000 description 45
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 44
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 40
• 239000011541 reaction mixture Substances 0.000 description 40
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 37
• 239000000725 suspension Substances 0.000 description 37
• 238000006243 chemical reaction Methods 0.000 description 36
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 35
• 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 34
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
• 239000002585 base Substances 0.000 description 30
• MGOLNIXAPIAKFM-UHFFFAOYSA-N 2-isocyanato-2-methylpropane Chemical compound CC(C)(C)N=C=O MGOLNIXAPIAKFM-UHFFFAOYSA-N 0.000 description 29
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
• 210000004027 cell Anatomy 0.000 description 27
• 229960001701 chloroform Drugs 0.000 description 26
• 229910000104 sodium hydride Inorganic materials 0.000 description 26
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 25
• 239000000741 silica gel Substances 0.000 description 25
• 229910002027 silica gel Inorganic materials 0.000 description 25
• 239000012312 sodium hydride Substances 0.000 description 25
• 238000004587 chromatography analysis Methods 0.000 description 24
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 239000007787 solid Substances 0.000 description 20
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 19
• 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 18
• 229910021529 ammonia Inorganic materials 0.000 description 18
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
• 239000002904 solvent Substances 0.000 description 18
• YBGDFSNTQAQYRD-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl YBGDFSNTQAQYRD-UHFFFAOYSA-N 0.000 description 17
• 239000004480 active ingredient Substances 0.000 description 17
• GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 16
• 108050007372 Fibroblast Growth Factor Proteins 0.000 description 16
• 102000018233 Fibroblast Growth Factor Human genes 0.000 description 16
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
• 229940126864 fibroblast growth factor Drugs 0.000 description 16
• 239000010410 layer Substances 0.000 description 16
• 238000002360 preparation method Methods 0.000 description 16
• 238000010828 elution Methods 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
• 235000019341 magnesium sulphate Nutrition 0.000 description 15
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
• 238000003756 stirring Methods 0.000 description 13
• 102400001368 Epidermal growth factor Human genes 0.000 description 12
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
• 239000002609 medium Substances 0.000 description 11
• 102000005962 receptors Human genes 0.000 description 11
• 108020003175 receptors Proteins 0.000 description 11
• GFIUKKVYDDTJLV-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-n-[3-(4-methylpiperazin-1-yl)propyl]pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(N)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 GFIUKKVYDDTJLV-UHFFFAOYSA-N 0.000 description 10
• 206010028980 Neoplasm Diseases 0.000 description 10
• 241000700159 Rattus Species 0.000 description 10
• 210000001715 carotid artery Anatomy 0.000 description 10
• 238000002425 crystallisation Methods 0.000 description 10
• 230000008025 crystallization Effects 0.000 description 10
• 238000000354 decomposition reaction Methods 0.000 description 10
• 201000010099 disease Diseases 0.000 description 10
• 238000001914 filtration Methods 0.000 description 10
• LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 9
• 229940093475 2-ethoxyethanol Drugs 0.000 description 9
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 238000011534 incubation Methods 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 229910052708 sodium Inorganic materials 0.000 description 9
• 210000004509 vascular smooth muscle cell Anatomy 0.000 description 9
• 239000000872 buffer Substances 0.000 description 8
• 201000011510 cancer Diseases 0.000 description 8
• 239000002775 capsule Substances 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 239000012071 phase Substances 0.000 description 8
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 8
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
• 229920002472 Starch Polymers 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 239000011324 bead Substances 0.000 description 7
• 230000006378 damage Effects 0.000 description 7
• WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 235000019198 oils Nutrition 0.000 description 7
• 239000008107 starch Substances 0.000 description 7
• 235000019698 starch Nutrition 0.000 description 7
• 239000000758 substrate Substances 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 6
• SMOWUDDAIFECTN-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-n-[3-(diethylamino)propyl]pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(NCCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl SMOWUDDAIFECTN-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
• 239000007864 aqueous solution Substances 0.000 description 6
• 230000035578 autophosphorylation Effects 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 239000003102 growth factor Substances 0.000 description 6
• 239000000543 intermediate Substances 0.000 description 6
• 230000003834 intracellular effect Effects 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
• 238000005406 washing Methods 0.000 description 6
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 5
• WXMGRWDSAQWVBJ-UHFFFAOYSA-N CN1CCN(CC1)CCCC1(N=CC2=C(N1)N=C(C=C2)N)N Chemical compound CN1CCN(CC1)CCCC1(N=CC2=C(N1)N=C(C=C2)N)N WXMGRWDSAQWVBJ-UHFFFAOYSA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
• 150000007513 acids Chemical class 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 239000012091 fetal bovine serum Substances 0.000 description 5
• 238000003818 flash chromatography Methods 0.000 description 5
• 239000012139 lysis buffer Substances 0.000 description 5
• 230000026731 phosphorylation Effects 0.000 description 5
• 238000006366 phosphorylation reaction Methods 0.000 description 5
• 239000006187 pill Substances 0.000 description 5
• 230000035755 proliferation Effects 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 5
• WMGVPDQNPUQRND-UHFFFAOYSA-N (2-methylphenyl)acetonitrile Chemical compound CC1=CC=CC=C1CC#N WMGVPDQNPUQRND-UHFFFAOYSA-N 0.000 description 4
• AOEJUUCUKRUCEF-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)acetonitrile Chemical compound ClC1=CC=CC(Cl)=C1CC#N AOEJUUCUKRUCEF-UHFFFAOYSA-N 0.000 description 4
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
