BRPI0807578A2 - macrociclo peptidomimético, composto, kit e métodos para sintetizar um macrociclo peptidomimético - Google Patents
macrociclo peptidomimético, composto, kit e métodos para sintetizar um macrociclo peptidomimético Download PDFInfo
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- BRPI0807578A2 BRPI0807578A2 BRPI0807578-6A BRPI0807578A BRPI0807578A2 BR PI0807578 A2 BRPI0807578 A2 BR PI0807578A2 BR PI0807578 A BRPI0807578 A BR PI0807578A BR PI0807578 A2 BRPI0807578 A2 BR PI0807578A2
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- Brazil
- Prior art keywords
- alkyl
- macrocycle
- methyl
- compound
- peptidomimetic macrocycle
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 94
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- 239000003446 ligand Substances 0.000 claims abstract description 26
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/006—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length of peptides containing derivatised side chain amino acids
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
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- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1075—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of amino acids or peptide residues
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- C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
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- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
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- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
- C07K7/56—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid
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- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
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Families Citing this family (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7192713B1 (en) | 1999-05-18 | 2007-03-20 | President And Fellows Of Harvard College | Stabilized compounds having secondary structure motifs |
| PL2332968T3 (pl) | 2003-11-05 | 2017-08-31 | Dana-Farber Cancer Institute, Inc. | Stabilizowane alfa-helikalne peptydy i ich zastosowania |
| WO2005118620A2 (en) * | 2004-05-27 | 2005-12-15 | New York University | Methods for preparing internally constraied peptides and peptidomimetics |
| EP2489360A1 (en) | 2006-11-15 | 2012-08-22 | Dana-Farber Cancer Institute, Inc. | Stabilized MAML peptides and uses thereof |
| US7981998B2 (en) * | 2006-12-14 | 2011-07-19 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| EP2094721B1 (en) | 2006-12-14 | 2018-02-14 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| EP2952522B1 (en) | 2007-01-31 | 2019-10-30 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| US7981999B2 (en) | 2007-02-23 | 2011-07-19 | Aileron Therapeutics, Inc. | Triazole macrocycle systems |
| ES2430067T3 (es) | 2007-03-28 | 2013-11-18 | President And Fellows Of Harvard College | Polipéptidos cosidos |
| EP2564865A1 (en) * | 2007-05-02 | 2013-03-06 | Dana-Farber Cancer Institute, Inc. | Methods of Modulating Cellular Homeostatic Pathways and Cellular Survival |
| EP2247298B1 (en) * | 2007-12-31 | 2016-08-31 | New York University | Control of viral-host membrane fusion with hydrogen bond surrogate-based artificial helices |
| CN104474529A (zh) * | 2008-02-08 | 2015-04-01 | 爱勒让治疗公司 | 治疗性的拟肽大环化合物 |
| AU2014201269B2 (en) * | 2008-02-08 | 2016-09-15 | Aileron Therapeutics, Inc. | Therapeutic peptidomimetic macrocycles |
| EP2310407A4 (en) * | 2008-04-08 | 2011-09-14 | Aileron Therapeutics Inc | BIOLOGICALLY ACTIVE PEPTIDOMIMETIC MACROCYCLES |
