AU2008245447C1 - Inhibitors of IAP - Google Patents
Inhibitors of IAP Download PDFInfo
- Publication number
- AU2008245447C1 AU2008245447C1 AU2008245447A AU2008245447A AU2008245447C1 AU 2008245447 C1 AU2008245447 C1 AU 2008245447C1 AU 2008245447 A AU2008245447 A AU 2008245447A AU 2008245447 A AU2008245447 A AU 2008245447A AU 2008245447 C1 AU2008245447 C1 AU 2008245447C1
- Authority
- AU
- Australia
- Prior art keywords
- compound
- mmol
- alkyl
- particular embodiment
- heterocycle
- 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.)
- Ceased
Links
- 239000003112 inhibitor Substances 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 197
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 5
- -1 tetrahydropyran-4-yl Chemical group 0.000 claims description 267
- 125000000217 alkyl group Chemical group 0.000 claims description 166
- 125000000623 heterocyclic group Chemical group 0.000 claims description 124
- 238000000034 method Methods 0.000 claims description 68
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 230000006907 apoptotic process Effects 0.000 claims description 22
- 102000011727 Caspases Human genes 0.000 claims description 19
- 108010076667 Caspases Proteins 0.000 claims description 19
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 16
- 230000005855 radiation Effects 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 11
- 230000027455 binding Effects 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 108091007065 BIRCs Proteins 0.000 claims description 9
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 230000001640 apoptogenic effect Effects 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 229960004679 doxorubicin Drugs 0.000 claims description 5
- 230000001939 inductive effect Effects 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 230000001235 sensitizing effect Effects 0.000 claims description 5
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 4
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 4
- 230000002018 overexpression Effects 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 229930012538 Paclitaxel Natural products 0.000 claims description 3
- 229940009456 adriamycin Drugs 0.000 claims description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 3
- 229960004316 cisplatin Drugs 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 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 3
- NNJPGOLRFBJNIW-HNNXBMFYSA-N (-)-demecolcine Chemical compound C1=C(OC)C(=O)C=C2[C@@H](NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-HNNXBMFYSA-N 0.000 claims description 2
- VTBOTOBFGSVRMA-UHFFFAOYSA-N 1-Methylcyclohexanol Chemical compound CC1(O)CCCCC1 VTBOTOBFGSVRMA-UHFFFAOYSA-N 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 108010006654 Bleomycin Proteins 0.000 claims description 2
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 2
- NNJPGOLRFBJNIW-UHFFFAOYSA-N Demecolcine Natural products C1=C(OC)C(=O)C=C2C(NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-UHFFFAOYSA-N 0.000 claims description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 2
- 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 2
- 229960001561 bleomycin Drugs 0.000 claims description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 2
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 2
- 229940127093 camptothecin Drugs 0.000 claims description 2
- 229960001338 colchicine Drugs 0.000 claims description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 2
- 229960004397 cyclophosphamide Drugs 0.000 claims description 2
- 229960000684 cytarabine Drugs 0.000 claims description 2
- 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 2
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 claims description 2
- 229960004039 finasteride Drugs 0.000 claims description 2
- 229960000390 fludarabine Drugs 0.000 claims description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims description 2
- 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 2
