CA2491041A1 - Peptide inhibitors of smac protein binding to inhibitor of apoptosis proteins (iap) - Google Patents
Peptide inhibitors of smac protein binding to inhibitor of apoptosis proteins (iap) Download PDFInfo
- Publication number
- CA2491041A1 CA2491041A1 CA002491041A CA2491041A CA2491041A1 CA 2491041 A1 CA2491041 A1 CA 2491041A1 CA 002491041 A CA002491041 A CA 002491041A CA 2491041 A CA2491041 A CA 2491041A CA 2491041 A1 CA2491041 A1 CA 2491041A1
- Authority
- CA
- Canada
- Prior art keywords
- cycloalkyl
- alkyl
- phenyl
- substituted
- het
- 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.)
- Abandoned
Links
- 239000003112 inhibitor Substances 0.000 title abstract description 7
- 108091007065 BIRCs Proteins 0.000 title description 8
- 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 title description 7
- 108090000765 processed proteins & peptides Proteins 0.000 title description 7
- 101710156605 Diablo homolog, mitochondrial Proteins 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 46
- 230000002062 proliferating effect Effects 0.000 claims abstract description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
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- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
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- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 11
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- 230000002685 pulmonary effect Effects 0.000 description 1
- 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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- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical class C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
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- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
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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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K38/06—Tripeptides
-
- 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
- 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
- C07D207/08—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 hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- 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
- C07D207/08—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 hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- 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
-
- 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
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- 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
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- 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
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
-
- 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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39315002P | 2002-07-02 | 2002-07-02 | |
| US60/393,150 | 2002-07-02 | ||
| PCT/EP2003/007005 WO2004005248A1 (en) | 2002-07-02 | 2003-07-01 | Peptide inhibitors of smac protein binding to inhibitor of apoptosis proteins (iap) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2491041A1 true CA2491041A1 (en) | 2004-01-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002491041A Abandoned CA2491041A1 (en) | 2002-07-02 | 2003-07-01 | Peptide inhibitors of smac protein binding to inhibitor of apoptosis proteins (iap) |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US20060128632A1 (enExample) |
| EP (1) | EP1519918A1 (enExample) |
| JP (1) | JP4541882B2 (enExample) |
| CN (1) | CN100384819C (enExample) |
| AU (1) | AU2003249920A1 (enExample) |
| BR (1) | BR0312408A (enExample) |
| CA (1) | CA2491041A1 (enExample) |
| WO (1) | WO2004005248A1 (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7579320B2 (en) | 2006-03-16 | 2009-08-25 | Aegera Therapeutics, Inc. | IAP BIR domain binding compounds |
| US7772177B2 (en) | 2005-05-18 | 2010-08-10 | Aegera Therapeutics, Inc. | BIR domain binding compounds |
| US8063095B2 (en) | 2005-10-25 | 2011-11-22 | Pharmascience Inc. | IAP BIR domain binding compounds |
| US9284350B2 (en) | 2010-02-12 | 2016-03-15 | Pharmascience Inc. | IAP BIR domain binding compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7291615B2 (en) | 2003-05-01 | 2007-11-06 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
| 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 |
| BRPI0507482A (pt) * | 2004-02-05 | 2007-07-17 | Novartis Ag | combinação de (a) um inibidor de dna topoisomerase e (b) um inibidor de iap |
| CA2558615C (en) | 2004-03-23 | 2013-10-29 | Genentech, Inc. | Azabicyclo-octane inhibitors of iap |
| EP2253614B1 (en) * | 2004-04-07 | 2012-09-19 | Novartis AG | Inhibitors of IAP |
| MXPA06014969A (es) * | 2004-07-02 | 2007-02-08 | Genentech Inc | Inhibidores de iap. |