| US20110144303A1 (en) * | 2008-04-08 | 2011-06-16 | Aileron Therapeutics, Inc. | Biologically Active Peptidomimetic Macrocycles |
| US20110250685A1 (en) * | 2008-06-03 | 2011-10-13 | Nash Huw M | Compositions and methods for enhancing cellular transport of biomolecules |
| EP2356139A4 (en) * | 2008-07-23 | 2013-01-09 | Harvard College | LIGURE COMBINED POLYPEPTIDES |
| WO2010033617A2 (en) * | 2008-09-16 | 2010-03-25 | The Research Foundation Of State University Of New York | Stapled peptides and method of synthesis |
| EP2342214A1 (en) * | 2008-09-22 | 2011-07-13 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US20120101047A1 (en) * | 2008-09-22 | 2012-04-26 | Aileron Therapetics Inc. | Peptidomimetic macrocycles |
| WO2010034029A1 (en) * | 2008-09-22 | 2010-03-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| EP2334697A1 (en) * | 2008-09-22 | 2011-06-22 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| BRPI0918948A2 (pt) * | 2008-09-22 | 2015-12-15 | Aileron Therapeutics Inc | macrociclos peptidomiméticos |
| EP3492492A1 (en) | 2008-09-22 | 2019-06-05 | Aileron Therapeutics, Inc. | Methods for preparing purified polypeptide compositions |
| CA2743177A1 (en) * | 2008-11-24 | 2010-05-27 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with improved properties |
| CA2744088A1 (en) | 2009-01-14 | 2010-07-22 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| JP5677980B2 (ja) * | 2009-01-23 | 2015-02-25 | パシフィック・サイエンティフィック・エナジェティック・マテリアルズ・カンパニー | 鉛フリー起爆薬の調合 |
| ES2512717T3 (es) * | 2009-02-27 | 2014-10-24 | Mimetogen Pharmaceuticals Inc. | Compuestos cíclicos peptidomiméticos para el tratamiento de la retinitis pigmentosa |
| US9163330B2 (en) | 2009-07-13 | 2015-10-20 | President And Fellows Of Harvard College | Bifunctional stapled polypeptides and uses thereof |
| CA2774973A1 (en) | 2009-09-22 | 2011-03-31 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CN102655875A (zh) * | 2009-10-14 | 2012-09-05 | 爱勒让治疗公司 | 改善的拟肽大环化合物 |
| JP5868864B2 (ja) | 2009-11-16 | 2016-02-24 | サントル ナスィオナル ド ラ ルシェルシュ スィアンティフィク(セ.エン.エル.エス.) | 固相ペプチド合成により製造されるペプチドを精製するための化合物及び方法 |
| US9227995B2 (en) * | 2010-04-23 | 2016-01-05 | Øyvind Jacobsen | Peptides |
| PL2603600T3 (pl) * | 2010-08-13 | 2019-06-28 | Aileron Therapeutics, Inc. | Makrocykle peptidomometyczne |
| WO2012040459A2 (en) | 2010-09-22 | 2012-03-29 | President And Fellows Of Harvard College | Beta-catenin targeting peptides and uses thereof |
| WO2012051405A1 (en) | 2010-10-13 | 2012-04-19 | Bristol-Myers Squibb Company | Methods for preparing macrocycles and macrocycle stabilized peptides |
| FR2967072B1 (fr) | 2010-11-05 | 2013-03-29 | Univ Dundee | Procede pour ameliorer la production de virus et semences vaccinales influenza |
| US10822374B2 (en) | 2010-11-12 | 2020-11-03 | Dana-Farber Cancer Institute, Inc. | Cancer therapies and diagnostics |
| WO2012083078A2 (en) | 2010-12-15 | 2012-06-21 | The Research Foundation Of State University Of New York | Croos-linked peptides and proteins, methods of making same, and uses thereof |
| WO2012173846A2 (en) * | 2011-06-06 | 2012-12-20 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US9487562B2 (en) | 2011-06-17 | 2016-11-08 | President And Fellows Of Harvard College | Stabilized polypeptides as regulators of RAB GTPase function |
| CA2852468A1 (en) | 2011-10-18 | 2013-04-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocyles |
| EP2771008A4 (en) * | 2011-10-28 | 2015-04-08 | Merck Sharp & Dohme | MACROCYCLES FOR INCREASING P53 ACTIVITY AND USES THEREOF |
