PL205957B1 - Podstawione pirydyny i pirydazyny z aktywnością hamowania angiogenezy, kompozycje farmaceutyczne je zawierające i ich zastosowanie do wytwarzania leków - Google Patents

Info

Publication number

PL205957B1

PL205957B1 PL366342A PL36634200A PL205957B1 PL 205957 B1 PL205957 B1 PL 205957B1 PL 366342 A PL366342 A PL 366342A PL 36634200 A PL36634200 A PL 36634200A PL 205957 B1 PL205957 B1 PL 205957B1

Authority

PL

Poland

Prior art keywords

methyl

pyridazin

oxy

amino

furo

Prior art date

1999-09-28

Links

• Espacenet
• Global Dossier
• Discuss

• 230000033115 angiogenesis Effects 0.000 title claims abstract description 22
• 150000003222 pyridines Chemical class 0.000 title abstract description 6
• 230000002401 inhibitory effect Effects 0.000 title abstract description 4
• 150000004892 pyridazines Chemical class 0.000 title abstract description 4
• 238000000034 method Methods 0.000 claims abstract description 105
• 125000001424 substituent group Chemical group 0.000 claims abstract description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
• 241000124008 Mammalia Species 0.000 claims abstract description 9
• 230000002159 abnormal effect Effects 0.000 claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 7
• 150000001875 compounds Chemical class 0.000 claims description 168
• -1 1,3-benzothiazol-6-yl Chemical group 0.000 claims description 113
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
• 125000000217 alkyl group Chemical group 0.000 claims description 28
• 150000003839 salts Chemical class 0.000 claims description 21
• 206010028980 Neoplasm Diseases 0.000 claims description 19
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims description 18
• 229910052717 sulfur Inorganic materials 0.000 claims description 18
• 125000002619 bicyclic group Chemical group 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 17
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
• 125000004432 carbon atom Chemical group C* 0.000 claims description 16
• 229910052736 halogen Inorganic materials 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• 150000001412 amines Chemical class 0.000 claims description 14
• 229910052739 hydrogen Inorganic materials 0.000 claims description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 11
• 125000005843 halogen group Chemical group 0.000 claims description 11
• 150000002367 halogens Chemical class 0.000 claims description 11
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
• 230000015572 biosynthetic process Effects 0.000 claims description 10
• 125000006833 (C1-C5) alkylene group Chemical group 0.000 claims description 8
• 125000000623 heterocyclic group Chemical group 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 239000001257 hydrogen Substances 0.000 claims description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
• QFCXANHHBCGMAS-UHFFFAOYSA-N 4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(Cl)=CC=3)=NN=2)=C1 QFCXANHHBCGMAS-UHFFFAOYSA-N 0.000 claims description 5
• 206010012468 Dermatitis herpetiformis Diseases 0.000 claims description 5
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 5
• 206010015218 Erythema multiforme Diseases 0.000 claims description 5
• 201000004681 Psoriasis Diseases 0.000 claims description 5
• 206010038923 Retinopathy Diseases 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 230000000302 ischemic effect Effects 0.000 claims description 5
• 208000002780 macular degeneration Diseases 0.000 claims description 5
• 208000004644 retinal vein occlusion Diseases 0.000 claims description 5
• UFJYSFZNZCNDQQ-UHFFFAOYSA-N 4-[[4-(4-methoxyanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(OC)=CC=3)=NN=2)=C1 UFJYSFZNZCNDQQ-UHFFFAOYSA-N 0.000 claims description 4
• 208000017442 Retinal disease Diseases 0.000 claims description 4
• 208000029162 bladder disease Diseases 0.000 claims description 4
• 230000035755 proliferation Effects 0.000 claims description 4
• 230000007332 vesicle formation Effects 0.000 claims description 4
• ALMCKMCDCIQVFL-UHFFFAOYSA-N 4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(Cl)=CC=3)=NN=2)=C1 ALMCKMCDCIQVFL-UHFFFAOYSA-N 0.000 claims description 3
• ZZODKYPVJTYAQA-UHFFFAOYSA-N 4-[[4-(4-chloroanilino)thieno[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3SC=CC=3C(NC=3C=CC(Cl)=CC=3)=NN=2)=C1 ZZODKYPVJTYAQA-UHFFFAOYSA-N 0.000 claims description 3
• LDXWYEZKAMSFKC-UHFFFAOYSA-N 4-[[4-(4-methoxyanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]pyridine-2-carboxamide Chemical compound C1=CC(OC)=CC=C1NC(C=1C=COC=11)=NN=C1OCC1=CC=NC(C(N)=O)=C1 LDXWYEZKAMSFKC-UHFFFAOYSA-N 0.000 claims description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 3
• 125000004429 atom Chemical group 0.000 claims description 3
• 230000001747 exhibiting effect Effects 0.000 claims description 3
• DKUSPJDQVGZXQE-UHFFFAOYSA-N 4-[(4-anilinofuro[2,3-d]pyridazin-7-yl)oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC=CC=3)=NN=2)=C1 DKUSPJDQVGZXQE-UHFFFAOYSA-N 0.000 claims description 2
• FAYKYGVTAZJBFA-UHFFFAOYSA-N 4-[[4-(1,3-benzodioxol-5-ylamino)thieno[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3SC=CC=3C(NC=3C=C4OCOC4=CC=3)=NN=2)=C1 FAYKYGVTAZJBFA-UHFFFAOYSA-N 0.000 claims description 2
• IDLLLASUQRBCHK-UHFFFAOYSA-N 4-[[4-(1h-indazol-5-ylamino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=C4C=NNC4=CC=3)=NN=2)=C1 IDLLLASUQRBCHK-UHFFFAOYSA-N 0.000 claims description 2
• PFUMBUZTNYEVKX-UHFFFAOYSA-N 4-[[4-(3,4-dichloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=C(Cl)C(Cl)=CC=3)=NN=2)=C1 PFUMBUZTNYEVKX-UHFFFAOYSA-N 0.000 claims description 2
• JLTRXMUHOLIDDV-UHFFFAOYSA-N 4-[[4-(4-bromoanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(Br)=CC=3)=NN=2)=C1 JLTRXMUHOLIDDV-UHFFFAOYSA-N 0.000 claims description 2
• YXKLNJHBYAACTK-UHFFFAOYSA-N 4-[[4-(4-bromoanilino)thieno[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3SC=CC=3C(NC=3C=CC(Br)=CC=3)=NN=2)=C1 YXKLNJHBYAACTK-UHFFFAOYSA-N 0.000 claims description 2
• XHSHOWRXRUPCIZ-UHFFFAOYSA-N 4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-(2-hydroxyethyl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NCCO)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(Cl)=CC=3)=NN=2)=C1 XHSHOWRXRUPCIZ-UHFFFAOYSA-N 0.000 claims description 2