• HGIPWJYTPOHUGK-UHFFFAOYSA-N 6-(2,6-dibromophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N)=NC=C2C=C1C1=C(Br)C=CC=C1Br HGIPWJYTPOHUGK-UHFFFAOYSA-N 0.000 description 4
• GSZFEVQHOLXFAM-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-n-[4-(diethylamino)butyl]pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(NCCCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl GSZFEVQHOLXFAM-UHFFFAOYSA-N 0.000 description 4
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
• 206010006187 Breast cancer Diseases 0.000 description 4
• 208000026310 Breast neoplasm Diseases 0.000 description 4
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
• 241000238631 Hexapoda Species 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
• 229910000564 Raney nickel Inorganic materials 0.000 description 4
• 229920004890 Triton X-100 Polymers 0.000 description 4
• 239000013504 Triton X-100 Substances 0.000 description 4
• 239000003814 drug Substances 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 239000012458 free base Substances 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 239000003446 ligand Substances 0.000 description 4
• 235000019359 magnesium stearate Nutrition 0.000 description 4
• 230000005012 migration Effects 0.000 description 4
• 150000005054 naphthyridines Chemical class 0.000 description 4
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 238000002953 preparative HPLC Methods 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 159000000018 pyrido[2,3-d]pyrimidines Chemical class 0.000 description 4
• FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 4
• PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 4
• 229940048086 sodium pyrophosphate Drugs 0.000 description 4
• 239000000829 suppository Substances 0.000 description 4
• 239000000454 talc Substances 0.000 description 4
• 229910052623 talc Inorganic materials 0.000 description 4
• 235000019818 tetrasodium diphosphate Nutrition 0.000 description 4
• 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 4
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 4
• 239000001993 wax Substances 0.000 description 4
• RRWSNCZYJCOEFX-UHFFFAOYSA-N 1-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl RRWSNCZYJCOEFX-UHFFFAOYSA-N 0.000 description 3
• QEXJMEVOCZLJQX-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-phenylurea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NC=2C=CC=CC=2)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 QEXJMEVOCZLJQX-UHFFFAOYSA-N 0.000 description 3
• CLVSAAPONJRSGJ-UHFFFAOYSA-N 1-cyclohexyl-3-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NC2CCCCC2)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 CLVSAAPONJRSGJ-UHFFFAOYSA-N 0.000 description 3
• MKVMEJKNLUWFSQ-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[4-(diethylamino)butylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(NCCCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl MKVMEJKNLUWFSQ-UHFFFAOYSA-N 0.000 description 3
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
• GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 3
• TWMYIGNIDPMOSD-UHFFFAOYSA-N 4,6-diaminopyridine-3-carbonitrile Chemical compound NC1=CC(N)=C(C#N)C=N1 TWMYIGNIDPMOSD-UHFFFAOYSA-N 0.000 description 3
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
• ISXZPSNKEFBZAN-UHFFFAOYSA-N 6-(2,6-difluorophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N)=NC=C2C=C1C1=C(F)C=CC=C1F ISXZPSNKEFBZAN-UHFFFAOYSA-N 0.000 description 3
• LSHICSIXTRDLPS-UHFFFAOYSA-N 6-(2,6-dimethylphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound CC1=CC=CC(C)=C1C1=CC2=CN=C(N)N=C2N=C1N LSHICSIXTRDLPS-UHFFFAOYSA-N 0.000 description 3
• PXXVXCWWSSHPCZ-UHFFFAOYSA-N 6-(2-methylphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound CC1=CC=CC=C1C1=CC2=CN=C(N)N=C2N=C1N PXXVXCWWSSHPCZ-UHFFFAOYSA-N 0.000 description 3
• FSLPGUGDRBZVCQ-UHFFFAOYSA-N 6-(3-methoxyphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound COC1=CC=CC(C=2C(=NC3=NC(N)=NC=C3C=2)N)=C1 FSLPGUGDRBZVCQ-UHFFFAOYSA-N 0.000 description 3
• ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 3
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 3
• 108020004414 DNA Proteins 0.000 description 3
• 241000196324 Embryophyta Species 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 3
• 108091008606 PDGF receptors Proteins 0.000 description 3
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 3
• 208000027418 Wounds and injury Diseases 0.000 description 3
• 125000003545 alkoxy group Chemical group 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• 210000001367 artery Anatomy 0.000 description 3
• 210000000269 carotid artery external Anatomy 0.000 description 3
• 239000003610 charcoal Substances 0.000 description 3
• 125000004093 cyano group Chemical group *C#N 0.000 description 3
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 3
• 235000011180 diphosphates Nutrition 0.000 description 3
• 239000012153 distilled water Substances 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 239000006167 equilibration buffer Substances 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• 235000019634 flavors Nutrition 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 239000003365 glass fiber Substances 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 238000010348 incorporation Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 208000014674 injury Diseases 0.000 description 3
• 239000006166 lysate Substances 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• 239000003960 organic solvent Substances 0.000 description 3
• DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 3
• UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 3
• 150000003230 pyrimidines Chemical class 0.000 description 3
• 229940048084 pyrophosphate Drugs 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 230000002441 reversible effect Effects 0.000 description 3
• 230000019491 signal transduction Effects 0.000 description 3
• 238000012289 standard assay Methods 0.000 description 3
• 238000004809 thin layer chromatography Methods 0.000 description 3
• XLVOWGDFXAVSFE-UHFFFAOYSA-N (4-amino-2-methylsulfanylpyrimidin-5-yl)methanol Chemical compound CSC1=NC=C(CO)C(N)=N1 XLVOWGDFXAVSFE-UHFFFAOYSA-N 0.000 description 2
• DPPREWYRSZWSKZ-UHFFFAOYSA-N 1-(2-amino-6-pyridin-3-ylpyrido[2,3-d]pyrimidin-7-yl)-3-tert-butylurea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=CC=CN=C1 DPPREWYRSZWSKZ-UHFFFAOYSA-N 0.000 description 2
• XAMVWASPGSOCIU-UHFFFAOYSA-N 1-[2-amino-6-(2,3-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=CC=CC(Cl)=C1Cl XAMVWASPGSOCIU-UHFFFAOYSA-N 0.000 description 2
• DHGWCHIUBOKFPY-UHFFFAOYSA-N 1-[2-amino-6-(2,3-dimethylphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC1=CC=CC(C=2C(=NC3=NC(N)=NC=C3C=2)NC(=O)NC(C)(C)C)=C1C DHGWCHIUBOKFPY-UHFFFAOYSA-N 0.000 description 2
