DE60210819T2 - Pyrazolopyridazinderivate - Google Patents

Info

Publication number

DE60210819T2

DE60210819T2 DE60210819T DE60210819T DE60210819T2 DE 60210819 T2 DE60210819 T2 DE 60210819T2 DE 60210819 T DE60210819 T DE 60210819T DE 60210819 T DE60210819 T DE 60210819T DE 60210819 T2 DE60210819 T2 DE 60210819T2

Authority

DE

Germany

Prior art keywords

pyridazin

pyrazolo

alkyl

pyrimidinamine

hydrogen

Prior art date

2001-12-17

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

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• DPMA
• Discuss

• 150000001875 compounds Chemical class 0.000 claims description 261
• -1 -NR 4 R 5 Chemical group 0.000 claims description 155
• 125000000217 alkyl group Chemical group 0.000 claims description 102
• 239000001257 hydrogen Substances 0.000 claims description 84
• 229910052739 hydrogen Inorganic materials 0.000 claims description 84
• 125000003118 aryl group Chemical group 0.000 claims description 79
• 125000000623 heterocyclic group Chemical group 0.000 claims description 76
• 125000001072 heteroaryl group Chemical group 0.000 claims description 72
• 150000002431 hydrogen Chemical class 0.000 claims description 68
• 150000003839 salts Chemical class 0.000 claims description 64
• 239000012453 solvate Substances 0.000 claims description 53
• 229910052736 halogen Inorganic materials 0.000 claims description 49
• 150000002367 halogens Chemical class 0.000 claims description 49
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 48
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 46
• 238000000034 method Methods 0.000 claims description 36
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 35
• 238000011282 treatment Methods 0.000 claims description 35
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 33
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 32
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 31
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
• 206010028980 Neoplasm Diseases 0.000 claims description 26
• 125000003545 alkoxy group Chemical group 0.000 claims description 25
• 125000002947 alkylene group Chemical group 0.000 claims description 25
• 201000011510 cancer Diseases 0.000 claims description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
• 229910052757 nitrogen Inorganic materials 0.000 claims description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• 239000002585 base Substances 0.000 claims description 18
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 17
• 125000004450 alkenylene group Chemical group 0.000 claims description 17
• 150000001412 amines Chemical class 0.000 claims description 17
• 125000000732 arylene group Chemical group 0.000 claims description 15
• 125000004419 alkynylene group Chemical group 0.000 claims description 14
• 125000005724 cycloalkenylene group Chemical group 0.000 claims description 14
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 14
• 125000005549 heteroarylene group Chemical group 0.000 claims description 14
• 125000003342 alkenyl group Chemical group 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 229910005965 SO 2 Inorganic materials 0.000 claims description 12
• 125000000304 alkynyl group Chemical group 0.000 claims description 11
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 10
• 238000002560 therapeutic procedure Methods 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 8
• 230000008569 process Effects 0.000 claims description 8
• 238000002360 preparation method Methods 0.000 claims description 7
• XKYJKKJKDAGKNZ-UHFFFAOYSA-N 3-[2-(cyclopropylamino)pyrimidin-4-yl]-7h-pyrazolo[1,5-b]pyridazin-6-one Chemical compound C1=NN2N=C(O)C=CC2=C1C(N=1)=CC=NC=1NC1CC1 XKYJKKJKDAGKNZ-UHFFFAOYSA-N 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• OJNPXUBDVGTOJJ-UHFFFAOYSA-N n-cyclopropyl-4-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1=NN2N=C(OC)C=CC2=C1C(N=1)=CC=NC=1NC1CC1 OJNPXUBDVGTOJJ-UHFFFAOYSA-N 0.000 claims description 6
• 230000002265 prevention Effects 0.000 claims description 6
• 125000003107 substituted aryl group Chemical group 0.000 claims description 6
• ZRWNCIWVANTRGL-UHFFFAOYSA-N n-(3-morpholin-4-ylpropyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound N=1C=CC(C2=C3C=CC=NN3N=C2)=NC=1NCCCN1CCOCC1 ZRWNCIWVANTRGL-UHFFFAOYSA-N 0.000 claims description 5
• NEWXQDRWGLAOAY-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(Cl)=CC=C1CNC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 NEWXQDRWGLAOAY-UHFFFAOYSA-N 0.000 claims description 5
• RVSCHTJBVVTPSV-UHFFFAOYSA-N n-cyclopropyl-4-[6-(4-fluorophenyl)pyrazolo[1,5-b]pyridazin-3-yl]pyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1C1=NN2N=CC(C=3N=C(NC4CC4)N=CC=3)=C2C=C1 RVSCHTJBVVTPSV-UHFFFAOYSA-N 0.000 claims description 5
• GBRORGYPYNNDGL-UHFFFAOYSA-N 1-(dimethylamino)-3-[4-[[4-(6-morpholin-4-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-yl]amino]phenoxy]propan-2-ol Chemical compound C1=CC(OCC(O)CN(C)C)=CC=C1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)N2CCOCC2)=N1 GBRORGYPYNNDGL-UHFFFAOYSA-N 0.000 claims description 4
• PSTOACKLPREGGX-UHFFFAOYSA-N 1-[3-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]propyl]pyrrolidin-2-one Chemical compound O=C1CCCN1CCCNC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 PSTOACKLPREGGX-UHFFFAOYSA-N 0.000 claims description 4
• CWRTWFWDDAJOMG-UHFFFAOYSA-N 3-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]benzonitrile Chemical compound N#CC1=CC=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 CWRTWFWDDAJOMG-UHFFFAOYSA-N 0.000 claims description 4
• FLUPOKVTJQLXSE-UHFFFAOYSA-N 4-(2-butylpyrazolo[1,5-b]pyridazin-3-yl)-n-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Chemical compound CCCCC1=NN2N=CC=CC2=C1C(N=1)=CC=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 FLUPOKVTJQLXSE-UHFFFAOYSA-N 0.000 claims description 4
• DKXUHTCPDJKABE-UHFFFAOYSA-N 4-(2-butylpyrazolo[1,5-b]pyridazin-3-yl)-n-cyclopropylpyrimidin-2-amine Chemical compound CCCCC1=NN2N=CC=CC2=C1C(N=1)=CC=NC=1NC1CC1 DKXUHTCPDJKABE-UHFFFAOYSA-N 0.000 claims description 4
• RBIONWHBBUZDRJ-UHFFFAOYSA-N 4-(2-ethylpyrazolo[1,5-b]pyridazin-3-yl)-n-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Chemical compound CCC1=NN2N=CC=CC2=C1C(N=1)=CC=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 RBIONWHBBUZDRJ-UHFFFAOYSA-N 0.000 claims description 4
• CEOSCLCDTBXJBH-UHFFFAOYSA-N 4-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)-n-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Chemical compound C1=NN2N=C(OC)C=CC2=C1C(N=1)=CC=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 CEOSCLCDTBXJBH-UHFFFAOYSA-N 0.000 claims description 4
• QKNZQSYOXRAXPX-UHFFFAOYSA-N 4-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 QKNZQSYOXRAXPX-UHFFFAOYSA-N 0.000 claims description 4
• NZEMZNIMMYPXRT-UHFFFAOYSA-N 4-[6-(2-chlorophenyl)pyrazolo[1,5-b]pyridazin-3-yl]-n-cyclopropylpyrimidin-2-amine Chemical compound ClC1=CC=CC=C1C1=NN2N=CC(C=3N=C(NC4CC4)N=CC=3)=C2C=C1 NZEMZNIMMYPXRT-UHFFFAOYSA-N 0.000 claims description 4
• VHNFQSZQXINXSV-UHFFFAOYSA-N 4-[6-(4-fluorophenyl)pyrazolo[1,5-b]pyridazin-3-yl]-n-(4-methoxyphenyl)pyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)C=2C=CC(F)=CC=2)=N1 VHNFQSZQXINXSV-UHFFFAOYSA-N 0.000 claims description 4
• AKAGBRZFDUGGEX-UHFFFAOYSA-N 4-[6-(4-fluorophenyl)pyrazolo[1,5-b]pyridazin-3-yl]-n-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)C=2C=CC(F)=CC=2)=N1 AKAGBRZFDUGGEX-UHFFFAOYSA-N 0.000 claims description 4
• QTYPVJBVNHCPHH-UHFFFAOYSA-N 4-n,4-n-dimethyl-1-n-[4-(6-morpholin-4-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-yl]benzene-1,4-diamine Chemical compound C1=CC(N(C)C)=CC=C1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)N2CCOCC2)=N1 QTYPVJBVNHCPHH-UHFFFAOYSA-N 0.000 claims description 4
• JOSDAWJORYYQIX-UHFFFAOYSA-N 4-pyrazolo[1,5-b]pyridazin-3-yl-n-(2,2,2-trifluoroethyl)pyrimidin-2-amine Chemical compound FC(F)(F)CNC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 JOSDAWJORYYQIX-UHFFFAOYSA-N 0.000 claims description 4
• BVUVQUIZCFRPJG-UHFFFAOYSA-N 4-pyrazolo[1,5-b]pyridazin-3-yl-n-(3,4,5-trimethoxyphenyl)pyrimidin-2-amine Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 BVUVQUIZCFRPJG-UHFFFAOYSA-N 0.000 claims description 4
• VKVKUKGJNTVGRG-UHFFFAOYSA-N 4-pyrazolo[1,5-b]pyridazin-3-yl-n-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine Chemical compound FC(F)(F)C1=CC=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 VKVKUKGJNTVGRG-UHFFFAOYSA-N 0.000 claims description 4
• SRXHNQITQCEZCO-UHFFFAOYSA-N 4-pyridazin-3-ylpyrimidin-2-amine Chemical compound NC1=NC=CC(C=2N=NC=CC=2)=N1 SRXHNQITQCEZCO-UHFFFAOYSA-N 0.000 claims description 4
