CN102834389A - 二聚化iap抑制剂 - Google Patents
二聚化iap抑制剂 Download PDFInfo
- Publication number
- CN102834389A CN102834389A CN2011800177078A CN201180017707A CN102834389A CN 102834389 A CN102834389 A CN 102834389A CN 2011800177078 A CN2011800177078 A CN 2011800177078A CN 201180017707 A CN201180017707 A CN 201180017707A CN 102834389 A CN102834389 A CN 102834389A
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- CN
- China
- Prior art keywords
- alkylidene
- alkyl
- oxo
- fluoro
- compound
- 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.)
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- 239000003112 inhibitor Substances 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 182
- 230000006907 apoptotic process Effects 0.000 claims abstract description 21
- 230000001737 promoting effect Effects 0.000 claims abstract description 4
- 125000001118 alkylidene group Chemical group 0.000 claims description 125
- -1 1H- indyls Chemical group 0.000 claims description 110
- 125000006332 fluoro benzoyl group Chemical group 0.000 claims description 86
- 150000003839 salts Chemical class 0.000 claims description 82
- 229910052757 nitrogen Inorganic materials 0.000 claims description 80
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 75
- 229910052760 oxygen Inorganic materials 0.000 claims description 57
- 229910052717 sulfur Inorganic materials 0.000 claims description 56
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 51
- 125000001072 heteroaryl group Chemical group 0.000 claims description 49
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 38
- 238000011282 treatment Methods 0.000 claims description 36
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 33
- 201000010099 disease Diseases 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
- 239000013543 active substance Substances 0.000 claims description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid group Chemical group C(CCCCCC(=O)O)(=O)O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 claims description 28
- 238000006467 substitution reaction Methods 0.000 claims description 28
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
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- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 16
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- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
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- 102000002259 TNF-Related Apoptosis-Inducing Ligand Receptors Human genes 0.000 claims description 8
- 101710183280 Topoisomerase Proteins 0.000 claims description 8
- 125000004419 alkynylene group Chemical group 0.000 claims description 8
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- 150000004579 taxol derivatives Chemical class 0.000 claims description 8
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
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- CYMRPDYINXWJFU-UHFFFAOYSA-N 2-carbamoylbenzoic acid Chemical compound NC(=O)C1=CC=CC=C1C(O)=O CYMRPDYINXWJFU-UHFFFAOYSA-N 0.000 claims description 6
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 6
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical class C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000005936 piperidyl group Chemical group 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 4
- 125000004653 anthracenylene group Chemical group 0.000 claims description 4
- LJJQENSFXLXPIV-UHFFFAOYSA-N fluorenylidene Chemical group C1=CC=C2[C]C3=CC=CC=C3C2=C1 LJJQENSFXLXPIV-UHFFFAOYSA-N 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical group C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 3
- DKYBVKMIZODYKL-UHFFFAOYSA-N 1,3-diazinane Chemical compound C1CNCNC1 DKYBVKMIZODYKL-UHFFFAOYSA-N 0.000 claims description 3
- 125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 claims description 3
- 125000004959 2,6-naphthylene group Chemical group [H]C1=C([H])C2=C([H])C([*:1])=C([H])C([H])=C2C([H])=C1[*:2] 0.000 claims description 3
- 125000004069 aziridinyl group Chemical group 0.000 claims description 3
- 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 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30811410P | 2010-02-25 | 2010-02-25 | |
| US61/308,114 | 2010-02-25 | ||
| US33392710P | 2010-05-12 | 2010-05-12 | |
| US61/333,927 | 2010-05-12 | ||
| US38841010P | 2010-09-30 | 2010-09-30 | |
| US61/388,410 | 2010-09-30 | ||