• ZYLRLSRJFNDDOX-UHFFFAOYSA-N 1-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-(3-morpholin-4-ylpropyl)thiourea Chemical compound N=1C2=NC(N)=NC=C2C=C(C=2C(=CC=CC=2Cl)Cl)C=1NC(=S)NCCCN1CCOCC1 ZYLRLSRJFNDDOX-UHFFFAOYSA-N 0.000 description 2
• GQMZTFFTTCUZAW-UHFFFAOYSA-N 1-[2-amino-6-(2,6-dimethylphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC1=CC=CC(C)=C1C1=CC2=CN=C(N)N=C2N=C1NC(=O)NC(C)(C)C GQMZTFFTTCUZAW-UHFFFAOYSA-N 0.000 description 2
• CYJBQAMTIYIBGY-UHFFFAOYSA-N 1-[2-amino-6-(2-bromo-6-chlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=C(Cl)C=CC=C1Br CYJBQAMTIYIBGY-UHFFFAOYSA-N 0.000 description 2
• DVOMFFXZBJHQPZ-UHFFFAOYSA-N 1-[2-amino-6-(2-methoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound COC1=CC=CC=C1C1=CC2=CN=C(N)N=C2N=C1NC(=O)NC(C)(C)C DVOMFFXZBJHQPZ-UHFFFAOYSA-N 0.000 description 2
• MEGWJRRCEUYDCB-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-propan-2-ylurea Chemical compound N=1C=C2C=C(C=3C(=CC=CC=3Cl)Cl)C(NC(=O)NC(C)C)=NC2=NC=1NCCCN1CCN(C)CC1 MEGWJRRCEUYDCB-UHFFFAOYSA-N 0.000 description 2
• GCTRVFZGBTUDPW-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[4-(diethylamino)butylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea Chemical compound CCNC(=O)NC1=NC2=NC(NCCCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl GCTRVFZGBTUDPW-UHFFFAOYSA-N 0.000 description 2
• XTUXOBJKZJZVKD-UHFFFAOYSA-N 1-tert-butyl-3-[2-[3-(4-methylpiperazin-1-yl)propylamino]-6-(2,3,5,6-tetramethylphenyl)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NC(C)(C)C)=N2)C=3C(=C(C)C=C(C)C=3C)C)C2=N1 XTUXOBJKZJZVKD-UHFFFAOYSA-N 0.000 description 2
• VCNDNCLJYTUPOX-UHFFFAOYSA-N 1-tert-butyl-3-[2-[3-(diethylamino)propylamino]-6-(2,6-dimethylphenyl)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(NCCCN(CC)CC)=NC=C2C=C1C1=C(C)C=CC=C1C VCNDNCLJYTUPOX-UHFFFAOYSA-N 0.000 description 2
• CADIAVLAXLUJAC-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dibromophenyl)-2-[3-(diethylamino)propylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(NCCCN(CC)CC)=NC=C2C=C1C1=C(Br)C=CC=C1Br CADIAVLAXLUJAC-UHFFFAOYSA-N 0.000 description 2
• CTVVRRLXHQIPMG-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]thiourea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=S)NC(C)(C)C)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 CTVVRRLXHQIPMG-UHFFFAOYSA-N 0.000 description 2
• KTQXUWCOAYRSAJ-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[3-(dimethylamino)propyl-methylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(N(C)CCCN(C)C)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl KTQXUWCOAYRSAJ-UHFFFAOYSA-N 0.000 description 2
• MTLAYWHXNFJDJN-UHFFFAOYSA-N 2,4-diaminopyridine-3-carbaldehyde Chemical compound NC1=CC=NC(N)=C1C=O MTLAYWHXNFJDJN-UHFFFAOYSA-N 0.000 description 2
• OEJZMMCGURACCJ-UHFFFAOYSA-N 2-(2,6-dibromophenyl)acetonitrile Chemical compound BrC1=CC=CC(Br)=C1CC#N OEJZMMCGURACCJ-UHFFFAOYSA-N 0.000 description 2
• LXKNAUOWEJWGTE-UHFFFAOYSA-N 2-(3-methoxyphenyl)acetonitrile Chemical compound COC1=CC=CC(CC#N)=C1 LXKNAUOWEJWGTE-UHFFFAOYSA-N 0.000 description 2
• SYLPFMGSMMAKMB-UHFFFAOYSA-N 2-amino-6-(4-methoxyphenyl)-8h-pyrido[2,3-d]pyrimidin-7-one Chemical compound C1=CC(OC)=CC=C1C1=CC2=CN=C(N)N=C2N=C1O SYLPFMGSMMAKMB-UHFFFAOYSA-N 0.000 description 2
• KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
• OIPHWUPMXHQWLR-UHFFFAOYSA-N 2-pyridin-3-ylacetonitrile Chemical compound N#CCC1=CC=CN=C1 OIPHWUPMXHQWLR-UHFFFAOYSA-N 0.000 description 2
• BMVSAKPRNWZCPG-UHFFFAOYSA-N 2-pyridin-4-ylacetonitrile Chemical compound N#CCC1=CC=NC=C1 BMVSAKPRNWZCPG-UHFFFAOYSA-N 0.000 description 2
• RFCMDTOLDNJWEN-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)-1,6-naphthyridine-2,7-diamine Chemical compound C1=C2C=NC(N)=CC2=NC(N)=C1C1=C(Cl)C=CC=C1Cl RFCMDTOLDNJWEN-UHFFFAOYSA-N 0.000 description 2
• RGUABPVONIGVAT-UHFFFAOYSA-N 3-(4-methylpiperazin-1-yl)propan-1-amine Chemical compound CN1CCN(CCCN)CC1 RGUABPVONIGVAT-UHFFFAOYSA-N 0.000 description 2
• NKXPRYBNUGINBZ-UHFFFAOYSA-N 4,6-diamino-2-bromopyridine-3-carbonitrile Chemical compound NC1=CC(N)=C(C#N)C(Br)=N1 NKXPRYBNUGINBZ-UHFFFAOYSA-N 0.000 description 2
• BCEFDMYFAAAFPE-UHFFFAOYSA-N 4-(3-isothiocyanatopropyl)morpholine Chemical compound S=C=NCCCN1CCOCC1 BCEFDMYFAAAFPE-UHFFFAOYSA-N 0.000 description 2
• XYIJRLBJDUKMMQ-UHFFFAOYSA-N 4-amino-2-anilinopyrimidine-5-carbaldehyde Chemical compound C1=C(C=O)C(N)=NC(NC=2C=CC=CC=2)=N1 XYIJRLBJDUKMMQ-UHFFFAOYSA-N 0.000 description 2
• RKWMXFMTFOSKMW-UHFFFAOYSA-N 4-amino-2-anilinopyrimidine-5-carbonitrile Chemical compound C1=C(C#N)C(N)=NC(NC=2C=CC=CC=2)=N1 RKWMXFMTFOSKMW-UHFFFAOYSA-N 0.000 description 2
• WDHFCSOENXEMRC-UHFFFAOYSA-N 4-amino-2-chloropyrimidine-5-carbonitrile Chemical compound NC1=NC(Cl)=NC=C1C#N WDHFCSOENXEMRC-UHFFFAOYSA-N 0.000 description 2
• FGONQMFYFJRAIG-UHFFFAOYSA-N 4-amino-2-methylsulfanylpyrimidine-5-carbaldehyde Chemical compound CSC1=NC=C(C=O)C(N)=N1 FGONQMFYFJRAIG-UHFFFAOYSA-N 0.000 description 2
• CPNIVRSAZPYQHW-UHFFFAOYSA-N 6-(2,3,6-trichlorophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N)=NC=C2C=C1C1=C(Cl)C=CC(Cl)=C1Cl CPNIVRSAZPYQHW-UHFFFAOYSA-N 0.000 description 2
• PWRJGKAHSHSJEF-UHFFFAOYSA-N 6-(2,3-dichlorophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N)=NC=C2C=C1C1=CC=CC(Cl)=C1Cl PWRJGKAHSHSJEF-UHFFFAOYSA-N 0.000 description 2
• NIWMAVIWPDWZBX-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-n-[3-(dimethylamino)-2,2-dimethylpropyl]pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(NCC(C)(C)CN(C)C)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl NIWMAVIWPDWZBX-UHFFFAOYSA-N 0.000 description 2
• OYWFWQBUOPFTNQ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-n-[3-(dimethylamino)propyl]-2-n-methylpyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N(C)CCCN(C)C)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl OYWFWQBUOPFTNQ-UHFFFAOYSA-N 0.000 description 2
• ZGAIQKMSOMVUIS-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-n-[3-(dimethylamino)propyl]pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(NCCCN(C)C)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl ZGAIQKMSOMVUIS-UHFFFAOYSA-N 0.000 description 2
• LRPHIAJXODIASX-UHFFFAOYSA-N 6-(2,6-dimethoxyphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound COC1=CC=CC(OC)=C1C1=CC2=CN=C(N)N=C2N=C1N LRPHIAJXODIASX-UHFFFAOYSA-N 0.000 description 2
• PUEXEFHIGSVSAO-UHFFFAOYSA-N 6-(2-bromo-6-chlorophenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N)=NC=C2C=C1C1=C(Cl)C=CC=C1Br PUEXEFHIGSVSAO-UHFFFAOYSA-N 0.000 description 2
• GKEDIANRJLFUNR-UHFFFAOYSA-N 6-phenylpyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N)=NC=C2C=C1C1=CC=CC=C1 GKEDIANRJLFUNR-UHFFFAOYSA-N 0.000 description 2