- 229960005277 gemcitabine Drugs 0.000 claims description 2
- 229960000485 methotrexate Drugs 0.000 claims description 2
- 229960004857 mitomycin Drugs 0.000 claims description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound 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
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
- 229960001603 tamoxifen Drugs 0.000 claims description 2
- 229940063683 taxotere Drugs 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 2
- 229960000303 topotecan Drugs 0.000 claims description 2
- 229960003048 vinblastine Drugs 0.000 claims description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 2
- 229960004528 vincristine Drugs 0.000 claims description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 2
- HCFRWBBJISAZNK-UHFFFAOYSA-N 4-Hydroxycyclohexylcarboxylic acid Chemical compound OC1CCC(C(O)=O)CC1 HCFRWBBJISAZNK-UHFFFAOYSA-N 0.000 claims 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000005647 linker group Chemical group 0.000 abstract description 7
- 238000005304 joining Methods 0.000 abstract description 4
- 230000036210 malignancy Effects 0.000 abstract 1
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 173
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 153
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 102
- 125000003118 aryl group Chemical group 0.000 description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- 239000000243 solution Substances 0.000 description 81
- 235000019439 ethyl acetate Nutrition 0.000 description 77
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 72
- 239000000203 mixture Substances 0.000 description 65
- 229910052736 halogen Inorganic materials 0.000 description 63
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 58
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 55
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- 150000002367 halogens Chemical group 0.000 description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 49
- 125000003545 alkoxy group Chemical group 0.000 description 47
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- 125000001072 heteroaryl group Chemical group 0.000 description 44
- 125000002252 acyl group Chemical group 0.000 description 42
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
- 125000001188 haloalkyl group Chemical group 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 33
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 32
- 239000012267 brine Substances 0.000 description 31
- 229910052757 nitrogen Inorganic materials 0.000 description 31
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
- 239000007787 solid Substances 0.000 description 31
- 125000003710 aryl alkyl group Chemical group 0.000 description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 27
- 239000000539 dimer Substances 0.000 description 27
- 125000001424 substituent group Chemical group 0.000 description 26
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 150000001412 amines Chemical class 0.000 description 23
- 239000000523 sample Substances 0.000 description 23
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 22
- 229940024606 amino acid Drugs 0.000 description 21
- 235000001014 amino acid Nutrition 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 21
- 239000011734 sodium Substances 0.000 description 21
- 125000003396 thiol group Chemical class [H]S* 0.000 description 21
- 229910001868 water Inorganic materials 0.000 description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 20
- 238000003818 flash chromatography Methods 0.000 description 20
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 19
- 229910004298 SiO 2 Inorganic materials 0.000 description 19
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 19
- 229940093499 ethyl acetate Drugs 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000010410 layer Substances 0.000 description 18
