RU2466131C2 - Имидазопиридиновые ингибиторы iap - Google Patents
Имидазопиридиновые ингибиторы iap Download PDFInfo
- Publication number
- RU2466131C2 RU2466131C2 RU2009127800/04A RU2009127800A RU2466131C2 RU 2466131 C2 RU2466131 C2 RU 2466131C2 RU 2009127800/04 A RU2009127800/04 A RU 2009127800/04A RU 2009127800 A RU2009127800 A RU 2009127800A RU 2466131 C2 RU2466131 C2 RU 2466131C2
- Authority
- RU
- Russia
- Prior art keywords
- alkyl
- mmol
- group
- halogen
- optionally substituted
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title abstract description 5
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 110
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 5
- 201000010099 disease Diseases 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 114
- 229910052736 halogen Inorganic materials 0.000 claims description 54
- 150000002367 halogens Chemical class 0.000 claims description 52
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 45
- 125000001424 substituent group Chemical group 0.000 claims description 45
- 125000003545 alkoxy group Chemical group 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 102000011727 Caspases Human genes 0.000 claims description 21
- 108010076667 Caspases Proteins 0.000 claims description 21
- 230000006907 apoptotic process Effects 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 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 15
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 12
- 230000027455 binding Effects 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 9
- 230000001640 apoptogenic effect Effects 0.000 claims description 8
- 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
- 108091007065 BIRCs Proteins 0.000 claims description 6
- 229960004679 doxorubicin Drugs 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 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
- 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
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 230000002018 overexpression Effects 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
- 230000001939 inductive effect Effects 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- 230000001235 sensitizing effect Effects 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
- 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
- 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
- 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 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
- 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
- 125000005843 halogen group Chemical group 0.000 claims 2
- 239000000126 substance Substances 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 5
- 230000003211 malignant effect Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- -1 amino, cyano, nitro, amidino, guanidino Chemical group 0.000 description 224
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 101
- 125000000623 heterocyclic group Chemical group 0.000 description 87
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- 239000000203 mixture Substances 0.000 description 60
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 38
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 37
- 125000002252 acyl group Chemical group 0.000 description 35
- 239000000243 solution Substances 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- 125000003118 aryl group Chemical group 0.000 description 26
- 125000006239 protecting group Chemical group 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 20
- 125000004043 oxo group Chemical group O=* 0.000 description 18
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- 229910052717 sulfur Inorganic materials 0.000 description 16
- 125000003396 thiol group Chemical group [H]S* 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- 102000004169 proteins and genes Human genes 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 235000018102 proteins Nutrition 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- 229910004298 SiO 2 Inorganic materials 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 125000001072 heteroaryl group Chemical group 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 11
- 229940024606 amino acid Drugs 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 11
- 125000003710 aryl alkyl group Chemical group 0.000 description 11
- 239000013058 crude material Substances 0.000 description 11
- 150000001413 amino acids Chemical group 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 201000009030 Carcinoma Diseases 0.000 description 9
- 102100033189 Diablo IAP-binding mitochondrial protein Human genes 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- 125000002837 carbocyclic group Chemical group 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- 108010049207 Death Domain Receptors Proteins 0.000 description 8
- 102000009058 Death Domain Receptors Human genes 0.000 description 8
- 108700031544 X-Linked Inhibitor of Apoptosis Proteins 0.000 description 8
- 102000050257 X-Linked Inhibitor of Apoptosis Human genes 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
- 238000001959 radiotherapy Methods 0.000 description 8
- 239000011347 resin Substances 0.000 description 8