| PCT/EP2011/052662 WO2011104266A1 (en) | 2010-02-25 | 2011-02-23 | Dimeric iap inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102834389A true CN102834389A (zh) | 2012-12-19 |
Family
ID=44476672
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011800177078A Pending CN102834389A (zh) | 2010-02-25 | 2011-02-23 | 二聚化iap抑制剂 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8445440B2 (enExample) |
| EP (1) | EP2539333A1 (enExample) |
| JP (1) | JP2013520466A (enExample) |
| KR (1) | KR20130010894A (enExample) |
| CN (1) | CN102834389A (enExample) |
| AR (1) | AR080253A1 (enExample) |
| BR (1) | BR112012021291A2 (enExample) |
| CA (1) | CA2790302A1 (enExample) |
| EA (1) | EA201201177A1 (enExample) |
| MX (1) | MX2012009894A (enExample) |
| TW (1) | TW201141846A (enExample) |
| UY (1) | UY33236A (enExample) |
| WO (1) | WO2011104266A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109705191A (zh) * | 2017-10-25 | 2019-05-03 | 广东东阳光药业有限公司 | Iap抑制剂及其在药物中的应用 |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100317593A1 (en) * | 2009-06-12 | 2010-12-16 | Astrazeneca Ab | 2,3-dihydro-1h-indene compounds |
| UY33794A (es) | 2010-12-13 | 2012-07-31 | Novartis Ag | Inhibidores diméricos de las iap |
| US20140243276A1 (en) | 2011-09-30 | 2014-08-28 | Tetralogic Pharmaceuticals Corporation | Smac mimetic (birinapant) for use in the treatment of proliferative diseases (cancer) |
| EP2882740B1 (en) * | 2012-08-09 | 2017-03-01 | Bristol-Myers Squibb Company | Iap antagonists |
| US20140135270A1 (en) * | 2012-11-09 | 2014-05-15 | Ensemble Therapeutics Corp. | Macrocyclic compounds for inhibition of inhibitors of apoptosis |
| SG11201509525XA (en) | 2013-06-25 | 2016-01-28 | Inst Medical W & E Hall | Method of treating intracellular infection |
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008014236A1 (en) * | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| WO2008085610A1 (en) * | 2006-11-28 | 2008-07-17 | Novartis Ag | Use of iap inhibitors for the treatment of acute myeloid leukemia |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6041077B2 (ja) | 1976-09-06 | 1985-09-13 | 喜徳 喜谷 | １，２‐ジアミノシクロヘキサン異性体のシス白金（２）錯体 |
| US5281620A (en) | 1986-12-23 | 1994-01-25 | Cancer Research Campaign Technology Limited | Compounds having antitumor and antibacterial properties |
| PE20010306A1 (es) | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
| GB0018891D0 (en) | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
| JP2002037626A (ja) | 2000-07-27 | 2002-02-06 | Internatl Superconductivity Technology Center | ビスマス系高温超電導体の製造方法。 |
| PE20020354A1 (es) | 2000-09-01 | 2002-06-12 | Novartis Ag | Compuestos de hidroxamato como inhibidores de histona-desacetilasa (hda) |
| US6995162B2 (en) | 2001-01-12 | 2006-02-07 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
| TWI275390B (en) | 2002-04-30 | 2007-03-11 | Wyeth Corp | Process for the preparation of 7-substituted-3- quinolinecarbonitriles |
| JP2006514096A (ja) | 2002-11-27 | 2006-04-27 | アイアールエム・リミテッド・ライアビリティ・カンパニー | 癌細胞においてアポトーシスを誘導するための方法および組成物 |
| JP2007524596A (ja) | 2003-02-28 | 2007-08-30 | トランスフォーム・ファーマシューティカルズ・インコーポレイテッド | 共結晶医薬組成物 |
| CA2552937A1 (en) | 2004-02-05 | 2005-08-18 | Novartis Ag | Combination of (a) a dna topoisomerase inhibitor and (b) an iap inhibitor |
| US7309792B2 (en) * | 2004-03-01 | 2007-12-18 | Board Of Regents, The University Of Texas System | Dimeric small molecule potentiators of apoptosis |
| 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 |
| 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 |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| CA2617642A1 (en) | 2005-08-09 | 2007-02-22 | Tetralogic Pharmaceuticals Corporation | Treatment of proliferative disorders |
| CA2564872C (en) * | 2005-10-25 | 2010-12-21 | Aegera Therapeutics Inc. | Iap bir domain binding compounds |
| AU2006331964A1 (en) * | 2005-12-20 | 2007-07-05 | Novartis Ag | Combination of an IAP-inhibitor and a taxane7 |
| 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. |
| US8202902B2 (en) * | 2006-05-05 | 2012-06-19 | The Regents Of The University Of Michigan | Bivalent SMAC mimetics and the uses thereof |
| SG171682A1 (en) | 2006-05-16 | 2011-06-29 | Aegera Therapeutics Inc | Iap bir domain binding compounds |
| 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 |
| WO2008014238A2 (en) | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| EP2049563B1 (en) | 2006-07-24 | 2014-03-12 | Tetralogic Pharmaceuticals Corporation | Dimeric iap antagonists |
