884492-66-4Relevant articles and documents
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.
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.
