31027-31-3Relevant articles and documents
Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression
Lakkaniga, Naga Rajiv,Zhang, Lingtian,Belachew, Binyam,Gunaganti, Naresh,Frett, Brendan,Li, Hong-yu
, (2020/07/25)
Aurora Kinase B is a serine-threonine kinase known to be overexpressed in several cancers, with no inhibitors approved for clinical use. Herein, we present the discovery and optimization of a series of novel quinazoline-based Aurora Kinase B inhibitors. The lead inhibitor SP-96 shows sub-nanomolar potency in Aurora B enzymatic assays (IC50 = 0.316 ± 0.031 nM). We identified the important pharmacophore features resulting in selectivity against receptor tyrosine kinases. Particularly, SP-96 shows >2000 fold selectivity against FLT3 and KIT which is important for normal hematopoiesis. This could diminish the adverse effect of neutropenia reported in the clinical trials of the Aurora B inhibitor Barasertib, which inhibits FLT3 and KIT in addition to Aurora B. Enzyme kinetics of SP-96 shows non-ATP-competitive inhibition which makes it a first-in-class inhibitor. Further, SP-96 shows selective growth inhibition in NCI60 screening, including inhibition of MDA-MD-468, a Triple Negative Breast Cancer cell line.
Synthesis of unsymmetrical phenylurea derivatives via oxidative cross coupling of aryl formamides with amines under metal-free conditions
Reddy, Nagireddy Veera,Kumar, Pailla Santhosh,Reddy, Peddi Sudhir,Kantam, Mannepalli Lakshmi,Reddy, Kallu Rajender
supporting information, p. 805 - 809 (2015/02/19)
A new synthetic approach for phenylurea derivatives involving the cross coupling of N-aryl formamides with amines through the formation of isocyanate intermediates in the presence of hypervalent iodine reagents is described.
Metal free oxidative coupling of aryl formamides with alcohols for the synthesis of carbamates
Reddy, N. Veera,Prasad, K. Rajendra,Reddy, P. Sudhir,Lakshmi Kantam,Reddy, K. Rajender
supporting information, p. 2172 - 2175 (2014/04/03)
A direct transformation of N-aryl formamides to the corresponding carbamates via the formation of isocyanate intermediates is achieved in good yields using hypervalent iodine as an oxidant. This journal is