• PGFMVPZMGVTWMA-UHFFFAOYSA-N [3-[2-(cyclopropylamino)pyrimidin-4-yl]pyrazolo[1,5-b]pyridazin-6-yl] trifluoromethanesulfonate Chemical compound C1=NN2N=C(OS(=O)(=O)C(F)(F)F)C=CC2=C1C(N=1)=CC=NC=1NC1CC1 PGFMVPZMGVTWMA-UHFFFAOYSA-N 0.000 claims description 4
• 230000003013 cytotoxicity Effects 0.000 claims description 4
• 231100000135 cytotoxicity Toxicity 0.000 claims description 4
• MYOUKRZQKNFETG-UHFFFAOYSA-N n-(2-chlorophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound ClC1=CC=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 MYOUKRZQKNFETG-UHFFFAOYSA-N 0.000 claims description 4
• DENIPLMYQYHPPA-UHFFFAOYSA-N n-(3-nitrophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound [O-][N+](=O)C1=CC=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 DENIPLMYQYHPPA-UHFFFAOYSA-N 0.000 claims description 4
• ONTYJGWYVMEOIF-UHFFFAOYSA-N n-(4-chlorophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(Cl)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 ONTYJGWYVMEOIF-UHFFFAOYSA-N 0.000 claims description 4
• SPYYDYXTVMRMEZ-UHFFFAOYSA-N n-(4-fluorophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 SPYYDYXTVMRMEZ-UHFFFAOYSA-N 0.000 claims description 4
• WPYZRTGDEWJZIP-UHFFFAOYSA-N n-(4-methoxyphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 WPYZRTGDEWJZIP-UHFFFAOYSA-N 0.000 claims description 4
• PBWVSMSYTVNKEU-UHFFFAOYSA-N n-(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)-1,3-benzoxazol-2-amine Chemical compound C1=NN2N=CC=CC2=C1C1=NC(NC=2OC3=CC=CC=C3N=2)=NC=C1 PBWVSMSYTVNKEU-UHFFFAOYSA-N 0.000 claims description 4
• IWGZWYKKIFMJCQ-UHFFFAOYSA-N n-(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)-3h-benzimidazol-5-amine Chemical compound C1=NN2N=CC=CC2=C1C1=NC(NC=2C=C3NC=NC3=CC=2)=NC=C1 IWGZWYKKIFMJCQ-UHFFFAOYSA-N 0.000 claims description 4
• SYAYIIIJZNUJPQ-UHFFFAOYSA-N n-[3-(1,3-oxazol-5-yl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound N=1C=CC(C2=C3C=CC=NN3N=C2)=NC=1NC(C=1)=CC=CC=1C1=CN=CO1 SYAYIIIJZNUJPQ-UHFFFAOYSA-N 0.000 claims description 4
• PWQDMUJHLRNRTQ-UHFFFAOYSA-N n-[3-(4-methylpiperazin-1-yl)propyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CN(C)CCN1CCCNC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 PWQDMUJHLRNRTQ-UHFFFAOYSA-N 0.000 claims description 4
• NKEZMLRTYBINTC-UHFFFAOYSA-N n-[3-chloro-4-(4-methylpiperazin-1-yl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C(=C1)Cl)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 NKEZMLRTYBINTC-UHFFFAOYSA-N 0.000 claims description 4
• AJAGHHORROJWRU-UHFFFAOYSA-N n-[3-methyl-4-(4-methylpiperazin-1-yl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C(=C1)C)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 AJAGHHORROJWRU-UHFFFAOYSA-N 0.000 claims description 4
• ZOTNSCLLJKXGSD-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C(=C1)C(F)(F)F)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 ZOTNSCLLJKXGSD-UHFFFAOYSA-N 0.000 claims description 4
• RRUGSPOGOGBMMW-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-4-(2-methylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2C)=N1 RRUGSPOGOGBMMW-UHFFFAOYSA-N 0.000 claims description 4
• AUAUBVTWWCYNPP-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 AUAUBVTWWCYNPP-UHFFFAOYSA-N 0.000 claims description 4
• DQKZVZRKPRQVEU-UHFFFAOYSA-N n-[4-(diethylaminomethyl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(CN(CC)CC)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 DQKZVZRKPRQVEU-UHFFFAOYSA-N 0.000 claims description 4
• LTNXNHHGQLANQP-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopropylamino)pyrimidin-4-yl]pyrazolo[1,5-b]pyridazin-6-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC(NC4CCCC4)=NN3N=C2)=N1 LTNXNHHGQLANQP-UHFFFAOYSA-N 0.000 claims description 4
• FAGYWTJBSZCMQC-UHFFFAOYSA-N n-cyclopropyl-4-(2-methylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound CC1=NN2N=CC=CC2=C1C(N=1)=CC=NC=1NC1CC1 FAGYWTJBSZCMQC-UHFFFAOYSA-N 0.000 claims description 4
• RNTPQNNOOQMIBD-UHFFFAOYSA-N n-cyclopropyl-4-(6-ethenylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1=NN2N=C(C=C)C=CC2=C1C(N=1)=CC=NC=1NC1CC1 RNTPQNNOOQMIBD-UHFFFAOYSA-N 0.000 claims description 4
• RLKIXFRFDGFKOP-UHFFFAOYSA-N n-cyclopropyl-4-(6-morpholin-4-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)N2CCOCC2)=N1 RLKIXFRFDGFKOP-UHFFFAOYSA-N 0.000 claims description 4
• PTXSJBYEFKLJDV-UHFFFAOYSA-N n-cyclopropyl-4-(6-phenylsulfanylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC(SC=4C=CC=CC=4)=NN3N=C2)=N1 PTXSJBYEFKLJDV-UHFFFAOYSA-N 0.000 claims description 4
• MFBCYZQBHGCRST-UHFFFAOYSA-N n-cyclopropyl-4-(6-propan-2-yloxypyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1=NN2N=C(OC(C)C)C=CC2=C1C(N=1)=CC=NC=1NC1CC1 MFBCYZQBHGCRST-UHFFFAOYSA-N 0.000 claims description 4
• DVNFZJOHZGRBGM-UHFFFAOYSA-N n-cyclopropyl-4-(6-pyrrolidin-1-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)N2CCCC2)=N1 DVNFZJOHZGRBGM-UHFFFAOYSA-N 0.000 claims description 4
• URAYKDQWSJUBED-UHFFFAOYSA-N n-cyclopropyl-4-[6-(2-fluoropyridin-4-yl)pyrazolo[1,5-b]pyridazin-3-yl]pyrimidin-2-amine Chemical compound C1=NC(F)=CC(C2=NN3N=CC(=C3C=C2)C=2N=C(NC3CC3)N=CC=2)=C1 URAYKDQWSJUBED-UHFFFAOYSA-N 0.000 claims description 4
• OAIXSJCARVACKE-UHFFFAOYSA-N n-cyclopropyl-n-methyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound N=1C=CC(C2=C3C=CC=NN3N=C2)=NC=1N(C)C1CC1 OAIXSJCARVACKE-UHFFFAOYSA-N 0.000 claims description 4
• LIYXXFOSHNQSRD-UHFFFAOYSA-N n-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound N=1C=CC(C2=C3C=CC=NN3N=C2)=NC=1NC1=CC=CC=C1 LIYXXFOSHNQSRD-UHFFFAOYSA-N 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 230000001225 therapeutic effect Effects 0.000 claims description 4
• 229940079593 drug Drugs 0.000 claims description 3
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
• QGMKFIGNGWVOSE-UHFFFAOYSA-N n-(1,3-benzodioxol-5-yl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=NN2N=CC=CC2=C1C1=NC(NC2=CC=C3OCOC3=C2)=NC=C1 QGMKFIGNGWVOSE-UHFFFAOYSA-N 0.000 claims description 3
• WIIIHAKKVLVGJX-UHFFFAOYSA-N n-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=NN2N=CC=CC2=C1C1=NC(NC=2C=C3OCCOC3=CC=2)=NC=C1 WIIIHAKKVLVGJX-UHFFFAOYSA-N 0.000 claims description 3
• WKITVSVNTNNVLF-UHFFFAOYSA-N n-(3,5-dimethylphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 WKITVSVNTNNVLF-UHFFFAOYSA-N 0.000 claims description 3
• GBNWWXHUOVAUHT-UHFFFAOYSA-N n-(3-methoxyphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound COC1=CC=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 GBNWWXHUOVAUHT-UHFFFAOYSA-N 0.000 claims description 3
• RVBOIHXTZQGXRV-UHFFFAOYSA-N n-(4-nitrophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC([N+](=O)[O-])=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 RVBOIHXTZQGXRV-UHFFFAOYSA-N 0.000 claims description 3
• GBYZMXCPDFNNOB-UHFFFAOYSA-N n-[3-methoxy-5-(trifluoromethyl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound FC(F)(F)C1=CC(OC)=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 GBYZMXCPDFNNOB-UHFFFAOYSA-N 0.000 claims description 3
• CAGHIASAHLPQMS-UHFFFAOYSA-N n-cyclopropyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 CAGHIASAHLPQMS-UHFFFAOYSA-N 0.000 claims description 3
• YRSCDRTXWYUNBB-UHFFFAOYSA-N 4-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]benzonitrile Chemical compound C1=CC(C#N)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 YRSCDRTXWYUNBB-UHFFFAOYSA-N 0.000 claims description 2
• DWCXDNWLEOSGIS-UHFFFAOYSA-N CS(=O)(=O)O.CC(CCNC1=NC=CC(=N1)C=1C=NN2N=CC=CC21)NC Chemical compound CS(=O)(=O)O.CC(CCNC1=NC=CC(=N1)C=1C=NN2N=CC=CC21)NC DWCXDNWLEOSGIS-UHFFFAOYSA-N 0.000 claims description 2
• 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 3
• 125000001475 halogen functional group Chemical group 0.000 claims 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 165
• 238000001819 mass spectrum Methods 0.000 description 162
• 238000000132 electrospray ionisation Methods 0.000 description 144
• 239000007787 solid Substances 0.000 description 115
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 111
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 103
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
• 239000000243 solution Substances 0.000 description 74
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 66
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 66
• 235000002639 sodium chloride Nutrition 0.000 description 57
• 239000000203 mixture Substances 0.000 description 55
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 51
• 235000019439 ethyl acetate Nutrition 0.000 description 49
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