• LWWGPNUXJGOHGP-UHFFFAOYSA-N 6-pyridin-4-ylpyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N)=NC=C2C=C1C1=CC=NC=C1 LWWGPNUXJGOHGP-UHFFFAOYSA-N 0.000 description 2
• HLDNDPHRIZUSCB-UHFFFAOYSA-N 7-chloro-6-(4-methoxyphenyl)pyrido[2,3-d]pyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1C1=CC2=CN=C(N)N=C2N=C1Cl HLDNDPHRIZUSCB-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 108010039627 Aprotinin Proteins 0.000 description 2
• 108010081589 Becaplermin Proteins 0.000 description 2
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
• VRXHPUGMMXSXDQ-UHFFFAOYSA-N CN1CCN(CC1)CCCC2(NC3=NC(=C(C=C3C=N2)C4=C(C=CC=C4Cl)Cl)N)N Chemical compound CN1CCN(CC1)CCCC2(NC3=NC(=C(C=C3C=N2)C4=C(C=CC=C4Cl)Cl)N)N VRXHPUGMMXSXDQ-UHFFFAOYSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• 230000006820 DNA synthesis Effects 0.000 description 2
• 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 2
• 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 2
• 102000009465 Growth Factor Receptors Human genes 0.000 description 2
• 108010009202 Growth Factor Receptors Proteins 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• BVSCURMUOFKZCE-UHFFFAOYSA-N N,N-dimethylpyrimidine-2-carboximidamide Chemical compound CN(C)C(=N)C1=NC=CC=N1 BVSCURMUOFKZCE-UHFFFAOYSA-N 0.000 description 2
• ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
• 239000007868 Raney catalyst Substances 0.000 description 2
• 102000001332 SRC Human genes 0.000 description 2
• 108060006706 SRC Proteins 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 2
• 101800004564 Transforming growth factor alpha Proteins 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• 102100031167 Tyrosine-protein kinase CSK Human genes 0.000 description 2
• 101710086605 Tyrosine-protein kinase CSK Proteins 0.000 description 2
• 241000700605 Viruses Species 0.000 description 2
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 150000008065 acid anhydrides Chemical class 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 150000003973 alkyl amines Chemical class 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 150000001409 amidines Chemical class 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 229940088710 antibiotic agent Drugs 0.000 description 2
• 210000002376 aorta thoracic Anatomy 0.000 description 2
• 229960004405 aprotinin Drugs 0.000 description 2
• 150000004982 aromatic amines Chemical class 0.000 description 2
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 210000004004 carotid artery internal Anatomy 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000024245 cell differentiation Effects 0.000 description 2
• 239000013592 cell lysate Substances 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• 208000029742 colonic neoplasm Diseases 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 238000005056 compaction Methods 0.000 description 2
• KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 2
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000002934 diuretic Substances 0.000 description 2
• 229940030606 diuretics Drugs 0.000 description 2
• 238000013156 embolectomy Methods 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• QINRQIZOBCQKAZ-UHFFFAOYSA-N ethyl 4-amino-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)N=C1N QINRQIZOBCQKAZ-UHFFFAOYSA-N 0.000 description 2
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
• 239000012634 fragment Substances 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 230000014509 gene expression Effects 0.000 description 2
• 239000001963 growth medium Substances 0.000 description 2
• 239000004009 herbicide Substances 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
• 239000012948 isocyanate Substances 0.000 description 2
• 239000004816 latex Substances 0.000 description 2
• 229920000126 latex Polymers 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• 108020004999 messenger RNA Proteins 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• 150000002739 metals Chemical class 0.000 description 2
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• JILXUIANNUALRZ-UHFFFAOYSA-N n',n'-diethylbutane-1,4-diamine Chemical compound CCN(CC)CCCCN JILXUIANNUALRZ-UHFFFAOYSA-N 0.000 description 2
• UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 2
• QOHMWDJIBGVPIF-UHFFFAOYSA-N n',n'-diethylpropane-1,3-diamine Chemical compound CCN(CC)CCCN QOHMWDJIBGVPIF-UHFFFAOYSA-N 0.000 description 2
• HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 2
• 239000012434 nucleophilic reagent Substances 0.000 description 2
• 230000002018 overexpression Effects 0.000 description 2
• 230000003950 pathogenic mechanism Effects 0.000 description 2
• SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 230000000704 physical effect Effects 0.000 description 2
• 239000002798 polar solvent Substances 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 230000002980 postoperative effect Effects 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• WZUYRUCXPBGUOM-UHFFFAOYSA-N pyrido[3,2-d]pyrimidin-2-amine Chemical compound N1=CC=CC2=NC(N)=NC=C21 WZUYRUCXPBGUOM-UHFFFAOYSA-N 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 239000004299 sodium benzoate Substances 0.000 description 2
• 235000010234 sodium benzoate Nutrition 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 239000011775 sodium fluoride Substances 0.000 description 2
• 235000013024 sodium fluoride Nutrition 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 239000011877 solvent mixture Substances 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 239000002562 thickening agent Substances 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• 229910000166 zirconium phosphate Inorganic materials 0.000 description 2
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 description 1
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• 150000005056 1,6-naphthyridines Chemical class 0.000 description 1
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
• YJOFXQWQYIOWNT-UHFFFAOYSA-N 1-(2-amino-6-phenylpyrido[2,3-d]pyrimidin-7-yl)-3-tert-butylurea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=CC=CC=C1 YJOFXQWQYIOWNT-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• NNYHIJGVHOAIGK-UHFFFAOYSA-N 1-[2-amino-6-(2,3,5,6-tetramethylphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC1=CC(C)=C(C)C(C=2C(=NC3=NC(N)=NC=C3C=2)NC(=O)NC(C)(C)C)=C1C NNYHIJGVHOAIGK-UHFFFAOYSA-N 0.000 description 1
• SMLFOSIGUQORAV-UHFFFAOYSA-N 1-[2-amino-6-(2,4,6-trimethylphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC1=CC(C)=CC(C)=C1C1=CC2=CN=C(N)N=C2N=C1NC(=O)NC(C)(C)C SMLFOSIGUQORAV-UHFFFAOYSA-N 0.000 description 1
• BXEDCNVFSZUBPI-UHFFFAOYSA-N 1-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea Chemical compound CCNC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl BXEDCNVFSZUBPI-UHFFFAOYSA-N 0.000 description 1