• BRBRAVUMEGGHJZ-UHFFFAOYSA-N 4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-[2-(dimethylamino)ethyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NCCN(C)C)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(Cl)=CC=3)=NN=2)=C1 BRBRAVUMEGGHJZ-UHFFFAOYSA-N 0.000 claims description 2
• FPABXUQFXXLLJT-UHFFFAOYSA-N 4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-ethylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NCC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(Cl)=CC=3)=NN=2)=C1 FPABXUQFXXLLJT-UHFFFAOYSA-N 0.000 claims description 2
• TXQXILXAUFGWDV-UHFFFAOYSA-N 4-[[4-(4-chloroanilino)thieno[2,3-d]pyridazin-7-yl]oxymethyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC(COC=2C=3SC=CC=3C(NC=3C=CC(Cl)=CC=3)=NN=2)=C1 TXQXILXAUFGWDV-UHFFFAOYSA-N 0.000 claims description 2
• JSAXYHAKCHLJFE-UHFFFAOYSA-N 4-[[4-(4-fluoroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(F)=CC=3)=NN=2)=C1 JSAXYHAKCHLJFE-UHFFFAOYSA-N 0.000 claims description 2
• XYMBNBOCISDYKU-UHFFFAOYSA-N 4-[[4-(4-fluoroanilino)thieno[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3SC=CC=3C(NC=3C=CC(F)=CC=3)=NN=2)=C1 XYMBNBOCISDYKU-UHFFFAOYSA-N 0.000 claims description 2
• ZANUYXSDZRSTRI-UHFFFAOYSA-N 4-[[4-(4-hydroxyanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-N-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(O)=CC=3)=NN=2)=C1 ZANUYXSDZRSTRI-UHFFFAOYSA-N 0.000 claims description 2
• AMABXWIFLUQJRQ-UHFFFAOYSA-N 4-[[4-(4-methoxyanilino)thieno[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3SC=CC=3C(NC=3C=CC(OC)=CC=3)=NN=2)=C1 AMABXWIFLUQJRQ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
• RJWBTWIBUIGANW-UHFFFAOYSA-M 4-chlorobenzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-M 0.000 claims description 2
• 229910002651 NO3 Inorganic materials 0.000 claims description 2
• DWQZXWRCUYGESU-UHFFFAOYSA-N [4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]pyridin-2-yl]-morpholin-4-ylmethanone Chemical compound C1=CC(Cl)=CC=C1NC(C=1C=COC=11)=NN=C1OCC1=CC=NC(C(=O)N2CCOCC2)=C1 DWQZXWRCUYGESU-UHFFFAOYSA-N 0.000 claims description 2
• SQQQXSSFWNOBBG-UHFFFAOYSA-N [4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]pyridin-2-yl]methanol Chemical compound C1=NC(CO)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(Cl)=CC=3)=NN=2)=C1 SQQQXSSFWNOBBG-UHFFFAOYSA-N 0.000 claims description 2
• 150000003857 carboxamides Chemical class 0.000 claims description 2
• AVWHXRPSVGAKQT-UHFFFAOYSA-N n-methyl-4-[[4-(3-methylanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=C(C)C=CC=3)=NN=2)=C1 AVWHXRPSVGAKQT-UHFFFAOYSA-N 0.000 claims description 2
• FQETZIFFBVRCOQ-UHFFFAOYSA-N n-methyl-4-[[4-(4-methylanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(C)=CC=3)=NN=2)=C1 FQETZIFFBVRCOQ-UHFFFAOYSA-N 0.000 claims description 2
• WIXQBTDDGXLNBV-UHFFFAOYSA-N n-methyl-4-[[4-(4-morpholin-4-ylanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(=CC=3)N3CCOCC3)=NN=2)=C1 WIXQBTDDGXLNBV-UHFFFAOYSA-N 0.000 claims description 2
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
• RCPHXEZEKHMLCD-UHFFFAOYSA-N 4-[[4-(2,3-dihydro-1h-inden-5-ylamino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=C4CCCC4=CC=3)=NN=2)=C1 RCPHXEZEKHMLCD-UHFFFAOYSA-N 0.000 claims 1
• HMNSECOWULWJJW-UHFFFAOYSA-N 4-[[4-(2-methoxyanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C(=CC=CC=3)OC)=NN=2)=C1 HMNSECOWULWJJW-UHFFFAOYSA-N 0.000 claims 1
• BMHNJUQGRNQQHT-UHFFFAOYSA-N 4-[[4-(3,4-difluoroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=C(F)C(F)=CC=3)=NN=2)=C1 BMHNJUQGRNQQHT-UHFFFAOYSA-N 0.000 claims 1
• KSUBTPJTXVUWOE-UHFFFAOYSA-N 4-[[4-(3-chloro-4-fluoroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=C(Cl)C(F)=CC=3)=NN=2)=C1 KSUBTPJTXVUWOE-UHFFFAOYSA-N 0.000 claims 1
• QTBCALYQDPEUOG-UHFFFAOYSA-N 4-[[4-(3-chloro-4-methoxyanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=C(Cl)C(OC)=CC=3)=NN=2)=C1 QTBCALYQDPEUOG-UHFFFAOYSA-N 0.000 claims 1
• YYWPNTUZTLEPKX-UHFFFAOYSA-N 4-[[4-(3-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=C(Cl)C=CC=3)=NN=2)=C1 YYWPNTUZTLEPKX-UHFFFAOYSA-N 0.000 claims 1
• IPXJMLCTWUHZAN-UHFFFAOYSA-N 4-[[4-(3-methoxyanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=C(OC)C=CC=3)=NN=2)=C1 IPXJMLCTWUHZAN-UHFFFAOYSA-N 0.000 claims 1
• WFSITOFCDNLHHZ-UHFFFAOYSA-N 4-[[4-[4-[acetyl(methyl)amino]anilino]furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(=CC=3)N(C)C(C)=O)=NN=2)=C1 WFSITOFCDNLHHZ-UHFFFAOYSA-N 0.000 claims 1
• 238000010276 construction Methods 0.000 claims 1
• BSEADEATBQYGKA-UHFFFAOYSA-N n-methyl-4-[[4-(3-methylanilino)thieno[2,3-d]pyridazin-7-yl]oxymethyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3SC=CC=3C(NC=3C=C(C)C=CC=3)=NN=2)=C1 BSEADEATBQYGKA-UHFFFAOYSA-N 0.000 claims 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
• 125000003118 aryl group Chemical group 0.000 abstract description 6
• 239000000463 material Substances 0.000 abstract description 4
• 230000008569 process Effects 0.000 abstract description 2
• 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 130
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 112
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 70
• 235000019439 ethyl acetate Nutrition 0.000 description 63
• 238000002360 preparation method Methods 0.000 description 61
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 59
• 239000000203 mixture Substances 0.000 description 59
• 239000000543 intermediate Substances 0.000 description 54
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
• 238000006243 chemical reaction Methods 0.000 description 51
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
• 239000011541 reaction mixture Substances 0.000 description 45
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
• 239000000047 product Substances 0.000 description 36
• 239000007787 solid Substances 0.000 description 34
• 239000002904 solvent Substances 0.000 description 33
• 239000000243 solution Substances 0.000 description 32
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
• 238000005160 1H NMR spectroscopy Methods 0.000 description 26
• 238000010992 reflux Methods 0.000 description 26