• 238000006243 chemical reaction Methods 0.000 description 47
• 239000002904 solvent Substances 0.000 description 37
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 36
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
• AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 34
• 229960004132 diethyl ether Drugs 0.000 description 34
• 230000000694 effects Effects 0.000 description 30
• 239000003921 oil Substances 0.000 description 30
• 235000019198 oils Nutrition 0.000 description 28
• 108091007914 CDKs Proteins 0.000 description 27
• 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 26
• 239000012044 organic layer Substances 0.000 description 23
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 23
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 22
• 229910017604 nitric acid Inorganic materials 0.000 description 22
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
• 239000000460 chlorine Substances 0.000 description 21
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
• 125000004432 carbon atom Chemical group C* 0.000 description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
• 239000011541 reaction mixture Substances 0.000 description 18
• 238000006467 substitution reaction Methods 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
• 239000010410 layer Substances 0.000 description 17
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
• 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 16
• 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 16
• 125000004414 alkyl thio group Chemical group 0.000 description 16
• 210000004027 cell Anatomy 0.000 description 16
• 239000003112 inhibitor Substances 0.000 description 16
• 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 15
• 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 15
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
• 241000124008 Mammalia Species 0.000 description 15
• 125000001188 haloalkyl group Chemical group 0.000 description 15
• 239000000843 powder Substances 0.000 description 15
• 125000001424 substituent group Chemical group 0.000 description 15
• 125000004647 alkyl sulfenyl group Chemical group 0.000 description 14
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 14
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 14
• 208000035475 disorder Diseases 0.000 description 13
• 125000004043 oxo group Chemical group O=* 0.000 description 13
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 13
• RWOJNAKNHZUALN-UHFFFAOYSA-N 2-[4-(4-methylpiperazin-1-yl)phenyl]guanidine Chemical compound C1CN(C)CCN1C1=CC=C(NC(N)=N)C=C1 RWOJNAKNHZUALN-UHFFFAOYSA-N 0.000 description 12
• 230000022131 cell cycle Effects 0.000 description 12
• 238000001914 filtration Methods 0.000 description 12
• 238000009472 formulation Methods 0.000 description 12
• 125000005843 halogen group Chemical group 0.000 description 12
• 238000005481 NMR spectroscopy Methods 0.000 description 11
• AYTUUEWDUBHMBC-UHFFFAOYSA-N 2-cyclopropylguanidine Chemical compound NC(=N)NC1CC1 AYTUUEWDUBHMBC-UHFFFAOYSA-N 0.000 description 10
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 10
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
• SXVMCNSTLISYOI-UHFFFAOYSA-M pyridazin-1-ium-1-amine;iodide Chemical compound [I-].N[N+]1=CC=CC=N1 SXVMCNSTLISYOI-UHFFFAOYSA-M 0.000 description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
• 239000004215 Carbon black (E152) Substances 0.000 description 9
• 239000004480 active ingredient Substances 0.000 description 9
• 229930195733 hydrocarbon Natural products 0.000 description 9
• 229910000027 potassium carbonate Inorganic materials 0.000 description 9
• 239000003826 tablet Substances 0.000 description 9
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 125000005115 alkyl carbamoyl group Chemical group 0.000 description 8
• 125000005431 alkyl carboxamide group Chemical group 0.000 description 8
• DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 8
• 239000002246 antineoplastic agent Substances 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
• 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 7
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 7
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
• 231100000433 cytotoxic Toxicity 0.000 description 7
• 230000001472 cytotoxic effect Effects 0.000 description 7
• 102000004169 proteins and genes Human genes 0.000 description 7
• 108090000623 proteins and genes Proteins 0.000 description 7
• 150000004892 pyridazines Chemical class 0.000 description 7
• 238000010898 silica gel chromatography Methods 0.000 description 7
• JNONTUJTPUSDJZ-SOFGYWHQSA-N (e)-3-(dimethylamino)-1-(2-methylpyrazolo[1,5-b]pyridazin-3-yl)prop-2-en-1-one Chemical compound N1=CC=CC2=C(C(=O)/C=C/N(C)C)C(C)=NN21 JNONTUJTPUSDJZ-SOFGYWHQSA-N 0.000 description 6
• HOMNJJMKJWBJRH-UHFFFAOYSA-N 1-(2-methylpyrazolo[1,5-b]pyridazin-3-yl)ethanone Chemical compound N1=CC=CC2=C(C(=O)C)C(C)=NN21 HOMNJJMKJWBJRH-UHFFFAOYSA-N 0.000 description 6
• AAGSYRLSDSGSBC-UHFFFAOYSA-N 1-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)ethanone Chemical compound N1=C(OC)C=CC2=C(C(C)=O)C=NN21 AAGSYRLSDSGSBC-UHFFFAOYSA-N 0.000 description 6
• VIAYDFPWMKUHDL-UHFFFAOYSA-N 2-[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]guanidine Chemical compound C1CN(C)CCN1C1=CC=C(NC(N)=N)C=C1C(F)(F)F VIAYDFPWMKUHDL-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• HSFWRNGVRCDJHI-UHFFFAOYSA-N Acetylene Chemical compound C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 6
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 125000002252 acyl group Chemical group 0.000 description 6
• 238000011319 anticancer therapy Methods 0.000 description 6
• 229940034982 antineoplastic agent Drugs 0.000 description 6
• 125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 description 6
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 6
• 150000003857 carboxamides Chemical class 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 238000002512 chemotherapy Methods 0.000 description 6
• 239000006071 cream Substances 0.000 description 6
• 229940127089 cytotoxic agent Drugs 0.000 description 6
• 239000003085 diluting agent Substances 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 238000010438 heat treatment Methods 0.000 description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 238000002156 mixing Methods 0.000 description 6
• 108090000765 processed proteins & peptides Proteins 0.000 description 6
• SJWAIUCYYFOCSM-VOTSOKGWSA-N (e)-3-(dimethylamino)-1-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)prop-2-en-1-one Chemical compound N1=C(OC)C=CC2=C(C(=O)\C=C\N(C)C)C=NN21 SJWAIUCYYFOCSM-VOTSOKGWSA-N 0.000 description 5
• 102000003903 Cyclin-dependent kinases Human genes 0.000 description 5
• 108090000266 Cyclin-dependent kinases Proteins 0.000 description 5
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 5
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
• 102000001253 Protein Kinase Human genes 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 239000013543 active substance Substances 0.000 description 5
• 125000004423 acyloxy group Chemical class 0.000 description 5
• 125000004453 alkoxycarbonyl group Chemical class 0.000 description 5
• 125000003435 aroyl group Chemical class 0.000 description 5
• 125000005333 aroyloxy group Chemical class 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 238000000576 coating method Methods 0.000 description 5
• 239000000314 lubricant Substances 0.000 description 5
• 230000001404 mediated effect Effects 0.000 description 5
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
• 230000003647 oxidation Effects 0.000 description 5
• 238000007254 oxidation reaction Methods 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
• 108060006633 protein kinase Proteins 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• 150000008648 triflates Chemical class 0.000 description 5
• CPHPBDSNTXAPGJ-VQHVLOKHSA-N (e)-3-(dimethylamino)-1-(2-ethylpyrazolo[1,5-b]pyridazin-3-yl)prop-2-en-1-one Chemical compound N1=CC=CC2=C(C(=O)\C=C\N(C)C)C(CC)=NN21 CPHPBDSNTXAPGJ-VQHVLOKHSA-N 0.000 description 4
• KJTVNGACEOTXGU-BQYQJAHWSA-N (e)-3-(dimethylamino)-1-(6-propan-2-yloxypyrazolo[1,5-b]pyridazin-3-yl)prop-2-en-1-one Chemical compound N1=C(OC(C)C)C=CC2=C(C(=O)\C=C\N(C)C)C=NN21 KJTVNGACEOTXGU-BQYQJAHWSA-N 0.000 description 4
• LWQMYKGTECUFAO-FNORWQNLSA-N (e)-3-(dimethylamino)-1-pyrazolo[1,5-b]pyridazin-3-ylprop-2-en-1-one Chemical compound N1=CC=CC2=C(C(=O)/C=C/N(C)C)C=NN21 LWQMYKGTECUFAO-FNORWQNLSA-N 0.000 description 4
• RVOAAUDTOXHKBN-UHFFFAOYSA-N 1-(2-ethylpyrazolo[1,5-b]pyridazin-3-yl)ethanone Chemical compound N1=CC=CC2=C(C(C)=O)C(CC)=NN21 RVOAAUDTOXHKBN-UHFFFAOYSA-N 0.000 description 4