- 229920005989 resin Polymers 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 125000001188 haloalkyl group Chemical group 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 6
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 6
- 239000011593 sulfur Substances 0.000 description 6
- 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 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 229910052693 Europium Inorganic materials 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 229960003767 alanine Drugs 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- WCSAZSDUOPCTPR-LBPRGKRZSA-N benzyl (2s)-2-(2-bromoacetyl)pyrrolidine-1-carboxylate Chemical compound BrCC(=O)[C@@H]1CCCN1C(=O)OCC1=CC=CC=C1 WCSAZSDUOPCTPR-LBPRGKRZSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 125000005884 carbocyclylalkyl group Chemical group 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 235000014620 theaflavin Nutrition 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 1
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 1
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 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
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 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
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
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- 230000004572 zinc-binding Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87082106P | 2006-12-19 | 2006-12-19 | |
| US60/870,821 | 2006-12-19 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2009127800A RU2009127800A (ru) | 2011-01-27 |
| RU2466131C2 true RU2466131C2 (ru) | 2012-11-10 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2009127800/04A RU2466131C2 (ru) | 2006-12-19 | 2007-12-14 | Имидазопиридиновые ингибиторы iap |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US8063218B2 (enExample) |
| EP (1) | EP2125809A1 (enExample) |
| JP (1) | JP2010513561A (enExample) |
| KR (1) | KR20090094461A (enExample) |
| CN (1) | CN101605786A (enExample) |
| AU (1) | AU2007337104A1 (enExample) |
| BR (1) | BRPI0719481A2 (enExample) |
| CA (1) | CA2671607A1 (enExample) |
| IL (1) | IL198927A0 (enExample) |
| NZ (1) | NZ577150A (enExample) |
| RU (1) | RU2466131C2 (enExample) |
| WO (1) | WO2008079735A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2819398C2 (ru) * | 2019-05-10 | 2024-05-20 | Чиа Тай Тяньцин Фармасьютикал Груп Ко., Лтд. | Кристаллическая форма миметика smac, применяемого в качестве ингибитора iap, и способ ее получения |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006020060A2 (en) | 2004-07-15 | 2006-02-23 | Tetralogic Pharmaceuticals Corporation | Iap binding compounds |
| KR20120127754A (ko) | 2004-12-20 | 2012-11-23 | 제넨테크, 인크. | Ｉａｐ의 피롤리딘 억제제 |
| DK1851200T3 (da) | 2005-02-25 | 2014-04-14 | Tetralogic Pharm Corp | Dimere iap-inhibitorer |
| JP4954983B2 (ja) | 2005-05-18 | 2012-06-20 | ファーマサイエンス・インコーポレイテッド | Ｂｉｒドメイン結合化合物 |
| US20100256046A1 (en) * | 2009-04-03 | 2010-10-07 | Tetralogic Pharmaceuticals Corporation | Treatment of proliferative disorders |
| RU2418807C2 (ru) | 2005-10-25 | 2011-05-20 | Аегера Терапьютикс Инк. | Соединения, связывающие bir домены iap |
| TWI543988B (zh) | 2006-03-16 | 2016-08-01 | 科學製藥股份有限公司 | 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 |
| SG10201407457UA (en) | 2006-05-16 | 2014-12-30 | Pharmascience Inc | Iap bir domain binding compounds |
| WO2008014240A2 (en) * | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| WO2008014229A2 (en) * | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| JP5452223B2 (ja) * | 2006-07-24 | 2014-03-26 | 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阻害剤 |
| US20100056495A1 (en) * | 2006-07-24 | 2010-03-04 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| WO2008014238A2 (en) * | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| CL2007002167A1 (es) * | 2006-07-24 | 2009-01-23 | Tetralogic Pharm Corp | Compuestos derivados de indol, antagonistas iap; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto en el tratamiento de cancer. |
| NZ598890A (en) * | 2007-04-30 | 2013-10-25 | Genentech Inc | Inhibitors of iap |
| CA2686638A1 (en) * | 2007-05-07 | 2008-11-13 | Tetralogic Pharmaceuticals Corp. | Tnf.alpha. gene expression as a biomarker of sensitivity to antagonists of inhibitor of apoptosis proteins |
| PL2240506T3 (pl) * | 2008-01-11 | 2013-05-31 | Genentech Inc | Inhibitory IAP |
| CA2730448A1 (en) * | 2008-08-02 | 2010-02-11 | Genentech, Inc. | Inhibitors of iap |
| JP2012500272A (ja) * | 2008-08-16 | 2012-01-05 | ジェネンテック， インコーポレイテッド | Ｉａｐのアザインドールインヒビター |
| US8283372B2 (en) * | 2009-07-02 | 2012-10-09 | Tetralogic Pharmaceuticals Corp. | 2-(1H-indol-3-ylmethyl)-pyrrolidine dimer as a SMAC mimetic |
| AR077688A1 (es) | 2009-08-04 | 2011-09-14 | Takeda Pharmaceutical | Compuestos heterociclicos, utiles en el tratamiento de cancer |
| SG181797A1 (en) | 2009-12-18 | 2012-07-30 | Idenix Pharmaceuticals Inc | 5,5-fused arylene or heteroarylene hepatitis c virus inhibitors |
| MX340870B (es) | 2010-02-12 | 2016-07-27 | Pharmascience Inc | Compuestos de unión del dominio de repetición de inhibidores de proteínas de apoptosis de baculovirus. |