• 238000004809 thin layer chromatography Methods 0.000 description 26
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 23
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 22
• 238000004128 high performance liquid chromatography Methods 0.000 description 22
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
• 235000019441 ethanol Nutrition 0.000 description 21
• 239000002244 precipitate Substances 0.000 description 21
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
• 239000002253 acid Substances 0.000 description 20
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 19
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 19
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 19
• 210000004027 cell Anatomy 0.000 description 19
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 16
• 239000000725 suspension Substances 0.000 description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
• 238000007429 general method Methods 0.000 description 15
• 238000012360 testing method Methods 0.000 description 15
• 102000001554 Hemoglobins Human genes 0.000 description 14
• 108010054147 Hemoglobins Proteins 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• 238000005481 NMR spectroscopy Methods 0.000 description 13
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
• 239000000460 chlorine Substances 0.000 description 13
• 239000012043 crude product Substances 0.000 description 13
• 239000007858 starting material Substances 0.000 description 13
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• 230000005764 inhibitory process Effects 0.000 description 12
• 239000010410 layer Substances 0.000 description 12
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• 239000003795 chemical substances by application Substances 0.000 description 11
• QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 10
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
• 229910052786 argon Inorganic materials 0.000 description 10
• 108010082117 matrigel Proteins 0.000 description 10
• 239000012044 organic layer Substances 0.000 description 10
• 238000002390 rotary evaporation Methods 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 239000000741 silica gel Substances 0.000 description 9
• 229910002027 silica gel Inorganic materials 0.000 description 9
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• 239000003054 catalyst Substances 0.000 description 8
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 8
• 238000003818 flash chromatography Methods 0.000 description 8
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 238000001816 cooling Methods 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• KXDJPLSALUSYNT-UHFFFAOYSA-N furo[3,2-c]pyridazine Chemical compound N1=CC=C2OC=CC2=N1 KXDJPLSALUSYNT-UHFFFAOYSA-N 0.000 description 7
• 238000010438 heat treatment Methods 0.000 description 7
• 230000014759 maintenance of location Effects 0.000 description 7
• 230000003287 optical effect Effects 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• 238000012746 preparative thin layer chromatography Methods 0.000 description 7
• 239000002002 slurry Substances 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
• 150000003573 thiols Chemical class 0.000 description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 150000007513 acids Chemical class 0.000 description 6
• 244000309464 bull Species 0.000 description 6
• 239000006227 byproduct Substances 0.000 description 6
• 201000011510 cancer Diseases 0.000 description 6
• 239000012467 final product Substances 0.000 description 6
• 239000000796 flavoring agent Substances 0.000 description 6
• 150000002500 ions Chemical class 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 238000002844 melting Methods 0.000 description 6
• 230000008018 melting Effects 0.000 description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
• 239000003765 sweetening agent Substances 0.000 description 6
• DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 6
• 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 5
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 5
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 5
• 239000007995 HEPES buffer Substances 0.000 description 5
• 230000037396 body weight Effects 0.000 description 5
• 230000003197 catalytic effect Effects 0.000 description 5
• 239000007859 condensation product Substances 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 235000003599 food sweetener Nutrition 0.000 description 5
• 230000001404 mediated effect Effects 0.000 description 5
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 235000019198 oils Nutrition 0.000 description 5
• DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 5
• 239000000523 sample Substances 0.000 description 5
• 239000012279 sodium borohydride Substances 0.000 description 5
• 229910000033 sodium borohydride Inorganic materials 0.000 description 5
• 239000000758 substrate Substances 0.000 description 5
• 238000001308 synthesis method Methods 0.000 description 5
• 230000004862 vasculogenesis Effects 0.000 description 5
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 4
• 150000005751 4-halopyridines Chemical class 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
• 235000019483 Peanut oil Nutrition 0.000 description 4
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
• 150000001299 aldehydes Chemical class 0.000 description 4
• 239000007900 aqueous suspension Substances 0.000 description 4
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 4
• 210000004204 blood vessel Anatomy 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 229910052799 carbon Inorganic materials 0.000 description 4
• 229910002092 carbon dioxide Inorganic materials 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 239000003086 colorant Substances 0.000 description 4
• 238000009833 condensation Methods 0.000 description 4
• 230000005494 condensation Effects 0.000 description 4
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
• 150000005690 diesters Chemical class 0.000 description 4
• 235000014113 dietary fatty acids Nutrition 0.000 description 4
• POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