• DONVVOKVPHOQSF-UHFFFAOYSA-N 1-(6-propan-2-yloxypyrazolo[1,5-b]pyridazin-3-yl)ethanone Chemical compound N1=C(OC(C)C)C=CC2=C(C(C)=O)C=NN21 DONVVOKVPHOQSF-UHFFFAOYSA-N 0.000 description 4
• XAHXLPHHSIIXPR-UHFFFAOYSA-N 1-pyrazolo[1,5-b]pyridazin-3-ylethanone Chemical compound N1=CC=CC2=C(C(=O)C)C=NN21 XAHXLPHHSIIXPR-UHFFFAOYSA-N 0.000 description 4
• BZGIGIXURRLWCE-UHFFFAOYSA-N 2-(2,2,2-trifluoroethyl)guanidine Chemical compound NC(N)=NCC(F)(F)F BZGIGIXURRLWCE-UHFFFAOYSA-N 0.000 description 4
• HKPHVFFQXHMOHX-UHFFFAOYSA-N 2-(2-chlorophenyl)guanidine Chemical compound NC(=N)NC1=CC=CC=C1Cl HKPHVFFQXHMOHX-UHFFFAOYSA-N 0.000 description 4
• DXUWATABALHSNY-UHFFFAOYSA-N 2-(3,4,5-trimethoxyphenyl)guanidine Chemical compound COC1=CC(NC(N)=N)=CC(OC)=C1OC DXUWATABALHSNY-UHFFFAOYSA-N 0.000 description 4
• MZLGFUWJJQGNSE-UHFFFAOYSA-N 2-(3-chloro-4-morpholin-4-ylphenyl)guanidine Chemical compound ClC1=CC(NC(=N)N)=CC=C1N1CCOCC1 MZLGFUWJJQGNSE-UHFFFAOYSA-N 0.000 description 4
• GRSCIMXGMTUWQD-UHFFFAOYSA-N 2-(3-cyanophenyl)guanidine Chemical compound NC(=N)NC1=CC=CC(C#N)=C1 GRSCIMXGMTUWQD-UHFFFAOYSA-N 0.000 description 4
• UXOUIFWYBYHKQA-UHFFFAOYSA-N 2-(3-morpholin-4-ylpropyl)guanidine Chemical compound NC(N)=NCCCN1CCOCC1 UXOUIFWYBYHKQA-UHFFFAOYSA-N 0.000 description 4
• JJBYIQPAELFTOD-UHFFFAOYSA-N 2-(3-nitrophenyl)guanidine Chemical compound NC(=N)NC1=CC=CC([N+]([O-])=O)=C1 JJBYIQPAELFTOD-UHFFFAOYSA-N 0.000 description 4
• DHVVFUFEJNDDKN-UHFFFAOYSA-N 2-(3h-benzimidazol-5-yl)guanidine Chemical compound NC(=N)NC1=CC=C2N=CNC2=C1 DHVVFUFEJNDDKN-UHFFFAOYSA-N 0.000 description 4
• CYYQVFZVCJFKES-UHFFFAOYSA-N 2-[(4-chlorophenyl)methyl]guanidine Chemical compound NC(N)=NCC1=CC=C(Cl)C=C1 CYYQVFZVCJFKES-UHFFFAOYSA-N 0.000 description 4
• YJPMIGWGPIORCQ-UHFFFAOYSA-N 2-[3-(1,3-oxazol-5-yl)phenyl]guanidine Chemical compound NC(=N)NC1=CC=CC(C=2OC=NC=2)=C1 YJPMIGWGPIORCQ-UHFFFAOYSA-N 0.000 description 4
• BKTZIZAWQMGVPX-UHFFFAOYSA-N 2-[3-(4-methylpiperazin-1-yl)propyl]guanidine Chemical compound CN1CCN(CCCNC(N)=N)CC1 BKTZIZAWQMGVPX-UHFFFAOYSA-N 0.000 description 4
• CPVHXMXPICPCIC-UHFFFAOYSA-N 2-[3-(dimethylamino)propyl]guanidine Chemical compound CN(C)CCCN=C(N)N CPVHXMXPICPCIC-UHFFFAOYSA-N 0.000 description 4
• ATESHHKXEZPZJE-UHFFFAOYSA-N 2-[3-chloro-4-(4-methylpiperazin-1-yl)phenyl]guanidine Chemical compound C1CN(C)CCN1C1=CC=C(NC(N)=N)C=C1Cl ATESHHKXEZPZJE-UHFFFAOYSA-N 0.000 description 4
• WXHAKLOKRJOHCT-UHFFFAOYSA-N 3-(2-methylsulfanylpyrimidin-4-yl)-7h-pyrazolo[1,5-b]pyridazin-6-one Chemical compound CSC1=NC=CC(C2=C3C=CC(O)=NN3N=C2)=N1 WXHAKLOKRJOHCT-UHFFFAOYSA-N 0.000 description 4
• WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 4
• ACOQMBCUCSILLI-UHFFFAOYSA-N 3-acetyl-7h-pyrazolo[1,5-b]pyridazin-6-one Chemical compound N1=C(O)C=CC2=C(C(=O)C)C=NN21 ACOQMBCUCSILLI-UHFFFAOYSA-N 0.000 description 4
• ASFHDLDAWYTMJS-UHFFFAOYSA-N 3-methoxypyridazine Chemical compound COC1=CC=CN=N1 ASFHDLDAWYTMJS-UHFFFAOYSA-N 0.000 description 4
• MOZNZNKHRXRLLF-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C=C1 MOZNZNKHRXRLLF-UHFFFAOYSA-N 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• XIWRFILASNDQLM-UHFFFAOYSA-N 4-[3-(2-methylsulfanylpyrimidin-4-yl)pyrazolo[1,5-b]pyridazin-6-yl]morpholine Chemical compound CSC1=NC=CC(C2=C3C=CC(=NN3N=C2)N2CCOCC2)=N1 XIWRFILASNDQLM-UHFFFAOYSA-N 0.000 description 4
• SECBGKYJKCNDID-UHFFFAOYSA-N 4-iodo-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC(I)=N1 SECBGKYJKCNDID-UHFFFAOYSA-N 0.000 description 4
• RGSBOIOBKBSQLS-UHFFFAOYSA-N 6-(4-fluorophenyl)-3-(2-methylsulfanylpyrimidin-4-yl)pyrazolo[1,5-b]pyridazine Chemical compound CSC1=NC=CC(C2=C3C=CC(=NN3N=C2)C=2C=CC(F)=CC=2)=N1 RGSBOIOBKBSQLS-UHFFFAOYSA-N 0.000 description 4
• WHJJXBNMUBSOEN-UHFFFAOYSA-N 6-methoxy-3-(2-methylsulfanylpyrimidin-4-yl)pyrazolo[1,5-b]pyridazine Chemical compound C1=NN2N=C(OC)C=CC2=C1C1=CC=NC(SC)=N1 WHJJXBNMUBSOEN-UHFFFAOYSA-N 0.000 description 4
• 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 4
• 102000016736 Cyclin Human genes 0.000 description 4
• 108050006400 Cyclin Proteins 0.000 description 4
• 102000001301 EGF receptor Human genes 0.000 description 4
• 108060006698 EGF receptor Proteins 0.000 description 4
• 102000009465 Growth Factor Receptors Human genes 0.000 description 4
• 108010009202 Growth Factor Receptors Proteins 0.000 description 4
• 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
• 108091008606 PDGF receptors Proteins 0.000 description 4
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 4
• RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 108091008605 VEGF receptors Proteins 0.000 description 4
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 4
• 230000002159 abnormal effect Effects 0.000 description 4
• 230000004913 activation Effects 0.000 description 4
• 150000001298 alcohols Chemical class 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 150000001555 benzenes Chemical group 0.000 description 4
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 239000011248 coating agent Substances 0.000 description 4
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 4
• 229960004397 cyclophosphamide Drugs 0.000 description 4
• 239000002254 cytotoxic agent Substances 0.000 description 4
• 231100000599 cytotoxic agent Toxicity 0.000 description 4
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 229960004679 doxorubicin Drugs 0.000 description 4
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 229960004198 guanidine Drugs 0.000 description 4
• 210000004209 hair Anatomy 0.000 description 4
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 4
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• ZGPQUFZDMCAFGN-UHFFFAOYSA-N n-(4-methylsulfonylphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 ZGPQUFZDMCAFGN-UHFFFAOYSA-N 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 239000000047 product Substances 0.000 description 4
• 238000001959 radiotherapy Methods 0.000 description 4
• 239000002002 slurry Substances 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
• RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 4
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
• 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 4
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
• 0 **1C=N[n]2nc(*)c(-c3nc(*)ncc3)c2C=C1 Chemical compound **1C=N[n]2nc(*)c(-c3nc(*)ncc3)c2C=C1 0.000 description 3
• 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 3
• POAOYUHQDCAZBD-UHFFFAOYSA-N 2-butoxyethanol Chemical compound CCCCOCCO POAOYUHQDCAZBD-UHFFFAOYSA-N 0.000 description 3
• MKARNSWMMBGSHX-UHFFFAOYSA-N 3,5-dimethylaniline Chemical compound CC1=CC(C)=CC(N)=C1 MKARNSWMMBGSHX-UHFFFAOYSA-N 0.000 description 3
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
• HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 3
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 3
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
• 206010028116 Mucosal inflammation Diseases 0.000 description 3
• 201000010927 Mucositis Diseases 0.000 description 3
• 235000008331 Pinus X rigitaeda Nutrition 0.000 description 3
• 235000011613 Pinus brutia Nutrition 0.000 description 3
• 241000018646 Pinus brutia Species 0.000 description 3
• 108050002653 Retinoblastoma protein Proteins 0.000 description 3
• 230000018199 S phase Effects 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 230000033228 biological regulation Effects 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 239000007819 coupling partner Substances 0.000 description 3
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
• 229960005420 etoposide Drugs 0.000 description 3
• 230000012010 growth Effects 0.000 description 3
• 125000004438 haloalkoxy group Chemical group 0.000 description 3
• 125000005553 heteroaryloxy group Chemical class 0.000 description 3
• 150000002430 hydrocarbons Chemical class 0.000 description 3
• 239000000543 intermediate Substances 0.000 description 3
• 238000002844 melting Methods 0.000 description 3
• 230000008018 melting Effects 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• 230000011278 mitosis Effects 0.000 description 3
• ULKTXVYWINYRCP-UHFFFAOYSA-N n-cyclopropyl-4-(6-thiophen-2-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)C=2SC=CC=2)=N1 ULKTXVYWINYRCP-UHFFFAOYSA-N 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• 239000006072 paste Substances 0.000 description 3
• 230000026731 phosphorylation Effects 0.000 description 3
• 238000006366 phosphorylation reaction Methods 0.000 description 3
• 229920000642 polymer Polymers 0.000 description 3
