CA2500729A1 - Synergistic methods and compositions for treating cancer - Google Patents
Synergistic methods and compositions for treating cancer Download PDFInfo
- Publication number
- CA2500729A1 CA2500729A1 CA002500729A CA2500729A CA2500729A1 CA 2500729 A1 CA2500729 A1 CA 2500729A1 CA 002500729 A CA002500729 A CA 002500729A CA 2500729 A CA2500729 A CA 2500729A CA 2500729 A1 CA2500729 A1 CA 2500729A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- hydroxy
- phenyl
- ethylamino
- pyridin
- Prior art date
- 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.)
- Abandoned
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 36
- 201000011510 cancer Diseases 0.000 title claims abstract description 19
- 230000002195 synergetic effect Effects 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims description 28
- 239000000203 mixture Substances 0.000 title description 11
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 claims abstract description 41
- 229940121647 egfr inhibitor Drugs 0.000 claims abstract description 41
- 239000003112 inhibitor Substances 0.000 claims abstract description 39
- 238000011282 treatment Methods 0.000 claims abstract description 28
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 229960005395 cetuximab Drugs 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- -1 -OR60 Chemical group 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical group C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 4
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229960001433 erlotinib Drugs 0.000 claims description 4
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 4
- 229960002584 gefitinib Drugs 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- RTYFZPODWDIXLP-GJICFQLNSA-N 2-[4-[2-[4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazin-1-yl]acetamide dihydrochloride Chemical compound Cl.Cl.C1([C@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2CCN(CC(N)=O)CC2)=CC=CC(Cl)=C1 RTYFZPODWDIXLP-GJICFQLNSA-N 0.000 claims description 2
- DNHZEERCHBYLQP-PEQFZTOTSA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[(3R)-3-methylpiperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one dihydrochloride Chemical compound Cl.Cl.C[C@@H]1CN(CCN1)c1cc(C)c2nc([nH]c2c1)-c1c(NC[C@@H](O)c2cccc(Cl)c2)cc[nH]c1=O DNHZEERCHBYLQP-PEQFZTOTSA-N 0.000 claims description 2
- LLZHPHMONQMZQE-PPLJNSMQSA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(2-methylsulfanylethyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one dihydrochloride Chemical compound Cl.Cl.C1CN(CCSC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NC[C@@H](O)C=3C=C(Cl)C=CC=3)=O)C2=C1 LLZHPHMONQMZQE-PPLJNSMQSA-N 0.000 claims description 2
- 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 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- IKELJUFKSAJTLQ-SFHVURJKSA-N chembl391158 Chemical compound C([C@@H](CO)NC1=C(C(NC=C1)=O)C=1NC=2C=C(C=C(C=2N=1)C)N1C=NC=C1)C1=CC=CC(F)=C1 IKELJUFKSAJTLQ-SFHVURJKSA-N 0.000 claims description 2
- ZWVZORIKUNOTCS-OAQYLSRUSA-N chembl401930 Chemical compound C1([C@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2CCOCC2)=CC=CC(Cl)=C1 ZWVZORIKUNOTCS-OAQYLSRUSA-N 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- OTXBWGUYZNKPMG-UHFFFAOYSA-N isofulminic acid Chemical compound O[N+]#[C-] OTXBWGUYZNKPMG-UHFFFAOYSA-N 0.000 claims description 2
- 229960001972 panitumumab Drugs 0.000 claims description 2
- 239000000651 prodrug Substances 0.000 claims description 2
- 229940002612 prodrug Drugs 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 5
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical class C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 claims 1
- OTOIUCLFSQHFOX-UHFFFAOYSA-N 3-sulfonylmorpholine Chemical class O=S(=O)=C1COCCN1 OTOIUCLFSQHFOX-UHFFFAOYSA-N 0.000 claims 1
- NHNGZQRXZBFUGF-XMMPIXPASA-N 4-[[(2S)-2-(3-chlorophenyl)-2-methoxyethyl]amino]-3-[6-[4-(2-hydroxyethyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C([C@@H](OC)C=1C=C(Cl)C=CC=1)NC=1C=CNC(=O)C=1C(NC1=C2)=NC1=C(C)C=C2N1CCN(CCO)CC1 NHNGZQRXZBFUGF-XMMPIXPASA-N 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- XPTAUSRPHWOZPN-UHFFFAOYSA-N morpholin-4-yl hydrogen sulfate Chemical class OS(=O)(=O)ON1CCOCC1 XPTAUSRPHWOZPN-UHFFFAOYSA-N 0.000 claims 1
- 150000002780 morpholines Chemical class 0.000 claims 1
- WVUNYSQLFKLYNI-AATRIKPKSA-N pelitinib Chemical group C=12C=C(NC(=O)\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 WVUNYSQLFKLYNI-AATRIKPKSA-N 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 150000004885 piperazines Chemical class 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000168 pyrrolyl group Chemical group 0.000 claims 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical class C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims 1
- 125000001425 triazolyl group Chemical group 0.000 claims 1
- 101710184277 Insulin-like growth factor 1 receptor Proteins 0.000 description 36
- 150000001875 compounds Chemical class 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 16
- 229940125904 compound 1 Drugs 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 13
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 13
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 13
- 239000003814 drug Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 239000002246 antineoplastic agent Substances 0.000 description 8