| WO2013071039A1 (en) * | 2011-11-09 | 2013-05-16 | Ensemble Therapeutics | Macrocyclic compounds for inhibition of inhibitors of apoptosis |
| EP2809660B1 (en) | 2012-02-02 | 2016-01-20 | Ensemble Therapeutics Corporation | Macrocyclic compounds for modulating il-17 |
| MX362492B (es) | 2012-02-15 | 2019-01-21 | Aileron Therapeutics Inc | Macrociclos peptidomiméticos. |
| HK1205454A1 (en) | 2012-02-15 | 2015-12-18 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| US9278984B2 (en) | 2012-08-08 | 2016-03-08 | Pacific Scientific Energetic Materials Company | Method for preparation of a lead-free primary explosive |
| HRP20210707T1 (hr) | 2012-09-26 | 2021-09-17 | President And Fellows Of Harvard College | Prolinom blokirani označeni peptidi i njihova uporaba |
| SG11201503052RA (en) | 2012-11-01 | 2015-05-28 | Aileron Therapeutics Inc | Disubstituted amino acids and methods of preparation and use thereof |
| CA2895504A1 (en) | 2012-12-20 | 2014-06-26 | Merck Sharp & Dohme Corp. | Substituted imidazopyridines as hdm2 inhibitors |
| WO2014138429A2 (en) | 2013-03-06 | 2014-09-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and use thereof in regulating hif1alpha |
| SG11201508431VA (en) | 2013-03-13 | 2015-11-27 | Harvard College | Stapled and stitched polypeptides and uses thereof |
| EP3008081B1 (en) | 2013-06-14 | 2017-08-30 | President and Fellows of Harvard College | Stabilized polypeptide insulin receptor modulators |
| CA2924109A1 (en) | 2013-09-13 | 2015-03-19 | The California Institute For Biomedical Research | Modified therapeutic agents and compositions thereof |
| SG10201810496XA (en) * | 2013-10-28 | 2018-12-28 | Naurex Inc | Nmda receptor modulators and prodrugs, salts, and uses thereof |
| JP6572497B2 (ja) | 2013-12-18 | 2019-09-11 | ザ・スクリップス・リサーチ・インスティテュート | 修飾された治療剤、ステープル留めされたペプチド脂質複合体、及びそれらの組成物 |
| US10533039B2 (en) | 2014-05-21 | 2020-01-14 | President And Fellows Of Harvard College | Ras inhibitory peptides and uses thereof |
| AU2015315007C1 (en) * | 2014-09-11 | 2021-06-03 | Seagen Inc. | Targeted delivery of tertiary amine-containing drug substances |
| US10905739B2 (en) | 2014-09-24 | 2021-02-02 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and formulations thereof |
| SG11201702223UA (en) * | 2014-09-24 | 2017-04-27 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| AU2016235424A1 (en) | 2015-03-20 | 2017-10-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| WO2017004548A1 (en) | 2015-07-01 | 2017-01-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| EP3347372A4 (en) | 2015-09-10 | 2019-09-04 | Aileron Therapeutics, Inc. | PEPTIDOMIMETIC MACROCYCLES AS MODULATORS OF MCL-1 |
| US11229708B2 (en) | 2015-12-04 | 2022-01-25 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| WO2017218949A2 (en) * | 2016-06-17 | 2017-12-21 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| US11198715B2 (en) | 2016-07-22 | 2021-12-14 | Massachusetts Institute Of Technology | Selective Bfl-1 peptides |
| RU2019109008A (ru) | 2016-09-30 | 2020-10-30 | Фуджифилм Корпорэйшн | Циклический пептид, подложка для аффинной хроматографии, меченое антитело, конъюгат антитела с лекарственным средством и фармацевтический препарат |
| EP3679036A1 (en) | 2017-09-08 | 2020-07-15 | Seattle Genetics, Inc. | Process for the preparation of tubulysins and intermediates thereof |
| CN112119085B (zh) | 2017-12-15 | 2025-04-01 | 丹娜-法伯癌症研究院有限公司 | 稳定肽-介导的靶向蛋白降解 |
| US11091522B2 (en) | 2018-07-23 | 2021-08-17 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| WO2020060975A1 (en) * | 2018-09-17 | 2020-03-26 | Massachusetts Institute Of Technology | Peptides selective for bcl-2 family proteins |