• 239000011736 potassium bicarbonate Substances 0.000 description 3
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
• 230000002062 proliferating effect Effects 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 3
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 3
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
• 239000002994 raw material Substances 0.000 description 3
• 210000004761 scalp Anatomy 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 239000006188 syrup Substances 0.000 description 3
• 235000020357 syrup Nutrition 0.000 description 3
• 239000007885 tablet disintegrant Substances 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 238000011200 topical administration Methods 0.000 description 3
• 230000000699 topical effect Effects 0.000 description 3
• 239000001993 wax Substances 0.000 description 3
• RRCMGJCFMJBHQC-UHFFFAOYSA-N (2-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1Cl RRCMGJCFMJBHQC-UHFFFAOYSA-N 0.000 description 2
• YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 description 2
• 125000006591 (C2-C6) alkynylene group Chemical group 0.000 description 2
• MZXHAQHOJNFWMS-PKNBQFBNSA-N (e)-1-(2-butylpyrazolo[1,5-b]pyridazin-3-yl)-3-(dimethylamino)prop-2-en-1-one Chemical compound N1=CC=CC2=C(C(=O)\C=C\N(C)C)C(CCCC)=NN21 MZXHAQHOJNFWMS-PKNBQFBNSA-N 0.000 description 2
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
• UGWLVPRDJISIRN-UHFFFAOYSA-N 1-(2-butylpyrazolo[1,5-b]pyridazin-3-yl)ethanone Chemical compound N1=CC=CC2=C(C(C)=O)C(CCCC)=NN21 UGWLVPRDJISIRN-UHFFFAOYSA-N 0.000 description 2
• HJORCZCMNWLHMB-UHFFFAOYSA-N 1-(3-aminopropyl)pyrrolidin-2-one Chemical compound NCCCN1CCCC1=O HJORCZCMNWLHMB-UHFFFAOYSA-N 0.000 description 2
• BOYVZXJHUROLHZ-UHFFFAOYSA-N 1-(4-aminophenoxy)-3-(dimethylamino)propan-2-ol Chemical compound CN(C)CC(O)COC1=CC=C(N)C=C1 BOYVZXJHUROLHZ-UHFFFAOYSA-N 0.000 description 2
• VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 2
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 2
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 2
• KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 2
• FNGZREDJXWXRBW-UHFFFAOYSA-N 2-(1,3-benzoxazol-2-yl)guanidine Chemical compound C1=CC=C2OC(N=C(N)N)=NC2=C1 FNGZREDJXWXRBW-UHFFFAOYSA-N 0.000 description 2
• BAEUIPJYUMAYSN-UHFFFAOYSA-N 2-(3,5-dimethylphenyl)guanidine;nitric acid Chemical compound O[N+]([O-])=O.CC1=CC(C)=CC(N=C(N)N)=C1 BAEUIPJYUMAYSN-UHFFFAOYSA-N 0.000 description 2
• ZSJNJAJDBNFVCA-UHFFFAOYSA-N 2-(4-chlorophenyl)guanidine Chemical compound NC(=N)NC1=CC=C(Cl)C=C1 ZSJNJAJDBNFVCA-UHFFFAOYSA-N 0.000 description 2
• VEMGTEYSZCHJBT-UHFFFAOYSA-N 2-(4-cyanophenyl)guanidine;nitric acid Chemical compound O[N+]([O-])=O.NC(N)=NC1=CC=C(C#N)C=C1 VEMGTEYSZCHJBT-UHFFFAOYSA-N 0.000 description 2
• STTLMODNENPLQQ-UHFFFAOYSA-N 2-(4-fluorophenyl)guanidine Chemical compound NC(N)=NC1=CC=C(F)C=C1 STTLMODNENPLQQ-UHFFFAOYSA-N 0.000 description 2
• VGFALHATLLBXIT-UHFFFAOYSA-N 2-(4-methoxyphenyl)guanidine Chemical compound COC1=CC=C(N=C(N)N)C=C1 VGFALHATLLBXIT-UHFFFAOYSA-N 0.000 description 2
• IFYPQHGXCVZZMW-UHFFFAOYSA-N 2-(6-chloro-1h-benzimidazol-2-yl)guanidine Chemical compound C1=C(Cl)C=C2NC(N=C(N)N)=NC2=C1 IFYPQHGXCVZZMW-UHFFFAOYSA-N 0.000 description 2
• XOMHDUZSIINNDA-UHFFFAOYSA-N 2-[3-(2-oxopyrrolidin-1-yl)propyl]guanidine Chemical compound NC(=N)NCCCN1CCCC1=O XOMHDUZSIINNDA-UHFFFAOYSA-N 0.000 description 2
• UNZKIANEZWFDER-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]guanidine Chemical compound NC(N)=NC1=CC=CC(C(F)(F)F)=C1 UNZKIANEZWFDER-UHFFFAOYSA-N 0.000 description 2
• HNLIDWZRHSZHPO-UHFFFAOYSA-N 2-[3-methyl-4-(4-methylpiperazin-1-yl)phenyl]guanidine Chemical compound C1CN(C)CCN1C1=CC=C(NC(N)=N)C=C1C HNLIDWZRHSZHPO-UHFFFAOYSA-N 0.000 description 2
• RLXZVWWVBVXVPL-UHFFFAOYSA-N 2-[4-(diethylaminomethyl)phenyl]guanidine Chemical compound CCN(CC)CC1=CC=C(NC(N)=N)C=C1 RLXZVWWVBVXVPL-UHFFFAOYSA-N 0.000 description 2
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 2
• CASDLXCHUTYPAO-UHFFFAOYSA-N 2-chloro-n-phenylaniline Chemical compound ClC1=CC=CC=C1NC1=CC=CC=C1 CASDLXCHUTYPAO-UHFFFAOYSA-N 0.000 description 2
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
• QRJZGVVKGFIGLI-UHFFFAOYSA-N 2-phenylguanidine Chemical compound NC(=N)NC1=CC=CC=C1 QRJZGVVKGFIGLI-UHFFFAOYSA-N 0.000 description 2
• XEFRNCLPPFDWAC-UHFFFAOYSA-N 3,4,5-trimethoxyaniline Chemical compound COC1=CC(N)=CC(OC)=C1OC XEFRNCLPPFDWAC-UHFFFAOYSA-N 0.000 description 2
• AIELNJDAOGTASK-UHFFFAOYSA-N 3-(1,3-oxazol-5-yl)aniline Chemical compound NC1=CC=CC(C=2OC=NC=2)=C1 AIELNJDAOGTASK-UHFFFAOYSA-N 0.000 description 2
• NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 description 2
• LOCKPKWGFIBYLB-UHFFFAOYSA-N 3-chloro-4-(4-methylpiperazin-1-yl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C=C1Cl LOCKPKWGFIBYLB-UHFFFAOYSA-N 0.000 description 2
• BBUAXVLPFRRBQR-UHFFFAOYSA-N 3-chloro-4-morpholin-4-ylaniline Chemical compound ClC1=CC(N)=CC=C1N1CCOCC1 BBUAXVLPFRRBQR-UHFFFAOYSA-N 0.000 description 2
• XBJLKXOOHLLTPG-UHFFFAOYSA-N 3-chloro-6-methoxypyridazine Chemical compound COC1=CC=C(Cl)N=N1 XBJLKXOOHLLTPG-UHFFFAOYSA-N 0.000 description 2
• VVMXAXVHQDIGRF-UHFFFAOYSA-N 3-methyl-4-(4-methylpiperazin-1-yl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C=C1C VVMXAXVHQDIGRF-UHFFFAOYSA-N 0.000 description 2
• VNRHTFXMONFRSL-UHFFFAOYSA-N 3-nitro-n-phenylaniline Chemical compound [O-][N+](=O)C1=CC=CC(NC=2C=CC=CC=2)=C1 VNRHTFXMONFRSL-UHFFFAOYSA-N 0.000 description 2
• WFRXSXUDWCVSPI-UHFFFAOYSA-N 3h-benzimidazol-5-amine Chemical compound NC1=CC=C2NC=NC2=C1 WFRXSXUDWCVSPI-UHFFFAOYSA-N 0.000 description 2
• AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 2
• PRIMSUJUKMYIQS-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C=C1C(F)(F)F PRIMSUJUKMYIQS-UHFFFAOYSA-N 0.000 description 2
• IARPVBSELLNETO-UHFFFAOYSA-N 4-(diaminomethylideneamino)-n-[2-(diethylamino)ethyl]benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(NC(N)=N)C=C1 IARPVBSELLNETO-UHFFFAOYSA-N 0.000 description 2
• AFHLJRYAVLIEMS-UHFFFAOYSA-N 4-(diethylaminomethyl)aniline Chemical compound CCN(CC)CC1=CC=C(N)C=C1 AFHLJRYAVLIEMS-UHFFFAOYSA-N 0.000 description 2
• VSZVMUGJWVQEOS-UHFFFAOYSA-N 4-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 VSZVMUGJWVQEOS-UHFFFAOYSA-N 0.000 description 2
• YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 description 2
• DFOHHQRGDOQMKG-UHFFFAOYSA-N 4-chloro-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC(Cl)=N1 DFOHHQRGDOQMKG-UHFFFAOYSA-N 0.000 description 2
• ZQPNFOFVPZSCAR-UHFFFAOYSA-N 4-ethynyl-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC(C#C)=N1 ZQPNFOFVPZSCAR-UHFFFAOYSA-N 0.000 description 2
• LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 2
• SXTSBZBQQRIYCU-UHFFFAOYSA-N 4-guanidinobenzoic acid Chemical compound NC(=N)NC1=CC=C(C(O)=O)C=C1 SXTSBZBQQRIYCU-UHFFFAOYSA-N 0.000 description 2
• XJEVFFNOMKXBLU-UHFFFAOYSA-N 4-methylsulfonylaniline Chemical compound CS(=O)(=O)C1=CC=C(N)C=C1 XJEVFFNOMKXBLU-UHFFFAOYSA-N 0.000 description 2
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
• FUXVKZWTXQUGMW-FQEVSTJZSA-N 9-Aminocamptothecin Chemical compound C1=CC(N)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 FUXVKZWTXQUGMW-FQEVSTJZSA-N 0.000 description 2
• 244000215068 Acacia senegal Species 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
• 101150012716 CDK1 gene Proteins 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 102000002554 Cyclin A Human genes 0.000 description 2
• 108010068192 Cyclin A Proteins 0.000 description 2
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
• 230000006820 DNA synthesis Effects 0.000 description 2
• WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 2
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 2
• XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
• GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
• BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 2
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
• 150000001204 N-oxides Chemical class 0.000 description 2
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
• 229930012538 Paclitaxel Natural products 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 description 2
• 230000001594 aberrant effect Effects 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
• 150000001241 acetals Chemical class 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 2
• OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 2
• 229960003459 allopurinol Drugs 0.000 description 2
• CHKQALUEEULCPZ-UHFFFAOYSA-N amino 2,4,6-trimethylbenzenesulfonate Chemical group CC1=CC(C)=C(S(=O)(=O)ON)C(C)=C1 CHKQALUEEULCPZ-UHFFFAOYSA-N 0.000 description 2
• YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 2
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
• 230000000118 anti-neoplastic effect Effects 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 125000005163 aryl sulfanyl group Chemical group 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
• 235000012216 bentonite Nutrition 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229910052796 boron Inorganic materials 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
• 229960002092 busulfan Drugs 0.000 description 2
• XRGPFNGLRSIPSA-UHFFFAOYSA-N butyn-2-one Chemical compound CC(=O)C#C XRGPFNGLRSIPSA-UHFFFAOYSA-N 0.000 description 2
• 229940127093 camptothecin Drugs 0.000 description 2
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
• JFOYSMKTEGQVHB-UHFFFAOYSA-N carbonic acid;2-(4-methylsulfonylphenyl)guanidine Chemical compound OC(O)=O.CS(=O)(=O)C1=CC=C(N=C(N)N)C=C1 JFOYSMKTEGQVHB-UHFFFAOYSA-N 0.000 description 2
• QDEMKSFGEKESRT-UHFFFAOYSA-N carbonic acid;2-(4-sulfamoylphenyl)guanidine Chemical compound OC(O)=O.NC(N)=NC1=CC=C(S(N)(=O)=O)C=C1 QDEMKSFGEKESRT-UHFFFAOYSA-N 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 229960004562 carboplatin Drugs 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
• 229960005243 carmustine Drugs 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 229960000590 celecoxib Drugs 0.000 description 2
• RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 2
• 230000032823 cell division Effects 0.000 description 2
• 238000000451 chemical ionisation Methods 0.000 description 2
• 230000000973 chemotherapeutic effect Effects 0.000 description 2
• 208000022605 chemotherapy-induced alopecia Diseases 0.000 description 2
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
• 229960004630 chlorambucil Drugs 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 229960004316 cisplatin Drugs 0.000 description 2
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 238000006352 cycloaddition reaction Methods 0.000 description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 229960000684 cytarabine Drugs 0.000 description 2
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
• CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 229960003668 docetaxel Drugs 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• 229960001904 epirubicin Drugs 0.000 description 2
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 2
• 150000002170 ethers Chemical class 0.000 description 2
• 229940052303 ethers for general anesthesia Drugs 0.000 description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
• 238000011049 filling Methods 0.000 description 2
• 239000012467 final product Substances 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 229960002949 fluorouracil Drugs 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 230000014509 gene expression Effects 0.000 description 2
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
• 238000005469 granulation Methods 0.000 description 2
• 230000003179 granulation Effects 0.000 description 2
• 239000003102 growth factor Substances 0.000 description 2
• 210000003780 hair follicle Anatomy 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• LTAPKZGQTMVYMX-UHFFFAOYSA-N hex-3-yn-2-one Chemical compound CCC#CC(C)=O LTAPKZGQTMVYMX-UHFFFAOYSA-N 0.000 description 2
• UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 229910000043 hydrogen iodide Inorganic materials 0.000 description 2
• 229960000908 idarubicin Drugs 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 229940090044 injection Drugs 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 229960004768 irinotecan Drugs 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 229960002247 lomustine Drugs 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 230000036210 malignancy Effects 0.000 description 2
• OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 2
• 229950008959 marimastat Drugs 0.000 description 2
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
• 229960001924 melphalan Drugs 0.000 description 2
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
• LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
• CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 2
• 229960004857 mitomycin Drugs 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• DBNQIOANXZVWIP-UHFFFAOYSA-N n,n-dimethyl-1,1-bis[(2-methylpropan-2-yl)oxy]methanamine Chemical compound CC(C)(C)OC(N(C)C)OC(C)(C)C DBNQIOANXZVWIP-UHFFFAOYSA-N 0.000 description 2
• RPRZAINAFJBVOV-UHFFFAOYSA-N n-cyclopropyl-4-(2-ethylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound CCC1=NN2N=CC=CC2=C1C(N=1)=CC=NC=1NC1CC1 RPRZAINAFJBVOV-UHFFFAOYSA-N 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 230000003287 optical effect Effects 0.000 description 2
• 229960001756 oxaliplatin Drugs 0.000 description 2
• DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
• BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 2
• ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
• 229960001592 paclitaxel Drugs 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 229940080469 phosphocellulose Drugs 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 229960003171 plicamycin Drugs 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 description 2
• 229960003387 progesterone Drugs 0.000 description 2
• 239000000186 progesterone Substances 0.000 description 2
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 238000003345 scintillation counting Methods 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 229960001603 tamoxifen Drugs 0.000 description 2
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 125000003396 thiol group Chemical class [H]S* 0.000 description 2
• ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 2
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 2
• 229960000303 topotecan Drugs 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 229910052723 transition metal Inorganic materials 0.000 description 2
• 150000003624 transition metals Chemical class 0.000 description 2
• QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
• 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
• 241000701447 unidentified baculovirus Species 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 229960003048 vinblastine Drugs 0.000 description 2
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
• 229960004528 vincristine Drugs 0.000 description 2
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
• GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 2
• OMJKFYKNWZZKTK-POHAHGRESA-N (5z)-5-(dimethylaminohydrazinylidene)imidazole-4-carboxamide Chemical compound CN(C)N\N=C1/N=CN=C1C(N)=O OMJKFYKNWZZKTK-POHAHGRESA-N 0.000 description 1
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 description 1
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 1
• GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
• LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
• POPVUKGJWNLYGW-UHFFFAOYSA-N (hydroxyamino) hydrogen sulfate Chemical compound ONOS(O)(=O)=O POPVUKGJWNLYGW-UHFFFAOYSA-N 0.000 description 1
• DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
• XGNXYCFREOZBOL-UHFFFAOYSA-N 1,3-benzodioxol-5-amine Chemical compound NC1=CC=C2OCOC2=C1 XGNXYCFREOZBOL-UHFFFAOYSA-N 0.000 description 1
• IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• 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
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• ZFYUCIPARAFUGP-UHFFFAOYSA-N 1h-pyridazin-2-amine Chemical class NN1NC=CC=C1 ZFYUCIPARAFUGP-UHFFFAOYSA-N 0.000 description 1
• BZKOZYWGZKRTIB-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-6-amine Chemical compound O1CCOC2=CC(N)=CC=C21 BZKOZYWGZKRTIB-UHFFFAOYSA-N 0.000 description 1
• QAVCQCQQTYJKSO-UHFFFAOYSA-N 2-chloro-11-cyclopropyl-4-methyl-5h-dipyrido[2,3-b:2',3'-f][1,4]diazepin-6-one Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC(Cl)=NC=2N1C1CC1 QAVCQCQQTYJKSO-UHFFFAOYSA-N 0.000 description 1
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
• RGUABPVONIGVAT-UHFFFAOYSA-N 3-(4-methylpiperazin-1-yl)propan-1-amine Chemical compound CN1CCN(CCCN)CC1 RGUABPVONIGVAT-UHFFFAOYSA-N 0.000 description 1
• LBVZCSKDTGDAQW-UHFFFAOYSA-N 3-[(2-oxo-1,3-oxazolidin-3-yl)phosphanyl]-1,3-oxazolidin-2-one;hydrochloride Chemical compound [Cl-].O=C1OCCN1[PH2+]N1C(=O)OCC1 LBVZCSKDTGDAQW-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
• ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
• UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 1