- 230000007761 synergistic anti-cancer Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000000890 drug combination Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 101150088952 IGF1 gene Proteins 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- HZQLLKQPXMHIMZ-UHFFFAOYSA-N N-[1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]-2-fluoroacetamide Chemical compound N=1C=2C(C)=CC(N3CCC(CC3)NC(=O)CF)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 HZQLLKQPXMHIMZ-UHFFFAOYSA-N 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000009096 combination chemotherapy Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- 230000005751 tumor progression Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WDELNBOQCPAGPI-KRWDZBQOSA-N (2s)-2-[[6-chloro-5-(6-imidazol-1-yl-4-methyl-1h-benzimidazol-2-yl)pyrimidin-4-yl]amino]-3-phenylpropan-1-ol Chemical compound C([C@@H](CO)NC1=NC=NC(Cl)=C1C=1NC=2C=C(C=C(C=2N=1)C)N1C=NC=C1)C1=CC=CC=C1 WDELNBOQCPAGPI-KRWDZBQOSA-N 0.000 description 1
- OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 description 1
- LWELCYJSAYQTOX-UHFFFAOYSA-N 1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]-N-(2-fluoroethoxy)piperidine-4-carboxamide Chemical compound N=1C=2C(C)=CC(N3CCC(CC3)C(=O)NOCCF)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 LWELCYJSAYQTOX-UHFFFAOYSA-N 0.000 description 1
- ZLEMMUBHALJEGB-UHFFFAOYSA-N 1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]-N-(2-methoxyethoxy)piperidine-4-carboxamide Chemical compound C1CC(C(=O)NOCCOC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 ZLEMMUBHALJEGB-UHFFFAOYSA-N 0.000 description 1
- WKJBSMLANQKUCC-UHFFFAOYSA-N 1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]-N-methoxypiperidine-4-carboxamide Chemical compound C1CC(C(=O)NOC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 WKJBSMLANQKUCC-UHFFFAOYSA-N 0.000 description 1
- VVIPLSCLYCWUQT-UHFFFAOYSA-N 3-[4-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazin-1-yl]propanenitrile Chemical compound N=1C=2C(C)=CC(N3CCN(CCC#N)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 VVIPLSCLYCWUQT-UHFFFAOYSA-N 0.000 description 1
- OBHSRNCZUIOTPY-OAQYLSRUSA-N 3-[4-bromo-6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-1H-pyridin-2-one Chemical compound C([C@@H](O)C=1C=C(Cl)C=CC=1)NC=1C=CNC(=O)C=1C(NC1=C2)=NC1=C(Br)C=C2CN1CCOCC1 OBHSRNCZUIOTPY-OAQYLSRUSA-N 0.000 description 1
- QIEKBURWQYYQLT-UHFFFAOYSA-N 3-[6-(4-acetylpiperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-1H-pyridin-2-one Chemical compound C1CN(C(=O)C)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 QIEKBURWQYYQLT-UHFFFAOYSA-N 0.000 description 1
- DGQFUGZAZIEOTL-SANMLTNESA-N 3-[6-(4-benzylpiperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-1H-pyridin-2-one Chemical compound C([C@@H](CO)NC1=C(C(NC=C1)=O)C=1NC=2C=C(C=C(C=2N=1)C)N1CCN(CC=2C=CC=CC=2)CC1)C1=CC=CC=C1 DGQFUGZAZIEOTL-SANMLTNESA-N 0.000 description 1
- HGDHHEZBLVABGA-UHFFFAOYSA-N 3-[6-[4-(2-chloroacetyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)CCl)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 HGDHHEZBLVABGA-UHFFFAOYSA-N 0.000 description 1
- LYLOFPYPQFPUJE-HXUWFJFHSA-N 3-[[(2s)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-4-(4-methyl-6-morpholin-4-yl-1h-benzimidazol-2-yl)-1,2-dihydropyrrol-5-one Chemical compound C1([C@H](O)CNC2=C(C(NC2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2CCOCC2)=CC=CC(Cl)=C1 LYLOFPYPQFPUJE-HXUWFJFHSA-N 0.000 description 1
- DEIREGFZHJAQSJ-UHFFFAOYSA-N 3-[[2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-4-(4-methyl-6-morpholin-4-yl-1h-benzimidazol-2-yl)-1,2-dihydropyrrol-5-one Chemical compound C1=C(Br)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCOCC2)C(=O)NC1 DEIREGFZHJAQSJ-UHFFFAOYSA-N 0.000 description 1
- PDCLYKLETQOZQF-UHFFFAOYSA-N 3-[[2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-4-(4-methyl-6-morpholin-4-yl-1h-benzimidazol-2-yl)-1,2-dihydropyrrol-5-one Chemical compound C1=C(Cl)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCOCC2)C(=O)NC1 PDCLYKLETQOZQF-UHFFFAOYSA-N 0.000 description 1
- CLWRLQRRLJJWJG-JOCHJYFZSA-N 4-[2-[4-[[(2S)-2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazine-1-carbaldehyde Chemical compound C1=C(Br)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCN(CC2)C=O)C(=O)NC=C1 CLWRLQRRLJJWJG-JOCHJYFZSA-N 0.000 description 1
- ZVNYXNHAMHULPF-UHFFFAOYSA-N 4-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazine-1-carboxylic acid Chemical compound ClC=1C=C(C=CC1)C(CNC1=C(C(NC=C1)=O)C=1NC2=C(N1)C(=CC(=C2)N2CCN(CC2)C(=O)O)C)O ZVNYXNHAMHULPF-UHFFFAOYSA-N 0.000 description 1
- AMJILRTVLRYXLQ-HXUWFJFHSA-N 4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1([C@@H](CO)NC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C=NC=C2)=CC=CC=C1 AMJILRTVLRYXLQ-HXUWFJFHSA-N 0.000 description 1
- QCDSKOUKWJFTKU-OFNKIYASSA-N 4-[[(1S,2R)-1-hydroxy-2,3-dihydro-1H-inden-2-yl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound Cc1cc(cc2[nH]c(nc12)-c1c(N[C@@H]2Cc3ccccc3[C@@H]2O)cc[nH]c1=O)-n1ccnc1 QCDSKOUKWJFTKU-OFNKIYASSA-N 0.000 description 1
- LQRBWXDBMNHGCK-FQEVSTJZSA-N 4-[[(2R)-2-hydroxy-2-phenylethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1([C@@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C=NC=C2)=CC=CC=C1 LQRBWXDBMNHGCK-FQEVSTJZSA-N 0.000 description 1
- QSATVYVNCXNSPW-QFIPXVFZSA-N 4-[[(2S)-1-hydroxy-3-naphthalen-2-ylpropan-2-yl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C=1C=2NC(C=3C(NC=CC=3N[C@H](CO)CC=3C=C4C=CC=CC4=CC=3)=O)=NC=2C(C)=CC=1N1C=CN=C1 QSATVYVNCXNSPW-QFIPXVFZSA-N 0.000 description 1