| WO2008014240A2 (en) | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| US20100144650A1 (en) | 2006-07-24 | 2010-06-10 | 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 |
| JP2010507096A (ja) * | 2006-10-19 | 2010-03-04 | ノバルティス アーゲー | 有機化合物 |
| WO2008066854A2 (en) | 2006-11-28 | 2008-06-05 | Novartis Ag | Methods and compositions for inducing apoptosis in cancer cells |
| KR101149449B1 (ko) | 2007-03-20 | 2012-05-25 | 삼성전자주식회사 | 오디오 신호의 인코딩 방법 및 장치, 그리고 오디오 신호의디코딩 방법 및 장치 |
| CA2684169C (en) * | 2007-04-12 | 2012-06-19 | Joyant Pharmaceuticals, Inc. | Smac mimetic dimers and trimers useful as anti-cancer agents |
| AU2008245447C1 (en) | 2007-04-30 | 2014-11-20 | Genentech, Inc. | Inhibitors of IAP |
| WO2008137930A1 (en) | 2007-05-07 | 2008-11-13 | Tetralogic Pharmaceuticals Corp. | TNFα GENE EXPRESSION AS A BIOMARKER OF SENSITIVITY TO ANTAGONISTS OF INHIBITOR OF APOPTOSIS PROTEINS |
| JP5658565B2 (ja) | 2007-09-12 | 2015-01-28 | ジェネンテック， インコーポレイテッド | ホスホイノシチド３−キナーゼ阻害剤化合物と化学療法剤との組合せ、および使用方法 |
| JP5348725B2 (ja) | 2007-10-25 | 2013-11-20 | ジェネンテック， インコーポレイテッド | チエノピリミジン化合物の製造方法 |
| EP2058312A1 (en) | 2007-11-09 | 2009-05-13 | Universita' degli Studi di Milano | SMAC mimetic compounds as apoptosis inducers |
| CN101970457A (zh) | 2008-01-11 | 2011-02-09 | 健泰科生物技术公司 | Iap抑制剂 |
| US20110288116A1 (en) | 2008-01-24 | 2011-11-24 | Tetralogic Pharmaceuitcal Corporation | Iap inhibitors |
| US20110117081A1 (en) | 2008-05-05 | 2011-05-19 | Aegera Therapeutics, Inc. | Functionalized pyrrolidines and use thereof as iap inhibitors |
| US8168784B2 (en) | 2008-06-20 | 2012-05-01 | Abbott Laboratories | Processes to make apoptosis promoters |
| US20110171171A1 (en) | 2008-06-27 | 2011-07-14 | Aegera Therapeutics, Inc. | Bridged secondary amines and use thereof as iap bir domain binding compounds |
| EP2318395A4 (en) | 2008-08-02 | 2011-10-26 | Genentech Inc | IPA INHIBITORS |
| WO2010015090A1 (en) | 2008-08-07 | 2010-02-11 | Aegera Therapeutics Inc. | Functionalized pyrrolidines and use thereof as iap inhibitors |
| US8399683B2 (en) | 2008-09-17 | 2013-03-19 | Tetralogic Pharmaceuticals | IAP inhibitors |
| EP2350641B1 (en) | 2008-09-22 | 2014-09-24 | Amgen Inc. | A combination of a tnf alpha inhibitor, an iap inhibitor and a trail receptor agonist for use in treating cancer |
| US8283372B2 (en) | 2009-07-02 | 2012-10-09 | Tetralogic Pharmaceuticals Corp. | 2-(1H-indol-3-ylmethyl)-pyrrolidine dimer as a SMAC mimetic |
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2011
- 2011-02-21 UY UY0001033236A patent/UY33236A/es not_active Application Discontinuation
- 2011-02-23 JP JP2012554332A patent/JP2013520466A/ja active Pending
- 2011-02-23 BR BR112012021291A patent/BR112012021291A2/pt not_active IP Right Cessation
- 2011-02-23 KR KR1020127024875A patent/KR20130010894A/ko not_active Withdrawn
- 2011-02-23 US US13/033,463 patent/US8445440B2/en not_active Expired - Fee Related
- 2011-02-23 EA EA201201177A patent/EA201201177A1/ru unknown
- 2011-02-23 MX MX2012009894A patent/MX2012009894A/es active IP Right Grant
- 2011-02-23 CN CN2011800177078A patent/CN102834389A/zh active Pending
- 2011-02-23 EP EP11705532A patent/EP2539333A1/en not_active Withdrawn
- 2011-02-23 CA CA2790302A patent/CA2790302A1/en not_active Abandoned
- 2011-02-23 AR ARP110100547A patent/AR080253A1/es unknown
- 2011-02-23 WO PCT/EP2011/052662 patent/WO2011104266A1/en not_active Ceased
- 2011-02-24 TW TW100106289A patent/TW201141846A/zh unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008014236A1 (en) * | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| WO2008085610A1 (en) * | 2006-11-28 | 2008-07-17 | Novartis Ag | Use of iap inhibitors for the treatment of acute myeloid leukemia |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109705191A (zh) * | 2017-10-25 | 2019-05-03 | 广东东阳光药业有限公司 | Iap抑制剂及其在药物中的应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| BR112012021291A2 (pt) | 2016-10-25 |
| WO2011104266A1 (en) | 2011-09-01 |
| JP2013520466A (ja) | 2013-06-06 |
| US8445440B2 (en) | 2013-05-21 |
| EP2539333A1 (en) | 2013-01-02 |
| TW201141846A (en) | 2011-12-01 |
| CA2790302A1 (en) | 2011-09-01 |
| EA201201177A1 (ru) | 2013-04-30 |
| AR080253A1 (es) | 2012-03-21 |
| AU2011219862A1 (en) | 2012-09-06 |
| KR20130010894A (ko) | 2013-01-29 |
| UY33236A (es) | 2011-09-30 |
| US20110206690A1 (en) | 2011-08-25 |
| MX2012009894A (es) | 2012-09-12 |
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