• UWSPFMUDTQWGIS-UHFFFAOYSA-N 3-n-methyl-1-n-(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)butane-1,3-diamine Chemical compound CNC(C)CCNC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 UWSPFMUDTQWGIS-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
• QDPPIHBIRIEZND-UHFFFAOYSA-N 6-chloro-n-(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)-1h-benzimidazol-2-amine Chemical compound C1=NN2N=CC=CC2=C1C1=NC(NC2=NC3=CC=C(C=C3N2)Cl)=NC=C1 QDPPIHBIRIEZND-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
• 206010051113 Arterial restenosis Diseases 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
• 206010003645 Atopy Diseases 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 108090001008 Avidin Proteins 0.000 description 1
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• SCGJEJQBXNKTHD-UHFFFAOYSA-N CC1C=N[n]2ncc(-c3ccnc(NC4=CC(c5cnc[o]5)=CCC4)n3)c2C1 Chemical compound CC1C=N[n]2ncc(-c3ccnc(NC4=CC(c5cnc[o]5)=CCC4)n3)c2C1 SCGJEJQBXNKTHD-UHFFFAOYSA-N 0.000 description 1
• JDISMDCQRJLWQD-UHFFFAOYSA-N CCCC1(C)C=NN=CC=C1 Chemical compound CCCC1(C)C=NN=CC=C1 JDISMDCQRJLWQD-UHFFFAOYSA-N 0.000 description 1
• DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 244000132059 Carica parviflora Species 0.000 description 1
• 235000014653 Carica parviflora Nutrition 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 102000002427 Cyclin B Human genes 0.000 description 1
• 108010068150 Cyclin B Proteins 0.000 description 1
• 102000003910 Cyclin D Human genes 0.000 description 1
• 108090000259 Cyclin D Proteins 0.000 description 1
• 108010058546 Cyclin D1 Proteins 0.000 description 1
• 102000003909 Cyclin E Human genes 0.000 description 1
• 108090000257 Cyclin E Proteins 0.000 description 1
• 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 1
• 102000013698 Cyclin-Dependent Kinase 6 Human genes 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
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
• 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 1
• 241000206672 Gelidium Species 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
• 108010024636 Glutathione Proteins 0.000 description 1
• 102000005720 Glutathione transferase Human genes 0.000 description 1
• 108010070675 Glutathione transferase Proteins 0.000 description 1
• 108010069236 Goserelin Proteins 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
• 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
• 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• GNIWAQQRDUGBIA-UHFFFAOYSA-N O=Cc1n[n]2ncc(-c3ccnc(NC4CC4)n3)c2cc1 Chemical compound O=Cc1n[n]2ncc(-c3ccnc(NC4CC4)n3)c2cc1 GNIWAQQRDUGBIA-UHFFFAOYSA-N 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 108010039918 Polylysine Proteins 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 238000006619 Stille reaction Methods 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical class O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
• 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• 229920002253 Tannate Polymers 0.000 description 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 206010057362 Underdose Diseases 0.000 description 1
• 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• 238000002441 X-ray diffraction Methods 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
• AUYLVPGDOVEOML-UHFFFAOYSA-N [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-[4-(piperidin-1-ylmethoxy)phenyl]methanone Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 AUYLVPGDOVEOML-UHFFFAOYSA-N 0.000 description 1
• ZKHQWZAMYRWXGA-KNYAHOBESA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] dihydroxyphosphoryl hydrogen phosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)O[32P](O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KNYAHOBESA-N 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 231100000230 acceptable toxicity Toxicity 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 208000038016 acute inflammation Diseases 0.000 description 1
• 230000006022 acute inflammation Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 229940009456 adriamycin Drugs 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 125000003158 alcohol group Chemical group 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 125000003282 alkyl amino group Chemical group 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229960000473 altretamine Drugs 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000000539 amino acid group Chemical group 0.000 description 1
• 229960002932 anastrozole Drugs 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000002280 anti-androgenic effect Effects 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 229940124650 anti-cancer therapies Drugs 0.000 description 1
• 229940046836 anti-estrogen Drugs 0.000 description 1
• 230000001833 anti-estrogenic effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 239000003886 aromatase inhibitor Substances 0.000 description 1
• 229940046844 aromatase inhibitors Drugs 0.000 description 1
• 239000008122 artificial sweetener Substances 0.000 description 1
• 235000021311 artificial sweeteners Nutrition 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 238000010009 beating Methods 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 229960000997 bicalutamide Drugs 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 238000009395 breeding Methods 0.000 description 1
• 230000001488 breeding effect Effects 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000001767 chemoprotection Effects 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 230000006020 chronic inflammation Effects 0.000 description 1
• 229940090805 clavulanate Drugs 0.000 description 1
• HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 230000000112 colonic effect Effects 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000004966 cyanoalkyl group Chemical group 0.000 description 1
• 239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 1
• 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
• 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000006317 cyclopropyl amino group Chemical group 0.000 description 1
• 229960000978 cyproterone acetate Drugs 0.000 description 1
• UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
• 229960003901 dacarbazine Drugs 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 125000004663 dialkyl amino group Chemical group 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
• IRUNKQSGDBYUDC-UHFFFAOYSA-N diethoxymethyl acetate Chemical compound CCOC(OCC)OC(C)=O IRUNKQSGDBYUDC-UHFFFAOYSA-N 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
• 239000001177 diphosphate Substances 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 150000004141 diterpene derivatives Chemical class 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 229950004203 droloxifene Drugs 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 239000013583 drug formulation Substances 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 229940009662 edetate Drugs 0.000 description 1
• 229950005627 embonate Drugs 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 229950000206 estolate Drugs 0.000 description 1
• 239000000328 estrogen antagonist Substances 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 229940075383 etoposide injection Drugs 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 229960000255 exemestane Drugs 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 230000000893 fibroproliferative effect Effects 0.000 description 1
• DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
• 229960004039 finasteride Drugs 0.000 description 1
• 239000010419 fine particle Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 150000005699 fluoropyrimidines Chemical class 0.000 description 1
• MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
• 229960002074 flutamide Drugs 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 125000001543 furan-2,5-diyl group Chemical group O1C(=CC=C1*)* 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 230000008570 general process Effects 0.000 description 1
• 229960001731 gluceptate Drugs 0.000 description 1
• KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229940049906 glutamate Drugs 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
• 229960003690 goserelin acetate Drugs 0.000 description 1
• 235000015220 hamburgers Nutrition 0.000 description 1
• 201000011066 hemangioma Diseases 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 239000008309 hydrophilic cream Substances 0.000 description 1
• 150000002440 hydroxy compounds Chemical class 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• IIXGBDGCPUYARL-UHFFFAOYSA-N hydroxysulfamic acid Chemical compound ONS(O)(=O)=O IIXGBDGCPUYARL-UHFFFAOYSA-N 0.000 description 1
