5269-60-3Relevant academic research and scientific papers
De-novo designed library of benzoylureas as inhibitors of BCL-X L: Synthesis, structural and biochemical characterization
Brady, Ryan M.,Vom, Amelia,Roy, Michael J.,Toovey, Nathan,Smith, Brian J.,Moss, Rebecca M.,Hatzis, Effie,Huang, David C. S.,Parisot, John P.,Yang, Hong,Street, Ian P.,Colman, Peter M.,Czabotar, Peter E.,Baell, Jonathan B.,Lessene, Guillaume
, p. 1323 - 1343 (2014/03/21)
The prosurvival BCL-2 proteins are attractive yet challenging targets for medicinal chemists. Their involvement in the initiation and progression of many, if not all, tumors makes them prime targets for developing new anticancer therapies. We present our approach based on de novo structure-based drug design. Using known structural information from complexes engaging opposing members of the BCL-2 family of proteins, we designed peptidomimetic compounds using a benzoylurea scaffold to reproduce key interactions between these proteins. A library stemming from the initial de novo designed scaffold led to the discovery of ligands with low micromolar potency (KD = 4 μM) and selectivity for BCL-XL. These compounds bind in the canonical BH3 binding groove in a binding mode distinct from previously known BCL-2 inhibitors. The results of our study provide insight into the design of a new class of antagonists targeting a challenging class of protein-protein interactions.
Alpha-helical mimetics
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Page/Page column 71, (2011/05/18)
Benzoyl urea derivatives that are alpha helical peptides mimetics that mimic BH3-only proteins, compositions containing them, their conjugation to cell-targeting-moieties, and their use in the regulation of cell death are disclosed. The benzoyl urea derivatives are capable of binding to and neutralizing pro-survival Bcl-2 proteins. Use of benzoyl urea derivatives in the treatment and/or prophylaxis of diseases or conditions associated with deregulation of cell death are also described.
ALPHA-HELICAL MIMETICS
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Page/Page column 137-138, (2010/02/15)
Benzoyl urea derivatives that are alpha helical peptide mimetics that mimic BH3-only proteins, compositions containing them, their conjugation to cell-targeting moieties, and their use in the regulation of cell death are disclosed. The benzoyl urea derivatives are capable of binding to and neutralising pro-survival Bcl-2 proteins. Use of the benzoyl urea derivatives in the treatment and/or prophylaxis of diseases or conditions associated with deregulation of cell death are also disclosed.
Synthesis of lipidated eNOS peptides by combining enzymatic, noble metal- and acid-mediated protecting group techniques with solid phase peptide synthesis and fragment condensation in solution
Machauer, Rainer,Waldmann, Herbert
, p. 2940 - 2956 (2007/10/03)
Lipid-modified proteins play decisive roles in important biological processes such as signal transduction, organization of the cytoskeleton, and vesicular transport. Lipidated peptides embodying the characteristic partial structures of their parent lipida
SYNTHESIS OF THE AMIDE OF THE C-TERMINAL TETRAPEPTIDE OF THE SEQUENCE OF OXYTOCIN
Ivanov, A. K.,Antonov, A. A.,Donetskii, I. A.
, p. 344 - 349 (2007/10/02)
The synthesis has been effected of the amide of the tetrapeptide forming the sequence 6-9 of oxytocin with the use of benzyl protection of the thiol function of cysteine by two main schemes 1+3 and 2+2.The advantageousness of performing the synthesis by the 2+2 scheme has been shown.The overall yield of tetrapeptide using the method of condensation with the formation of mixed anhydrides amounted to 51percent by the scheme proposed.
Efficient "One-Pot" Synthesis of N-Trityl Amino Acids
Barlos, Kleomenis,Papaioannou, Dionysios,Theodoropoulos, Dimitrios
, p. 1324 - 1326 (2007/10/02)
A sequential procedure has been developed whereby neutral amino acids 1 were tritylated via their corresponding trimethylsilyl esters 2 to afford, after mild hydrolysis, N-trityl amino acids 3 in high yields and purity.Hydroxy amino acids 4 were preferent