- WGKQPIGFIPWZNV-KRWDZBQOSA-N 4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-5-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyrimidin-6-one Chemical compound C([C@@H](CO)NC1=C(C(NC=N1)=O)C=1NC=2C=C(C=C(C=2N=1)C)N1C=NC=C1)C1=CC=CC=C1 WGKQPIGFIPWZNV-KRWDZBQOSA-N 0.000 description 1
- MZHLCADPMKFBDN-KRWDZBQOSA-N 4-[[(2S)-1-hydroxy-3-pyridin-4-ylpropan-2-yl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C([C@@H](CO)NC1=C(C(NC=C1)=O)C=1NC=2C=C(C=C(C=2N=1)C)N1C=NC=C1)C1=CC=NC=C1 MZHLCADPMKFBDN-KRWDZBQOSA-N 0.000 description 1
- QQUOABRZUGYNQT-HSZRJFAPSA-N 4-[[(2S)-2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-(2-morpholin-4-ylethoxy)-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(OCCN4CCOCC4)=CC(C)=C3N=2)C(=O)NC=C1 QQUOABRZUGYNQT-HSZRJFAPSA-N 0.000 description 1
- XSHAQUDGMYHMSJ-JOCHJYFZSA-N 4-[[(2S)-2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCN(C)CC2)C(=O)NC=C1 XSHAQUDGMYHMSJ-JOCHJYFZSA-N 0.000 description 1
- DNTQJDXWGFMNLI-OPAMFIHVSA-N 4-[[(2S)-2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[(2R)-2-methylmorpholin-4-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2C[C@@H](C)OCC2)C(=O)NC=C1 DNTQJDXWGFMNLI-OPAMFIHVSA-N 0.000 description 1
- DNTQJDXWGFMNLI-KSFYIVLOSA-N 4-[[(2S)-2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[(2S)-2-methylmorpholin-4-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2C[C@H](C)OCC2)C(=O)NC=C1 DNTQJDXWGFMNLI-KSFYIVLOSA-N 0.000 description 1
- XTGIVFQBEPPGGX-PGRDOPGGSA-N 4-[[(2S)-2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[(2R)-2-(fluoromethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2C[C@H](CF)OCC2)C(=O)NC=C1 XTGIVFQBEPPGGX-PGRDOPGGSA-N 0.000 description 1
- LUSNIDFBBMXWAZ-XMSQKQJNSA-N 4-[[(2S)-2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[(2R)-2-(hydroxymethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2C[C@H](CO)OCC2)C(=O)NC=C1 LUSNIDFBBMXWAZ-XMSQKQJNSA-N 0.000 description 1
- XTGIVFQBEPPGGX-XMSQKQJNSA-N 4-[[(2S)-2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[(2S)-2-(fluoromethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2C[C@@H](CF)OCC2)C(=O)NC=C1 XTGIVFQBEPPGGX-XMSQKQJNSA-N 0.000 description 1
- ODUJFBNSLMAOSE-WMZHIEFXSA-N 4-[[(2S)-2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[(2S)-2-(methoxymethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CO[C@H](COC)CN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NC[C@@H](O)C=3C=C(Br)C(OC)=CC=3)=O)C2=C1 ODUJFBNSLMAOSE-WMZHIEFXSA-N 0.000 description 1
- PUHIHKJDRCRYTD-OAQYLSRUSA-N 4-[[(2S)-2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-(5,6-dihydro-4H-pyrimidin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Cl)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2C=NCCC2)C(=O)NC=C1 PUHIHKJDRCRYTD-OAQYLSRUSA-N 0.000 description 1
- XNQQOBWDWJLPKE-PGRDOPGGSA-N 4-[[(2S)-2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[(2R)-2-(fluoromethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Cl)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2C[C@H](CF)OCC2)C(=O)NC=C1 XNQQOBWDWJLPKE-PGRDOPGGSA-N 0.000 description 1
- RJOLTVNZKRBSOZ-XMSQKQJNSA-N 4-[[(2S)-2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[(2R)-2-(hydroxymethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Cl)C(OC)=CC=C1[C@H](O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2C[C@H](CO)OCC2)C(=O)NC=C1 RJOLTVNZKRBSOZ-XMSQKQJNSA-N 0.000 description 1
- PKNHVWJAADMUFX-AUSIDOKSSA-N 4-[[(2S)-2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[(2R)-2-(methoxymethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CO[C@@H](COC)CN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NC[C@@H](O)C=3C=C(Cl)C(OC)=CC=3)=O)C2=C1 PKNHVWJAADMUFX-AUSIDOKSSA-N 0.000 description 1
- PKNHVWJAADMUFX-WMZHIEFXSA-N 4-[[(2S)-2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[(2S)-2-(methoxymethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CO[C@H](COC)CN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NC[C@@H](O)C=3C=C(Cl)C(OC)=CC=3)=O)C2=C1 PKNHVWJAADMUFX-WMZHIEFXSA-N 0.000 description 1
- GAUMNPIAVGVDBX-HSZRJFAPSA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-(2-morpholin-4-ylethoxy)-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C=1C=2NC(C=3C(NC=CC=3NC[C@@H](O)C=3C=C(Cl)C=CC=3)=O)=NC=2C(C)=CC=1OCCN1CCOCC1 GAUMNPIAVGVDBX-HSZRJFAPSA-N 0.000 description 1
- IIJGLRWTELJRPH-KSFYIVLOSA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[(2S)-2-methylmorpholin-4-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CO[C@@H](C)CN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NC[C@@H](O)C=3C=C(Cl)C=CC=3)=O)C2=C1 IIJGLRWTELJRPH-KSFYIVLOSA-N 0.000 description 1
- DACIYZDSXDZZSX-HSZRJFAPSA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[(4-methylpiperazin-1-yl)methyl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CN(C)CCN1CC1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NC[C@@H](O)C=3C=C(Cl)C=CC=3)=O)C2=C1 DACIYZDSXDZZSX-HSZRJFAPSA-N 0.000 description 1
- YNIARPVUHAXJQZ-LJQANCHMSA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-(2-hydroxyethoxy)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1([C@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(OCCO)C=C(C=3N=2)C)=CC=CC(Cl)=C1 YNIARPVUHAXJQZ-LJQANCHMSA-N 0.000 description 1
- CJCXXSGEMIIROV-HXUWFJFHSA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-(2-methoxyethoxy)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1([C@H](O)CNC2=C(C(NC=C2)=O)C2=NC3=C(C)C=C(C=C3N2)OCCOC)=CC=CC(Cl)=C1 CJCXXSGEMIIROV-HXUWFJFHSA-N 0.000 description 1
