CN101595121A - 作为iap抑制剂的吡咯烷衍生物 - Google Patents
作为iap抑制剂的吡咯烷衍生物 Download PDFInfo
- Publication number
- CN101595121A CN101595121A CNA2007800458268A CN200780045826A CN101595121A CN 101595121 A CN101595121 A CN 101595121A CN A2007800458268 A CNA2007800458268 A CN A2007800458268A CN 200780045826 A CN200780045826 A CN 200780045826A CN 101595121 A CN101595121 A CN 101595121A
- Authority
- CN
- China
- Prior art keywords
- tetramethyleneimine
- methylamino
- ethyl
- cyclohexyl
- oxo
- 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.)
- Pending
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- 108091007065 BIRCs Proteins 0.000 title abstract description 8
- 239000003112 inhibitor Substances 0.000 title abstract description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 125000003118 aryl group Chemical group 0.000 claims description 71
- -1 amino, amino Chemical group 0.000 claims description 58
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 48
- 229910052799 carbon Inorganic materials 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000000460 chlorine Substances 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 26
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 125000005493 quinolyl group Chemical group 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 125000005907 alkyl ester group Chemical group 0.000 claims description 7
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 6
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 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 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000005210 alkyl ammonium group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000005605 benzo group Chemical group 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 230000004663 cell proliferation Effects 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 5
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005864 Sulphur Substances 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims description 4
- 239000012964 benzotriazole Substances 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 230000002062 proliferating effect Effects 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- KRPAJLYSLFNDOA-UHFFFAOYSA-N mephenesin carbamate Chemical compound CC1=CC=CC=C1OCC(O)COC(N)=O KRPAJLYSLFNDOA-UHFFFAOYSA-N 0.000 claims description 3
- 229950006838 mephenesin carbamate Drugs 0.000 claims description 3
- 150000005054 naphthyridines Chemical class 0.000 claims description 3
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 claims description 3
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 3
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims description 3
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 claims description 3
- 125000002130 sulfonic acid ester group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N tetrahydro-isoquinoline Natural products C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 2
- PIZNQHDTOZMVBH-UHFFFAOYSA-N thionylimide Chemical compound N=S=O PIZNQHDTOZMVBH-UHFFFAOYSA-N 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- 238000003756 stirring Methods 0.000 description 44
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 31
- 239000012043 crude product Substances 0.000 description 29
- 239000000203 mixture Substances 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 29
- 239000002585 base Substances 0.000 description 27
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- 238000005406 washing Methods 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 239000011734 sodium Substances 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000007787 solid Substances 0.000 description 15
- 239000012141 concentrate Substances 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
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- 238000003818 flash chromatography Methods 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
- 102100033189 Diablo IAP-binding mitochondrial protein Human genes 0.000 description 11
- 150000001721 carbon Chemical group 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- ITBASFJZHKONHG-UHFFFAOYSA-N 4-(5-bromopyridin-3-yl)-4-oxobutanal Chemical compound BrC1=CN=CC(C(=O)CCC=O)=C1 ITBASFJZHKONHG-UHFFFAOYSA-N 0.000 description 10
- 101710101225 Diablo IAP-binding mitochondrial protein Proteins 0.000 description 10
- 230000006907 apoptotic process Effects 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 238000010790 dilution Methods 0.000 description 9
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- 229910002027 silica gel Inorganic materials 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- 102100024319 Intestinal-type alkaline phosphatase Human genes 0.000 description 6