• 238000010828 elution Methods 0.000 description 4
• 150000002170 ethers Chemical class 0.000 description 4
• 239000000194 fatty acid Substances 0.000 description 4
• 229930195729 fatty acid Natural products 0.000 description 4
• 150000004665 fatty acids Chemical class 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
• 235000013355 food flavoring agent Nutrition 0.000 description 4
• 235000011187 glycerol Nutrition 0.000 description 4
• 230000002140 halogenating effect Effects 0.000 description 4
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 150000002576 ketones Chemical class 0.000 description 4
• 239000006166 lysate Substances 0.000 description 4
• 239000000312 peanut oil Substances 0.000 description 4
• 102000013415 peroxidase activity proteins Human genes 0.000 description 4
• 108040007629 peroxidase activity proteins Proteins 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 230000019491 signal transduction Effects 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 229910052938 sodium sulfate Inorganic materials 0.000 description 4
• 235000011152 sodium sulphate Nutrition 0.000 description 4
• 238000001228 spectrum Methods 0.000 description 4
• 239000012089 stop solution Substances 0.000 description 4
• 235000011149 sulphuric acid Nutrition 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• 230000002792 vascular Effects 0.000 description 4
• 239000003039 volatile agent Substances 0.000 description 4
• OGFAWKRXZLGJSK-UHFFFAOYSA-N 1-(2,4-dihydroxyphenyl)-2-(4-nitrophenyl)ethanone Chemical compound OC1=CC(O)=CC=C1C(=O)CC1=CC=C([N+]([O-])=O)C=C1 OGFAWKRXZLGJSK-UHFFFAOYSA-N 0.000 description 3
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 3
• AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 3
• FHTDDANQIMVWKZ-UHFFFAOYSA-N 1h-pyridine-4-thione Chemical compound SC1=CC=NC=C1 FHTDDANQIMVWKZ-UHFFFAOYSA-N 0.000 description 3
• LEWZOBYWGWKNCK-UHFFFAOYSA-N 2,3-dihydro-1h-inden-5-amine Chemical compound NC1=CC=C2CCCC2=C1 LEWZOBYWGWKNCK-UHFFFAOYSA-N 0.000 description 3
• UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 3
• AAVPRMAZRUIWCB-UHFFFAOYSA-N 4-(hydroxymethyl)-n-methylpyridine-2-carboxamide Chemical compound CNC(=O)C1=CC(CO)=CC=N1 AAVPRMAZRUIWCB-UHFFFAOYSA-N 0.000 description 3
• 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
• 206010021143 Hypoxia Diseases 0.000 description 3
• 239000007832 Na2SO4 Substances 0.000 description 3
• 229910020656 PBr5 Inorganic materials 0.000 description 3
• 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 3
• 235000021355 Stearic acid Nutrition 0.000 description 3
• 229920004890 Triton X-100 Polymers 0.000 description 3
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• 150000001408 amides Chemical class 0.000 description 3
• 229910021529 ammonia Inorganic materials 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 235000013877 carbamide Nutrition 0.000 description 3
• 239000001569 carbon dioxide Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 238000004440 column chromatography Methods 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• PXSFGMATQMURKO-UHFFFAOYSA-N dichloromethane;methanol;propan-2-one Chemical compound OC.ClCCl.CC(C)=O PXSFGMATQMURKO-UHFFFAOYSA-N 0.000 description 3
• 238000010790 dilution Methods 0.000 description 3
• 239000012895 dilution Substances 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 238000001035 drying Methods 0.000 description 3
• 238000000132 electrospray ionisation Methods 0.000 description 3
• 239000003480 eluent Substances 0.000 description 3
• 239000003995 emulsifying agent Substances 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 239000003623 enhancer Substances 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 230000014509 gene expression Effects 0.000 description 3
• 230000012010 growth Effects 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 238000005040 ion trap Methods 0.000 description 3
• 235000010445 lecithin Nutrition 0.000 description 3
• 239000000787 lecithin Substances 0.000 description 3
• 229940067606 lecithin Drugs 0.000 description 3
• 229940057995 liquid paraffin Drugs 0.000 description 3
• 239000012139 lysis buffer Substances 0.000 description 3
• 239000011159 matrix material Substances 0.000 description 3
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
• 239000012434 nucleophilic reagent Substances 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
• 239000004006 olive oil Substances 0.000 description 3
• 235000008390 olive oil Nutrition 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 230000035515 penetration Effects 0.000 description 3
• UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 3
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 3
• 230000026731 phosphorylation Effects 0.000 description 3
• 238000006366 phosphorylation reaction Methods 0.000 description 3
• LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical class C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 3
• 239000001509 sodium citrate Substances 0.000 description 3
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
• HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 3
• 239000008117 stearic acid Substances 0.000 description 3
• 150000003457 sulfones Chemical class 0.000 description 3
• 238000013271 transdermal drug delivery Methods 0.000 description 3
• 238000000825 ultraviolet detection Methods 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
• FAYAYUOZWYJNBD-UHFFFAOYSA-N 1,3-benzothiazol-6-amine Chemical compound NC1=CC=C2N=CSC2=C1 FAYAYUOZWYJNBD-UHFFFAOYSA-N 0.000 description 2
• KXAHDPKQOFASEB-UHFFFAOYSA-N 1,4-dibromoisoquinoline Chemical compound C1=CC=C2C(Br)=CN=C(Br)C2=C1 KXAHDPKQOFASEB-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• SNGXGJOICJQMMM-UHFFFAOYSA-N 2h-isoquinolin-1-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1.C1=CC=C2C(=O)NC=CC2=C1 SNGXGJOICJQMMM-UHFFFAOYSA-N 0.000 description 2
• JADVVTZXHQUFLS-UHFFFAOYSA-N 3,4-dichloropyridazine Chemical class ClC1=CC=NN=C1Cl JADVVTZXHQUFLS-UHFFFAOYSA-N 0.000 description 2
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
• IHCCAYCGZOLTEU-UHFFFAOYSA-N 3-furoic acid Chemical compound OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