| CA3221611A1 (en) | 2021-06-09 | 2022-12-15 | Weijun Shen | Long-acting dual gip/glp-1 peptide conjugates and methods of use |
Family Cites Families (112)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4000259A (en) * | 1975-06-16 | 1976-12-28 | American Home Products Corporation | Cyclic dodecapeptide analogs of somatostatin and intermediates |
| US4438270A (en) | 1977-07-11 | 1984-03-20 | Merrell Toraude Et Compagnie | α-Halomethyl derivatives of α-amino acids |
| US4191754A (en) * | 1979-02-28 | 1980-03-04 | Merck & Co., Inc. | Bicyclic somatostatin analogs |
| AU3439589A (en) | 1988-03-24 | 1989-10-16 | Terrapin Diagnostics, Inc. | Molecular sticks for controlling protein conformation |
| US5650133A (en) * | 1990-01-19 | 1997-07-22 | Nycomed Salutar | Macrocyclic polyaza dichelates linked through ring nitrogens via an amide or ester functionality |
| CA2047042A1 (en) | 1990-07-19 | 1992-01-20 | John Hannah | Cyclic hiv principal neutralizing determinant peptides |
| US5364851A (en) * | 1991-06-14 | 1994-11-15 | International Synthecon, Llc | Conformationally restricted biologically active peptides, methods for their production and uses thereof |
| GB9114949D0 (en) | 1991-07-11 | 1991-08-28 | Smithkline Beecham Plc | Novel compounds |
| US5411860A (en) * | 1992-04-07 | 1995-05-02 | The Johns Hopkins University | Amplification of human MDM2 gene in human tumors |
| AU6770794A (en) | 1993-04-23 | 1994-11-21 | Herbert J. Evans | Polypeptides that include conformation-constraining groups which flank a protein-protein interaction site |
| US5446128A (en) | 1993-06-18 | 1995-08-29 | The Board Of Trustees Of The University Of Illinois | Alpha-helix mimetics and methods relating thereto |
| US5622852A (en) * | 1994-10-31 | 1997-04-22 | Washington University | Bcl-x/Bcl-2 associated cell death regulator |
| US6287787B1 (en) * | 1993-11-24 | 2001-09-11 | Torrey Pines Institute For Molecular Studies | Dimeric oligopeptide mixture sets |
| US5824483A (en) | 1994-05-18 | 1998-10-20 | Pence Inc. | Conformationally-restricted combinatiorial library composition and method |
| US5770377A (en) * | 1994-07-20 | 1998-06-23 | University Of Dundee | Interruption of binding of MDM2 and P53 protein and therapeutic application thereof |
| US6169073B1 (en) * | 1995-02-16 | 2001-01-02 | Bayer Corporation | Peptides and peptidomimetics with structural similarity to human p53 that activate p53 function |
| US5675001A (en) * | 1995-03-14 | 1997-10-07 | Hoffman/Barrett, L.L.C. | Heteroatom-functionalized porphyrazines and multimetallic complexes and polymers derived therefrom |
| EP0832096B1 (en) | 1995-05-04 | 2001-07-18 | The Scripps Research Institute | Synthesis of proteins by native chemical ligation |
| US5811515A (en) * | 1995-06-12 | 1998-09-22 | California Institute Of Technology | Synthesis of conformationally restricted amino acids, peptides, and peptidomimetics by catalytic ring closing metathesis |
| US5840833A (en) * | 1995-10-27 | 1998-11-24 | Molecumetics, Ltd | Alpha-helix mimetics and methods relating thereto |
| US5849954A (en) * | 1996-01-18 | 1998-12-15 | Research Corporation Technologies, Inc. | Method of peptide synthesis |
| US5849691A (en) | 1996-02-20 | 1998-12-15 | The United States Of America As Represented By The Department Of Health And Human Services | Peptidomimetic inhibitors of cathepsin D and plasmepsins I and II |
| US5817752A (en) * | 1996-06-06 | 1998-10-06 | La Jolla Pharmaceutical Company | Cyclic polypeptides comprising a thioether linkage and methods for their preparation |