| EP1773766B1 (en) | 2004-07-15 | 2014-04-02 | Tetralogic Pharmaceuticals Corporation | Iap binding compounds |
| ATE477254T1 (de) * | 2004-12-20 | 2010-08-15 | Genentech Inc | Pyrrolidine als inhibitoren von iap |
| BRPI0607988A2 (pt) * | 2005-02-25 | 2009-10-27 | Tetralogic Pharmaceuticals | composto, composição farmacêutica, e método para induzir apoptose em uma célula |
| DE102005017116A1 (de) * | 2005-04-13 | 2006-10-26 | Novartis Ag | Hemmstoffe für Inhibitoren von Apoptose Proteinen (IAP) |
| AU2006254538A1 (en) | 2005-05-25 | 2006-12-07 | 2Curex Aps | Compounds modifying apoptosis |
| US8318717B2 (en) | 2005-05-25 | 2012-11-27 | 2Curex | Compounds modifying apoptosis |
| US20100256046A1 (en) * | 2009-04-03 | 2010-10-07 | Tetralogic Pharmaceuticals Corporation | Treatment of proliferative disorders |
| CN101374829A (zh) * | 2005-12-19 | 2009-02-25 | 健泰科生物技术公司 | Iap的抑制剂 |
| ES2684120T3 (es) | 2005-12-20 | 2018-10-01 | Novartis Ag | Combinación de un inhibidor de IAP y un taxano |
| CA2634743C (en) * | 2005-12-23 | 2014-07-29 | Zealand Pharma A/S | Modified lysine-mimetic compounds |
| AU2007250443B2 (en) * | 2006-05-16 | 2013-06-13 | Pharmascience Inc. | IAP BIR domain binding compounds |
| WO2008014252A2 (en) | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Iap inhibitors |
| US20100144650A1 (en) * | 2006-07-24 | 2010-06-10 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| AR063943A1 (es) * | 2006-07-24 | 2009-03-04 | 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 |
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| PE20110224A1 (es) | 2006-08-02 | 2011-04-05 | Novartis Ag | PROCEDIMIENTO PARA LA SINTESIS DE UN PEPTIDOMIMETICO DE Smac INHIBIDOR DE IAP, Y COMPUESTOS INTERMEDIARIOS PARA LA SINTESIS DEL MISMO |
| RU2009117701A (ru) | 2006-10-12 | 2010-11-20 | Новартис АГ (CH) | Производные пирролидина в качестве ингибиторов iap |
| JP5394249B2 (ja) | 2006-11-28 | 2014-01-22 | ノバルティス アーゲー | Ｉａｐ阻害剤とｆｌｔ３阻害剤の組合せ剤 |
| JP2010513561A (ja) * | 2006-12-19 | 2010-04-30 | ジェネンテック， インコーポレイテッド | Ｉａｐのイミダゾピリジンインヒビター |
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Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5801012A (en) * | 1996-09-17 | 1998-09-01 | Northwestern University | Methods and compositions for generating angiostatin |
| EP1210362A2 (en) * | 1999-09-01 | 2002-06-05 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Identification of peptides that facilitate uptake and cytoplasmic and/or nuclear transport of proteins, dna and viruses |
| 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 |
| DE10105041A1 (de) * | 2001-02-05 | 2002-08-14 | Tell Pharm Ag Hergiswil | Tripeptide und Tripeptid-Derivate für die Behandlung neurodegenerativer Krankheiten |
-
2003
- 2003-07-01 CA CA002491041A patent/CA2491041A1/en not_active Abandoned
- 2003-07-01 WO PCT/EP2003/007005 patent/WO2004005248A1/en not_active Ceased
- 2003-07-01 EP EP03762570A patent/EP1519918A1/en not_active Withdrawn
- 2003-07-01 CN CNB038156571A patent/CN100384819C/zh not_active Expired - Fee Related
- 2003-07-01 BR BR0312408-8A patent/BR0312408A/pt not_active IP Right Cessation
- 2003-07-01 US US10/519,042 patent/US20060128632A1/en not_active Abandoned
- 2003-07-01 AU AU2003249920A patent/AU2003249920A1/en not_active Abandoned
- 2003-07-01 JP JP2004518651A patent/JP4541882B2/ja not_active Expired - Fee Related
-
2005
- 2005-08-12 US US11/203,370 patent/US20060052311A1/en not_active Abandoned
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7772177B2 (en) | 2005-05-18 | 2010-08-10 | Aegera Therapeutics, Inc. | BIR domain binding compounds |
| US8575113B2 (en) | 2005-05-18 | 2013-11-05 | Pharmascience Inc. | BIR domain binding compounds |
| US8063095B2 (en) | 2005-10-25 | 2011-11-22 | Pharmascience Inc. | IAP BIR domain binding compounds |
| US7579320B2 (en) | 2006-03-16 | 2009-08-25 | Aegera Therapeutics, Inc. | IAP BIR domain binding compounds |
| US7645741B2 (en) | 2006-03-16 | 2010-01-12 | Aegera Therapeutics, Inc. | IAP BIR domain binding compounds |
| US8765681B2 (en) | 2006-03-16 | 2014-07-01 | Pharmascience Inc. | IAP BIR domain binding compounds |
| US9365614B2 (en) | 2006-03-16 | 2016-06-14 | Pharmascience Inc. | IAP BIR domain binding compounds |
| US9284350B2 (en) | 2010-02-12 | 2016-03-15 | Pharmascience Inc. | IAP BIR domain binding compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4541882B2 (ja) | 2010-09-08 |
| BR0312408A (pt) | 2005-04-19 |
| WO2004005248A1 (en) | 2004-01-15 |
| US20060052311A1 (en) | 2006-03-09 |
| CN100384819C (zh) | 2008-04-30 |
| US20060128632A1 (en) | 2006-06-15 |
| CN1665784A (zh) | 2005-09-07 |
| AU2003249920A1 (en) | 2004-01-23 |
| EP1519918A1 (en) | 2005-04-06 |
| JP2006501181A (ja) | 2006-01-12 |
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