ZA200305533B - 2-Phenyl benzimidazoles and imidazo-[4,5]-pyridines as Cds1/Chk2-inhibitors and adjuvants to chemotherapy or radiation therapy in the treatment of cancer. - Google Patents
2-Phenyl benzimidazoles and imidazo-[4,5]-pyridines as Cds1/Chk2-inhibitors and adjuvants to chemotherapy or radiation therapy in the treatment of cancer. Download PDFInfo
- Publication number
- ZA200305533B ZA200305533B ZA200305533A ZA200305533A ZA200305533B ZA 200305533 B ZA200305533 B ZA 200305533B ZA 200305533 A ZA200305533 A ZA 200305533A ZA 200305533 A ZA200305533 A ZA 200305533A ZA 200305533 B ZA200305533 B ZA 200305533B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- acid amide
- carboxylic acid
- benzoimidazole
- chloro
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 56
- 238000011282 treatment Methods 0.000 title claims abstract description 53
- 201000011510 cancer Diseases 0.000 title claims abstract description 42
- 101150095530 CDS1 gene Proteins 0.000 title abstract description 23
- 239000002671 adjuvant Substances 0.000 title abstract description 17
- 239000003112 inhibitor Substances 0.000 title abstract description 4
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical class C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 title abstract description 3
- 238000002512 chemotherapy Methods 0.000 title abstract description 3
- 238000001959 radiotherapy Methods 0.000 title abstract description 3
- DWYHDSLIWMUSOO-UHFFFAOYSA-N 2-phenyl-1h-benzimidazole Chemical class C1=CC=CC=C1C1=NC2=CC=CC=C2N1 DWYHDSLIWMUSOO-UHFFFAOYSA-N 0.000 title 1
- -1 piperazin-diyl Chemical group 0.000 claims description 185
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 48
- 150000001875 compounds Chemical class 0.000 claims description 46
- 229910052799 carbon Inorganic materials 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 239000000126 substance Substances 0.000 claims description 36
- 150000001721 carbon Chemical group 0.000 claims description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 150000001408 amides Chemical class 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 24
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 230000000254 damaging effect Effects 0.000 claims description 16
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 15
- 125000002950 monocyclic group Chemical group 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000001246 bromo group Chemical group Br* 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000002541 furyl group Chemical group 0.000 claims description 10
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 10
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 9
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 7
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 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 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 3
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 3
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- 125000004544 purin-8-yl group Chemical group N1=CN=C2N=C(NC2=C1)* 0.000 claims description 3
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
- OEVNSTIIQXLQST-UHFFFAOYSA-N 2-[4-(4-methoxyphenoxy)phenyl]-3h-benzimidazole-5-carboxylic acid Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(C=2NC3=CC=C(C=C3N=2)C(O)=O)C=C1 OEVNSTIIQXLQST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- 125000004245 indazol-3-yl group Chemical group [H]N1N=C(*)C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
- 125000004258 purin-2-yl group Chemical group [H]N1C2=NC(*)=NC([H])=C2N([H])C1([H])[H] 0.000 claims description 2