• TWRURKGAWDEAGJ-UHFFFAOYSA-N 1-[2-amino-6-(2,6-difluorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(N)=NC=C2C=C1C1=C(F)C=CC=C1F TWRURKGAWDEAGJ-UHFFFAOYSA-N 0.000 description 1
• OSGFIMXOHVZTAR-UHFFFAOYSA-N 1-[2-amino-6-(3,5-dimethylphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound CC1=CC(C)=CC(C=2C(=NC3=NC(N)=NC=C3C=2)NC(=O)NC(C)(C)C)=C1 OSGFIMXOHVZTAR-UHFFFAOYSA-N 0.000 description 1
• DXAXMTYXAGATCT-UHFFFAOYSA-N 1-[2-amino-6-(3-methoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea Chemical compound COC1=CC=CC(C=2C(=NC3=NC(N)=NC=C3C=2)NC(=O)NC(C)(C)C)=C1 DXAXMTYXAGATCT-UHFFFAOYSA-N 0.000 description 1
• OARIOETVQLMGFJ-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[2-(diethylamino)ethylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea Chemical compound CCNC(=O)NC1=NC2=NC(NCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl OARIOETVQLMGFJ-UHFFFAOYSA-N 0.000 description 1
• DFSRCPBSJAXTNU-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-(2-methoxyphenyl)urea Chemical compound COC1=CC=CC=C1NC(=O)NC1=NC2=NC(NCCCN3CCN(C)CC3)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl DFSRCPBSJAXTNU-UHFFFAOYSA-N 0.000 description 1
• MEYPNOVFXMUEAG-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-(3-methoxyphenyl)urea Chemical compound COC1=CC=CC(NC(=O)NC=2C(=CC3=CN=C(NCCCN4CCN(C)CC4)N=C3N=2)C=2C(=CC=CC=2Cl)Cl)=C1 MEYPNOVFXMUEAG-UHFFFAOYSA-N 0.000 description 1
• LVEXBQONPVYXPA-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-(4-methoxyphenyl)urea Chemical compound C1=CC(OC)=CC=C1NC(=O)NC1=NC2=NC(NCCCN3CCN(C)CC3)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl LVEXBQONPVYXPA-UHFFFAOYSA-N 0.000 description 1
• CGTDZZXDWFMLEF-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-(4-methylphenyl)urea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NC=2C=CC(C)=CC=2)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 CGTDZZXDWFMLEF-UHFFFAOYSA-N 0.000 description 1
• ODSISTOLPDZKMR-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-naphthalen-1-ylurea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NC=2C3=CC=CC=C3C=CC=2)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 ODSISTOLPDZKMR-UHFFFAOYSA-N 0.000 description 1
• BGVUHUGORDBBDW-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-octylurea Chemical compound N=1C=C2C=C(C=3C(=CC=CC=3Cl)Cl)C(NC(=O)NCCCCCCCC)=NC2=NC=1NCCCN1CCN(C)CC1 BGVUHUGORDBBDW-UHFFFAOYSA-N 0.000 description 1
• UHTBPLNTPWPALO-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[3-(diethylamino)propylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-ethylurea Chemical compound CCNC(=O)NC1=NC2=NC(NCCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl UHTBPLNTPWPALO-UHFFFAOYSA-N 0.000 description 1
• HDKFOWNECFEDEY-UHFFFAOYSA-N 1-[6-(2,6-dichlorophenyl)-2-[4-(diethylamino)butylamino]pyrido[2,3-d]pyrimidin-7-yl]-3-(3-morpholin-4-ylpropyl)thiourea Chemical compound N=1C2=NC(NCCCCN(CC)CC)=NC=C2C=C(C=2C(=CC=CC=2Cl)Cl)C=1NC(=S)NCCCN1CCOCC1 HDKFOWNECFEDEY-UHFFFAOYSA-N 0.000 description 1
• XARWOHKDCBRPBQ-UHFFFAOYSA-N 1-benzyl-3-[6-(2,6-dichlorophenyl)-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound C1CN(C)CCN1CCCNC1=NC=C(C=C(C(NC(=O)NCC=2C=CC=CC=2)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 XARWOHKDCBRPBQ-UHFFFAOYSA-N 0.000 description 1
• CZQIJQFTRGDODI-UHFFFAOYSA-N 1-bromo-4-isocyanatobenzene Chemical compound BrC1=CC=C(N=C=O)C=C1 CZQIJQFTRGDODI-UHFFFAOYSA-N 0.000 description 1
• BCMYXYHEMGPZJN-UHFFFAOYSA-N 1-chloro-2-isocyanatoethane Chemical compound ClCCN=C=O BCMYXYHEMGPZJN-UHFFFAOYSA-N 0.000 description 1
• RQAVSDINDRNIKL-UHFFFAOYSA-N 1-chloro-3-isocyanatopropane Chemical compound ClCCCN=C=O RQAVSDINDRNIKL-UHFFFAOYSA-N 0.000 description 1
• ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 1
• LSALXSOZDWYUQQ-UHFFFAOYSA-N 1-cyclohexyl-3-[6-(2,6-dichlorophenyl)-2-[4-(diethylamino)butylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound N=1C2=NC(NCCCCN(CC)CC)=NC=C2C=C(C=2C(=CC=CC=2Cl)Cl)C=1NC(=O)NC1CCCCC1 LSALXSOZDWYUQQ-UHFFFAOYSA-N 0.000 description 1
• BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
• SUVCZZADQDCIEQ-UHFFFAOYSA-N 1-isocyanato-2-methoxybenzene Chemical compound COC1=CC=CC=C1N=C=O SUVCZZADQDCIEQ-UHFFFAOYSA-N 0.000 description 1
• NPOVTGVGOBJZPY-UHFFFAOYSA-N 1-isocyanato-3-methoxybenzene Chemical compound COC1=CC=CC(N=C=O)=C1 NPOVTGVGOBJZPY-UHFFFAOYSA-N 0.000 description 1
• QZTWVDCKDWZCLV-UHFFFAOYSA-N 1-isocyanato-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(N=C=O)C=C1 QZTWVDCKDWZCLV-UHFFFAOYSA-N 0.000 description 1
• FMDGXCSMDZMDHZ-UHFFFAOYSA-N 1-isocyanato-4-methoxybenzene Chemical compound COC1=CC=C(N=C=O)C=C1 FMDGXCSMDZMDHZ-UHFFFAOYSA-N 0.000 description 1
• VBHCPGFCIQDXGZ-UHFFFAOYSA-N 1-isocyanatoadamantane Chemical compound C1C(C2)CC3CC2CC1(N=C=O)C3 VBHCPGFCIQDXGZ-UHFFFAOYSA-N 0.000 description 1
• BDQNKCYCTYYMAA-UHFFFAOYSA-N 1-isocyanatonaphthalene Chemical compound C1=CC=C2C(N=C=O)=CC=CC2=C1 BDQNKCYCTYYMAA-UHFFFAOYSA-N 0.000 description 1
• DYQFCTCUULUMTQ-UHFFFAOYSA-N 1-isocyanatooctane Chemical compound CCCCCCCCN=C=O DYQFCTCUULUMTQ-UHFFFAOYSA-N 0.000 description 1
• OQURWGJAWSLGQG-UHFFFAOYSA-N 1-isocyanatopropane Chemical compound CCCN=C=O OQURWGJAWSLGQG-UHFFFAOYSA-N 0.000 description 1
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
• GZAGGTZIWRFAFM-UHFFFAOYSA-N 1-tert-butyl-3-[2-(tert-butylcarbamoylamino)-6-(2-methylphenyl)pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC1=CC=CC=C1C1=CC2=CN=C(NC(=O)NC(C)(C)C)N=C2N=C1NC(=O)NC(C)(C)C GZAGGTZIWRFAFM-UHFFFAOYSA-N 0.000 description 1
• MFSBWOHCIGSWTP-UHFFFAOYSA-N 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-[3-(dimethylamino)propylamino]pyrido[2,3-d]pyrimidin-7-yl]urea Chemical compound CC(C)(C)NC(=O)NC1=NC2=NC(NCCCN(C)C)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl MFSBWOHCIGSWTP-UHFFFAOYSA-N 0.000 description 1
• HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
• KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 1
• 125000003456 2,6-dinitrophenyl group Chemical group [H]C1=C([H])C(=C(*)C(=C1[H])[N+]([O-])=O)[N+]([O-])=O 0.000 description 1
• RGNMZRMZCWNPPU-UHFFFAOYSA-N 2-(2,3,5,6-tetramethylphenyl)acetonitrile Chemical compound CC1=CC(C)=C(C)C(CC#N)=C1C RGNMZRMZCWNPPU-UHFFFAOYSA-N 0.000 description 1
• ZUZLGSONCFESPE-UHFFFAOYSA-N 2-(2,3,6-trichlorophenyl)acetonitrile Chemical compound ClC1=CC=C(Cl)C(CC#N)=C1Cl ZUZLGSONCFESPE-UHFFFAOYSA-N 0.000 description 1
• CZLINJDTCHACEH-UHFFFAOYSA-N 2-(2,3-dichlorophenyl)acetonitrile Chemical compound ClC1=CC=CC(CC#N)=C1Cl CZLINJDTCHACEH-UHFFFAOYSA-N 0.000 description 1