- KPFSRAAWPJUHQV-OAQYLSRUSA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-(5,6-dihydro-4H-pyrimidin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1([C@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C=NCCC2)=CC=CC(Cl)=C1 KPFSRAAWPJUHQV-OAQYLSRUSA-N 0.000 description 1
- UHOVHYKNOIFMRB-NFBKMPQASA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[(2R)-2-(methoxymethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CO[C@@H](COC)CN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NC[C@@H](O)C=3C=C(Cl)C=CC=3)=O)C2=C1 UHOVHYKNOIFMRB-NFBKMPQASA-N 0.000 description 1
- WHJWUUJEQQJCLJ-DENIHFKCSA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[(2S)-2-(fluoromethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1([C@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C[C@@H](CF)OCC2)=CC=CC(Cl)=C1 WHJWUUJEQQJCLJ-DENIHFKCSA-N 0.000 description 1
- WLCQPUNMZDWNNT-VZVZJDIGSA-N 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[(3R)-4-(2-methoxyethyl)-3-methylpiperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one dihydrochloride Chemical compound Cl.Cl.C1[C@@H](C)N(CCOC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NC[C@@H](O)C=3C=C(Cl)C=CC=3)=O)C2=C1 WLCQPUNMZDWNNT-VZVZJDIGSA-N 0.000 description 1
- AATRIKZDGKCSFA-UZUQRXQVSA-N 4-[[(2S)-2-(7-bromo-2,3-dihydro-1-benzofuran-4-yl)-2-hydroxyethyl]amino]-3-[6-[(2S)-2-(fluoromethyl)morpholin-4-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C=1C=2NC(C=3C(NC=CC=3NC[C@@H](O)C=3C=4CCOC=4C(Br)=CC=3)=O)=NC=2C(C)=CC=1N1CCO[C@H](CF)C1 AATRIKZDGKCSFA-UZUQRXQVSA-N 0.000 description 1
- LQRBWXDBMNHGCK-HXUWFJFHSA-N 4-[[(2S)-2-hydroxy-2-phenylethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1([C@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C=NC=C2)=CC=CC=C1 LQRBWXDBMNHGCK-HXUWFJFHSA-N 0.000 description 1
- GCHQRFUKBLZIMY-IBGZPJMESA-N 4-[[(2S)-2-hydroxy-2-pyridin-2-ylethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1([C@@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C=NC=C2)=CC=CC=N1 GCHQRFUKBLZIMY-IBGZPJMESA-N 0.000 description 1
- FSDYMRXZPHZFJS-UHFFFAOYSA-N 4-[[2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCOCC2)C(=O)NC=C1 FSDYMRXZPHZFJS-UHFFFAOYSA-N 0.000 description 1
- PZSACZRLMBGKSF-VEXWJQHLSA-N 4-[[2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[(2S)-2-morpholin-4-ylpropoxy]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound BrC=1C=C(C=CC1OC)C(CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)OC[C@H](C)N2CCOCC2)O PZSACZRLMBGKSF-VEXWJQHLSA-N 0.000 description 1
- IMMXVSIPHLGTTG-UHFFFAOYSA-N 4-[[2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoropropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Br)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCN(CCCF)CC2)C(=O)NC=C1 IMMXVSIPHLGTTG-UHFFFAOYSA-N 0.000 description 1
- MQPZCABORBJAFW-UHFFFAOYSA-N 4-[[2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl]amino]-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCOCC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=C(F)C(Cl)=C1 MQPZCABORBJAFW-UHFFFAOYSA-N 0.000 description 1
- MQKSVRLGJFYTRI-UHFFFAOYSA-N 4-[[2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl]amino]-3-(4-methyl-6-piperazin-1-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCNCC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=C(F)C(Cl)=C1 MQKSVRLGJFYTRI-UHFFFAOYSA-N 0.000 description 1
- LGLHDKFGXZEGKW-UHFFFAOYSA-N 4-[[2-(3-chloro-4-fluorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoropropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCCF)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=C(F)C(Cl)=C1 LGLHDKFGXZEGKW-UHFFFAOYSA-N 0.000 description 1
- IYAZTZOPWLFGSM-UHFFFAOYSA-N 4-[[2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C1=C(Cl)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCOCC2)C(=O)NC=C1 IYAZTZOPWLFGSM-UHFFFAOYSA-N 0.000 description 1
- VTMIHYCOXBGSOX-UHFFFAOYSA-N 4-[[2-(3-chloro-4-methoxyphenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoropropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1=C(Cl)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCN(CCCF)CC2)C(=O)NC=C1 VTMIHYCOXBGSOX-UHFFFAOYSA-N 0.000 description 1
- ZEBVMFXVTKXQJX-VEXWJQHLSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[(2S)-2-morpholin-4-ylpropoxy]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound ClC=1C=C(C=CC1)C(CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)OC[C@H](C)N2CCOCC2)O ZEBVMFXVTKXQJX-VEXWJQHLSA-N 0.000 description 1
- INGPCXNUMNHUML-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(2-methylsulfinylacetyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)CS(C)=O)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 INGPCXNUMNHUML-UHFFFAOYSA-N 0.000 description 1
- ODKOFIIUMZVPOY-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(2-methylsulfonylacetyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)CS(C)(=O)=O)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 ODKOFIIUMZVPOY-UHFFFAOYSA-N 0.000 description 1
- IAOSNXWODOEZQA-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(2-methylsulfonylethyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCS(C)(=O)=O)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 IAOSNXWODOEZQA-UHFFFAOYSA-N 0.000 description 1
- UIBLHEZWESDKHO-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(2-thiomorpholin-4-ylacetyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)CN3CCSCC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 UIBLHEZWESDKHO-UHFFFAOYSA-N 0.000 description 1