| US5663316A (en) * | 1996-06-18 | 1997-09-02 | Clontech Laboratories, Inc. | BBC6 gene for regulation of cell death |
| US7083983B2 (en) | 1996-07-05 | 2006-08-01 | Cancer Research Campaign Technology Limited | Inhibitors of the interaction between P53 and MDM2 |
| US5955593A (en) * | 1996-09-09 | 1999-09-21 | Washington University | BH3 interacting domain death agonist |
| US5965703A (en) * | 1996-09-20 | 1999-10-12 | Idun Pharmaceuticals | Human bad polypeptides, encoding nucleic acids and methods of use |
| US5856445A (en) * | 1996-10-18 | 1999-01-05 | Washington University | Serine substituted mutants of BCL-XL /BCL-2 associated cell death regulator |
| US6271198B1 (en) * | 1996-11-06 | 2001-08-07 | Genentech, Inc. | Constrained helical peptides and methods of making same |
| WO1998046631A1 (en) | 1997-04-11 | 1998-10-22 | Eli Lilly And Company | Combinatorial libraries of peptidomimetic macrocycles and processes therefor |
| CA2304124A1 (en) * | 1997-09-17 | 1999-03-25 | The Walter And Eliza Hall Institute Of Medical Research | Bci-2-like protein bim and methods of use thereof |
| US6326354B1 (en) * | 1998-08-19 | 2001-12-04 | Washington University | Modulation of apoptosis with bid |
| EP1216309A2 (en) | 1999-03-01 | 2002-06-26 | Variagenics, Inc. | Methods for targeting rna molecules |
| IL145406A0 (en) * | 1999-03-29 | 2002-06-30 | Procter & Gamble | Melanocortin receptor ligands |
| US6713280B1 (en) * | 1999-04-07 | 2004-03-30 | Thomas Jefferson University | Enhancement of peptide cellular uptake |
| US7192713B1 (en) | 1999-05-18 | 2007-03-20 | President And Fellows Of Harvard College | Stabilized compounds having secondary structure motifs |
| DE10009341A1 (de) * | 2000-02-22 | 2001-09-06 | Florian Kern | Verfahren zur antigen-spezifischen Stimulation von T-Lymphozyten |
| WO2002013833A2 (en) * | 2000-08-16 | 2002-02-21 | Georgetown University Medical Center | SMALL MOLECULE INHIBITORS TARGETED AT Bcl-2 |
| US20050054770A1 (en) | 2001-03-09 | 2005-03-10 | Spatola Arno F. | Helicomimetics and stabilized lxxll peptidomimetics |
| US20040106548A1 (en) * | 2001-09-07 | 2004-06-03 | Schmidt Michelle A | Conformationally constrained labeled peptides for imaging and therapy |
| WO2003057158A2 (en) * | 2001-12-31 | 2003-07-17 | Dana-Farber Cancer Institute, Inc. | Method of treating apoptosis and compositions thereof |
| EP1468013A4 (en) | 2002-01-03 | 2005-03-16 | Yissum Res Dev Co | CYCLIC PEPTIDES WITH CARBON SKELETON HAVING RESTRICTED CONFORMATION |
| WO2003070892A2 (en) | 2002-02-15 | 2003-08-28 | The Regents Of The University Of Michigan | Inhibitors of rgs proteins |
| US20030166138A1 (en) * | 2002-02-21 | 2003-09-04 | Todd Kinsella | Cyclic peptides and analogs useful to treat allergies |
| EP2226316B1 (en) * | 2002-05-30 | 2016-01-13 | The Scripps Research Institute | Copper-catalysed ligation of azides and acetylenes |
| AU2003261774A1 (en) | 2002-09-06 | 2004-03-29 | Kaneka Corporation | PROCESS FOR PRODUCING L-Alpha-METHYLCYSTEINE DERIVATIVE |
| JP2006516383A (ja) * | 2002-09-09 | 2006-07-06 | デイナ−ファーバー キャンサー インスティチュート,インコーポレイテッド | Bh3ペプチドおよびその使用方法 |
| EP2135868A1 (en) * | 2002-11-07 | 2009-12-23 | Kosan Biosciences Incorporated | Trans-9, 10-dehydroepothilone c and d, analogs thereof and methods of making the same |
| US20070032417A1 (en) | 2002-12-24 | 2007-02-08 | Walter And Eliza Hall Institute Of Medical Research | Peptides and therapeutic uses thereof |
| EP1452868A2 (en) | 2003-02-27 | 2004-09-01 | Pepscan Systems B.V. | Method for selecting a candidate drug compound |
| AU2003902743A0 (en) * | 2003-06-02 | 2003-06-19 | Promics Pty Limited | Process for the preparation of cyclic peptides |