• LMSFFEULKIPPOK-UHFFFAOYSA-N 4-(4-chloroanilino)-n-methyl-7-[[2-(methylcarbamoyl)pyridin-4-yl]methoxy]furo[2,3-d]pyridazine-2-carboxamide Chemical compound N1=NC(OCC=2C=C(N=CC=2)C(=O)NC)=C2OC(C(=O)NC)=CC2=C1NC1=CC=C(Cl)C=C1 LMSFFEULKIPPOK-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 108010035532 Collagen Proteins 0.000 description 2
• 102000008186 Collagen Human genes 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 238000002965 ELISA Methods 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
• 241001529936 Murinae Species 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• 150000001204 N-oxides Chemical class 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 229910019201 POBr3 Inorganic materials 0.000 description 2
• 229910019213 POCl3 Inorganic materials 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000004698 Polyethylene Substances 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 229940121369 angiogenesis inhibitor Drugs 0.000 description 2
• 239000004037 angiogenesis inhibitor Substances 0.000 description 2
• 239000000010 aprotic solvent Substances 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 235000010216 calcium carbonate Nutrition 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 150000001733 carboxylic acid esters Chemical class 0.000 description 2
• 229960000541 cetyl alcohol Drugs 0.000 description 2
• 239000007795 chemical reaction product Substances 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
• 229920001436 collagen Polymers 0.000 description 2
• 125000000950 dibromo group Chemical group Br* 0.000 description 2
• 150000001991 dicarboxylic acids Chemical class 0.000 description 2
• 125000003963 dichloro group Chemical group Cl* 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• FXJUUMGKLWHCNZ-UHFFFAOYSA-N dimethyl furan-2,3-dicarboxylate Chemical compound COC(=O)C=1C=COC=1C(=O)OC FXJUUMGKLWHCNZ-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000000694 effects Effects 0.000 description 2
• 230000013020 embryo development Effects 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 210000002889 endothelial cell Anatomy 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 150000002191 fatty alcohols Chemical class 0.000 description 2
• 150000002194 fatty esters Chemical class 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• DNXDYHALMANNEJ-UHFFFAOYSA-N furan-2,3-dicarboxylic acid Chemical compound OC(=O)C=1C=COC=1C(O)=O DNXDYHALMANNEJ-UHFFFAOYSA-N 0.000 description 2
• 108020001507 fusion proteins Proteins 0.000 description 2
• 102000037865 fusion proteins Human genes 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 150000004820 halides Chemical class 0.000 description 2
• 150000008282 halocarbons Chemical class 0.000 description 2
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 150000002430 hydrocarbons Chemical class 0.000 description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
• 230000003301 hydrolyzing effect Effects 0.000 description 2
• 230000007954 hypoxia Effects 0.000 description 2
• 150000003949 imides Chemical class 0.000 description 2
• 238000002513 implantation Methods 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 2
• SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 2
• 229910000359 iron(II) sulfate Inorganic materials 0.000 description 2
• TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 108020004999 messenger RNA Proteins 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 2
• OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000012038 nucleophile Substances 0.000 description 2
• WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 125000001095 phosphatidyl group Chemical group 0.000 description 2
• WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
• 229920000573 polyethylene Polymers 0.000 description 2
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
• 229920000053 polysorbate 80 Polymers 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
• 235000003441 saturated fatty acids Nutrition 0.000 description 2
• 150000004671 saturated fatty acids Chemical class 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
• 235000011069 sorbitan monooleate Nutrition 0.000 description 2
• 239000001593 sorbitan monooleate Substances 0.000 description 2
• 229940035049 sorbitan monooleate Drugs 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 210000001179 synovial fluid Anatomy 0.000 description 2
• 150000003505 terpenes Chemical class 0.000 description 2
• 235000007586 terpenes Nutrition 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• HIHKYDVSWLFRAY-UHFFFAOYSA-N thiophene-2,3-dicarboxylic acid Chemical compound OC(=O)C=1C=CSC=1C(O)=O HIHKYDVSWLFRAY-UHFFFAOYSA-N 0.000 description 2
• QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 210000004881 tumor cell Anatomy 0.000 description 2
• JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 2
• 150000004670 unsaturated fatty acids Chemical class 0.000 description 2
• 235000021122 unsaturated fatty acids Nutrition 0.000 description 2
• 150000003672 ureas Chemical class 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• 238000010792 warming Methods 0.000 description 2
• XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
• MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-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
• NRQHBNNTBIDSRK-YRNVUSSQSA-N (4e)-4-[(4-methoxyphenyl)methylidene]-2-methyl-1,3-oxazol-5-one Chemical compound C1=CC(OC)=CC=C1\C=C\1C(=O)OC(C)=N/1 NRQHBNNTBIDSRK-YRNVUSSQSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• POPVUKGJWNLYGW-UHFFFAOYSA-N (hydroxyamino) hydrogen sulfate Chemical compound ONOS(O)(=O)=O POPVUKGJWNLYGW-UHFFFAOYSA-N 0.000 description 1
• BOSAWIQFTJIYIS-UHFFFAOYSA-N 1,1,1-trichloro-2,2,2-trifluoroethane Chemical compound FC(F)(F)C(Cl)(Cl)Cl BOSAWIQFTJIYIS-UHFFFAOYSA-N 0.000 description 1
• ZXUJWPHOPHHZLR-UHFFFAOYSA-N 1,1,1-trichloro-2-fluoroethane Chemical compound FCC(Cl)(Cl)Cl ZXUJWPHOPHHZLR-UHFFFAOYSA-N 0.000 description 1
• JXDSEHLVLUASEI-UHFFFAOYSA-N 1,3-dibromoisoquinoline Chemical compound C1=CC=C2C(Br)=NC(Br)=CC2=C1 JXDSEHLVLUASEI-UHFFFAOYSA-N 0.000 description 1
