884492-66-4Relevant academic research and scientific papers
Protecting-Group-Free Amidation of Amino Acids using Lewis Acid Catalysts
Sabatini, Marco T.,Karaluka, Valerija,Lanigan, Rachel M.,Boulton, Lee T.,Badland, Matthew,Sheppard, Tom D.
supporting information, p. 7033 - 7043 (2018/05/04)
Amidation of unprotected amino acids has been investigated using a variety of ‘classical“ coupling reagents, stoichiometric or catalytic group(IV) metal salts, and boron Lewis acids. The scope of the reaction was explored through the attempted synthesis of amides derived from twenty natural, and several unnatural, amino acids, as well as a wide selection of primary and secondary amines. The study also examines the synthesis of medicinally relevant compounds, and the scalability of this direct amidation approach. Finally, we provide insight into the chemoselectivity observed in these reactions.
Design and synthesis of benzodiazepine analogs as isoform-selective human lysine deacetylase inhibitors
Reddy, D. Rajasekhar,Ballante, Flavio,Zhou, Nancy J.,Marshall, Garland R.
supporting information, p. 531 - 553 (2017/01/24)
A comprehensive investigation was performed to identify new benzodiazepine (BZD) derivatives as potent and selective human lysine deacetylase inhibitors (hKDACis). A total of 108 BZD compounds were designed, synthesized and from that 104 compounds were biologically evaluated against human lysine deacetylases (hKDACs) 1, 3 and 8 (class I) and 6 (class IIb). The most active compounds showed mid-nanomolar potencies against hKDACs 1, 3 and 6 and micromolar activity against hKDAC8, while a promising compound (6q) showed selectivity towards hKDAC3 among the different enzyme isoforms. An hKDAC6 homology model, refined by molecular dynamics simulation was generated, and molecular docking studies performed to rationalize the dominant ligand-residue interactions as well as to define structure-activity-relationships. Experimental results confirmed the usefulness of the benzodiazepine moiety as capping group when pursuing hKDAC isoform-selectivity inhibition, suggesting its continued use when designing new hKDACis.
An Atom-Economical Method to Prepare Enantiopure Benzodiazepines with N-Carboxyanhydrides
Fier, Patrick S.,Whittaker, Aaron M.
supporting information, p. 1454 - 1457 (2017/03/23)
The development of a rapid, one-pot synthesis of diazepinones with simple reagents is described. N-Carboxyanhydrides (NCAs) are employed as amino acid building blocks that react with o-ketoanilines sequentially as electrophiles and nucleophiles to form diazepinones with water and carbon dioxide as byproducts. Notably, these reactions enable the coupling of stereodefined amino acid derived NCAs without racemization. This method is demonstrated by an improved synthesis of a key intermediate toward a bromodomain and extra-terminal (BET) bromodomain inihibitor.
Synthesis and biological evaluation of 1,4-benzodiazepin-2-ones with antitrypanosomal activity
Spencer, John,Rathnam, Rajendra P.,Harvey, Alan L.,Clements, Carol J.,Clark, Rachel L.,Barrett, Michael P.,Wong, Pui Ee,Male, Louise,Coles, Simon J.,MacKay, Simon P.
, p. 1802 - 1815 (2011/04/17)
A library of 1,4-benzodiazepines has been synthesized and evaluated against Trypanosoma brucei, a causative parasite of Human African trypanosomiasis. Benzodiazepines possessing a P2- transporter motif were found to have MIC values as low as 0.78 μM.
The design of non-peptide human Bradykinin B2 receptor antagonists employing the benzodiazepine peptidomimetic scaffold
Dziadulewicz, Edward K.,Brown, Michael C.,Dunstan, Andrew R.,Lee, Wai,Said, Najeeb B.,Garratt, Peter J.
, p. 463 - 468 (2007/10/03)
The Bradykinin B2 receptor antagonist HOE 140 (D-Arg-Arg-Pro-Hyp-Gly- Thi-Ser-D-Tic-Oic-Arg) has been used as a template for the de novo design and synthesis of a small number of non-peptide lead compounds based on the 1,4- benzodiazepin-2-one framework. Two of the compounds have been found to exhibit moderate K(i) values of 8.9 and 9.2 μM at the human Bradykinin B2 receptor.