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- 125000006239 protecting group Chemical group 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 125000004043 oxo group Chemical group O=* 0.000 description 17
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 16
- 150000001408 amides Chemical class 0.000 description 16
- 239000000178 monomer Substances 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 16
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 16
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 14
- ZHGNHOOVYPHPNJ-UHFFFAOYSA-N Amigdalin Chemical compound FC(F)(F)C(=O)OCC1OC(OCC2OC(OC(C#N)C3=CC=CC=C3)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C2OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C1OC(=O)C(F)(F)F ZHGNHOOVYPHPNJ-UHFFFAOYSA-N 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 235000018102 proteins Nutrition 0.000 description 14
- 238000006467 substitution reaction Methods 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
- 125000004104 aryloxy group Chemical group 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
- 229910052770 Uranium Inorganic materials 0.000 description 12
- 238000010168 coupling process Methods 0.000 description 12
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 230000008878 coupling Effects 0.000 description 11
- 238000005859 coupling reaction Methods 0.000 description 11
- 239000013058 crude material Substances 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 11
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- PMXCMJLOPOFPBT-HNNXBMFYSA-N purvalanol A Chemical compound C=12N=CN(C(C)C)C2=NC(N[C@@H](CO)C(C)C)=NC=1NC1=CC=CC(Cl)=C1 PMXCMJLOPOFPBT-HNNXBMFYSA-N 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
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- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
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- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
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- 238000002560 therapeutic procedure Methods 0.000 description 1
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- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
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- 125000005307 thiatriazolyl group Chemical group S1N=NN=C1* 0.000 description 1
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- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- IARSSOVWSJAVSZ-UHFFFAOYSA-N tris(dimethylamino)sulfanium Chemical compound CN(C)[S+](N(C)C)N(C)C IARSSOVWSJAVSZ-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D263/06—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by oxygen atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Steroid Compounds (AREA)
- Indole Compounds (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US91501007P | 2007-04-30 | 2007-04-30 | |
| US60/915,010 | 2007-04-30 | ||
| PCT/US2008/061891 WO2008134679A1 (en) | 2007-04-30 | 2008-04-29 | Inhibitors of iap |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013248173A Division AU2013248173A1 (en) | 2007-04-30 | 2013-10-17 | Inhibitors of IAP |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| AU2008245447A1 AU2008245447A1 (en) | 2008-11-06 |
| AU2008245447B2 AU2008245447B2 (en) | 2014-01-23 |
| AU2008245447C1 true AU2008245447C1 (en) | 2014-11-20 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2008245447A Ceased AU2008245447C1 (en) | 2007-04-30 | 2008-04-29 | Inhibitors of IAP |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US8907092B2 (OSRAM) |
| EP (1) | EP2148858A4 (OSRAM) |
| JP (1) | JP5368428B2 (OSRAM) |
| KR (1) | KR20100024923A (OSRAM) |
| CN (1) | CN101687787A (OSRAM) |
| AR (1) | AR066348A1 (OSRAM) |
| AU (1) | AU2008245447C1 (OSRAM) |
| BR (1) | BRPI0809867A2 (OSRAM) |
| CA (1) | CA2683392A1 (OSRAM) |
| CL (1) | CL2008001234A1 (OSRAM) |
| IL (1) | IL201379A0 (OSRAM) |
| MX (1) | MX2009011783A (OSRAM) |
| NZ (2) | NZ580226A (OSRAM) |
| PE (2) | PE20090211A1 (OSRAM) |
| RU (1) | RU2491276C2 (OSRAM) |
| TW (1) | TWI432212B (OSRAM) |
| WO (1) | WO2008134679A1 (OSRAM) |
| ZA (1) | ZA200906946B (OSRAM) |