• ODCNAEMHGMYADO-UHFFFAOYSA-N 1,4-dichlorophthalazine Chemical compound C1=CC=C2C(Cl)=NN=C(Cl)C2=C1 ODCNAEMHGMYADO-UHFFFAOYSA-N 0.000 description 1
• BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 1
• GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
• IKTPUTARUKSCDG-UHFFFAOYSA-N 1h-pyrazole-4,5-dicarboxylic acid Chemical compound OC(=O)C=1C=NNC=1C(O)=O IKTPUTARUKSCDG-UHFFFAOYSA-N 0.000 description 1
• YJMADHMYUJFMQE-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-5-amine Chemical compound NC1=CC=C2OCCC2=C1 YJMADHMYUJFMQE-UHFFFAOYSA-N 0.000 description 1
• ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 description 1
• VNJOEUSYAMPBAK-UHFFFAOYSA-N 2-methylbenzenesulfonic acid;hydrate Chemical compound O.CC1=CC=CC=C1S(O)(=O)=O VNJOEUSYAMPBAK-UHFFFAOYSA-N 0.000 description 1
• HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
• 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
• SCXDAPVNPLDQCS-UHFFFAOYSA-N 3,4-dibromofuro[3,2-c]pyridazine Chemical compound BrC1=NN=C2C=COC2=C1Br SCXDAPVNPLDQCS-UHFFFAOYSA-N 0.000 description 1
• IBWYHNOFSKJKKY-UHFFFAOYSA-N 3-chloropyridazine Chemical compound ClC1=CC=CN=N1 IBWYHNOFSKJKKY-UHFFFAOYSA-N 0.000 description 1
• MGRHBBRSAFPBIN-UHFFFAOYSA-N 3-fluoro-4-methylaniline Chemical compound CC1=CC=C(N)C=C1F MGRHBBRSAFPBIN-UHFFFAOYSA-N 0.000 description 1
• OSJPPGNTCRNQQC-UHFFFAOYSA-N 3-phosphoglyceric acid Chemical compound OC(=O)C(O)COP(O)(O)=O OSJPPGNTCRNQQC-UHFFFAOYSA-N 0.000 description 1
• YGYFCYSNQMVWKS-UHFFFAOYSA-N 4,7-dichlorothieno[2,3-d]pyridazine Chemical compound ClC1=NN=C(Cl)C2=C1C=CS2 YGYFCYSNQMVWKS-UHFFFAOYSA-N 0.000 description 1
• AHOYLOITOIOTSO-UHFFFAOYSA-N 4-(5-bromo-2,3-dihydroindol-1-yl)-7-(pyridin-4-ylmethoxy)furo[2,3-d]pyridazine Chemical compound C1CC2=CC(Br)=CC=C2N1C(C=1C=COC=11)=NN=C1OCC1=CC=NC=C1 AHOYLOITOIOTSO-UHFFFAOYSA-N 0.000 description 1
• NTZYWVGVUJTLIX-UHFFFAOYSA-N 4-[[1-(4-chloroanilino)isoquinolin-4-yl]methyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(CC=2C3=CC=CC=C3C(NC=3C=CC(Cl)=CC=3)=NC=2)=C1 NTZYWVGVUJTLIX-UHFFFAOYSA-N 0.000 description 1
• ZNBJYZFRLKDRAC-UHFFFAOYSA-N 4-[[1-(4-chloroanilino)isoquinolin-4-yl]methyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC(CC=2C3=CC=CC=C3C(NC=3C=CC(Cl)=CC=3)=NC=2)=C1 ZNBJYZFRLKDRAC-UHFFFAOYSA-N 0.000 description 1
• OHYAKZDLDRKXAP-UHFFFAOYSA-N 4-[[4-(1,3-benzodioxol-5-ylamino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=C4OCOC4=CC=3)=NN=2)=C1 OHYAKZDLDRKXAP-UHFFFAOYSA-N 0.000 description 1
• RKOPYARSKZEBBJ-UHFFFAOYSA-N 4-bromo-n-(4-chlorophenyl)isoquinolin-1-amine Chemical compound C1=CC(Cl)=CC=C1NC1=NC=C(Br)C2=CC=CC=C12 RKOPYARSKZEBBJ-UHFFFAOYSA-N 0.000 description 1
• BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 description 1
• HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 1
• PVMNPAUTCMBOMO-UHFFFAOYSA-N 4-chloropyridine Chemical compound ClC1=CC=NC=C1 PVMNPAUTCMBOMO-UHFFFAOYSA-N 0.000 description 1
• TTYVECQWCUJXCS-UHFFFAOYSA-N 4-fluoropyridine Chemical compound FC1=CC=NC=C1 TTYVECQWCUJXCS-UHFFFAOYSA-N 0.000 description 1
• SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
• VJIFABQJUYLAOS-UHFFFAOYSA-N 4-oxopent-2-ynedioic acid Chemical compound OC(=O)C#CC(=O)C(O)=O VJIFABQJUYLAOS-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
• QGNQEODJYRGEJX-UHFFFAOYSA-N 4h-isoquinoline-1,3-dione Chemical compound C1=CC=C2C(=O)NC(=O)CC2=C1 QGNQEODJYRGEJX-UHFFFAOYSA-N 0.000 description 1
• QEDCHCLHHGGYBT-UHFFFAOYSA-N 5-bromo-2,3-dihydro-1h-indole Chemical compound BrC1=CC=C2NCCC2=C1 QEDCHCLHHGGYBT-UHFFFAOYSA-N 0.000 description 1
• STTMIRCMVCOBQB-UHFFFAOYSA-N 7-chloro-n-(4-chlorophenyl)thieno[2,3-d]pyridazin-4-amine Chemical compound C1=CC(Cl)=CC=C1NC1=NN=C(Cl)C2=C1C=CS2 STTMIRCMVCOBQB-UHFFFAOYSA-N 0.000 description 1
• WSLLFCYGJBLBQS-UHFFFAOYSA-N 7-chloro-n-(4-methoxyphenyl)furo[2,3-d]pyridazin-4-amine Chemical compound C1=CC(OC)=CC=C1NC1=NN=C(Cl)C2=C1C=CO2 WSLLFCYGJBLBQS-UHFFFAOYSA-N 0.000 description 1
• VXYQISXSMNDTSX-UHFFFAOYSA-N 7-n-(1,3-benzothiazol-6-yl)-4-n-(2,3-dihydro-1h-inden-5-yl)thieno[2,3-d]pyridazine-4,7-diamine Chemical compound C1=C2N=CSC2=CC(NC2=NN=C(C=3C=CSC=32)NC2=CC=C3CCCC3=C2)=C1 VXYQISXSMNDTSX-UHFFFAOYSA-N 0.000 description 1
• WDJHALXBUFZDSR-UHFFFAOYSA-N Acetoacetic acid Natural products CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 201000003076 Angiosarcoma Diseases 0.000 description 1
• 201000004569 Blindness Diseases 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 108091016585 CD44 antigen Proteins 0.000 description 1
• WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 102000012422 Collagen Type I Human genes 0.000 description 1
• 108010022452 Collagen Type I Proteins 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 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 1
• DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
• 206010012441 Dermatitis bullous Diseases 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
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
• RDOFJDLLWVCMRU-UHFFFAOYSA-N Diisobutyl adipate Chemical compound CC(C)COC(=O)CCCCC(=O)OCC(C)C RDOFJDLLWVCMRU-UHFFFAOYSA-N 0.000 description 1
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
• 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
• 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
• 101800003838 Epidermal growth factor Proteins 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• 244000165918 Eucalyptus papuana Species 0.000 description 1
• 208000009386 Experimental Arthritis Diseases 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
• DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000001258 Hemangiosarcoma Diseases 0.000 description 1
• 102000008055 Heparan Sulfate Proteoglycans Human genes 0.000 description 1
• 229920002971 Heparan sulfate Polymers 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 102000000589 Interleukin-1 Human genes 0.000 description 1
• 108010002352 Interleukin-1 Proteins 0.000 description 1
• 102000004889 Interleukin-6 Human genes 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• LCGISIDBXHGCDW-VKHMYHEASA-N L-glutamine amide Chemical compound NC(=O)[C@@H](N)CCC(N)=O LCGISIDBXHGCDW-VKHMYHEASA-N 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