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 2
- FNLQDVXHDNFXIY-UHFFFAOYSA-N 3h-benzimidazole-5-carboxamide Chemical compound NC(=O)C1=CC=C2NC=NC2=C1 FNLQDVXHDNFXIY-UHFFFAOYSA-N 0.000 claims 6
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 2
- OWOPCMLGEOLRDH-UHFFFAOYSA-N 2-[4-(3-chloro-4-methylphenoxy)phenyl]-3h-benzimidazole-5-carboxamide Chemical compound C1=C(Cl)C(C)=CC=C1OC1=CC=C(C=2NC3=CC=C(C=C3N=2)C(N)=O)C=C1 OWOPCMLGEOLRDH-UHFFFAOYSA-N 0.000 claims 1
- VFKVTJOBPHIFKV-UHFFFAOYSA-N 2-[4-[4-(4-nitrophenyl)piperazin-1-yl]phenyl]-3h-benzimidazole-5-carboxamide Chemical compound N=1C2=CC(C(=O)N)=CC=C2NC=1C(C=C1)=CC=C1N(CC1)CCN1C1=CC=C([N+]([O-])=O)C=C1 VFKVTJOBPHIFKV-UHFFFAOYSA-N 0.000 claims 1
- UFINQTABZSAHAA-UHFFFAOYSA-N 2-[4-[4-chloro-3-(dimethylamino)phenoxy]phenyl]-3h-benzimidazole-5-carboxamide Chemical compound C1=C(Cl)C(N(C)C)=CC(OC=2C=CC(=CC=2)C=2NC3=CC(=CC=C3N=2)C(N)=O)=C1 UFINQTABZSAHAA-UHFFFAOYSA-N 0.000 claims 1
- QSATYODVTPXBHQ-UHFFFAOYSA-N 2-[4-[4-chloro-3-(methanesulfonamido)phenoxy]phenyl]-3h-benzimidazole-5-carboxamide Chemical compound C1=C(Cl)C(NS(=O)(=O)C)=CC(OC=2C=CC(=CC=2)C=2NC3=CC(=CC=C3N=2)C(N)=O)=C1 QSATYODVTPXBHQ-UHFFFAOYSA-N 0.000 claims 1
- QHGFZMGCLAYOHF-UHFFFAOYSA-N 2-[6-[(3,4-dichlorophenyl)sulfamoyl]pyridin-3-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1C(C=N1)=CC=C1S(=O)(=O)NC1=CC=C(Cl)C(Cl)=C1 QHGFZMGCLAYOHF-UHFFFAOYSA-N 0.000 claims 1
- BVGJBRNVONUDJY-UHFFFAOYSA-N 2-[6-[(4-chlorophenyl)sulfamoyl]pyridin-3-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1C(C=N1)=CC=C1S(=O)(=O)NC1=CC=C(Cl)C=C1 BVGJBRNVONUDJY-UHFFFAOYSA-N 0.000 claims 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 101100256746 Mus musculus Setdb1 gene Proteins 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- 150000001556 benzimidazoles Chemical class 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 37
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 19
- 230000005865 ionizing radiation Effects 0.000 description 17
- 230000002950 deficient Effects 0.000 description 14
- 230000002401 inhibitory effect Effects 0.000 description 14
- 150000003254 radicals Chemical group 0.000 description 13
- 230000006907 apoptotic process Effects 0.000 description 10
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 125000000623 heterocyclic group Chemical group 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 7
- 229930195733 hydrocarbon Natural products 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 230000005855 radiation Effects 0.000 description 7
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000000304 alkynyl group Chemical group 0.000 description 6
- 230000000973 chemotherapeutic effect Effects 0.000 description 6
- 230000034994 death Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- PBCZSGKMGDDXIJ-HQCWYSJUSA-N 7-hydroxystaurosporine Chemical compound N([C@H](O)C1=C2C3=CC=CC=C3N3C2=C24)C(=O)C1=C2C1=CC=CC=C1N4[C@H]1C[C@@H](NC)[C@@H](OC)[C@]3(C)O1 PBCZSGKMGDDXIJ-HQCWYSJUSA-N 0.000 description 5
- 230000005778 DNA damage Effects 0.000 description 5
- 231100000277 DNA damage Toxicity 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 238000003782 apoptosis assay Methods 0.000 description 4
- 230000005522 programmed cell death Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 102000000872 ATM Human genes 0.000 description 3
- 101000785063 Homo sapiens Serine-protein kinase ATM Proteins 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 125000004103 aminoalkyl group Chemical group 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 230000025084 cell cycle arrest Effects 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 108700020463 BRCA1 Proteins 0.000 description 2
