Synthesis and evaluation of 2,7-diamino-thiazolo[4,5-d] pyrimidine analogues as anti-tumor epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors

Lin, Ronghui; Johnson, Sigmond G.; Connolly, Peter J.; Wetter, Steven K.; Binnun, Eva; Hughes, Terry V.; Murray, William V.; Pandey, Niranjan B.; Moreno-Mazza, Sandra; Adams, Mary; Fuentes‐Pesquera, Angel R.; Middleton, Steven A.

doi:10.1016/j.bmcl.2009.02.067

Cited by 116 publications

(32 citation statements)

References 21 publications

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“…A chemically diverse set of 60 EGFR TK inhibitors [35][36][37] with IC 50 values spanning a wide range from 0.38 nM to 17900 nM were taken for 3D QSAR model development. The molecules were rationally divided into training and test sets of 26 and 34 compounds respectively ( Figure 2; Tables 1 and 2) using the Catalyst/Discovery Studio-based standard guidelines.…”

Section: Selection Of Moleculesmentioning

confidence: 99%

Pharmacophore modelling, molecular docking and virtual screening for EGFR (HER 1) tyrosine kinase inhibitors

Gupta¹,

Bhunia²,

Balaramnavar³

et al. 2011

SAR and QSAR in Environmental Research

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A pharmacophore model has been developed using diverse classes of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors useful in the treatment of human tumours. Among the top 10 generated hypotheses, the second hypothesis, with one hydrogen bond acceptor, one ring aromatic and three hydrophobic features, was found to be the best on the basis of Cat Scramble validation as well as test set prediction (r(training) = 0.89, r(test) = 0.82). The model also maps well to the external test set molecules as well as clinically active molecules and corroborates the docking studies. Finally, 10 hits were identified as potential leads after virtual screening of ZINC database for EGFR TK inhibition. The study may facilitate the designing and discovery of novel EGFR TK inhibitors.

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Section: Selection Of Moleculesmentioning

confidence: 99%

Pharmacophore modelling, molecular docking and virtual screening for EGFR (HER 1) tyrosine kinase inhibitors

Gupta¹,

Bhunia²,

Balaramnavar³

et al. 2011

SAR and QSAR in Environmental Research

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“…The structures of compounds 14-18 are gathered as training set compounds used to generate qualitative pharmacophore models [70] and they were designed specially to be HER2 inhibitors (IC 50 < 20 nM). 2, 7-Diamino-thiazolo [4,5-d]pyrimidine analogue 21 showed potent and selective EGFR inhibitory activities and inhibited in vitro cellular proliferation in EGFR-overexpressing human tumor cells [71]. The compounds 22, 23, 25 have retained the 4-benzyloxyaniline portion of lapatinib and show potent and selective EGFR/ErbB-2 enzyme inhibition [27,[42][43].…”

Section: "The T790m Mutation and Dual Egfr/her2 Inhibitor"mentioning

confidence: 98%

Exploration of Chemical Space Based on 4-Anilinoquinazoline

Li¹,

Hou²,

Wang³

et al. 2012

CMC

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Chemical space is defined as all possible small organic molecules, including those present in biological systems, which is so vast that so far only a tiny fraction of it has been explored. Indeed, a thorough examination of all "chemical space" is practically impossible. The success of three EGFR inhibitors (Gefitnib, Erlotinib, Lapatinib) suggests that 4-anilinoquinazoline scaffold is still worth developing in the future. To date hundreds of this sort of derivatives have been synthesized and show potent anticancer activities. Most of the compounds have been proved to be EGFR/HER2 kinase inhibitors, binding at the hinge region of the ATP site and some lead compounds have been optimized against a number of different kinases, including VEGFR-2, Src, Aurora A/B, Tpl, Clk and PDE10A. Now there is now a rich pipeline of novel anticancer agents based on 4-anilinoquinazoline in early phase clinical trials. This review will highlight the exploration of chemical space of 4-anilinoquinazoline in the past ten years and we hope that increasing knowledge of the SAR and cellular processes underlying the antitumor-activity of anilinoquinazoline derivatives will be beneficial to the rational design of new generation of small molecule anticancer drugs.

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“…Pyrimido pyrimidines are annulated uracils that have attracted considerable interest in recent years. Derivatives of pyrimido pyrimidine are known to display a wide range of pharmacological activities, such as antiviral [6], antibacterial [7], antitumor [8], anti-inflammatory [9], antifungal [10], and antileishmanial agent [11] and their potent binding affinity towards the tyrosine kinase domain of epidermal growth factor receptor [12] has also been demonstrated.…”

Section: Introductionmentioning

confidence: 98%

Distereoselective one-pot synthesis of pyrimidopyrimidines using sulfated tin oxide as a reusable catalyst: An extension of Biginelli-type reaction

Magar

Thorat²,

Thorat

et al. 2013

Chinese Chemical Letters

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Synthesis and evaluation of 2,7-diamino-thiazolo[4,5-d] pyrimidine analogues as anti-tumor epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors

Cited by 116 publications

References 21 publications

Pharmacophore modelling, molecular docking and virtual screening for EGFR (HER 1) tyrosine kinase inhibitors

Pharmacophore modelling, molecular docking and virtual screening for EGFR (HER 1) tyrosine kinase inhibitors

Exploration of Chemical Space Based on 4-Anilinoquinazoline

Distereoselective one-pot synthesis of pyrimidopyrimidines using sulfated tin oxide as a reusable catalyst: An extension of Biginelli-type reaction

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