• 108010085895 Laminin Proteins 0.000 description 1
• 239000005639 Lauric acid Substances 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
• GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• HXFOXFJUNFFYMO-BYPYZUCNSA-N N-alpha-acetyl-L-asparagine Chemical compound CC(=O)N[C@H](C(O)=O)CC(N)=O HXFOXFJUNFFYMO-BYPYZUCNSA-N 0.000 description 1
• 206010029113 Neovascularisation Diseases 0.000 description 1
• BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical class C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 235000021314 Palmitic acid Nutrition 0.000 description 1
• 206010034277 Pemphigoid Diseases 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 1
• 108010077895 Sarcosine Proteins 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 108090000054 Syndecan-2 Proteins 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical class C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 1
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
• 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
• 108091008605 VEGF receptors Proteins 0.000 description 1
• 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
• 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
• 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
• 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 1
• 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
• 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 1
• 206010047141 Vasodilatation Diseases 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 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 1
• CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
• 229960004308 acetylcysteine Drugs 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000001361 adipic acid Substances 0.000 description 1
• 235000011037 adipic acid Nutrition 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 125000003158 alcohol group Chemical group 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 210000000648 angioblast Anatomy 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 239000003899 bactericide agent Substances 0.000 description 1
• 210000002469 basement membrane Anatomy 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000008512 biological response Effects 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 229940045348 brown mixture Drugs 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 244000309466 calf Species 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• GGNALUCSASGNCK-UHFFFAOYSA-N carbon dioxide;propan-2-ol Chemical compound O=C=O.CC(C)O GGNALUCSASGNCK-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 229920003086 cellulose ether Polymers 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 150000003983 crown ethers Chemical class 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000000058 cyclopentadienyl group Chemical class C1(=CC=CC1)* 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 230000002074 deregulated effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 229950006137 dexfosfoserine Drugs 0.000 description 1
• WOWBFOBYOAGEEA-UHFFFAOYSA-N diafenthiuron Chemical compound CC(C)C1=C(NC(=S)NC(C)(C)C)C(C(C)C)=CC(OC=2C=CC=CC=2)=C1 WOWBFOBYOAGEEA-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
• 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
• 238000009792 diffusion process Methods 0.000 description 1
• 229940031769 diisobutyl adipate Drugs 0.000 description 1
• 229940031578 diisopropyl adipate Drugs 0.000 description 1
• VHILMKFSCRWWIJ-UHFFFAOYSA-N dimethyl acetylenedicarboxylate Chemical compound COC(=O)C#CC(=O)OC VHILMKFSCRWWIJ-UHFFFAOYSA-N 0.000 description 1
• CGDDISBFSPJVPK-UHFFFAOYSA-N dimethyl thiophene-2,3-dicarboxylate Chemical compound COC(=O)C=1C=CSC=1C(=O)OC CGDDISBFSPJVPK-UHFFFAOYSA-N 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Chemical class C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
• 229940116977 epidermal growth factor Drugs 0.000 description 1
• DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
• NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• MCRPKBUFXAKDKI-UHFFFAOYSA-N ethyl pyridine-4-carboxylate Chemical compound CCOC(=O)C1=CC=NC=C1 MCRPKBUFXAKDKI-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 230000029142 excretion Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000011536 extraction buffer Substances 0.000 description 1
• 238000013100 final test Methods 0.000 description 1
• 150000003948 formamides Chemical class 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• PONAXVAFSSUYFZ-UHFFFAOYSA-N furo[2,3-d]pyridazine Chemical compound N1=NC=C2OC=CC2=C1 PONAXVAFSSUYFZ-UHFFFAOYSA-N 0.000 description 1
• DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
• 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 150000001261 hydroxy acids Chemical class 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 230000001146 hypoxic effect Effects 0.000 description 1
• 238000007901 in situ hybridization Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 229940100601 interleukin-6 Drugs 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 230000026045 iodination Effects 0.000 description 1
• 238000006192 iodination reaction Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 150000002505 iron Chemical class 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
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000002537 isoquinolines Chemical class 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 239000008297 liquid dosage form Substances 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 239000011565 manganese chloride Substances 0.000 description 1
• 235000002867 manganese chloride Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 239000003226 mitogen Substances 0.000 description 1
• 239000011259 mixed solution Substances 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000004570 mortar (masonry) Substances 0.000 description 1
• UFGSVJMWQZYRDS-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-5-yl)-4-(pyridin-4-ylmethyl)isoquinolin-1-amine Chemical compound C=1N=C(NC=2C=C3CCCC3=CC=2)C2=CC=CC=C2C=1CC1=CC=NC=C1 UFGSVJMWQZYRDS-UHFFFAOYSA-N 0.000 description 1