• UMBJWBJQJMILOQ-UHFFFAOYSA-N 2-(2,3-dimethylphenyl)acetonitrile Chemical compound CC1=CC=CC(CC#N)=C1C UMBJWBJQJMILOQ-UHFFFAOYSA-N 0.000 description 1
• SDKQOGSGNPGPRN-UHFFFAOYSA-N 2-(2,4,6-trimethylphenyl)acetonitrile Chemical compound CC1=CC(C)=C(CC#N)C(C)=C1 SDKQOGSGNPGPRN-UHFFFAOYSA-N 0.000 description 1
• GVAYBGQTAADLJS-UHFFFAOYSA-N 2-(2,6-difluorophenyl)acetonitrile Chemical compound FC1=CC=CC(F)=C1CC#N GVAYBGQTAADLJS-UHFFFAOYSA-N 0.000 description 1
• GXVUZYLYWKWJIM-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanamine Chemical compound NCCOCCN GXVUZYLYWKWJIM-UHFFFAOYSA-N 0.000 description 1
• KEEAMGRPGIYUKK-UHFFFAOYSA-N 2-(2-bromo-6-chlorophenyl)acetonitrile Chemical compound ClC1=CC=CC(Br)=C1CC#N KEEAMGRPGIYUKK-UHFFFAOYSA-N 0.000 description 1
• MRDUURPIPLIGQX-UHFFFAOYSA-N 2-(2-chlorophenyl)acetonitrile Chemical compound ClC1=CC=CC=C1CC#N MRDUURPIPLIGQX-UHFFFAOYSA-N 0.000 description 1
• DWJKILXTMUGXOU-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetonitrile Chemical compound COC1=CC=CC=C1CC#N DWJKILXTMUGXOU-UHFFFAOYSA-N 0.000 description 1
• LMUKNQSVBFEUKR-UHFFFAOYSA-N 2-(3,5-dimethylphenyl)acetonitrile Chemical compound CC1=CC(C)=CC(CC#N)=C1 LMUKNQSVBFEUKR-UHFFFAOYSA-N 0.000 description 1
• ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 description 1
• ONXAWVPHXIYZJX-UHFFFAOYSA-N 2-[3-[[7-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-2-yl]amino]propyl-ethylamino]ethanol Chemical compound NC1=NC2=NC(NCCCN(CCO)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl ONXAWVPHXIYZJX-UHFFFAOYSA-N 0.000 description 1
• JESHNOQYLPIOKX-UHFFFAOYSA-N 2-[4-(diethylamino)butyl]-1H-pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=CC=C2C=NC(CCCCN(CC)CC)(N)NC2=N1 JESHNOQYLPIOKX-UHFFFAOYSA-N 0.000 description 1
• CSUYTYVFSPFEME-UHFFFAOYSA-N 2-amino-6-phenyl-8h-pyrido[2,3-d]pyrimidin-7-one Chemical compound OC1=NC2=NC(N)=NC=C2C=C1C1=CC=CC=C1 CSUYTYVFSPFEME-UHFFFAOYSA-N 0.000 description 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• MAHHICHAEAGUTG-UHFFFAOYSA-N 2-n-[3-(diethylamino)propyl]-6-(2,6-dimethylphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(NCCCN(CC)CC)=NC=C2C=C1C1=C(C)C=CC=C1C MAHHICHAEAGUTG-UHFFFAOYSA-N 0.000 description 1
• BPSNETAIJADFTO-UHFFFAOYSA-M 2-pyridin-2-ylacetate Chemical compound [O-]C(=O)CC1=CC=CC=N1 BPSNETAIJADFTO-UHFFFAOYSA-M 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• JWOOZNRBZKVDSO-UHFFFAOYSA-N 3,4-diaminopentan-1-ol Chemical compound CC(N)C(N)CCO JWOOZNRBZKVDSO-UHFFFAOYSA-N 0.000 description 1
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• AAKQZUJXZCJZTC-UHFFFAOYSA-N 3-(2,6-dimethoxyphenyl)propanenitrile Chemical compound COC1=CC=CC(OC)=C1CCC#N AAKQZUJXZCJZTC-UHFFFAOYSA-N 0.000 description 1
• ANDLRLQIXLXLNZ-UHFFFAOYSA-N 3-(2-methyl-2h-pyridin-1-yl)propan-1-amine Chemical compound CC1C=CC=CN1CCCN ANDLRLQIXLXLNZ-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
• ZAANQRSELTXKBG-UHFFFAOYSA-N 3-morpholin-4-ylpropylthiourea Chemical compound NC(=S)NCCCN1CCOCC1 ZAANQRSELTXKBG-UHFFFAOYSA-N 0.000 description 1
• UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 1
• ZMHKFNOWZCVHGQ-UHFFFAOYSA-N 4,6-diaminopyridine-3-carbaldehyde Chemical compound NC1=CC(N)=C(C=O)C=N1 ZMHKFNOWZCVHGQ-UHFFFAOYSA-N 0.000 description 1
• NXKRSMDVDRFSBV-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)butan-1-amine Chemical compound CN1CCN(CCCCN)CC1 NXKRSMDVDRFSBV-UHFFFAOYSA-N 0.000 description 1
• XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
• ZSPMKPYMGMYZHE-UHFFFAOYSA-N 4-[3-(4-methylpiperazin-1-yl)propyl]pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound CN1CCN(CC1)CCCC=1C2=C(N=C(N=1)N)N=C(C=C2)N ZSPMKPYMGMYZHE-UHFFFAOYSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• VHUGDPBELIKZGX-UHFFFAOYSA-N 6-(2,4,6-trimethylphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound CC1=CC(C)=CC(C)=C1C1=CC2=CN=C(N)N=C2N=C1N VHUGDPBELIKZGX-UHFFFAOYSA-N 0.000 description 1
• YALPLUAZYZHUDY-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-methylsulfanylpyrido[2,3-d]pyrimidin-7-amine Chemical compound NC1=NC2=NC(SC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl YALPLUAZYZHUDY-UHFFFAOYSA-N 0.000 description 1
• WLWCBZRYDSFGTG-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-n-[2-(diethylamino)ethyl]pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(NCCN(CC)CC)=NC=C2C=C1C1=C(Cl)C=CC=C1Cl WLWCBZRYDSFGTG-UHFFFAOYSA-N 0.000 description 1
• UKNJCSLSBCLQMO-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-n-[4-(4-methylpiperazin-1-yl)butyl]pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound C1CN(C)CCN1CCCCNC1=NC=C(C=C(C(N)=N2)C=3C(=CC=CC=3Cl)Cl)C2=N1 UKNJCSLSBCLQMO-UHFFFAOYSA-N 0.000 description 1
• WRTZLVDGGLFETL-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidine Chemical compound ClC1=CC=CC(Cl)=C1C1=CN=C(N=CN=C2)C2=C1 WRTZLVDGGLFETL-UHFFFAOYSA-N 0.000 description 1
• LVKCFDQNNKLLDO-UHFFFAOYSA-N 6-(2-methoxyphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound COC1=CC=CC=C1C1=CC2=CN=C(N)N=C2N=C1N LVKCFDQNNKLLDO-UHFFFAOYSA-N 0.000 description 1
• KFZWIGGEHMZNRC-UHFFFAOYSA-N 6-(3,5-dimethylphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound CC1=CC(C)=CC(C=2C(=NC3=NC(N)=NC=C3C=2)N)=C1 KFZWIGGEHMZNRC-UHFFFAOYSA-N 0.000 description 1
• MHLVRJLNPQOYEI-UHFFFAOYSA-N 6-(4-methoxyphenyl)pyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound C1=CC(OC)=CC=C1C1=CC2=CN=C(N)N=C2N=C1N MHLVRJLNPQOYEI-UHFFFAOYSA-N 0.000 description 1
• OECOQMBVYUMTEF-UHFFFAOYSA-N 6-pyridin-2-ylpyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N)=NC=C2C=C1C1=CC=CC=N1 OECOQMBVYUMTEF-UHFFFAOYSA-N 0.000 description 1
• BPVPZCUSRIUYQS-UHFFFAOYSA-N 6-pyridin-3-ylpyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound NC1=NC2=NC(N)=NC=C2C=C1C1=CC=CN=C1 BPVPZCUSRIUYQS-UHFFFAOYSA-N 0.000 description 1
• NIGTYDYMOIOELW-UHFFFAOYSA-N 7-n-butyl-6-phenylpyrido[2,3-d]pyrimidine-2,7-diamine Chemical compound CCCCNC1=NC2=NC(N)=NC=C2C=C1C1=CC=CC=C1 NIGTYDYMOIOELW-UHFFFAOYSA-N 0.000 description 1
• BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• 206010067484 Adverse reaction Diseases 0.000 description 1
• 244000291564 Allium cepa Species 0.000 description 1
• 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 241000201370 Autographa californica nucleopolyhedrovirus Species 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 241000167854 Bourreria succulenta Species 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• ASEHNGBSQVLWNP-UHFFFAOYSA-N C(C(C)O)O.CNCCCC1(C(C=C2C(N=C(N=C2)N)=N1)C1=CC(=CC(=C1)OC)OC)N Chemical compound C(C(C)O)O.CNCCCC1(C(C=C2C(N=C(N=C2)N)=N1)C1=CC(=CC(=C1)OC)OC)N ASEHNGBSQVLWNP-UHFFFAOYSA-N 0.000 description 1
• QNGIBFUXVFJACU-UHFFFAOYSA-N C(C)N(CCC1(N=CC2=C(N1)N=C(C=C2)N)N)CC Chemical compound C(C)N(CCC1(N=CC2=C(N1)N=C(C=C2)N)N)CC QNGIBFUXVFJACU-UHFFFAOYSA-N 0.000 description 1
