2,4-Diarylamino-pyrimidines as kinase inhibitors co-targeting IGF1R and EGFRL858R/T790M

Chan, Shingpan; Han, Kun; Qu, Rong; Tong, Linjiang; Li, Yingjun; Zhang, Zhang; Cheng, Huimin; Lu, Xiaoyun; Patterson, Adam V.; Smaill, Jeff B.; Ren, Xiaomei; Ding, Jian; Xie, Hua; Ding, Ke

doi:10.1016/j.bmcl.2015.07.089

Cited by 20 publications

(9 citation statements)

References 23 publications

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“…The reduction of 1-chloro-4-nitrobenzene (49) to the hydrochloride salt 50•HCl of the corresponding aniline has been successfully demonstrated at a scale of 100 mmol of input using potassium borohydride with the doped iron nanoparticles (Scheme 15). 114 Aniline 50 has in turn been elaborated using non-micellar or micellar methods to aminopyrimidine 51, 115 a compound that features in the synthesis of kinase inhibitors co-targeting IGF1R and EG-FR L858R/T790M , 117 as well as AXL 118 and the JAK-STAT signalling pathway. 119 Other examples of the application of a nitro reduction in a micellar medium include the synthesis of procainamide (52), and aminothiazole 53 used to make fructose 1,6-bisphosphatase inhibitors 120 and antimicrobial drug candidates (Scheme 15).…”

Section: Short Review Syn Thesismentioning

confidence: 99%

Micelle-Mediated Chemistry in Water for the Synthesis of Drug Candidates

Steven¹

2019

Synthesis

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Micellar reaction conditions, in a predominantly aqueous medium, have been developed for transformations commonly used by synthetic chemists working in the pharmaceutical industry to discover and develop drug candidates. The reactions covered in this review are the Suzuki–Miyaura, Miyaura borylation, Sonogashira coupling, transition-metal-catalysed CAr–N coupling, SNAr, amidation, and nitro reduction. Pharmaceutically relevant examples of these applications will be used to show how micellar conditions can offer advantages in yield, operational ease, amount of waste generated, transition-metal catalyst loading, and safety over the use of organic solvents, irrespective of the setting in which they are used.1 Introduction2 Micelles as Solubilising Agents3 Micelles as Nanoreactors4 Designer Surfactants5 A Critical Evaluation of the Case for Chemistry in Micelles6 Scope of Review7 Suzuki–Miyaura Coupling8 Miyaura Borylation9 Sonogashira Coupling10 Transition-Metal-Catalysed CAr–N Couplings11 SNAr12 Amidation13 Nitro Reduction14 Micellar Sequences15 Summary and Outlook

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Section: Short Review Syn Thesismentioning

confidence: 99%

Micelle-Mediated Chemistry in Water for the Synthesis of Drug Candidates

Steven¹

2019

Synthesis

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“…Taiho Pharma is known to be developing TAS-121 as an oral mutant EGFR selective inhibitor and is currently in Phase 1 clinical trials, but no structure has yet been disclosed. In addition, numerous additional pre-clinical T790M inhibitors have been described in the literature (For example, see: [59][60][61]).…”

Section: Resistance Mutationsmentioning

confidence: 99%

Small Molecule Inhibitors of the Epidermal Growth Factor Receptor

Finlay

Ward

2017

Topics in Medicinal Chemistry

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The epidermal growth factor receptor (EGFR) has emerged over the past two decades as a key target in therapeutic approaches to the treatment of non-small cell lung cancer (NSCLC). This chapter describes the evolution of the EGFR small molecule inhibitor field, from early exploratory work and growing insight into the role of EGFR activating mutations, through to the first approved therapies, gefitinib and erlotinib. Advances in understanding resistance to these initial therapies and the role of the T790M mutation are discussed, along with drug discovery efforts culminating in the discovery of a number of EGFR mutant selective inhibitors, including osimertinib (TAGRISSO TM), the first approved treatment for patients with EGFR T790M mutation-positive metastatic NSCLC.

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“…Walter AO and colleagues [59] found that NSCLC cells with acquired resistance to CO-1686 exhibited signs of epithelial-mesenchymal transition (EMT) and increased sensitivity to AKT inhibitors. Chan S et al [74] reported that IGF1R amplification was related to the secondary acquired resistance against the 2nd or 3rd generation EGFR inhibitor therapies. They have successfully identified a 2, 4-dia-rylamino-pyrimidines compound 8g, which strongly suppresses the proliferation of CO-1686-resistant H1975-IGF1R cancer cells, suggesting it is promising for future anticancer drug discovery.…”

Section: Acquired Resistance To Third-generation Tkismentioning

confidence: 99%

Development of epidermal growth factor receptor tyrosine kinase inhibitors against EGFR T790M. Mutation in non small-cell lung carcinoma

et al. 2016

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AbstractIndividualized therapies targeting epidermal growth factor receptor (EGFR) mutations show promises for the treatment of non small-cell lung carcinoma (NSCLC). However, disease progression almost invariably occurs 1 year after tyrosine kinase inhibitor (TKI) treatment. The most prominent mechanism of acquired resistance involves the secondary EGFR mutation, namely EGFR T790M, which accounts for 50%–60% of resistant tumors. A large amount of studies have focused on the development of effective strategies to treat TKI-resistant EGFR T790M mutation in lung tumors. Novel generations of EGFR inhibitors are producing encouraging results in patients with acquired resistance against EGFR T790M mutation. This review will summarize the novel inhibitors, which might overcome resistance against EGFR T790M mutation.

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2,4-Diarylamino-pyrimidines as kinase inhibitors co-targeting IGF1R and EGFRL858R/T790M

Cited by 20 publications

References 23 publications

Micelle-Mediated Chemistry in Water for the Synthesis of Drug Candidates

Micelle-Mediated Chemistry in Water for the Synthesis of Drug Candidates

Small Molecule Inhibitors of the Epidermal Growth Factor Receptor

Development of epidermal growth factor receptor tyrosine kinase inhibitors against EGFR T790M. Mutation in non small-cell lung carcinoma

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