• 230000003463 hyperproliferative effect Effects 0.000 description 1
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 210000004347 intestinal mucosa Anatomy 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 150000004694 iodide salts Chemical group 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 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
• 208000017169 kidney disease Diseases 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-M lactobionate Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-M 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 229960003881 letrozole Drugs 0.000 description 1
• HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 238000005567 liquid scintillation counting Methods 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• 229960004296 megestrol acetate Drugs 0.000 description 1
• RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
• 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
• 230000031864 metaphase Effects 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 229940102396 methyl bromide Drugs 0.000 description 1
• MDFRYRPNRLLJHT-UHFFFAOYSA-N methyl carbamimidate;sulfuric acid Chemical compound COC(N)=N.OS(O)(=O)=O MDFRYRPNRLLJHT-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 239000003595 mist Substances 0.000 description 1
• 239000002324 mouth wash Substances 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• 210000003097 mucus Anatomy 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• RUZOPLSOXYLSIU-UHFFFAOYSA-N n',n'-dimethyl-n-(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)propane-1,3-diamine Chemical compound CN(C)CCCNC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 RUZOPLSOXYLSIU-UHFFFAOYSA-N 0.000 description 1
• BXGTVNLGPMZLAZ-UHFFFAOYSA-N n'-ethylmethanediimine;hydrochloride Chemical compound Cl.CCN=C=N BXGTVNLGPMZLAZ-UHFFFAOYSA-N 0.000 description 1
• BLCLNMBMMGCOAS-UHFFFAOYSA-N n-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amin Chemical compound C1CCC(C(=O)NNC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(COC(C)(C)C)NC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 BLCLNMBMMGCOAS-UHFFFAOYSA-N 0.000 description 1
• FWECJQPLAGZXNZ-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-4-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]benzamide Chemical compound C1=CC(C(=O)NCCN(CC)CC)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 FWECJQPLAGZXNZ-UHFFFAOYSA-N 0.000 description 1
• AJLPDJZYNSSQJO-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-4-(6-propan-2-yloxypyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1=NN2N=C(OC(C)C)C=CC2=C1C(N=1)=CC=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 AJLPDJZYNSSQJO-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 239000007923 nasal drop Substances 0.000 description 1
• 229940100662 nasal drops Drugs 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 235000021096 natural sweeteners Nutrition 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 229960002653 nilutamide Drugs 0.000 description 1
• XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
• REOYYGKJQOLCPZ-UHFFFAOYSA-N nitric acid;2-(4-nitrophenyl)guanidine Chemical compound O[N+]([O-])=O.NC(N)=NC1=CC=C([N+]([O-])=O)C=C1 REOYYGKJQOLCPZ-UHFFFAOYSA-N 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• VJKHTMGYHCBXHV-UHFFFAOYSA-N oct-3-yn-2-one Chemical compound CCCCC#CC(C)=O VJKHTMGYHCBXHV-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229940014662 pantothenate Drugs 0.000 description 1
• 235000019161 pantothenic acid Nutrition 0.000 description 1
• 239000011713 pantothenic acid Substances 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000011236 particulate material Substances 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• DZOOXMGZVWHNAS-UHFFFAOYSA-N pent-3-yn-2-one Chemical compound CC#CC(C)=O DZOOXMGZVWHNAS-UHFFFAOYSA-N 0.000 description 1
• 235000019477 peppermint oil Nutrition 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 125000004344 phenylpropyl group Chemical group 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
• LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
• 238000003566 phosphorylation assay Methods 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 238000007747 plating Methods 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229920000747 poly(lactic acid) Polymers 0.000 description 1
• 239000002745 poly(ortho ester) Substances 0.000 description 1
• 229920001610 polycaprolactone Polymers 0.000 description 1
• 229920002721 polycyanoacrylate Polymers 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 239000004626 polylactic acid Substances 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 229920006324 polyoxymethylene Polymers 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
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• QPMDWIOUHQWKHV-ODZAUARKSA-M potassium;(z)-4-hydroxy-4-oxobut-2-enoate Chemical compound [K+].OC(=O)\C=C/C([O-])=O QPMDWIOUHQWKHV-ODZAUARKSA-M 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
• 239000011253 protective coating Substances 0.000 description 1
• 230000009822 protein phosphorylation Effects 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• DVUBDHRTVYLIPA-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine Chemical class C1=CC=CN2N=CC=C21 DVUBDHRTVYLIPA-UHFFFAOYSA-N 0.000 description 1
• XNSUDGUHSLGJCZ-UHFFFAOYSA-N pyrazolo[1,5-b]pyridazin-6-yl trifluoromethanesulfonate Chemical compound N1=CC=C2N1N=C(C=C2)OS(=O)(=O)C(F)(F)F XNSUDGUHSLGJCZ-UHFFFAOYSA-N 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• FNBIAQKEPYUKHX-UHFFFAOYSA-N pyridazin-3-yl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=CN=N1 FNBIAQKEPYUKHX-UHFFFAOYSA-N 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 238000011127 radiochemotherapy Methods 0.000 description 1
• 229960004622 raloxifene Drugs 0.000 description 1
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
• 238000011552 rat model Methods 0.000 description 1
• 239000012429 reaction media Substances 0.000 description 1
• 230000009703 regulation of cell differentiation Effects 0.000 description 1
• 230000021014 regulation of cell growth Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000002207 retinal effect Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 235000019204 saccharin Nutrition 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
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 238000002821 scintillation proximity assay Methods 0.000 description 1
• 239000000565 sealant Substances 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 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
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
• ABBQHOQBGMUPJH-UHFFFAOYSA-N sodium;2-hydroxybenzoic acid Chemical compound [Na+].OC(=O)C1=CC=CC=C1O ABBQHOQBGMUPJH-UHFFFAOYSA-N 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 238000013223 sprague-dawley female rat Methods 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
• 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003457 sulfones Chemical class 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 150000003464 sulfur compounds Chemical class 0.000 description 1
• 229910052815 sulfur oxide Inorganic materials 0.000 description 1
• 235000010269 sulphur dioxide Nutrition 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• 229950002757 teoclate Drugs 0.000 description 1
• DHHKPEUQJIEKOA-UHFFFAOYSA-N tert-butyl 2-[6-(nitromethyl)-6-bicyclo[3.2.0]hept-3-enyl]acetate Chemical compound C1C=CC2C(CC(=O)OC(C)(C)C)(C[N+]([O-])=O)CC21 DHHKPEUQJIEKOA-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 229960003604 testosterone Drugs 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 150000003573 thiols Chemical class 0.000 description 1
• MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
• 229960003087 tioguanine Drugs 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 229940100611 topical cream Drugs 0.000 description 1
• 229940100615 topical ointment Drugs 0.000 description 1
• XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
• 229960005026 toremifene Drugs 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
• BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 1
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
• UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
• 229960004355 vindesine Drugs 0.000 description 1
• 229960002066 vinorelbine Drugs 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052726 zirconium Inorganic materials 0.000 description 1
• 229930195724 β-lactose Natural products 0.000 description 1