Corrigendum to “Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation” [Bioorg. Med. Chem. Lett. 23 (2013) 3741–3748]

Molecular modeling based approach, synthesis, and cytotoxic activity of novel benzoin derivatives targeting phosphoinostide 3-kinase (PI3Kα)

“…To evaluate the performance of Glide dock program, we compared the docked pose of 1LT in PI3Ka (PDB ID: 4JPS) 29 to its native conformation in the crystal structure. Figure 6 shows the superposition of the Glide-generated 1LT pose and the native conformation in 4JPS.…”

“…11,13 Due to the oncogenic potential of PI3Ka and its negative regulator PTEN, PI3Ka has emerged as an attractive target for anticancer drug design. 14,15 Several chemical scaffolds have been designed and synthesized targeting PI3Ka [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] and some of these have been investigated in clinical trials. [31][32][33][34] We previously reported the pharmacophore features for PI3Ka inhibitors and identified potential inhibitors.…”

Identification and optimisation of 4,5-dihydrobenzo[1,2-d:3,4-d]bisthiazole and 4,5-dihydrothiazolo[4,5-h]quinazoline series of selective phosphatidylinositol-3 kinase alpha inhibitors

“…4 This formed part of a broader piece of work which started from the hit structures, exemplified by 1 in Figure 2, and culminated in the identification of alpelisib. 5,6 In this Letter we describe an additional extension of this work in which a further annulation was introduced to generate the tricyclic 4,5-dihydrobenzo [1,2-d:3,4-d]bisthiazole core, as exemplified by the general structure 2.…”

“…19 The structure revealed the expected binding interactions of the aminothiazole moiety within the hinge region, and for the proline-amide with the non-conserved PI3Ka-specific Q859 residue. 6 In addition, the starting hypothesis was validated with the methylene, introduced to close the central ring, making hydrophobic contacts with Y836.…”

Discovery of a novel tricyclic 4H-thiazolo[5′,4′:4,5]pyrano[2,3-c]pyridine-2-amino scaffold and its application in a PI3Kα inhibitor with high PI3K isoform selectivity and potent cellular activity

“…efforts aiming for selective PI3Kα inhibitors led to the discovery of BYL719 (1) as a clinical candidate 10 . Figure 1.…”