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- 238000010168 coupling process Methods 0.000 description 3
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- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
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- YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical compound N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
-
- 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
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic 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 |
|---|---|---|---|
| US82923406P | 2006-10-12 | 2006-10-12 | |
| US60/829,234 | 2006-10-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101595121A true CN101595121A (zh) | 2009-12-02 |
Family
ID=38984426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007800458268A Pending CN101595121A (zh) | 2006-10-12 | 2007-10-10 | 作为iap抑制剂的吡咯烷衍生物 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US8044209B2 (enExample) |
| EP (1) | EP2102229B1 (enExample) |
| JP (1) | JP5190062B2 (enExample) |
| KR (1) | KR20090065548A (enExample) |
| CN (1) | CN101595121A (enExample) |
| AU (1) | AU2007307763A1 (enExample) |
| BR (1) | BRPI0719221A2 (enExample) |
| CA (1) | CA2666112A1 (enExample) |
| MX (1) | MX2009003834A (enExample) |
| RU (1) | RU2009117701A (enExample) |
| WO (1) | WO2008045905A1 (enExample) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103237801A (zh) * | 2010-08-31 | 2013-08-07 | 韩美科学株式会社 | 对细胞有凋亡诱导活性的喹啉或喹唑啉衍生物 |
| CN103347874A (zh) * | 2010-12-13 | 2013-10-09 | 诺瓦提斯公司 | 二聚化iap抑制剂 |
| CN104870441A (zh) * | 2012-10-19 | 2015-08-26 | 阿斯特克斯治疗有限公司 | 双环杂环化合物及其治疗用途 |
| CN104870442A (zh) * | 2012-10-19 | 2015-08-26 | 阿斯特克斯治疗有限公司 | 双环杂环化合物及其治疗用途 |
| CN104870440B (zh) * | 2012-10-19 | 2018-10-19 | 阿斯特克斯治疗有限公司 | 双环杂环化合物及其治疗用途 |
| WO2019091492A1 (zh) * | 2017-11-13 | 2019-05-16 | 南京明德新药研发股份有限公司 | 用作iap抑制剂的smac模拟物及其用途 |
| 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 |
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| NZ516918A (en) | 2000-05-23 | 2004-06-25 | Vertex Pharma | Caspase inhibitors and uses thereof |
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| MX2007007195A (es) * | 2004-12-20 | 2007-10-08 | Genentech Inc | Inhibidores de pirrolidina de iap. |
| WO2007106192A2 (en) * | 2005-12-19 | 2007-09-20 | Genentech, Inc. | Inhibitors of iap |
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- 2007-10-10 RU RU2009117701/04A patent/RU2009117701A/ru not_active Application Discontinuation
- 2007-10-10 WO PCT/US2007/080875 patent/WO2008045905A1/en not_active Ceased
- 2007-10-10 BR BRPI0719221-5A patent/BRPI0719221A2/pt not_active Application Discontinuation
- 2007-10-10 EP EP07844058.3A patent/EP2102229B1/en not_active Not-in-force
- 2007-10-10 MX MX2009003834A patent/MX2009003834A/es unknown
- 2007-10-10 JP JP2009532544A patent/JP5190062B2/ja not_active Expired - Fee Related
- 2007-10-10 CN CNA2007800458268A patent/CN101595121A/zh active Pending
- 2007-10-10 CA CA002666112A patent/CA2666112A1/en not_active Abandoned
- 2007-10-10 KR KR1020097009617A patent/KR20090065548A/ko not_active Withdrawn
- 2007-10-10 US US12/445,435 patent/US8044209B2/en not_active Expired - Fee Related
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| CN111247161A (zh) * | 2017-11-13 | 2020-06-05 | 正大天晴药业集团股份有限公司 | 用作iap抑制剂的smac模拟物及其用途 |
| 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 |
| CN113677339A (zh) * | 2019-03-07 | 2021-11-19 | 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 |
| CN113677339B (zh) * | 2019-03-07 | 2023-08-01 | 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 |
| CN113748119A (zh) * | 2019-05-10 | 2021-12-03 | 正大天晴药业集团股份有限公司 | 一种用作iap抑制剂的smac模拟物的结晶及其制备方法 |
| WO2020228642A1 (zh) * | 2019-05-10 | 2020-11-19 | 正大天晴药业集团股份有限公司 | 一种用作iap抑制剂的smac模拟物的结晶及其制备方法 |
| CN113748119B (zh) * | 2019-05-10 | 2024-04-02 | 正大天晴药业集团股份有限公司 | 一种用作iap抑制剂的smac模拟物的结晶及其制备方法 |
| CN112521372A (zh) * | 2019-09-18 | 2021-03-19 | 南京华威医药科技集团有限公司 | 一种细胞凋亡蛋白抑制剂及其制备方法和用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5190062B2 (ja) | 2013-04-24 |
| KR20090065548A (ko) | 2009-06-22 |
| US20110015232A1 (en) | 2011-01-20 |
| EP2102229A1 (en) | 2009-09-23 |
| RU2009117701A (ru) | 2010-11-20 |
| US8044209B2 (en) | 2011-10-25 |
| BRPI0719221A2 (pt) | 2014-03-18 |
| CA2666112A1 (en) | 2008-04-17 |
| JP2010506847A (ja) | 2010-03-04 |
| AU2007307763A1 (en) | 2008-04-17 |
| WO2008045905A1 (en) | 2008-04-17 |
| MX2009003834A (es) | 2009-04-22 |
| EP2102229B1 (en) | 2014-03-26 |
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