| WO2005007675A2 (en) * | 2003-07-09 | 2005-01-27 | The Scripps Research Institute | TRIAZOLE ϵ-AMINO ACIDS |
| GB0317815D0 (en) | 2003-07-30 | 2003-09-03 | Amersham Health As | Imaging agents |
| DE602004014170D1 (de) * | 2003-10-03 | 2008-07-10 | Merck & Co Inc | Benzylether- und benzylamino-beta-sekretase-hemmer zur behandlung von alzheimer-krankheit |
| JP2007537989A (ja) | 2003-10-16 | 2007-12-27 | アプラーゲン ゲゼルシャフト ミット ベシュレンクテル ハフツング | 安定化ペプチド |
| PL2332968T3 (pl) | 2003-11-05 | 2017-08-31 | Dana-Farber Cancer Institute, Inc. | Stabilizowane alfa-helikalne peptydy i ich zastosowania |
| US8193310B2 (en) | 2004-03-19 | 2012-06-05 | The University Of Queensland | Alpha helical mimics, their uses and methods for their production |
| WO2005118620A2 (en) * | 2004-05-27 | 2005-12-15 | New York University | Methods for preparing internally constraied peptides and peptidomimetics |
| CN100335467C (zh) | 2004-06-04 | 2007-09-05 | 中国科学院上海有机化学研究所 | 一锅法区域选择性合成5-碘代-1,4-二取代-1,2,3-三氮唑化合物 |
| EP1602663A1 (en) * | 2004-06-04 | 2005-12-07 | Chiralix B.V. | Triazole-linked glycoamino acids and glycopeptides |
| EP1814860B1 (en) * | 2004-10-29 | 2009-06-03 | Schering Corporation | Substituted 5-carboxyamide pyrazoles and [1,2,4]triazoles as antiviral agents |
| JP5372380B2 (ja) | 2005-01-24 | 2013-12-18 | ペプスキャン システムズ ベー.フェー. | 結合化合物、免疫原性化合物およびペプチド模倣体 |
| US20070020620A1 (en) * | 2005-07-14 | 2007-01-25 | Finn M G | Compositions and methods for coupling a plurality of compounds to a scaffold |
| WO2008033557A2 (en) * | 2006-09-15 | 2008-03-20 | Siemens Medical Solutions Usa, Inc. | Click chemistry-derived cyclic peptidomimetics as integrin markers |
| EP2489360A1 (en) | 2006-11-15 | 2012-08-22 | Dana-Farber Cancer Institute, Inc. | Stabilized MAML peptides and uses thereof |
| US7981998B2 (en) * | 2006-12-14 | 2011-07-19 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| EP2094721B1 (en) | 2006-12-14 | 2018-02-14 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| EP2952522B1 (en) | 2007-01-31 | 2019-10-30 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| US7981999B2 (en) | 2007-02-23 | 2011-07-19 | Aileron Therapeutics, Inc. | Triazole macrocycle systems |
| ES2430067T3 (es) | 2007-03-28 | 2013-11-18 | President And Fellows Of Harvard College | Polipéptidos cosidos |
| EP2564865A1 (en) | 2007-05-02 | 2013-03-06 | Dana-Farber Cancer Institute, Inc. | Methods of Modulating Cellular Homeostatic Pathways and Cellular Survival |
| EP2247298B1 (en) | 2007-12-31 | 2016-08-31 | New York University | Control of viral-host membrane fusion with hydrogen bond surrogate-based artificial helices |
| EP3663318A1 (en) | 2008-01-07 | 2020-06-10 | Amgen Inc. | Method for making antibody fc-heterodimeric molecules using electrostatic steering effects |
| CN104474529A (zh) | 2008-02-08 | 2015-04-01 | 爱勒让治疗公司 | 治疗性的拟肽大环化合物 |
| EP2310407A4 (en) | 2008-04-08 | 2011-09-14 | Aileron Therapeutics Inc | BIOLOGICALLY ACTIVE PEPTIDOMIMETIC MACROCYCLES |
| US20110144303A1 (en) | 2008-04-08 | 2011-06-16 | Aileron Therapeutics, Inc. | Biologically Active Peptidomimetic Macrocycles |
| US20110250685A1 (en) | 2008-06-03 | 2011-10-13 | Nash Huw M | Compositions and methods for enhancing cellular transport of biomolecules |
| EP2356139A4 (en) | 2008-07-23 | 2013-01-09 | Harvard College | LIGURE COMBINED POLYPEPTIDES |
| BRPI0919414A2 (pt) | 2008-09-18 | 2017-07-11 | Univ New York | Inibição da interação entre hif-1alfa e p300/cbp com hélices à base de substituintes de ligação de hidrogênio |