• OGUVJPFBEGGUHL-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-5-yl)-4-pyridin-4-ylsulfanylisoquinolin-1-amine Chemical compound C1=C2CCCC2=CC=C1NC(C1=CC=CC=C11)=NC=C1SC1=CC=NC=C1 OGUVJPFBEGGUHL-UHFFFAOYSA-N 0.000 description 1
• GHEQDWPWNIMUQE-UHFFFAOYSA-N n-(3-fluoro-4-methylphenyl)-4-(pyridin-4-ylmethyl)isoquinolin-1-amine Chemical compound C1=C(F)C(C)=CC=C1NC(C1=CC=CC=C11)=NC=C1CC1=CC=NC=C1 GHEQDWPWNIMUQE-UHFFFAOYSA-N 0.000 description 1
• IHYNKGRWCDKNEG-UHFFFAOYSA-N n-(4-bromophenyl)-2,6-dihydroxybenzamide Chemical compound OC1=CC=CC(O)=C1C(=O)NC1=CC=C(Br)C=C1 IHYNKGRWCDKNEG-UHFFFAOYSA-N 0.000 description 1
• DFVKSVPVYDYCCD-UHFFFAOYSA-N n-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)isoquinolin-1-amine Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NC=C1CC1=CC=NC=C1 DFVKSVPVYDYCCD-UHFFFAOYSA-N 0.000 description 1
• DIDIJDSQKHOKKS-UHFFFAOYSA-N n-(4-chlorophenyl)-4-pyridin-4-ylsulfanylisoquinolin-1-amine Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NC=C1SC1=CC=NC=C1 DIDIJDSQKHOKKS-UHFFFAOYSA-N 0.000 description 1
• GKGXNXPBVLPLEC-UHFFFAOYSA-N n-(4-chlorophenyl)-7-(pyridin-4-ylmethoxy)furo[2,3-d]pyridazin-4-amine Chemical compound C1=CC(Cl)=CC=C1NC(C=1C=COC=11)=NN=C1OCC1=CC=NC=C1 GKGXNXPBVLPLEC-UHFFFAOYSA-N 0.000 description 1
• KUNQMTGPMLPMCP-UHFFFAOYSA-N n-(4-chlorophenyl)-7-(pyridin-4-ylmethoxy)thieno[2,3-d]pyridazin-4-amine Chemical compound C1=CC(Cl)=CC=C1NC(C=1C=CSC=11)=NN=C1OCC1=CC=NC=C1 KUNQMTGPMLPMCP-UHFFFAOYSA-N 0.000 description 1
• RVLAFRCLNCDGNF-UHFFFAOYSA-N n-(4-methoxyphenyl)-7-(pyridin-4-ylmethoxy)furo[2,3-d]pyridazin-4-amine Chemical compound C1=CC(OC)=CC=C1NC(C=1C=COC=11)=NN=C1OCC1=CC=NC=C1 RVLAFRCLNCDGNF-UHFFFAOYSA-N 0.000 description 1
• VNRMXOPCEVMSCQ-UHFFFAOYSA-N n-(4-pyridin-4-ylsulfanylisoquinolin-1-yl)-1,3-benzothiazol-6-amine Chemical compound C=1C=C2N=CSC2=CC=1NC(C1=CC=CC=C11)=NC=C1SC1=CC=NC=C1 VNRMXOPCEVMSCQ-UHFFFAOYSA-N 0.000 description 1
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• PXRQCAHBDKPEKP-UHFFFAOYSA-N n-[4-(pyridin-4-ylmethyl)isoquinolin-1-yl]-1,3-benzothiazol-6-amine Chemical compound C=1N=C(NC=2C=C3SC=NC3=CC=2)C2=CC=CC=C2C=1CC1=CC=NC=C1 PXRQCAHBDKPEKP-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
• KUDPGZONDFORKU-UHFFFAOYSA-N n-chloroaniline Chemical compound ClNC1=CC=CC=C1 KUDPGZONDFORKU-UHFFFAOYSA-N 0.000 description 1
• KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical compound CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 description 1
• 229920003052 natural elastomer Polymers 0.000 description 1
• 229920001206 natural gum Polymers 0.000 description 1
• 229920001194 natural rubber Polymers 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
• QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
• 239000012053 oil suspension Substances 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 230000027758 ovulation cycle Effects 0.000 description 1
• 150000003901 oxalic acid esters Chemical class 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
• BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 125000005498 phthalate group Chemical class 0.000 description 1
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical class C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
• IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical class NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 229920002635 polyurethane Polymers 0.000 description 1
• 239000004814 polyurethane Substances 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• ZOCLAPYLSUCOGI-UHFFFAOYSA-M potassium hydrosulfide Chemical compound [SH-].[K+] ZOCLAPYLSUCOGI-UHFFFAOYSA-M 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 230000001185 psoriatic effect Effects 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
• ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
• 229960004172 pyridoxine hydrochloride Drugs 0.000 description 1
• 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 1
• 239000011764 pyridoxine hydrochloride Substances 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 238000011552 rat model Methods 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 238000012552 review Methods 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
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229940054269 sodium pyruvate Drugs 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 238000001179 sorption measurement Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 229920003048 styrene butadiene rubber Polymers 0.000 description 1
• 150000005846 sugar alcohols Polymers 0.000 description 1
• 125000001174 sulfone group Chemical group 0.000 description 1
• 125000003375 sulfoxide group Chemical group 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 229920003051 synthetic elastomer Polymers 0.000 description 1
• 239000005061 synthetic rubber Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
• TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• NSSXUVVBLSMKOR-UHFFFAOYSA-N thieno[2,3-d]pyridazine-4,7-dione Chemical compound O=C1N=NC(=O)C2=C1C=CS2 NSSXUVVBLSMKOR-UHFFFAOYSA-N 0.000 description 1
• RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
• 229940033663 thimerosal Drugs 0.000 description 1
• 125000000101 thioether group Chemical group 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 150000003577 thiophenes Chemical class 0.000 description 1
• 201000002510 thyroid cancer Diseases 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
• 230000001131 transforming effect Effects 0.000 description 1
• 108091008578 transmembrane receptors Proteins 0.000 description 1
• 102000027257 transmembrane receptors Human genes 0.000 description 1
• ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
• 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 230000005747 tumor angiogenesis Effects 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• 210000001215 vagina Anatomy 0.000 description 1
• 210000003556 vascular endothelial cell Anatomy 0.000 description 1
• 230000008728 vascular permeability Effects 0.000 description 1
• 230000024883 vasodilation Effects 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1