- 102000036365 BRCA1 Human genes 0.000 description 2
- 101150072950 BRCA1 gene Proteins 0.000 description 2
- 230000005971 DNA damage repair Effects 0.000 description 2
- 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 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- OTPNDVKVEAIXTI-UHFFFAOYSA-N LSM-1274 Chemical compound C12=C3C4=C5C=CC=C[C]5N3C(O3)CCC3N2C2=CC=C[CH]C2=C1C1=C4C(=O)NC1=O OTPNDVKVEAIXTI-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 125000003435 aroyl group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000013043 chemical agent Substances 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000005936 piperidyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000028617 response to DNA damage stimulus Effects 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000004001 thioalkyl group Chemical group 0.000 description 2
- 210000001519 tissue Anatomy 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
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 125000005999 2-bromoethyl group Chemical group 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- GQGVBSHMRYHBTF-UOWFLXDJSA-N 4-amino-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one Chemical compound O=C1N=C(N)N=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 GQGVBSHMRYHBTF-UOWFLXDJSA-N 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 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
- PBCZSGKMGDDXIJ-UHFFFAOYSA-N 7beta-hydroxystaurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3C(O)NC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 PBCZSGKMGDDXIJ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- 101100220616 Caenorhabditis elegans chk-2 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 231100001074 DNA strand break Toxicity 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 1
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 208000037564 High-grade astrocytoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 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
- 101710178747 Phosphatidate cytidylyltransferase 1 Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 1
- 101000944321 Schizosaccharomyces pombe (strain 972 / ATCC 24843) Serine/threonine-protein kinase cds1 Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 108010079351 Tumor Suppressor Protein p14ARF Proteins 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000005256 alkoxyacyl group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 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 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=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
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000012820 cell cycle checkpoint Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000013000 chemical inhibitor Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 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 1
- 229960005420 etoposide Drugs 0.000 description 1
- 238000002474 experimental method Methods 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
- 229960000961 floxuridine Drugs 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 210000000442 hair follicle cell Anatomy 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 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 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 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
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 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 1