| BRPI0918948A2 (pt) | 2008-09-22 | 2015-12-15 | Aileron Therapeutics Inc | macrociclos peptidomiméticos |
| WO2010034029A1 (en) | 2008-09-22 | 2010-03-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| EP2334697A1 (en) | 2008-09-22 | 2011-06-22 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US20120101047A1 (en) | 2008-09-22 | 2012-04-26 | Aileron Therapetics Inc. | Peptidomimetic macrocycles |
| EP3492492A1 (en) * | 2008-09-22 | 2019-06-05 | Aileron Therapeutics, Inc. | Methods for preparing purified polypeptide compositions |
| EP2342214A1 (en) | 2008-09-22 | 2011-07-13 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CA2743177A1 (en) | 2008-11-24 | 2010-05-27 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with improved properties |
| CA2744088A1 (en) | 2009-01-14 | 2010-07-22 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US9163330B2 (en) | 2009-07-13 | 2015-10-20 | President And Fellows Of Harvard College | Bifunctional stapled polypeptides and uses thereof |
| CA2774973A1 (en) | 2009-09-22 | 2011-03-31 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CN102655875A (zh) | 2009-10-14 | 2012-09-05 | 爱勒让治疗公司 | 改善的拟肽大环化合物 |
| PL2603600T3 (pl) | 2010-08-13 | 2019-06-28 | Aileron Therapeutics, Inc. | Makrocykle peptidomometyczne |
| JP6239979B2 (ja) | 2011-03-04 | 2017-11-29 | ニューヨーク・ユニバーシティ | Rasの調節因子としての水素結合代替大環状分子 |
| WO2012173846A2 (en) | 2011-06-06 | 2012-12-20 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| AU2012301605A1 (en) | 2011-08-31 | 2014-04-17 | New York University | Thioether-,ether-, and alkylamine-linked hydrogen bond surrogate pertidomimentics |
| WO2013059530A2 (en) | 2011-10-18 | 2013-04-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CA2852468A1 (en) | 2011-10-18 | 2013-04-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocyles |
| MX362492B (es) | 2012-02-15 | 2019-01-21 | Aileron Therapeutics Inc | Macrociclos peptidomiméticos. |
| HK1205454A1 (en) | 2012-02-15 | 2015-12-18 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| SG11201503052RA (en) | 2012-11-01 | 2015-05-28 | Aileron Therapeutics Inc | Disubstituted amino acids and methods of preparation and use thereof |
| WO2014138429A2 (en) | 2013-03-06 | 2014-09-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and use thereof in regulating hif1alpha |
| US20170037086A1 (en) | 2014-04-09 | 2017-02-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with pth activity |
| US10905739B2 (en) | 2014-09-24 | 2021-02-02 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and formulations thereof |
| SG11201702223UA (en) | 2014-09-24 | 2017-04-27 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| AU2016235424A1 (en) | 2015-03-20 | 2017-10-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| WO2017004548A1 (en) | 2015-07-01 | 2017-01-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CA2989311A1 (en) | 2015-07-02 | 2017-01-05 | Dana-Farber Cancer Institute, Inc. | Stabilized anti-microbial peptides |
| US20170037105A1 (en) | 2015-08-03 | 2017-02-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CA2996685A1 (en) | 2015-09-03 | 2017-03-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| EP3347372A4 (en) | 2015-09-10 | 2019-09-04 | Aileron Therapeutics, Inc. | PEPTIDOMIMETIC MACROCYCLES AS MODULATORS OF MCL-1 |
| CN109414470A (zh) | 2016-03-21 | 2019-03-01 | 艾瑞朗医疗公司 | 用于拟肽大环化合物的伴随诊断工具 |
| WO2017205786A1 (en) | 2016-05-27 | 2017-11-30 | Aileron Therapeutics, Inc. | Cell permeable peptidomimetic macrocycles |
| WO2017218949A2 (en) | 2016-06-17 | 2017-12-21 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
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