- QLBZNPSNLVNWIT-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(3,3,3-trifluoropropyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCC(F)(F)F)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 QLBZNPSNLVNWIT-UHFFFAOYSA-N 0.000 description 1
- BDECAGGTSQFWTL-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(3,4,4-trifluorobut-3-enyl)piperazin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCC(F)=C(F)F)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 BDECAGGTSQFWTL-UHFFFAOYSA-N 0.000 description 1
- VQPODECQMREPQU-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2,2-difluoroacetyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)C(F)F)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 VQPODECQMREPQU-UHFFFAOYSA-N 0.000 description 1
- ZAKBVBOEYCRZJE-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2-fluoroethyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCF)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 ZAKBVBOEYCRZJE-UHFFFAOYSA-N 0.000 description 1
- UXGODHMBZZMTNL-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2-methoxyacetyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound C1CN(C(=O)COC)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 UXGODHMBZZMTNL-UHFFFAOYSA-N 0.000 description 1
- DWYUYEUFJJPGLV-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoro-2-hydroxypropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC(O)CF)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 DWYUYEUFJJPGLV-UHFFFAOYSA-N 0.000 description 1
- VUVAXIBXIAPBBM-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoropropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CCCF)CC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 VUVAXIBXIAPBBM-UHFFFAOYSA-N 0.000 description 1
- KKACLEOGRMSWFM-UHFFFAOYSA-N 4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(4-fluorobutanoyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)CCCF)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 KKACLEOGRMSWFM-UHFFFAOYSA-N 0.000 description 1
- SJEQKFKYXGQTRS-UHFFFAOYSA-N 4-[[2-(7-bromo-2,3-dihydro-1-benzofuran-5-yl)-2-hydroxyethyl]amino]-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one Chemical compound C=1C=2NC(C=3C(NC=CC=3NCC(O)C=3C=C(Br)C=4OCCC=4C=3)=O)=NC=2C(C)=CC=1N1CCOCC1 SJEQKFKYXGQTRS-UHFFFAOYSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 1
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- AGZWYQQHRJRPIX-VPMGYIILSA-N BrC=1C=C(C=CC1OC)[C@@H](CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)N2[C@H](C(OCC2)O)C)O Chemical compound BrC=1C=C(C=CC1OC)[C@@H](CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)N2[C@H](C(OCC2)O)C)O AGZWYQQHRJRPIX-VPMGYIILSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- LCASSGCXTUGCDS-ABQCGAOJSA-N ClC=1C=C(C=CC1)[C@@H](CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)N2[C@H](C(OCC2)O)C)O Chemical compound ClC=1C=C(C=CC1)[C@@H](CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)N2[C@H](C(OCC2)O)C)O LCASSGCXTUGCDS-ABQCGAOJSA-N 0.000 description 1
- BDQZUPKMJMVQEE-WEDVFNNRSA-N ClC=1C=C(C=CC1)[C@@H](CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)N2[C@H](C(OCC2)OC)C)O Chemical compound ClC=1C=C(C=CC1)[C@@H](CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)N2[C@H](C(OCC2)OC)C)O BDQZUPKMJMVQEE-WEDVFNNRSA-N 0.000 description 1
- BLMUEZVDGQGLQT-VPMGYIILSA-N ClC=1C=C(C=CC1OC)[C@@H](CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)N2[C@H](C(OCC2)O)C)O Chemical compound ClC=1C=C(C=CC1OC)[C@@H](CNC1=C(C(NC=C1)=O)C1=NC2=C(N1)C=C(C=C2C)N2[C@H](C(OCC2)O)C)O BLMUEZVDGQGLQT-VPMGYIILSA-N 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 208000012766 Growth delay Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 1
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 102000038455 IGF Type 1 Receptor Human genes 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 101100286588 Mus musculus Igfl gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- QAPZNKPZJJBBJP-UHFFFAOYSA-N N-[1-[2-[4-[[2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]acetamide Chemical compound C1=C(Br)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCC(CC2)NC(C)=O)C(=O)NC=C1 QAPZNKPZJJBBJP-UHFFFAOYSA-N 0.000 description 1
- QMPSWERXKSJDER-UHFFFAOYSA-N N-[1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]-2-hydroxyacetamide Chemical compound N=1C=2C(C)=CC(N3CCC(CC3)NC(=O)CO)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 QMPSWERXKSJDER-UHFFFAOYSA-N 0.000 description 1
- QKBUDEHLHMPUOI-UHFFFAOYSA-N N-[1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]acetamide Chemical compound C1CC(NC(=O)C)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NCC(O)C=3C=C(Cl)C=CC=3)=O)C2=C1 QKBUDEHLHMPUOI-UHFFFAOYSA-N 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- ABLYXLXBJMBVQN-JOCHJYFZSA-N chembl1097358 Chemical compound C1CN(C)CCN1C1=CC(C)=C(N=C(N2)C=3C(NC=CC=3NC[C@@H](O)C=3C=C(Cl)C=CC=3)=O)C2=C1 ABLYXLXBJMBVQN-JOCHJYFZSA-N 0.000 description 1
- NOTYZJDDBQLRNQ-SFHVURJKSA-N chembl245306 Chemical compound C([C@@H](CO)NC1=C(C(NC=C1)=O)C=1NC=2C=C(C=C(C=2N=1)C)N1C=NC=C1)C1=CC=C(Cl)C=C1 NOTYZJDDBQLRNQ-SFHVURJKSA-N 0.000 description 1
- QZBMIUISTXROQE-SFHVURJKSA-N chembl245366 Chemical compound C([C@@H](CO)NC1=C(C(NC=C1)=O)C=1NC=2C=C(C=C(C=2N=1)C)N1C=NC=C1)C1=CC=CC(Cl)=C1 QZBMIUISTXROQE-SFHVURJKSA-N 0.000 description 1
- SVOBCURLIYHUOI-KRWDZBQOSA-N chembl245369 Chemical compound C([C@@H](CO)NC1=C(C(NC=C1)=O)C=1NC=2C=C(C=C(C=2N=1)C)N1C=NC=C1)C1=CC=CC=C1Br SVOBCURLIYHUOI-KRWDZBQOSA-N 0.000 description 1