• MBQCFFPWKQYZNS-UHFFFAOYSA-N C(C)N(CCCC1(N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2C)C)N)N)CC Chemical compound C(C)N(CCCC1(N=CC2=C(N1)N=C(C(=C2)C2=C(C=CC=C2C)C)N)N)CC MBQCFFPWKQYZNS-UHFFFAOYSA-N 0.000 description 1
• VTGBKJXFRANFNM-UHFFFAOYSA-N C(CCC)C1(C(C=C2C(N=C(N=C2)N)=N1)C1=CC=CC=C1)N Chemical compound C(CCC)C1(C(C=C2C(N=C(N=C2)N)=N1)C1=CC=CC=C1)N VTGBKJXFRANFNM-UHFFFAOYSA-N 0.000 description 1
• SIGYUCATXAFEGK-UHFFFAOYSA-N CN1CCN(CC1)CCCC1(N=CC2=C(N1)N=C(C(=C2)C2=C(C(=CC(=C2C)C)C)C)N)N Chemical compound CN1CCN(CC1)CCCC1(N=CC2=C(N1)N=C(C(=C2)C2=C(C(=CC(=C2C)C)C)C)N)N SIGYUCATXAFEGK-UHFFFAOYSA-N 0.000 description 1
• 101100150905 Caenorhabditis elegans ham-3 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• OHWJUTIUJYXHFN-UHFFFAOYSA-N ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)N=CN(C)C)N=C1NCN(C)C Chemical compound ClC1=C(C(=CC=C1)Cl)C1=CC2=C(N=C(N=C2)N=CN(C)C)N=C1NCN(C)C OHWJUTIUJYXHFN-UHFFFAOYSA-N 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• 208000033999 Device damage Diseases 0.000 description 1
• 239000004375 Dextrin Substances 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• 102000001301 EGF receptor Human genes 0.000 description 1
• 108060006698 EGF receptor Proteins 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 108091008794 FGF receptors Proteins 0.000 description 1
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical group NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• YSWHPLCDIMUKFE-QWRGUYRKSA-N Glu-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 YSWHPLCDIMUKFE-QWRGUYRKSA-N 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 101000846416 Homo sapiens Fibroblast growth factor 1 Proteins 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
• IKQDZWFXVLLKLP-UHFFFAOYSA-N N-[7-(butylamino)-6-(3,5-dimethylphenyl)pyrido[2,3-d]pyrimidin-2-yl]formamide Chemical group CCCCNC1=NC2=NC(NC=O)=NC=C2C=C1C1=CC(C)=CC(C)=C1 IKQDZWFXVLLKLP-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
• OONZDIVMLDYNIW-UHFFFAOYSA-N N1(CCOCC1)CCCC1(N=CC2=C(N1)N=C(C=C2)N)N Chemical compound N1(CCOCC1)CCCC1(N=CC2=C(N1)N=C(C=C2)N)N OONZDIVMLDYNIW-UHFFFAOYSA-N 0.000 description 1
• FFNYEDIJMOFZKH-UHFFFAOYSA-N N1=CC=CC2=NC(C(=N)N)=NC=C21 Chemical class N1=CC=CC2=NC(C(=N)N)=NC=C21 FFNYEDIJMOFZKH-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 208000034827 Neointima Diseases 0.000 description 1
• 101100342977 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-1 gene Proteins 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 239000000020 Nitrocellulose Substances 0.000 description 1
• 108010058765 Oncogene Protein pp60(v-src) Proteins 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• 102100037596 Platelet-derived growth factor subunit A Human genes 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 229910019567 Re Re Inorganic materials 0.000 description 1
• 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
• WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• 241000193998 Streptococcus pneumoniae Species 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
• 208000002847 Surgical Wound Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 241000209140 Triticum Species 0.000 description 1
• 235000021307 Triticum Nutrition 0.000 description 1
• 206010057469 Vascular stenosis Diseases 0.000 description 1
• CGCOVQSKNBEYNN-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]urea Chemical compound NC(=O)NC1=CC=C(C(F)(F)F)C=C1 CGCOVQSKNBEYNN-UHFFFAOYSA-N 0.000 description 1
• FYJKEHKQUPSJDH-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;potassium Chemical compound [K].C[Si](C)(C)N[Si](C)(C)C FYJKEHKQUPSJDH-UHFFFAOYSA-N 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• TTWYZDPBDWHJOR-IDIVVRGQSA-L adenosine triphosphate disodium Chemical compound [Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O TTWYZDPBDWHJOR-IDIVVRGQSA-L 0.000 description 1
• 230000006838 adverse reaction Effects 0.000 description 1
• 230000004520 agglutination Effects 0.000 description 1
• 238000006136 alcoholysis reaction Methods 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000004703 alkoxides Chemical class 0.000 description 1
• 125000005360 alkyl sulfoxide group Chemical group 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• HXBPYFMVGFDZFT-UHFFFAOYSA-N allyl isocyanate Chemical compound C=CCN=C=O HXBPYFMVGFDZFT-UHFFFAOYSA-N 0.000 description 1
• AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
• 125000004103 aminoalkyl group Chemical group 0.000 description 1
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 230000002788 anti-peptide Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 229940030600 antihypertensive agent Drugs 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
• 210000003433 aortic smooth muscle cell Anatomy 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 159000000032 aromatic acids Chemical class 0.000 description 1
• 239000008122 artificial sweetener Substances 0.000 description 1
• 235000021311 artificial sweeteners Nutrition 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 239000003181 biological factor Substances 0.000 description 1
• 201000001531 bladder carcinoma Diseases 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 239000012888 bovine serum Substances 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• CMDZOENGSXWINU-UHFFFAOYSA-N c1cncnc1.OS(=O)(=O)OS(O)(=O)=O Chemical compound c1cncnc1.OS(=O)(=O)OS(O)(=O)=O CMDZOENGSXWINU-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• RYTLGWCJESCDMY-UHFFFAOYSA-N carbamimidoyl chloride Chemical compound NC(Cl)=N RYTLGWCJESCDMY-UHFFFAOYSA-N 0.000 description 1
• RTTSQSBCRXBLAU-UHFFFAOYSA-N carbamoyl bromide Chemical compound NC(Br)=O RTTSQSBCRXBLAU-UHFFFAOYSA-N 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000032823 cell division Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 229940081733 cetearyl alcohol Drugs 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000007810 chemical reaction solvent Substances 0.000 description 1
• 239000002975 chemoattractant Substances 0.000 description 1
• 235000019693 cherries Nutrition 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• 229960002023 chloroprocaine Drugs 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 150000003950 cyclic amides Chemical class 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 238000000326 densiometry Methods 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 150000001991 dicarboxylic acids Chemical group 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 229940043237 diethanolamine Drugs 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• 238000001962 electrophoresis Methods 0.000 description 1