Families Citing this family (93)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5230865B2 (ja) | 2004-07-15 | 2013-07-10 | テトラロジック ファーマシューティカルズ コーポレーション | Ｉａｐ結合性化合物 |
| ES2349110T5 (es) | 2004-12-20 | 2013-11-27 | Genentech, Inc. | Inhibidores de IAP derivados de pirrolidina |
| CN103083644B (zh) | 2005-02-25 | 2014-05-28 | 泰特拉洛吉克药业公司 | Iap二聚体抑制剂 |
| EP1883627B1 (en) | 2005-05-18 | 2018-04-18 | Pharmascience Inc. | Bir domain binding compounds |
| CA2564872C (en) | 2005-10-25 | 2010-12-21 | Aegera Therapeutics Inc. | Iap bir domain binding compounds |
| TWI504597B (zh) | 2006-03-16 | 2015-10-21 | Pharmascience Inc | 結合於細胞凋亡抑制蛋白（ｉａｐ）之桿狀病毒ｉａｐ重複序列（ｂｉｒ）區域之化合物 |
| EP2049563B1 (en) | 2006-07-24 | 2014-03-12 | Tetralogic Pharmaceuticals Corporation | Dimeric iap antagonists |
| AR064235A1 (es) | 2006-07-24 | 2009-03-25 | Tetralogic Pharmaceuticals Cor | Dipeptidos antagonistas de iap, una composicion farmaceutica que los comprende y el uso de los mismos para el tratamiento del cancer |
| CN101970457A (zh) * | 2008-01-11 | 2011-02-09 | 健泰科生物技术公司 | Iap抑制剂 |
| US9029411B2 (en) | 2008-01-25 | 2015-05-12 | Millennium Pharmaceuticals, Inc. | Thiophenes and uses thereof |
| EP2318395A4 (en) | 2008-08-02 | 2011-10-26 | Genentech Inc | IPA INHIBITORS |
| CN102395585A (zh) | 2009-01-30 | 2012-03-28 | 米伦纽姆医药公司 | 杂芳基化合物和其作为pi3k抑制剂的用途 |
| US8796314B2 (en) | 2009-01-30 | 2014-08-05 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| US9090601B2 (en) | 2009-01-30 | 2015-07-28 | Millennium Pharmaceuticals, Inc. | Thiazole derivatives |
| BRPI1011612A2 (pt) * | 2009-05-28 | 2019-09-24 | Tetralogic Pharm Corp | composto, composição farmacêutica, e, métodos para induzir apoptose em uma célula, para tratar câncer, e para tratar uma doença autoimune. |
| US8283372B2 (en) | 2009-07-02 | 2012-10-09 | Tetralogic Pharmaceuticals Corp. | 2-(1H-indol-3-ylmethyl)-pyrrolidine dimer as a SMAC mimetic |
| RU2554087C2 (ru) | 2009-12-18 | 2015-06-27 | Айденикс Фармасьютикалз, Инк. | 5,5-конденсированные ариленовые или гетероариленовые ингибиторы вируса гепатита с |
| EP3263583A1 (en) | 2010-02-12 | 2018-01-03 | Pharmascience Inc. | Iap bir domain binding compounds |
| UY33236A (es) | 2010-02-25 | 2011-09-30 | Novartis Ag | Inhibidores dimericos de las iap |
| PH12013500274A1 (en) | 2010-08-11 | 2013-03-04 | Millennium Pharm Inc | Heteroaryls and uses thereof |
| WO2012021611A1 (en) | 2010-08-11 | 2012-02-16 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| US8859768B2 (en) | 2010-08-11 | 2014-10-14 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| EP2627181A4 (en) | 2010-10-13 | 2014-03-19 | Millennium Pharm Inc | HETEROARYLE AND USES THEREOF |
| UY33794A (es) | 2010-12-13 | 2012-07-31 | Novartis Ag | Inhibidores diméricos de las iap |
| NO2755614T3 (OSRAM) | 2012-01-03 | 2018-03-31 | ||
| MX394449B (es) | 2012-01-12 | 2025-03-11 | Univ Yale | Compuestos y metodos para degradacion mejorada de proteinas y otros polipeptidos elegidos como blanco mediante una ubiquitina ligasa e3. |
| KR20150011822A (ko) | 2012-05-04 | 2015-02-02 | 노파르티스 아게 | Iap 억제제 요법을 위한 바이오마커 |
| US9498532B2 (en) | 2013-03-13 | 2016-11-22 | Novartis Ag | Antibody drug conjugates |
| KR20150131173A (ko) | 2013-03-15 | 2015-11-24 | 노파르티스 아게 | 항체 약물 접합체 |
| GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| US10300074B2 (en) | 2014-06-04 | 2019-05-28 | Sanford Burnham Prebys Medical Discovery Institute | Use of inhibitor of apoptosis protein (IAP) antagonists in HIV therapy |
| WO2016020791A1 (en) | 2014-08-05 | 2016-02-11 | Novartis Ag | Ckit antibody drug conjugates |
| US10071164B2 (en) | 2014-08-11 | 2018-09-11 | Yale University | Estrogen-related receptor alpha based protac compounds and associated methods of use |
| US9982045B2 (en) | 2014-08-12 | 2018-05-29 | Novartis Ag | Anti-CDH6 antibody drug conjugates |
| WO2016079527A1 (en) | 2014-11-19 | 2016-05-26 | Tetralogic Birinapant Uk Ltd | Combination therapy |