- YVAUBIJGQYRNAW-KRWDZBQOSA-N chembl392640 Chemical compound C([C@@H](CO)NC1=C(C(NC=C1)=O)C=1NC=2C=C(C=C(C=2N=1)C)N1C=NC=C1)C1=CC=CC=C1Cl YVAUBIJGQYRNAW-KRWDZBQOSA-N 0.000 description 1
- WASNZPFVELUKFM-FQEVSTJZSA-N chembl425303 Chemical compound C1([C@@H](O)CNC2=C(C(NC=C2)=O)C=2NC=3C=C(C=C(C=3N=2)C)N2C=NC=C2)=CC=CC(Cl)=C1 WASNZPFVELUKFM-FQEVSTJZSA-N 0.000 description 1
- IXRUDPNBDKEDFQ-UHFFFAOYSA-N chembl428222 Chemical compound N=1C=2C(C)=CC(N3C=NC=C3)=CC=2NC=1C(C(NC=C1)=O)=C1OCC1=CC=CC=N1 IXRUDPNBDKEDFQ-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229950008001 matuzumab Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229940127084 other anti-cancer agent Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- HGZGDQLQVHZNCX-UHFFFAOYSA-N oxolan-3-ylmethyl N-[1-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]carbamate Chemical compound N=1C=2C(C)=CC(N3CCC(CC3)NC(=O)OCC3COCC3)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 HGZGDQLQVHZNCX-UHFFFAOYSA-N 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000009596 postnatal growth Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- NDATWLNHARHTNE-UHFFFAOYSA-N prop-2-ynyl 4-[2-[4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazine-1-carboxylate Chemical compound N=1C=2C(C)=CC(N3CCN(CC3)C(=O)OCC#C)=CC=2NC=1C(C(NC=C1)=O)=C1NCC(O)C1=CC=CC(Cl)=C1 NDATWLNHARHTNE-UHFFFAOYSA-N 0.000 description 1
- XUWVIABDWDTJRZ-UHFFFAOYSA-N propan-2-ylazanide Chemical compound CC(C)[NH-] XUWVIABDWDTJRZ-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 150000003246 quinazolines Chemical class 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 201000006845 reticulosarcoma Diseases 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 239000000126 substance Substances 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
- 239000011885 synergistic combination Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- XPMYBIMPBQCZMX-UHFFFAOYSA-N tert-butyl 4-[2-[4-[[2-(3-bromo-4-methoxyphenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazine-1-carboxylate Chemical compound C1=C(Br)C(OC)=CC=C1C(O)CNC1=C(C=2NC3=CC(=CC(C)=C3N=2)N2CCN(CC2)C(=O)OC(C)(C)C)C(=O)NC=C1 XPMYBIMPBQCZMX-UHFFFAOYSA-N 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41541602P | 2002-10-02 | 2002-10-02 | |
| US60/415,416 | 2002-10-02 | ||
| PCT/US2003/030933 WO2004030625A2 (en) | 2002-10-02 | 2003-10-01 | Synergistic methods and compositions for treating cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2500729A1 true CA2500729A1 (en) | 2004-04-15 |
Family
ID=32069854
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002500729A Abandoned CA2500729A1 (en) | 2002-10-02 | 2003-10-01 | Synergistic methods and compositions for treating cancer |
| CA002500714A Abandoned CA2500714A1 (en) | 2002-10-02 | 2003-10-01 | Synergistic methods and compositions for treating cancer |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002500714A Abandoned CA2500714A1 (en) | 2002-10-02 | 2003-10-01 | Synergistic methods and compositions for treating cancer |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US20040106605A1 (https=) |
| EP (2) | EP1556051A2 (https=) |
| JP (2) | JP2006503866A (https=) |
| AU (2) | AU2003275364A1 (https=) |
| CA (2) | CA2500729A1 (https=) |
| TW (2) | TW200501960A (https=) |
| WO (2) | WO2004030627A2 (https=) |
Families Citing this family (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999001124A1 (en) * | 1996-12-03 | 1999-01-14 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
| US20020058286A1 (en) * | 1999-02-24 | 2002-05-16 | Danishefsky Samuel J. | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US20050271663A1 (en) * | 2001-06-28 | 2005-12-08 | Domantis Limited | Compositions and methods for treating inflammatory disorders |
| DK1399484T3 (da) * | 2001-06-28 | 2010-11-08 | Domantis Ltd | Dobbelt-specifik ligand og anvendelse af denne |
| US7217796B2 (en) | 2002-05-24 | 2007-05-15 | Schering Corporation | Neutralizing human anti-IGFR antibody |
| ES2263984T3 (es) * | 2002-06-28 | 2006-12-16 | Domantis Limited | Ligandos doble-especificos con una vida media serica aumentada. |
| US7696320B2 (en) | 2004-08-24 | 2010-04-13 | Domantis Limited | Ligands that have binding specificity for VEGF and/or EGFR and methods of use therefor |
| US9321832B2 (en) * | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
| DE60330407D1 (de) | 2002-08-23 | 2010-01-14 | Sloan Kettering Inst Cancer | Synthese von Epothilonen, Zwischenprodukte davon, Analoga und ihre Verwendung |
| US6921769B2 (en) | 2002-08-23 | 2005-07-26 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| US7649006B2 (en) | 2002-08-23 | 2010-01-19 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto and analogues thereof |
| AU2003290330A1 (en) * | 2002-12-27 | 2004-07-22 | Domantis Limited | Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand |
| KR100872204B1 (ko) * | 2003-10-15 | 2008-12-09 | 오에스아이 파마슈티컬스, 인코포레이티드 | 이미다조피라진 티로신 키나제 억제제 |
| JP2007510434A (ja) | 2003-11-12 | 2007-04-26 | シェーリング コーポレイション | 多重遺伝子発現のためのプラスミドシステム |
| US8017321B2 (en) | 2004-01-23 | 2011-09-13 | The Regents Of The University Of Colorado, A Body Corporate | Gefitinib sensitivity-related gene expression and products and methods related thereto |
| ATE514434T1 (de) | 2004-02-25 | 2011-07-15 | Dana Farber Cancer Inst Inc | Hemmer des insulinartigen wachstumsfaktor- rezeptors-1 zur hemmung von tumorzellwachstum |