| PT2611797T (pt) | 2010-08-31 | 2017-02-07 | Hanmi Science Co Ltd | Derivados de quinolina ou de quinazolina com atividade indutora de apoptose nas células |
| KR20140011773A (ko) * | 2012-07-19 | 2014-01-29 | 한미약품 주식회사 | 이중 저해 활성을 갖는 헤테로고리 유도체 |
| IL274598B2 (en) | 2017-11-13 | 2025-01-01 | Chia Tai Tianqing Pharmaceutical Group Co Ltd | SMAC mimetics used as IAP inhibitors and their use |
| CN112533898A (zh) | 2018-07-31 | 2021-03-19 | 日商泛美克斯股份有限公司 | 杂环化合物 |
| WO2020177765A1 (zh) * | 2019-03-07 | 2020-09-10 | 正大天晴药业集团股份有限公司 | Iap抑制剂与免疫检查点抑制剂的组合 |
| JP7587526B2 (ja) * | 2019-05-10 | 2024-11-20 | チア タイ ティエンチン ファーマシューティカル グループ カンパニー リミテッド | Ｉａｐ阻害剤としてのｓｍａｃ模倣物の結晶及びその製造方法 |
| US20220402935A1 (en) | 2019-07-31 | 2022-12-22 | Fimecs, Inc. | Heterocyclic compound |
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| WO2004005248A1 (en) * | 2002-07-02 | 2004-01-15 | Novartis Ag | Peptide inhibitors of smac protein binding to inhibitor of apoptosis proteins (iap) |
| WO2005097791A1 (en) * | 2004-04-07 | 2005-10-20 | Novartis Ag | Inhibitors of iap |
| WO2006069063A1 (en) * | 2004-12-20 | 2006-06-29 | Genentech, Inc. | Pyrrolidine inhibitors of iap |
| RU2005141059A (ru) * | 2003-06-26 | 2006-08-10 | Астразенека Аб (Se) | Новое имидазопиридиновое соединение ii с терапевтическим действием |
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| 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 |
| 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 |
| DE69303494T2 (de) | 1992-11-13 | 1997-01-16 | Idec Pharma Corp | Therapeutische verwendung von chimerischen und markierten antikörper gegen menschlichen b lymphozyt beschränkter differenzierung antigen für die behandlung von b-zell-lymphoma |
| US5559209A (en) * | 1993-02-18 | 1996-09-24 | The General Hospital Corporation | Regulator regions of G proteins |
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| 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 |
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| US7718600B2 (en) | 2000-09-29 | 2010-05-18 | The Trustees Of Princeton University | IAP binding compounds |
| 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 |
| JP2004531731A (ja) | 2001-05-31 | 2004-10-14 | ザ トラスティーズ オブ プリンストン ユニバーシテイ | Ｉａｐ結合ペプチドおよびｉａｐに結合する化合物を同定するアッセイ |
| US20030157522A1 (en) * | 2001-11-09 | 2003-08-21 | Alain Boudreault | Methods and reagents for peptide-BIR interaction screens |
| EP1495124A2 (en) | 2002-04-17 | 2005-01-12 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Smac-peptides as therapeutics against cancer and autoimmune diseases |
| 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 |
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| PE20110218A1 (es) * | 2006-08-02 | 2011-04-01 | 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 |
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-
2007
- 2007-12-14 RU RU2009127800/04A patent/RU2466131C2/ru not_active IP Right Cessation
- 2007-12-14 NZ NZ577150A patent/NZ577150A/en not_active IP Right Cessation
- 2007-12-14 BR BRPI0719481-1A patent/BRPI0719481A2/pt not_active IP Right Cessation
- 2007-12-14 KR KR1020097014996A patent/KR20090094461A/ko not_active Ceased
- 2007-12-14 EP EP07865673A patent/EP2125809A1/en not_active Withdrawn
- 2007-12-14 WO PCT/US2007/087532 patent/WO2008079735A1/en not_active Ceased
- 2007-12-14 CN CNA2007800473412A patent/CN101605786A/zh active Pending
- 2007-12-14 US US12/520,205 patent/US8063218B2/en not_active Expired - Fee Related
- 2007-12-14 AU AU2007337104A patent/AU2007337104A1/en not_active Abandoned
- 2007-12-14 CA CA002671607A patent/CA2671607A1/en not_active Abandoned
- 2007-12-14 JP JP2009543099A patent/JP2010513561A/ja not_active Ceased
-
2009
- 2009-05-25 IL IL198927A patent/IL198927A0/en unknown
-
2011
- 2011-09-26 US US13/245,531 patent/US20120015974A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004005248A1 (en) * | 2002-07-02 | 2004-01-15 | Novartis Ag | Peptide inhibitors of smac protein binding to inhibitor of apoptosis proteins (iap) |
| RU2005141059A (ru) * | 2003-06-26 | 2006-08-10 | Астразенека Аб (Se) | Новое имидазопиридиновое соединение ii с терапевтическим действием |
| WO2005097791A1 (en) * | 2004-04-07 | 2005-10-20 | Novartis Ag | Inhibitors of iap |
| WO2006069063A1 (en) * | 2004-12-20 | 2006-06-29 | Genentech, Inc. | Pyrrolidine inhibitors of iap |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2819398C2 (ru) * | 2019-05-10 | 2024-05-20 | Чиа Тай Тяньцин Фармасьютикал Груп Ко., Лтд. | Кристаллическая форма миметика smac, применяемого в качестве ингибитора iap, и способ ее получения |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2671607A1 (en) | 2008-07-03 |
| CN101605786A (zh) | 2009-12-16 |
| JP2010513561A (ja) | 2010-04-30 |
| WO2008079735A1 (en) | 2008-07-03 |
| EP2125809A1 (en) | 2009-12-02 |
| IL198927A0 (en) | 2010-02-17 |
| US20100130539A1 (en) | 2010-05-27 |
| RU2009127800A (ru) | 2011-01-27 |
| AU2007337104A1 (en) | 2008-07-03 |
| BRPI0719481A2 (pt) | 2014-02-11 |
| US20120015974A1 (en) | 2012-01-19 |
| KR20090094461A (ko) | 2009-09-07 |
| US8063218B2 (en) | 2011-11-22 |
| NZ577150A (en) | 2012-04-27 |
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