| WO2016097773A1 (en) | 2014-12-19 | 2016-06-23 | Children's Cancer Institute | Therapeutic iap antagonists for treating proliferative disorders |
| US12312316B2 (en) | 2015-01-20 | 2025-05-27 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| KR102564925B1 (ko) | 2015-01-20 | 2023-08-07 | 아비나스 오퍼레이션스, 인코포레이티드 | 안드로겐 수용체의 표적화된 분해를 위한 화합물 및 방법 |
| GB201506872D0 (en) | 2015-04-22 | 2015-06-03 | Ge Oil & Gas Uk Ltd | Novel compounds |
| EP3302482A4 (en) | 2015-06-05 | 2018-12-19 | Arvinas, Inc. | Tank-binding kinase-1 protacs and associated methods of use |
| WO2016203432A1 (en) | 2015-06-17 | 2016-12-22 | Novartis Ag | Antibody drug conjugates |
| EP3337476A4 (en) | 2015-08-19 | 2019-09-04 | Arvinas, Inc. | Compounds and methods for the targeted degradation of bromodomain-containing proteins |
| MA44334A (fr) | 2015-10-29 | 2018-09-05 | Novartis Ag | Conjugués d'anticorps comprenant un agoniste du récepteur de type toll |
| EP3535265A4 (en) | 2016-11-01 | 2020-07-08 | Arvinas, Inc. | PROTACS TARGETING ON TAU PROTEIN AND RELATED METHODS FOR USE |
| PL3689868T3 (pl) | 2016-12-01 | 2024-03-11 | Arvinas Operations, Inc. | Pochodne tetrahydronaftalenu i tetrahydroizochinoliny jako degradery receptorów estrogenowych |
| US11173211B2 (en) | 2016-12-23 | 2021-11-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides |
| CN117510491A (zh) | 2016-12-23 | 2024-02-06 | 阿尔维纳斯运营股份有限公司 | 用于迅速加速性纤维肉瘤多肽的靶向降解的化合物和方法 |
| WO2018118598A1 (en) | 2016-12-23 | 2018-06-28 | Arvinas, Inc. | Compounds and methods for the targeted degradation of fetal liver kinase polypeptides |
| CN110753693A (zh) | 2016-12-23 | 2020-02-04 | 阿尔维纳斯运营股份有限公司 | Egfr蛋白水解靶向嵌合分子和相关使用方法 |
| US11191741B2 (en) | 2016-12-24 | 2021-12-07 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide |
| IL300417A (en) | 2017-01-26 | 2023-04-01 | Arvinas Operations Inc | Bifunctional benzothiophene compounds, preparations containing them and their use in therapy |
| JOP20190187A1 (ar) | 2017-02-03 | 2019-08-01 | Novartis Ag | مترافقات عقار جسم مضاد لـ ccr7 |
| WO2018163051A1 (en) | 2017-03-06 | 2018-09-13 | Novartis Ag | Methods of treatment of cancer with reduced ubb expression |
| WO2018185618A1 (en) | 2017-04-03 | 2018-10-11 | Novartis Ag | Anti-cdh6 antibody drug conjugates and anti-gitr antibody combinations and methods of treatment |
| AR111651A1 (es) | 2017-04-28 | 2019-08-07 | Novartis Ag | Conjugados de anticuerpos que comprenden agonistas del receptor de tipo toll y terapias de combinación |
| WO2018215937A1 (en) | 2017-05-24 | 2018-11-29 | Novartis Ag | Interleukin-7 antibody cytokine engrafted proteins and methods of use in the treatment of cancer |
| CN111107868A (zh) | 2017-05-24 | 2020-05-05 | 诺华股份有限公司 | 抗体细胞因子移植蛋白及使用方法 |
| PE20251254A1 (es) | 2017-05-24 | 2025-05-06 | Novartis Ag | Proteinas de anticuerpo injertadas con citocina y metodos de uso en el tratamiento del cancer |
| US11485733B2 (en) | 2017-06-30 | 2022-11-01 | Bayer Animal Health Gmbh | Azaquinoline derivatives |
| US11161851B2 (en) * | 2017-11-06 | 2021-11-02 | Suzhou Pengxu Pharmatech Co. Ltd. | Processes to produce acalabrutinib |
| CN109836416B (zh) * | 2017-11-27 | 2023-02-03 | 苏州鹏旭医药科技有限公司 | 一种化合物的制备方法 |
| WO2019099926A1 (en) | 2017-11-17 | 2019-05-23 | Arvinas, Inc. | Compounds and methods for the targeted degradation of interleukin-1 receptor-associated kinase 4 polypeptides |
| MX2020010420A (es) | 2018-04-04 | 2020-12-11 | Arvinas Operations Inc | Moduladores de la proteólisis y métodos asociados de uso. |
| DK3820573T3 (da) | 2018-07-10 | 2023-10-23 | Novartis Ag | 3-(5-hydroxy-1-oxoisoindolin-2-yl)piperidin-2,6-dion-derivativer og anvendelse deraf ved behandling af ikaros family zinc finger 2 (ikzf2)-afhængige sygdomme |
| AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
| CN112912376A (zh) | 2018-08-20 | 2021-06-04 | 阿尔维纳斯运营股份有限公司 | 用于治疗神经变性疾病的具有E3泛素连接酶结合活性并靶向α-突触核蛋白的蛋白水解靶向嵌合(PROTAC)化合物 |
| WO2020089811A1 (en) | 2018-10-31 | 2020-05-07 | Novartis Ag | Dc-sign antibody drug conjugates |
| KR20210106437A (ko) | 2018-12-20 | 2021-08-30 | 노파르티스 아게 | 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체를 포함하는 투약 요법 및 약학적 조합물 |