| TWI378934B (en) * | 2004-04-02 | 2012-12-11 | Osi Pharm Inc | 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors |
| WO2005117553A2 (en) * | 2004-05-27 | 2005-12-15 | The Regents Of The University Of Colorado | Methods for prediction of clinical outcome to epidermal growth factor receptor inhibitors by cancer patients |
| EP1755608A1 (en) * | 2004-06-03 | 2007-02-28 | F.Hoffmann-La Roche Ag | Treatment with gemcitabine and an egfr-inhibitor |
| EP2283831A3 (en) | 2004-12-03 | 2013-10-23 | Merck Sharp & Dohme Corp. | Biomakers for pre-selection of patients for anti-IGF1R therapy |
| JP2008535790A (ja) * | 2005-03-03 | 2008-09-04 | サートリス ファーマシューティカルズ， インコーポレイテッド | サーチュインモジュレーターであるｎ−フェニルベンズアミド誘導体 |
| US8383357B2 (en) * | 2005-03-16 | 2013-02-26 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to epidermal growth factor receptor kinase inhibitors |
| CA2601157A1 (en) | 2005-03-16 | 2006-09-28 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to epidermal growth factor receptor kinase inhibitors |
| KR20080019249A (ko) | 2005-06-15 | 2008-03-03 | 쉐링 코포레이션 | 안정한 항체 제형 |
| US7855289B2 (en) | 2005-08-04 | 2010-12-21 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US8088928B2 (en) | 2005-08-04 | 2012-01-03 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| EP1910385B1 (en) * | 2005-08-04 | 2013-07-24 | Sirtris Pharmaceuticals, Inc. | Benzothiazoles and thiazolopyridines as sirtuin modulators |
| US8093401B2 (en) * | 2005-08-04 | 2012-01-10 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| US8580814B2 (en) * | 2006-04-03 | 2013-11-12 | Sunesis Pharmaceuticals, Inc. | Methods of using (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4- oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid for treatment of cancer |
| AU2006292278B2 (en) | 2005-09-20 | 2012-03-08 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| CA2632866A1 (en) * | 2005-12-01 | 2007-06-07 | Domantis Limited | Noncompetitive domain antibody formats that bind interleukin 1 receptor type 1 |
| US8575164B2 (en) * | 2005-12-19 | 2013-11-05 | OSI Pharmaceuticals, LLC | Combination cancer therapy |
| WO2007117400A2 (en) * | 2006-03-31 | 2007-10-18 | Janssen Pharmaceutica N.V. | Benzoimidazol-2-yl pyridines as modulators of the histamine h4 receptor |
| WO2007117399A2 (en) | 2006-03-31 | 2007-10-18 | Janssen Pharmaceutica N.V. | Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine h4 receptor |
| US20080045589A1 (en) * | 2006-05-26 | 2008-02-21 | Susan Kelley | Drug Combinations with Substituted Diaryl Ureas for the Treatment of Cancer |
| EP2120932B1 (en) * | 2006-12-20 | 2014-07-09 | Nerviano Medical Sciences S.r.l. | Indazole derivatives as kinase inhibitors for the treatment of cancer |
| US20090068110A1 (en) * | 2006-12-22 | 2009-03-12 | Genentech, Inc. | Antibodies to insulin-like growth factor receptor |
| TW200900070A (en) * | 2007-02-27 | 2009-01-01 | Osi Pharm Inc | Combination cancer therapy |
| JP5240739B2 (ja) * | 2007-04-13 | 2013-07-17 | オーエスアイ・フアーマシユーテイカルズ・エル・エル・シー | キナーゼ阻害剤に対する抗癌応答を予測する生物学的マーカー |
| WO2008149147A2 (en) * | 2007-06-06 | 2008-12-11 | Domantis Limited | Polypeptides, antibody variable domains and antagonists |
| TW200916472A (en) | 2007-06-20 | 2009-04-16 | Sirtris Pharmaceuticals Inc | Sirtuin modulating compounds |
| JP2011501660A (ja) * | 2007-10-03 | 2011-01-13 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | インスリン様成長因子−１受容体キナーゼ阻害剤に対する抗癌反応を予測する生物学的マーカー |
| JP2010540960A (ja) * | 2007-10-03 | 2010-12-24 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | インスリン様成長因子−１受容体キナーゼ阻害剤に対する抗癌反応を予測する生物学的マーカー |
| JP2011502984A (ja) * | 2007-11-01 | 2011-01-27 | サートリス ファーマシューティカルズ， インコーポレイテッド | サーチュインモジュレーターとしてのアミド誘導体 |
| CA2705138A1 (en) * | 2007-11-08 | 2009-05-14 | Sirtris Pharmaceuticals, Inc. | Solubilized thiazolopyridines |
| WO2009079001A1 (en) | 2007-12-18 | 2009-06-25 | Janssen Pharmaceutica N.V. | Bicyclic heteroaryl-substituted imidazoles as modulators of the histamine h4 receptor |
| DK2082745T3 (da) | 2007-12-28 | 2013-03-25 | Deutsches Krebsforsch | Kræftterapi med en parvovirus kombineret med kemoterapi |
| JP2011510018A (ja) * | 2008-01-18 | 2011-03-31 | オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド | 癌治療のためのイミダゾピラジノール誘導体 |
| RU2008106419A (ru) * | 2008-02-21 | 2009-08-27 | Закрытое акционерное общество "Ива фарм" (RU) | Лекарственные средства на основе олигоядерных координационных соединений d-металлов, способ терапевтического воздействия на организм пациента и способ повышения терапевтической эффективности фармакологически активного вещества |
| KR101189883B1 (ko) | 2008-03-27 | 2012-10-10 | 미쓰비시덴키 가부시키가이샤 | 엘리베이터의 제어 시스템 |
| EP2283020B8 (en) * | 2008-05-19 | 2012-12-12 | OSI Pharmaceuticals, LLC | Substituted imidazopyr-and imidazotri-azines |
| US9371311B2 (en) | 2008-06-30 | 2016-06-21 | Janssen Pharmaceutica Nv | Benzoimidazol-2-yl pyrimidine derivatives |
| EP2376502B1 (en) | 2008-12-19 | 2015-06-17 | GlaxoSmithKline LLC | Thiazolopyridine sirtuin modulating compounds |
| US20110171124A1 (en) * | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
| EP2408479A1 (en) | 2009-03-18 | 2012-01-25 | OSI Pharmaceuticals, LLC | Combination cancer therapy comprising administration of an egfr inhibitor and an igf-1r inhibitor |
| WO2010123792A1 (en) | 2009-04-20 | 2010-10-28 | Osi Pharmaceuticals, Inc. | Preparation of c-pyrazine-methylamines |
| EP2427192A1 (en) * | 2009-05-07 | 2012-03-14 | OSI Pharmaceuticals, LLC | Use of osi-906 for treating adrenocortical carcinoma |