- 229960001924 melphalan Drugs 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 125000004971 nitroalkyl group Chemical group 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 108700025694 p53 Genes Proteins 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 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
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction 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
- 125000004963 sulfonylalkyl group Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 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
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 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 1
- 229960000303 topotecan Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33030401P | 2001-10-19 | 2001-10-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200305533B true ZA200305533B (en) | 2004-10-18 |
Family
ID=23289169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200305533A ZA200305533B (en) | 2001-10-19 | 2003-07-17 | 2-Phenyl benzimidazoles and imidazo-[4,5]-pyridines as Cds1/Chk2-inhibitors and adjuvants to chemotherapy or radiation therapy in the treatment of cancer. |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US7271261B2 (enExample) |
| EP (1) | EP1435947B1 (enExample) |
| JP (1) | JP4637481B2 (enExample) |
| AT (1) | ATE369854T1 (enExample) |
| BR (1) | BR0206161A (enExample) |
| CA (1) | CA2464000C (enExample) |
| DE (1) | DE60221866T2 (enExample) |
| ES (1) | ES2292812T3 (enExample) |
| NO (1) | NO20032759L (enExample) |
| RS (1) | RS50939B (enExample) |
| WO (1) | WO2003032984A1 (enExample) |
| ZA (1) | ZA200305533B (enExample) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101899006B (zh) | 2002-08-19 | 2013-11-06 | 劳洛斯治疗公司 | 2，4，5-三取代的咪唑及其作为抗菌剂的用途 |
| DE10243027A1 (de) * | 2002-09-17 | 2004-03-25 | Bayer Ag | 2-Phenyl-benzimidazol-5-sulfonsäure aus isolierter 3,4-Diaminobenzol-sulfonsäure sowie deren Verwendung in kosmetischen Zubereitungen |
| JP4726235B2 (ja) | 2003-04-17 | 2011-07-20 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 癌の処置のためのチェックポイントキナーゼｃｄｓ１（ｃｈｋ２）インヒビターとしての２−フェニル−ベンズイミダゾールおよび２−フェニル−イミダゾ−‘４，５！−ピリジン誘導体 |
| US20050078598A1 (en) * | 2003-08-21 | 2005-04-14 | Anuj Batra | Enhancement to the multi-band OFDM physical layer |
| WO2005047266A1 (en) * | 2003-11-14 | 2005-05-26 | Lorus Therapeutics Inc. | Aryl imidazoles and their use as anti-cancer agents |
| CA2572218C (en) | 2004-06-30 | 2013-06-11 | Janssen Pharmaceutica, N.V. | Aryl-substituted benzimidazole and imidazopyridine ethers as anti-cancer agents |
| KR20060087386A (ko) | 2005-01-28 | 2006-08-02 | 주식회사 대웅제약 | 신규 벤조이미다졸 유도체 및 이를 함유하는 약제학적조성물 |
| CA2596013C (en) * | 2005-01-28 | 2012-06-05 | Daewoong Pharmaceutical Co., Ltd. | Benzoimidazole derivatives and pharmaceutical composition comprising the same |
| US7582634B2 (en) | 2005-02-18 | 2009-09-01 | Wyeth | 7-substituted imidazo[4,5-c]pyridine antagonists of gonadotropin releasing hormone receptor |
| US7538113B2 (en) | 2005-02-18 | 2009-05-26 | Wyeth | 4-substituted imidazo[4,5-c]pyridine antagonists of gonadotropin releasing hormone receptor |
| US7534796B2 (en) | 2005-02-18 | 2009-05-19 | Wyeth | Imidazo[4,5-b]pyridine antagonists of gonadotropin releasing hormone receptor |
| BRPI0608581A2 (pt) * | 2005-03-14 | 2010-01-19 | Transtech Pharma Inc | derivados de benzazol, composiÇÕes e mÉtodos de uso como inibidores de b-secretase |
| US7531542B2 (en) | 2005-05-18 | 2009-05-12 | Wyeth | Benzooxazole and benzothiazole antagonists of gonadotropin releasing hormone receptor |
| EP1915374B1 (en) | 2005-05-25 | 2014-04-02 | Lorus Therapeutics Inc. | 2-indolyl imidazo[4,5-d]phenanthroline derivatives and their use in the treatment of cancer |