| PE20211296A1 (es) | 2018-12-21 | 2021-07-20 | Novartis Ag | Anticuerpos anti-pmel17 y conjugados de los mismos |
| AU2020222345B2 (en) | 2019-02-15 | 2022-11-17 | Novartis Ag | 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
| US12479817B2 (en) | 2019-02-15 | 2025-11-25 | Novartis Ag | Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
| CN119954801A (zh) | 2019-07-17 | 2025-05-09 | 阿尔维纳斯运营股份有限公司 | Tau蛋白靶向化合物及相关使用方法 |
| EP4004221A4 (en) | 2019-07-25 | 2023-10-25 | Lanzatech, Inc. | SECONDARY ACETATE FERMENTATION |
| CN114514032A (zh) | 2019-08-02 | 2022-05-17 | 兰提欧派普有限公司 | 用于治疗癌症的血管紧张素2型(at2)受体激动剂 |
| MX2022002415A (es) | 2019-08-26 | 2022-03-22 | Arvinas Operations Inc | Metodos de tratamiento del cancer de mama con derivados de tetrahidronaftaleno como degradadores del receptor de estrogenos. |
| JP2023506958A (ja) | 2019-12-20 | 2023-02-20 | ノバルティス アーゲー | 骨髄線維症および骨髄異形成症候群を処置するための、デシタビンまたは抗ｐｄ－１抗体スパルタリズマブを伴うかまたは伴わない抗ｔｉｍ－３抗体ｍｂｇ４５３および抗ｔｇｆ－ベータ抗体ｎｉｓ７９３の組合せ |
| JP2023510426A (ja) | 2020-01-20 | 2023-03-13 | アストラゼネカ・アクチエボラーグ | 癌を治療するための上皮細胞増殖因子受容体チロシンキナーゼ阻害剤 |
| US20230181756A1 (en) | 2020-04-30 | 2023-06-15 | Novartis Ag | Ccr7 antibody drug conjugates for treating cancer |
| AU2021288224A1 (en) | 2020-06-11 | 2023-01-05 | Novartis Ag | ZBTB32 inhibitors and uses thereof |
| WO2021260528A1 (en) | 2020-06-23 | 2021-12-30 | Novartis Ag | Dosing regimen comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
| WO2022029573A1 (en) | 2020-08-03 | 2022-02-10 | Novartis Ag | Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
| JP2023539663A (ja) | 2020-08-28 | 2023-09-15 | アルビナス・オペレーションズ・インコーポレイテッド | 急速進行性線維肉腫タンパク質分解化合物及び関連する使用方法 |
| BR112023004656A2 (pt) | 2020-09-14 | 2023-05-09 | Arvinas Operations Inc | Formas cristalinas e amorfas de um composto para a degradação direcionada do receptor de estrogênio |
| TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗ＴＧＦβ抗體及其他治療劑用於治療增殖性疾病之用途 |
| US20240252668A1 (en) | 2021-04-16 | 2024-08-01 | Anne-Sophie BLUEMMEL | Antibody drug conjugates and methods for making thereof |
| AR125874A1 (es) | 2021-05-18 | 2023-08-23 | Novartis Ag | Terapias de combinación |
| WO2023214325A1 (en) | 2022-05-05 | 2023-11-09 | Novartis Ag | Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors |
| CN119301125A (zh) | 2022-07-26 | 2025-01-10 | 诺华股份有限公司 | Akr1c3依赖性kars抑制剂的晶型 |
| WO2024054591A1 (en) | 2022-09-07 | 2024-03-14 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use |
| EP4593818A1 (en) * | 2022-09-29 | 2025-08-06 | Tract Pharmaceuticals, Inc. | Compounds and compositions useful as inhibitors of iaps |
| US12448399B2 (en) | 2023-01-26 | 2025-10-21 | Arvinas Operations, Inc. | Cereblon-based KRAS degrading PROTACs and uses related thereto |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005084317A2 (en) * | 2004-03-01 | 2005-09-15 | Board Of Regents, The University Of Texas System | Dimeric small molecule potentiators of apoptosis |
| WO2006091972A2 (en) * | 2005-02-25 | 2006-08-31 | Tetralogic Pharmaceuticals | Dimeric iap inhibitors |
| US20070093428A1 (en) * | 2005-10-25 | 2007-04-26 | Aegera Therapeutics, Inc. | IAP BIR domain binding compounds |
| US20080050336A1 (en) * | 2006-08-11 | 2008-02-28 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE430062B (sv) | 1977-03-04 | 1983-10-17 | Pharmacia Fine Chemicals Ab | Kopplings- eller tioleringsreagens |
| DE2714880A1 (de) | 1977-04-02 | 1978-10-26 | Hoechst Ag | Cephemderivate und verfahren zu ihrer herstellung |
| FR2575753B1 (fr) | 1985-01-07 | 1987-02-20 | Adir | Nouveaux derives peptidiques a structure polycyclique azotee, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| DE3685626T2 (de) | 1985-09-26 | 1993-01-28 | Beckmann Research Inst Of The | Sequenzierung von peptiden. |
| US4935494A (en) | 1988-11-15 | 1990-06-19 | City Of Hope | C-terminal peptide and protein sequencing |
| CA2012306A1 (en) | 1989-03-28 | 1990-09-28 | Werner Neidhart | Amino acid derivatives |