| WO2010146059A2 (en) | 2009-06-16 | 2010-12-23 | F. Hoffmann-La Roche Ag | Biomarkers for igf-1r inhibitor therapy |
| CA2783665A1 (en) * | 2010-03-03 | 2011-09-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| US8927547B2 (en) | 2010-05-21 | 2015-01-06 | Noviga Research Ab | Pyrimidine derivatives |
| WO2012117396A1 (en) * | 2011-03-01 | 2012-09-07 | Novotyr Therapeutics Ltd | Tyrphostin derivative in combination with cytotoxic compounds for treating cancer |
| WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
| DK2688883T3 (en) | 2011-03-24 | 2016-09-05 | Noviga Res Ab | pyrimidine |
| EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
| JP6255038B2 (ja) | 2013-02-26 | 2017-12-27 | トリアクト セラピューティクス，インク． | 癌治療 |
| PT2964229T (pt) | 2013-03-06 | 2020-03-23 | Janssen Pharmaceutica Nv | Moduladores de piridina benzimidazol-2-ilo do recetor h4 de histamina |
| US9770454B2 (en) | 2013-07-14 | 2017-09-26 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | IGF-1R signaling pathway inhibitors useful in the treatment of neurodegenerative diseases |
| US9381246B2 (en) | 2013-09-09 | 2016-07-05 | Triact Therapeutics, Inc. | Cancer therapy |
| CN112353938A (zh) | 2015-02-05 | 2021-02-12 | 特尔诺沃有限公司 | 用于治疗癌症的irs/stat3双重调节剂与抗癌剂的组合 |
| GB201617627D0 (en) * | 2016-10-18 | 2016-11-30 | Cellcentric Ltd | Pharmaceutical compounds |
| US10479786B2 (en) * | 2016-12-13 | 2019-11-19 | Princeton Drug Discovery, Inc | Protein kinase inhibitors |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2643903A1 (fr) * | 1989-03-03 | 1990-09-07 | Union Pharma Scient Appl | Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux |
| US6337338B1 (en) * | 1998-12-15 | 2002-01-08 | Telik, Inc. | Heteroaryl-aryl ureas as IGF-1 receptor antagonists |
| KR20050037510A (ko) * | 2002-06-05 | 2005-04-22 | 세다르스-신나이 메디칼 센터 | 키나제 억제제를 사용하는 암 치료 방법 |
-
2003
- 2003-09-30 TW TW092127035A patent/TW200501960A/zh unknown
- 2003-10-01 WO PCT/US2003/031091 patent/WO2004030627A2/en not_active Ceased
- 2003-10-01 CA CA002500729A patent/CA2500729A1/en not_active Abandoned
- 2003-10-01 EP EP03774511A patent/EP1556051A2/en not_active Withdrawn
- 2003-10-01 EP EP03759640A patent/EP1551411A2/en not_active Withdrawn
- 2003-10-01 US US10/676,214 patent/US20040106605A1/en not_active Abandoned
- 2003-10-01 JP JP2004541936A patent/JP2006503866A/ja not_active Withdrawn
- 2003-10-01 JP JP2004541997A patent/JP2006503867A/ja not_active Withdrawn
- 2003-10-01 AU AU2003275364A patent/AU2003275364A1/en not_active Abandoned
- 2003-10-01 TW TW092127209A patent/TW200410689A/zh unknown
- 2003-10-01 US US10/677,067 patent/US20040072760A1/en not_active Abandoned
- 2003-10-01 AU AU2003282892A patent/AU2003282892A1/en not_active Abandoned
- 2003-10-01 CA CA002500714A patent/CA2500714A1/en not_active Abandoned
- 2003-10-01 WO PCT/US2003/030933 patent/WO2004030625A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004030625A3 (en) | 2004-06-24 |
| US20040106605A1 (en) | 2004-06-03 |
| AU2003275364A1 (en) | 2004-04-23 |
| TW200501960A (en) | 2005-01-16 |
| AU2003282892A1 (en) | 2004-04-23 |
| WO2004030625A2 (en) | 2004-04-15 |
| CA2500714A1 (en) | 2004-04-15 |
| EP1556051A2 (en) | 2005-07-27 |
| WO2004030627A2 (en) | 2004-04-15 |
| WO2004030627A3 (en) | 2004-07-01 |
| JP2006503866A (ja) | 2006-02-02 |
| JP2006503867A (ja) | 2006-02-02 |
| TW200410689A (en) | 2004-07-01 |
| EP1551411A2 (en) | 2005-07-13 |
| US20040072760A1 (en) | 2004-04-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20040106605A1 (en) | Synergistic methods and compositions for treating cancer | |
| AU2014372166B2 (en) | Pharmaceutical combinations | |
| US9241939B2 (en) | Combination of (a) a phosphoinositide 3-kinase inhibitor and (b) a modulator of RAS/RAF/MEK pathway | |
| US10617670B2 (en) | Synergistic auristatin combinations | |
| KR20220148847A (ko) | 다브라페닙, erk 억제제, 및 shp2 억제제를 포함하는 삼중 약학적 조합물 | |
| AU2014317119B2 (en) | Combination of a MEK inhibitor and an ERK inhibitor for use in treatment of hyperproliferative diseases | |
| US20060094674A1 (en) | Combination of mtor inhibitor and a tyrosine kinase inhibitor for the treatment of neoplasms | |
| UA125216C2 (uk) | Комбінована терапія | |
| CA2914310A1 (en) | Pharmaceutical combinations | |
| KR20240112932A (ko) | 암 치료를 위한 cdk2 억제제 및 cdk4 억제제를 포함하는 방법 및 투여 섭생법 | |
| KR20230112626A (ko) | 아베마시클립 및 6-(2,4-디클로로페닐)-5-[4-[(3s)-1-(3-플루오로프로필)피롤리딘-3-일]옥시페닐]-8,9-디히드로-7h-벤조[7]아눌렌-2-카복실산을 포함하는 병용물 | |
| WO2024137778A1 (en) | Cancer treatments using mta-cooperative prmt5 inhibitors | |
| CN120379663A (zh) | Dcc-3116和mapkap路径抑制剂组合用于治疗病症 | |
| Chu et al. | Basic and clinical pharmacology | |
| US20210145834A1 (en) | Combination of poziotinib with cytotoxic agent and/or other molecularly targeted agent and use thereof | |
| Yang et al. | ZD6474 induces growth arrest and apoptosis of GIST‐T1 cells, which is enhanced by concomitant use of sunitinib | |
| US20050075358A1 (en) | Methods for treating IGF1R-inhibitor induced hyperglycemia | |
| CN118510516A (zh) | 用于治疗套细胞淋巴瘤的包含阿贝西利和pi3k和/或mtor抑制剂的药物组合 | |
| TW202317126A (zh) | Ｅｇｆｒ抑制劑和ｐｅｒｋ活化劑組合療法 | |
| Barquero | Trilaciclib hydrochloride. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, Myelopreservation therapy, Treatment of small cell lung cancer, Treatment of triple-negative breast cancer | |
| CN101222925A (zh) | 嘧啶基氨基苯甲酰胺和mTOR激酶抑制剂的组合产品 | |
| HK40106272A (zh) | 组合疗法中的egfr抑制剂和perk活化剂及其用於治疗癌症的用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |