CA2594474C - Pharmaceutical compounds - Google Patents
Pharmaceutical compounds Download PDFInfo
- Publication number
- CA2594474C CA2594474C CA2594474A CA2594474A CA2594474C CA 2594474 C CA2594474 C CA 2594474C CA 2594474 A CA2594474 A CA 2594474A CA 2594474 A CA2594474 A CA 2594474A CA 2594474 C CA2594474 C CA 2594474C
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- Canada
- Prior art keywords
- group
- compound
- groups
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- carbocyclic
- 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.)
- Expired - Fee Related
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 345
- -1 fluorine) Chemical class 0.000 claims abstract description 254
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 184
- 150000003839 salts Chemical class 0.000 claims abstract description 184
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 161
- 125000001424 substituent group Chemical group 0.000 claims abstract description 146
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 126
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 111
- 239000001257 hydrogen Substances 0.000 claims abstract description 111
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 87
- 239000003112 inhibitor Substances 0.000 claims abstract description 86
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 83
- 239000011737 fluorine Substances 0.000 claims abstract description 79
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 79
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 79
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 70
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 63
- 150000002367 halogens Chemical class 0.000 claims abstract description 62
- 230000011664 signaling Effects 0.000 claims abstract description 59
- 231100000433 cytotoxic Toxicity 0.000 claims abstract description 56
- 230000001472 cytotoxic effect Effects 0.000 claims abstract description 56
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 54
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 51
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 51
- 239000012453 solvate Substances 0.000 claims abstract description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 36
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 28
- 125000004429 atom Chemical group 0.000 claims abstract description 26
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 22
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims abstract description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 103
- 125000001072 heteroaryl group Chemical group 0.000 claims description 85
- 125000003118 aryl group Chemical group 0.000 claims description 75
- 125000005842 heteroatom Chemical group 0.000 claims description 73
- 102000003903 Cyclin-dependent kinases Human genes 0.000 claims description 60
- 108090000266 Cyclin-dependent kinases Proteins 0.000 claims description 60
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 60
- 239000002253 acid Substances 0.000 claims description 57
- 230000000694 effects Effects 0.000 claims description 57
- 201000011510 cancer Diseases 0.000 claims description 53
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
- 238000011282 treatment Methods 0.000 claims description 52
- 229910052757 nitrogen Inorganic materials 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 45
- 239000000460 chlorine Substances 0.000 claims description 42
- 229910052801 chlorine Inorganic materials 0.000 claims description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
- 125000002950 monocyclic group Chemical group 0.000 claims description 39
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 38
- 201000010099 disease Diseases 0.000 claims description 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 34
- 239000003814 drug Substances 0.000 claims description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 30
- OVPNQJVDAFNBDN-UHFFFAOYSA-N 4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide Chemical compound ClC1=CC=CC(Cl)=C1C(=O)NC1=CNN=C1C(=O)NC1CCNCC1 OVPNQJVDAFNBDN-UHFFFAOYSA-N 0.000 claims description 26
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 26
- 229940127093 camptothecin Drugs 0.000 claims description 26
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 26
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 25
- 125000002619 bicyclic group Chemical group 0.000 claims description 25
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 25
- 125000001153 fluoro group Chemical group F* 0.000 claims description 25
- 229940122803 Vinca alkaloid Drugs 0.000 claims description 24
- 108091007914 CDKs Proteins 0.000 claims description 21
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 21
- 230000002401 inhibitory effect Effects 0.000 claims description 19
- 230000000340 anti-metabolite Effects 0.000 claims description 18
- 229940100197 antimetabolite Drugs 0.000 claims description 18
- 239000002256 antimetabolite Substances 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 17
- 125000003282 alkyl amino group Chemical group 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 230000004044 response Effects 0.000 claims description 17
- 125000004043 oxo group Chemical group O=* 0.000 claims description 16
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 15
- 230000010261 cell growth Effects 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 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 claims description 13
- 230000002159 abnormal effect Effects 0.000 claims description 13
- 229960005277 gemcitabine Drugs 0.000 claims description 13
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 238000002648 combination therapy Methods 0.000 claims description 12
- 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 claims description 12
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 11
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 229960004117 capecitabine Drugs 0.000 claims description 11
- 229960000684 cytarabine Drugs 0.000 claims description 11
- 238000009472 formulation Methods 0.000 claims description 11
- 229960000485 methotrexate Drugs 0.000 claims description 11
- 229960005079 pemetrexed Drugs 0.000 claims description 11
- 229960000303 topotecan Drugs 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 229940123237 Taxane Drugs 0.000 claims description 10
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 208000032839 leukemia Diseases 0.000 claims description 10
- 238000011321 prophylaxis Methods 0.000 claims description 10
- 229960003048 vinblastine Drugs 0.000 claims description 10
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
- 150000003058 platinum compounds Chemical class 0.000 claims description 8
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 claims description 8
- 230000004614 tumor growth Effects 0.000 claims description 8
- 101100243950 Arabidopsis thaliana PIE1 gene Chemical group 0.000 claims description 7
- 229930012538 Paclitaxel Natural products 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 claims description 7
- 210000000481 breast Anatomy 0.000 claims description 7
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 7
- 229960001592 paclitaxel Drugs 0.000 claims description 7
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 7
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 7
- 210000004881 tumor cell Anatomy 0.000 claims description 7
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 7
- 229960004528 vincristine Drugs 0.000 claims description 7
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 7
- 229960002066 vinorelbine Drugs 0.000 claims description 7
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical group 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 claims description 6
- 229960005420 etoposide Drugs 0.000 claims description 6
- 210000001685 thyroid gland Anatomy 0.000 claims description 6
- 101100509371 Arabidopsis thaliana CHR11 gene Proteins 0.000 claims description 5
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 5
- 230000003394 haemopoietic effect Effects 0.000 claims description 5
- 230000003389 potentiating effect Effects 0.000 claims description 5
- 230000008685 targeting Effects 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- MALIONKMKPITBV-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-n-[2-(4-sulfamoylphenyl)ethyl]acetamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)CC1=CC=C(O)C(Cl)=C1 MALIONKMKPITBV-UHFFFAOYSA-N 0.000 claims description 4
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 4
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 4
- 238000011319 anticancer therapy Methods 0.000 claims description 4
- 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 claims description 4
- 229960004562 carboplatin Drugs 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 claims description 4
- 229960003668 docetaxel Drugs 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 230000003325 follicular Effects 0.000 claims description 4
- 230000012010 growth Effects 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 3
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 3
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 3
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims description 3
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims description 3
- 230000001093 anti-cancer Effects 0.000 claims description 3
- 229940045985 antineoplastic platinum compound Drugs 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 3
- 229960000975 daunorubicin Drugs 0.000 claims description 3
- 238000003745 diagnosis Methods 0.000 claims description 3
- 229960001904 epirubicin Drugs 0.000 claims description 3
- 229960000908 idarubicin Drugs 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 3
- 201000008968 osteosarcoma Diseases 0.000 claims description 3
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 3
- 229960001756 oxaliplatin Drugs 0.000 claims description 3
- BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- 229960001278 teniposide Drugs 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
- CXBHMSHVCKEEGW-UHFFFAOYSA-N 4-(2,6-difluorobenzamido)-N-(piperidin-4-yl)-1H-pyrazole-3-carboxamide Chemical compound FC1=CC=CC(F)=C1C(=O)NC1=CNN=C1C(=O)NC1CCNCC1 CXBHMSHVCKEEGW-UHFFFAOYSA-N 0.000 claims description 2
- NPPBDFFMJNUJRY-UHFFFAOYSA-N 4-[(2-fluoro-6-methoxybenzoyl)amino]-n-piperidin-4-yl-1h-pyrazole-5-carboxamide Chemical compound COC1=CC=CC(F)=C1C(=O)NC1=CNN=C1C(=O)NC1CCNCC1 NPPBDFFMJNUJRY-UHFFFAOYSA-N 0.000 claims description 2
- 101100240520 Caenorhabditis elegans nhr-14 gene Chemical group 0.000 claims description 2
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 claims description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 claims description 2
- 201000010208 Seminoma Diseases 0.000 claims description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 2
- 201000006083 Xeroderma Pigmentosum Diseases 0.000 claims description 2
- KMLCRELJHYKIIL-UHFFFAOYSA-N [1-(azanidylmethyl)cyclohexyl]methylazanide;platinum(2+);sulfuric acid Chemical compound [Pt+2].OS(O)(=O)=O.[NH-]CC1(C[NH-])CCCCC1 KMLCRELJHYKIIL-UHFFFAOYSA-N 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 210000003679 cervix uteri Anatomy 0.000 claims description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 2
- 229940121647 egfr inhibitor Drugs 0.000 claims description 2
- 210000002615 epidermis Anatomy 0.000 claims description 2
- 210000000232 gallbladder Anatomy 0.000 claims description 2
- 125000005059 halophenyl group Chemical group 0.000 claims description 2
- 229950010897 iproplatin Drugs 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical group O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 2
- 229960001156 mitoxantrone Drugs 0.000 claims description 2
- 238000011275 oncology therapy Methods 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 229950004330 spiroplatin Drugs 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 208000001608 teratocarcinoma Diseases 0.000 claims description 2
- 208000010570 urinary bladder carcinoma Diseases 0.000 claims description 2
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| AR054425A1 (es) * | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
| US20080139620A1 (en) * | 2005-01-21 | 2008-06-12 | Astex Therapeutics Limited | Pyrazole Derivatives For The Inhibition Of Cdk's And Gsk's |
| US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
| JP2008528469A (ja) * | 2005-01-21 | 2008-07-31 | アステックス・セラピューティクス・リミテッド | ピラゾールキナーゼ阻害剤およびさらなる抗癌剤の組合せ剤 |
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| US20070166388A1 (en) * | 2005-02-18 | 2007-07-19 | Desai Neil P | Combinations and modes of administration of therapeutic agents and combination therapy |
| CN101133088B (zh) * | 2005-03-03 | 2011-04-13 | 三菱丽阳株式会社 | 聚合物粒子、含有它的树脂组合物、成型体 |
| ATE526378T1 (de) * | 2005-08-02 | 2011-10-15 | Tufts College | Verfahren zur stufenweisen ablagerung von seidenfibroinbeschichtungen |
| US20090318500A1 (en) * | 2006-05-05 | 2009-12-24 | Astex Therapeutics Limited | 4-(2, 6-Dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid (1-methanesulphonyl-piperidin-4-yl)-amide for the Treatment of Cancer |
| US20090142337A1 (en) * | 2006-05-08 | 2009-06-04 | Astex Therapeutics Limited | Pharmaceutical Combinations of Diazole Derivatives for Cancer Treatment |
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| EP2070924A1 (de) | 2007-12-10 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | Neue 2-Hetarylthiazol-4-carbonsäureamid-Derivative, deren Herstellung und Verwendung als Arzneimittel |
| EP2070916A1 (de) | 2007-12-10 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | 2-Aryl-thiazol-4-carbonsäureamid-Derivate, deren Herstellung und Verwendung als Arzneimittel |
| EP2070925A1 (de) | 2007-12-10 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | Neue 2-substituierte Tiazol-4-carbonsäureamid-Derivative deren Herstellung und Verwendung als Arzneimittel |
| JP2011528798A (ja) * | 2008-07-23 | 2011-11-24 | エフ.ホフマン−ラ ロシュ アーゲー | 抗血管形成療法のモニター |
| MX2011006167A (es) * | 2008-12-11 | 2011-07-28 | Abraxis Bioscience Llc | Combinaciones y modos de administracion de agentes terapeuticos y terapia de combinacion. |
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| CA2594474A1 (en) | 2006-07-27 |
| MX2007008810A (es) | 2007-11-21 |
| CN101146532B (zh) | 2012-05-09 |
| JP2008528468A (ja) | 2008-07-31 |
| KR20070098925A (ko) | 2007-10-05 |
| BRPI0606480A (pt) | 2008-03-11 |
| CN101146532A (zh) | 2008-03-19 |
| US20080161251A1 (en) | 2008-07-03 |
| JP5475234B2 (ja) | 2014-04-16 |
| AU2006207321A1 (en) | 2006-07-27 |
| KR101345002B1 (ko) | 2013-12-31 |
| AU2006207321B2 (en) | 2012-09-06 |
| EP1845974A1 (en) | 2007-10-24 |
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