| DK167813B1 (da) | 1989-12-07 | 1993-12-20 | Carlbiotech Ltd As | Pentapeptidderivat, farmaceutisk acceptable salte heraf, fremgangsmaade til fremstilling deraf og farmaceutisk praeparat indeholdende et saadant derivat |
| WO1992001938A1 (en) | 1990-07-20 | 1992-02-06 | City Of Hope | Derivatization of c-terminal proline |
| PT752248E (pt) | 1992-11-13 | 2001-01-31 | Idec Pharma Corp | Aplicacao terapeutica de anticorpos quimericos e marcados radioactivamente contra antigenios de diferenciacao restrita de linfocitos b humanos para o tratamento do linfoma de celulas b |
| US5559209A (en) | 1993-02-18 | 1996-09-24 | The General Hospital Corporation | Regulator regions of G proteins |
| JP2000500742A (ja) | 1995-10-30 | 2000-01-25 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
| AU7127298A (en) | 1997-04-14 | 1998-11-11 | Emory University | Serine protease inhibitors |
| US6335155B1 (en) | 1998-06-26 | 2002-01-01 | Sunesis Pharmaceuticals, Inc. | Methods for rapidly identifying small organic molecule ligands for binding to biological target molecules |
| US6472172B1 (en) | 1998-07-31 | 2002-10-29 | Schering Aktiengesellschaft | DNA encoding a novel human inhibitor-of-apoptosis protein |
| JP2002533726A (ja) | 1998-12-28 | 2002-10-08 | サネシス ファーマシューティカルス インコーポレイテッド | 結合のための小有機分子リガンドの同定 |
| US6608026B1 (en) | 2000-08-23 | 2003-08-19 | Board Of Regents, The University Of Texas System | Apoptotic compounds |
| AU2001286730A1 (en) | 2000-08-24 | 2002-03-04 | Thomas Jefferson University | An iap binding peptide or polypeptide and methods of using the same |
| AU2001293189A1 (en) | 2000-09-29 | 2002-04-08 | Trustees Of Princeton University | Compositions and methods for regulating apoptosis |
| US6992063B2 (en) | 2000-09-29 | 2006-01-31 | The Trustees Of Princeton University | Compositions and method for regulating apoptosis |
| WO2002030959A2 (en) | 2000-10-13 | 2002-04-18 | Abbott Laboratories | Peptides derived from smac (diablo) and methods of use therefor |
| WO2003010184A2 (en) | 2001-02-08 | 2003-02-06 | Thomas Jefferson University | A conserved xiap-interaction motif in caspase-9 and smac/diablo for mediating apoptosis |
| MXPA03008089A (es) | 2001-04-05 | 2004-01-22 | Torrent Pharmaceuticals Ltd | Compuestos heterociclicos para complicaciones relacionadas con el envejecimiento y vasculares diabeticas. |
| MXPA03010762A (es) | 2001-05-31 | 2005-03-07 | Univ Princeton | Peptidos enlazantes de iap y ensayos para identificar los compuestos que enlazan el iap. |
| WO2003040172A2 (en) | 2001-11-09 | 2003-05-15 | Aegera Therapeutics, Inc. | Methods and reagents for peptide-bir interaction screens |
| WO2003086470A2 (en) | 2002-04-17 | 2003-10-23 | Deutsches Krebsforschungszentrum | Smac-peptides as therapeutics against cancer and autoimmune diseases |
| CN100384819C (zh) | 2002-07-02 | 2008-04-30 | 诺瓦提斯公司 | 与细胞凋亡蛋白抑制剂结合的smac蛋白的肽抑制剂 |
| EP1578777B1 (en) | 2002-07-15 | 2008-11-26 | The Trustees of Princeton University | Iap binding compounds |
| WO2004017991A1 (en) | 2002-08-13 | 2004-03-04 | Cell Center Cologne Gmbh | Use of iap for the diagnosis and of iap-inhibitors for the treatment of hodgkin’s lymphomas |
| US20040171554A1 (en) | 2003-02-07 | 2004-09-02 | Genentech, Inc. | Compositions and methods for enhancing apoptosis |
| DE60322120D1 (de) | 2003-02-07 | 2008-08-21 | Genentech Inc | Zusammensetzungen und verfahren für verstärkte apoptose |
| IL156263A0 (en) | 2003-06-02 | 2004-01-04 | Hadasit Med Res Service | Livin-derived peptides, compositions and uses thereof |
| WO2005049853A2 (en) | 2003-11-13 | 2005-06-02 | Genentech, Inc. | Compositions and methods for screening pro-apoptotic compounds |
| CN1933847A (zh) | 2004-01-16 | 2007-03-21 | 密歇根大学董事会 | Smac肽模拟物及其应用 |
| CA2553874A1 (en) | 2004-01-16 | 2005-08-04 | The Regents Of The University Of Michigan | Conformationally constrained smac mimetics and the uses thereof |
| AU2005228950B2 (en) | 2004-03-23 | 2012-02-02 | Genentech, Inc. | Azabicyclo-octane inhibitors of IAP |