| US7582636B2 (en) | 2005-05-26 | 2009-09-01 | Wyeth | Piperazinylimidazopyridine and piperazinyltriazolopyridine antagonists of Gonadotropin Releasing Hormone receptor |
| KR20140000721A (ko) | 2005-06-23 | 2014-01-03 | 어레이 바이오파마 인크. | 벤즈이미다졸 화합물의 제조 방법 |
| US8334290B2 (en) | 2005-10-31 | 2012-12-18 | Merck Sharp & Dohme Corp. | CETP inhibitors |
| ES2438240T3 (es) | 2006-07-11 | 2014-01-16 | Daewoong Pharmaceutical Co., Ltd. | Nuevos derivados de biaril benzoimidazol y composición farmacéutica que los comprenden |
| FR2904314A1 (fr) * | 2006-07-26 | 2008-02-01 | Centre Nat Rech Scient | Composes pyridaziniques et pyrroliques lineaires, procedes d'obtention et applications |
| PE20080888A1 (es) * | 2006-10-18 | 2008-08-26 | Novartis Ag | COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE LA ACIL-TRANSFERASA DE ACIL-CoA-DIACIL-GLICEROL 1 (DGAT1) |
| BRPI0809193A2 (pt) | 2007-03-15 | 2014-09-23 | Novartis Ag | Compostos orgânicos e seus usos |
| BRPI0815731A2 (pt) * | 2007-08-23 | 2015-02-18 | Sanofi Aventis | Derivados de azoloarila, processo para a preparação da mesma, medicamentos contendo esses compostos e uso do mesmo |
| GB0719644D0 (en) | 2007-10-05 | 2007-11-14 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| CN101896472A (zh) * | 2007-12-13 | 2010-11-24 | 锡耶纳生物技术股份公司 | Hedgehog途径拮抗剂及其治疗应用 |
| JP2009171854A (ja) * | 2008-01-21 | 2009-08-06 | Olympus Corp | 細胞洗浄方法および移植物の製造方法 |
| GB0803018D0 (en) | 2008-02-19 | 2008-03-26 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| CA2720654A1 (en) * | 2008-04-22 | 2009-10-29 | Merck Frosst Canada Ltd. | Novel substituted heteroaromatic compounds as inhibitors of stearoyl-coenzyme a delta-9 desaturase |
| US20100041663A1 (en) | 2008-07-18 | 2010-02-18 | Novartis Ag | Organic Compounds as Smo Inhibitors |
| CA2758961A1 (en) | 2009-04-27 | 2010-11-04 | High Point Pharmaceuticals, Llc | Substituted isoquinoline derivatives, pharmaceutical compositions, and methods of use as .beta.-secretase inhibitors |
| CA2792339A1 (en) | 2010-03-23 | 2011-09-29 | High Point Pharmaceuticals, Llc | Substituted imidazo[1,2-b]pyridazine derivatives, pharmaceutical compositions, and methods of use as beta-secretase inhibitors |
| US8609672B2 (en) | 2010-08-27 | 2013-12-17 | University Of The Pacific | Piperazinylpyrimidine analogues as protein kinase inhibitors |
| EP2614160B1 (en) * | 2010-09-10 | 2016-04-06 | Bio-Rad Laboratories, Inc. | Detection of rna-interacting regions in dna |
| WO2012044043A2 (en) | 2010-09-28 | 2012-04-05 | Daewoong Pharmaceutical Co., Ltd. | Novel method of preparing benzoimidazole derivatives |
| EP2675913B1 (en) | 2011-02-15 | 2016-12-14 | Bio-Rad Laboratories, Inc. | Detecting methylation in a subpopulation of genomic dna |
| KR101387970B1 (ko) | 2011-04-20 | 2014-04-25 | 인제대학교 산학협력단 | 암 예방 및 치료용 조성물 및 건강기능식품 |
| ES2709003T3 (es) | 2011-11-09 | 2019-04-12 | Cancer Research Tech Ltd | Compuestos de 5-(piridin-2-il-amino)-pirazina-2-carbonitrilo y su uso terapéutico |
| SG11201407238VA (en) | 2012-05-15 | 2014-12-30 | Cancer Rec Tech Ltd | 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile and therapeutic uses thereof |
| KR20160042811A (ko) | 2013-03-20 | 2016-04-20 | 압토스 바이오사이언시스 인코포레이티드 | 2-치환 이미다조[4,5-d]페난쓰롤린 유도체 및 암 치료에 있어서의 이의 용도 |
| CN103288803B (zh) * | 2013-05-17 | 2017-10-31 | 郎恒元 | 苯并咪唑酰胺类化合物及其制备方法和应用 |
| WO2015051302A1 (en) | 2013-10-04 | 2015-04-09 | Aptose Biosciences Inc. | Compositions and methods for treating cancers |
| CN104194778B (zh) * | 2014-09-25 | 2016-03-30 | 黑龙江大学 | 磷氧基团修饰n-苯基-苯并咪唑电子传输材料、合成方法及电致磷光器件的制备方法 |