• 239000008393 encapsulating agent Substances 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• SIHZWGODIRRSRA-ONEGZZNKSA-N erbstatin Chemical compound OC1=CC=C(O)C(\C=C\NC=O)=C1 SIHZWGODIRRSRA-ONEGZZNKSA-N 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
• SNNHLSHDDGJVDM-UHFFFAOYSA-N ethyl 4-chloro-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)N=C1Cl SNNHLSHDDGJVDM-UHFFFAOYSA-N 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 238000012757 fluorescence staining Methods 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• HQVFCQRVQFYGRJ-UHFFFAOYSA-N formic acid;hydrate Chemical compound O.OC=O HQVFCQRVQFYGRJ-UHFFFAOYSA-N 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 229940075529 glyceryl stearate Drugs 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 238000010562 histological examination Methods 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
• 125000001183 hydrocarbyl group Chemical group 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
• 125000001841 imino group Chemical group [H]N=* 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 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
• 150000002513 isocyanates Chemical class 0.000 description 1
• YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 150000002540 isothiocyanates Chemical class 0.000 description 1
• 238000005304 joining Methods 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
• 108010052968 leupeptin Proteins 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 235000004213 low-fat Nutrition 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 125000005341 metaphosphate group Chemical group 0.000 description 1
• 229940087646 methanolamine Drugs 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000003226 mitogen Substances 0.000 description 1
• 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
• 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
• 235000019799 monosodium phosphate Nutrition 0.000 description 1
• 230000000877 morphologic effect Effects 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• CFXBHDGJSYIDEA-UHFFFAOYSA-N n'-[7-chloro-6-(4-methoxyphenyl)pyrido[2,3-d]pyrimidin-2-yl]-n,n-dimethylmethanimidamide Chemical compound C1=CC(OC)=CC=C1C1=CC2=CN=C(N=CN(C)C)N=C2N=C1Cl CFXBHDGJSYIDEA-UHFFFAOYSA-N 0.000 description 1
• OFCCYDUUBNUJIB-UHFFFAOYSA-N n,n-diethylcarbamoyl chloride Chemical compound CCN(CC)C(Cl)=O OFCCYDUUBNUJIB-UHFFFAOYSA-N 0.000 description 1
• DSWNRHCOGVRDOE-UHFFFAOYSA-N n,n-dimethylmethanimidamide Chemical compound CN(C)C=N DSWNRHCOGVRDOE-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• FVSUYFWWFUVGRG-UHFFFAOYSA-N naphthalen-1-ylurea Chemical compound C1=CC=C2C(NC(=O)N)=CC=CC2=C1 FVSUYFWWFUVGRG-UHFFFAOYSA-N 0.000 description 1
• 239000000025 natural resin Substances 0.000 description 1
• 235000021096 natural sweeteners Nutrition 0.000 description 1
• 230000008692 neointimal formation Effects 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 229920001220 nitrocellulos Polymers 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 150000002926 oxygen Chemical class 0.000 description 1
• 230000003076 paracrine Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 229940100460 peg-100 stearate Drugs 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 108010091212 pepstatin Proteins 0.000 description 1
• 229950000964 pepstatin Drugs 0.000 description 1
• FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229940049953 phenylacetate Drugs 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 229940080469 phosphocellulose Drugs 0.000 description 1
• XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 108010017843 platelet-derived growth factor A Proteins 0.000 description 1
• 229920002401 polyacrylamide Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229920000131 polyvinylidene Polymers 0.000 description 1
• 230000017363 positive regulation of growth Effects 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 230000009696 proliferative response Effects 0.000 description 1
• LZMATGARSSLFMQ-UHFFFAOYSA-N propan-2-ylurea Chemical compound CC(C)NC(N)=O LZMATGARSSLFMQ-UHFFFAOYSA-N 0.000 description 1
• KPBSJEBFALFJTO-UHFFFAOYSA-N propane-1-sulfonyl chloride Chemical compound CCCS(Cl)(=O)=O KPBSJEBFALFJTO-UHFFFAOYSA-N 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 239000003909 protein kinase inhibitor Substances 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical group C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 1
• CMMSUVYMWKBPQK-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine-2,4-diamine Chemical compound N1=CC=CC2=NC(N)=NC(N)=C21 CMMSUVYMWKBPQK-UHFFFAOYSA-N 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 238000011552 rat model Methods 0.000 description 1
• 239000012048 reactive intermediate Substances 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000003362 replicative effect Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000012679 serum free medium Substances 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 210000002460 smooth muscle Anatomy 0.000 description 1
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• PDEFQWNXOUGDJR-UHFFFAOYSA-M sodium;2,2-dichloropropanoate Chemical compound [Na+].CC(Cl)(Cl)C([O-])=O PDEFQWNXOUGDJR-UHFFFAOYSA-M 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 150000003457 sulfones Chemical group 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 229910021653 sulphate ion Inorganic materials 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000000057 synthetic resin Substances 0.000 description 1
• 229920003002 synthetic resin Polymers 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 229940052907 telazol Drugs 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 125000004001 thioalkyl group Chemical group 0.000 description 1
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 125000004665 trialkylsilyl group Chemical group 0.000 description 1
• FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 108010002164 tyrosine receptor Proteins 0.000 description 1
• 108091005990 tyrosine-phosphorylated proteins Proteins 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
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 150000003672 ureas Chemical class 0.000 description 1
• 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
• 238000005292 vacuum distillation Methods 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 230000004869 vascular alteration Effects 0.000 description 1
• 208000011733 vascular alteration Diseases 0.000 description 1
• 210000003556 vascular endothelial cell Anatomy 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 239000011345 viscous material Substances 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1