| ES2394441T3 (es) | 2004-04-07 | 2013-01-31 | Novartis Ag | Inhibidores de IAP |
| DK1778718T3 (da) | 2004-07-02 | 2014-11-10 | Genentech Inc | Iap-inhibitorer |
| EP2457895A1 (en) | 2004-07-12 | 2012-05-30 | Idun Pharmaceuticals, Inc. | Tetrapeptide analogs |
| JP5230865B2 (ja) | 2004-07-15 | 2013-07-10 | テトラロジック ファーマシューティカルズ コーポレーション | Ｉａｐ結合性化合物 |
| ES2349110T5 (es) * | 2004-12-20 | 2013-11-27 | Genentech, Inc. | Inhibidores de IAP derivados de pirrolidina |
| EP1883627B1 (en) | 2005-05-18 | 2018-04-18 | Pharmascience Inc. | Bir domain binding compounds |
| RU2451025C2 (ru) * | 2005-12-19 | 2012-05-20 | Дженентек, Инк. | Ингибиторы iap |
| TWI504597B (zh) | 2006-03-16 | 2015-10-21 | Pharmascience Inc | 結合於細胞凋亡抑制蛋白（ｉａｐ）之桿狀病毒ｉａｐ重複序列（ｂｉｒ）區域之化合物 |
| MX2008012053A (es) | 2006-03-21 | 2008-12-17 | Joyant Pharmaceuticals Inc | Promotores de apoptosis de molecula pequeña. |
| WO2008014238A2 (en) | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| PE20110220A1 (es) | 2006-08-02 | 2011-04-11 | Novartis Ag | DERIVADOS DE 2-OXO-ETIL-AMINO-PROPIONAMIDA-PIRROLIDIN-2-IL-SUSTITUIDOS COMO INHIBIDORES DEL ENLACE DE LA PROTEINA Smac AL INHIBIDOR DE LA PROTEINA DE APOPTOSIS |
| JP5190062B2 (ja) | 2006-10-12 | 2013-04-24 | ノバルティス アーゲー | Ｉａｐ阻害剤としてのピロリジン誘導体 |
| US8063218B2 (en) | 2006-12-19 | 2011-11-22 | Genentech, Inc. | Imidazopyridine inhibitors of IAP |
| CN101970457A (zh) | 2008-01-11 | 2011-02-09 | 健泰科生物技术公司 | Iap抑制剂 |
| EP2318395A4 (en) | 2008-08-02 | 2011-10-26 | Genentech Inc | IPA INHIBITORS |
| EP2318401A4 (en) | 2008-08-16 | 2013-10-30 | Genentech Inc | AZAINDOLI INHIBITORS OF IPA |
-
2008
- 2008-04-29 AU AU2008245447A patent/AU2008245447C1/en not_active Ceased
- 2008-04-29 CN CN200880022901A patent/CN101687787A/zh active Pending
- 2008-04-29 MX MX2009011783A patent/MX2009011783A/es not_active Application Discontinuation
- 2008-04-29 EP EP08747109A patent/EP2148858A4/en not_active Withdrawn
- 2008-04-29 RU RU2009144094/04A patent/RU2491276C2/ru not_active IP Right Cessation
- 2008-04-29 JP JP2010506573A patent/JP5368428B2/ja not_active Expired - Fee Related
- 2008-04-29 CA CA002683392A patent/CA2683392A1/en not_active Abandoned
- 2008-04-29 KR KR1020097024828A patent/KR20100024923A/ko not_active Abandoned
- 2008-04-29 PE PE2008000757A patent/PE20090211A1/es not_active Application Discontinuation
- 2008-04-29 NZ NZ580226A patent/NZ580226A/xx not_active IP Right Cessation
- 2008-04-29 AR ARP080101812A patent/AR066348A1/es not_active Application Discontinuation
- 2008-04-29 US US12/598,027 patent/US8907092B2/en not_active Expired - Fee Related
- 2008-04-29 NZ NZ598890A patent/NZ598890A/xx not_active IP Right Cessation
- 2008-04-29 WO PCT/US2008/061891 patent/WO2008134679A1/en not_active Ceased
- 2008-04-29 TW TW097115740A patent/TWI432212B/zh not_active IP Right Cessation
- 2008-04-29 PE PE2012001805A patent/PE20130150A1/es not_active Application Discontinuation
- 2008-04-29 BR BRPI0809867-0A patent/BRPI0809867A2/pt not_active IP Right Cessation
- 2008-04-29 CL CL200801234A patent/CL2008001234A1/es unknown
-
2009
- 2009-10-06 ZA ZA2009/06946A patent/ZA200906946B/en unknown
- 2009-10-11 IL IL201379A patent/IL201379A0/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005084317A2 (en) * | 2004-03-01 | 2005-09-15 | Board Of Regents, The University Of Texas System | Dimeric small molecule potentiators of apoptosis |
| WO2006091972A2 (en) * | 2005-02-25 | 2006-08-31 | Tetralogic Pharmaceuticals | Dimeric iap inhibitors |
| US20070093428A1 (en) * | 2005-10-25 | 2007-04-26 | Aegera Therapeutics, Inc. | IAP BIR domain binding compounds |
| US20080050336A1 (en) * | 2006-08-11 | 2008-02-28 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
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| ZA200906946B (en) | 2011-05-25 |
| AU2008245447A1 (en) | 2008-11-06 |
| RU2009144094A (ru) | 2011-06-10 |
| RU2491276C2 (ru) | 2013-08-27 |
| IL201379A0 (en) | 2010-05-31 |
| TWI432212B (zh) | 2014-04-01 |
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