| CA3037424A1 (en) * | 2016-09-20 | 2018-03-29 | Centre Leon Berard | Benzoimidazole derivatives as anticancer agents |
| CN111417395A (zh) | 2017-10-30 | 2020-07-14 | 艾普托斯生物科学公司 | 用于治疗癌症的芳基咪唑 |
| MA52954A (fr) | 2018-06-21 | 2021-04-28 | Cellestia Biotech Ag | Procédé pour la fabrication d'aminoéthers de diaryle et sels de chlorhydrate d'aminoéthers de diaryle |
| CN118994001A (zh) * | 2019-04-10 | 2024-11-22 | 塞莱斯蒂亚生物技术股份公司 | Notch信号传导途径抑制剂及其在癌症治疗的用途 |
| WO2020252353A1 (en) * | 2019-06-12 | 2020-12-17 | Vanderbilt University | Amino acid transport inhibitors and the uses thereof |
| US20230150998A1 (en) | 2021-09-27 | 2023-05-18 | Terns Pharmaceuticals, Inc. | Compounds as glp-1r agonists |
| US12024507B2 (en) | 2021-10-25 | 2024-07-02 | Terns Pharmaceuticals, Inc. | Compounds as GLP-1R agonists |
| KR20240150488A (ko) | 2022-02-23 | 2024-10-15 | 테른스 파마슈티칼스, 인크. | Glp-1r 작용제로서의 화합물 |
| KR20250166323A (ko) | 2023-04-07 | 2025-11-27 | 테른스 파마슈티칼스, 인크. | 간 장애 또는 심장대사 질환의 치료에 사용하기 위한 thr베타 효현제 및 glp-1r 효현제를 포함하는 조합 |
| CN119552166B (zh) * | 2024-11-29 | 2025-10-17 | 中国药科大学 | 一种parp1/cdk6双靶点抑制剂及其制备方法与应用 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3346575A1 (de) | 1983-12-23 | 1985-07-04 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue benzimidazole, ihre herstellung und diese verbindungen enthaltende arzneimittel |
| LU85544A1 (fr) | 1984-09-19 | 1986-04-03 | Cird | Derives heterocycliques aromatiques,leur procede de preparation et leur application dans les domaines therapeutique et cosmetique |
| DE3522230A1 (de) | 1985-06-21 | 1987-01-02 | Thomae Gmbh Dr K | Neue 2-arylimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| GB9108279D0 (en) * | 1991-04-18 | 1991-06-05 | Ucb Sa | A method of preparing 1h-benzimidazoles |
| US5821258A (en) | 1994-12-27 | 1998-10-13 | Mitsui Chemicals, Inc. | Phenylbenzimidazole derivatives |
| JP2000516611A (ja) | 1996-08-14 | 2000-12-12 | ワーナー―ランバート・コンパニー | Ｍｃｐ―１アンタゴニストとしての２―フェニルベンズイミダゾール誘導体 |
| US5942532A (en) | 1997-09-05 | 1999-08-24 | Ortho Pharmaceutical Corporation | 2-substituted phenyl-benzimidazole antibacterial agents |
| ES2281941T3 (es) | 1997-12-13 | 2007-10-01 | Bristol-Myers Squibb Company | Uso de pirazolo(3,4-b)piridina como inhibidores de quinasa dependiente de ciclina. |
| BR9910642A (pt) | 1998-05-22 | 2001-10-09 | Avanir Pharmaceuticals | Análogos de benzimidazol como reguladores descendentes de ige |
| KR20010100977A (ko) | 1998-11-03 | 2001-11-14 | 스타르크, 카르크 | 치환된 2-페닐벤즈이미다졸, 그의 제조 및 그의 용도 |
| GB9914825D0 (en) | 1999-06-24 | 1999-08-25 | Smithkline Beecham Spa | Novel compounds |
| YU54202A (sh) * | 2000-01-18 | 2006-01-16 | Agouron Pharmaceuticals Inc. | Jedinjenja indazola, farmaceutske smeše i postupci za stimulisanje i inhibiranje ćelijske proliferacije |
| GB0007934D0 (en) * | 2000-03-31 | 2000-05-17 | Darwin Discovery Ltd | Chemical compounds |
| DE10026435A1 (de) * | 2000-05-29 | 2002-04-18 | Osram Opto Semiconductors Gmbh | Kalzium-Magnesium-Chlorosilikat-Leuchtstoff und seine Anwendung bei Lumineszenz-Konversions-LED |
| JP4695819B2 (ja) * | 2000-05-29 | 2011-06-08 | パテント−トロイハント−ゲゼルシヤフト フユール エレクトリツシエ グリユーラムペン ミツト ベシユレンクテル ハフツング | Ｌｅｄをベースとする白色発光照明ユニット |
| AU2001274580A1 (en) | 2000-06-21 | 2002-01-02 | Chugai Seiyaku Kabushiki Kaisha | Cds1 gene-knockout cells and mouse and utilization thereof |
| US20060027785A1 (en) * | 2004-08-04 | 2006-02-09 | Intematix Corporation | Novel silicate-based yellow-green phosphors |
| US7311858B2 (en) * | 2004-08-04 | 2007-12-25 | Intematix Corporation | Silicate-based yellow-green phosphors |
| US20060279196A1 (en) * | 2005-06-02 | 2006-12-14 | Wei-Jen Hsu | White LED |
| JP2007231250A (ja) * | 2006-02-02 | 2007-09-13 | Nichia Chem Ind Ltd | 蛍光体及びそれを用いた発光装置 |
-
2002
- 2002-10-18 JP JP2003535787A patent/JP4637481B2/ja not_active Expired - Lifetime
- 2002-10-18 US US10/273,487 patent/US7271261B2/en not_active Expired - Lifetime
- 2002-10-18 EP EP02770620A patent/EP1435947B1/en not_active Expired - Lifetime
- 2002-10-18 ES ES02770620T patent/ES2292812T3/es not_active Expired - Lifetime
- 2002-10-18 WO PCT/US2002/033371 patent/WO2003032984A1/en not_active Ceased
- 2002-10-18 DE DE60221866T patent/DE60221866T2/de not_active Expired - Lifetime
- 2002-10-18 RS YUP-492/03A patent/RS50939B/sr unknown
- 2002-10-18 AT AT02770620T patent/ATE369854T1/de not_active IP Right Cessation
- 2002-10-18 BR BR0206161-9A patent/BR0206161A/pt not_active Application Discontinuation
- 2002-10-18 CA CA2464000A patent/CA2464000C/en not_active Expired - Lifetime
-
2003
- 2003-06-17 NO NO20032759A patent/NO20032759L/no unknown
- 2003-07-17 ZA ZA200305533A patent/ZA200305533B/en unknown
-
2007
- 2007-08-02 US US11/832,789 patent/US7504414B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US20030176438A1 (en) | 2003-09-18 |
| ATE369854T1 (de) | 2007-09-15 |
| CA2464000C (en) | 2011-04-19 |
| CA2464000A1 (en) | 2003-04-24 |
| US7271261B2 (en) | 2007-09-18 |
| RS50939B (sr) | 2010-08-31 |
| US20080009493A1 (en) | 2008-01-10 |
| WO2003032984A8 (en) | 2003-11-20 |
| EP1435947B1 (en) | 2007-08-15 |
| ES2292812T3 (es) | 2008-03-16 |
| DE60221866D1 (de) | 2007-09-27 |
| NO20032759L (no) | 2003-08-18 |
| JP4637481B2 (ja) | 2011-02-23 |
| DE60221866T2 (de) | 2008-05-29 |
| BR0206161A (pt) | 2005-02-01 |
| YU49203A (sh) | 2006-05-25 |
| NO20032759D0 (no) | 2003-06-17 |
| US7504414B2 (en) | 2009-03-17 |
| EP1435947A1 (en) | 2004-07-14 |
| WO2003032984A1 (en) | 2003-04-24 |
| JP2005506349A (ja) | 2005-03-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200305533B (en) | 2-Phenyl benzimidazoles and imidazo-[4,5]-pyridines as Cds1/Chk2-inhibitors and adjuvants to chemotherapy or radiation therapy in the treatment of cancer. | |
| TWI579284B (zh) | 咪唑并吡咯啶酮化合物 | |
| JP2025000632A (ja) | 組み合わせ療法 | |
| RU2515972C2 (ru) | Диазакарбазолы и способы применения | |
| AU754734B2 (en) | Indazole bioisostere replacement of catechol in therapeutically active compounds | |
| RU2650895C2 (ru) | Соединения замещенных пиразолонов и способы использования | |
| EP3277276B1 (en) | Methods of administering glutaminase inhibitors | |
| RU2660354C2 (ru) | Комбинированные продукты, содержащие ингибиторы тирозинкиназ, и их применение | |
| PH12014501504B1 (en) | THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES | |
| PT2318389E (pt) | Derivados de piridazina como inibidores de smo | |
| AU2018218522B2 (en) | Hydrocarbylsulfonyl-substituted pyridines and their use in the treatment of cancer | |
| JP6636153B2 (ja) | ピリジン及び癌治療におけるそれらの使用 | |
| JP2024540839A (ja) | Ｋｒａｓ ｇ１２ｄ阻害剤とｓｈｐ－２阻害剤との併用療法 | |
| AU2015294889B2 (en) | Combination therapy | |
| SK12612003A3 (sk) | Benzimidazoly, ktoré sú účinné pri liečbe sexuálnej dysfunkcie | |
| US7687639B2 (en) | Substituted benzimidazoles and imidazo-[4,5]-pyridines | |
| CN103221094B (zh) | Mdm2/4及p53相互作用抑制剂的结晶型 | |
| DE102005061655A1 (de) | Diazepinone | |
| JP2002114684A (ja) | 尿路疾患治療剤 | |
| RU2002107421A (ru) | Алкоксизамещенные бензимидазольные соединения, содержащие их фармацевтические препараты и способы их применения | |
| CZ155096A3 (en) | Aminoalkylaminopyridine derivatives, process of their preparation and pharmaceutical composition containing thereof | |
| HK40013960B (en) | Methods of using indazole-3-carboxamides and their use as wnt/b-catenin signaling pathway inhibitors | |
| MX2008007866A (es) | Diazepinonas |