Truncated structures used in search for new lead compounds and in a retrospective analysis of thienopyrimidine-based EGFR inhibitors

Design and Synthesis of 4‐Anilinothieno[2,3‐d]pyrimidine‐Based Compounds as Dual EGFR/HER‐2 Inhibitors

“…The target thienopyrimidines bearing a 4‐benzyloxyanilino tail ( 5a–h and 8a–h ) were synthesized via pathways outlined in Schemes . The synthesis of the corresponding key intermediates ( 2a–h ) depending on using of Williamson ether synthesis which was accomplished by stirring of p ‐nitrophenol in dimethylformamide with the appropriate benzyl bromide derivatives to afford the nitro derivatives in higher yields and high purity ( 1a–h ) . 4‐Benzyloxyanilines were synthesized through reduction of their corresponding nitro derivatives using Fe powder in NH 4 Cl and 70% ethanol (Scheme ).…”

“…The synthesis of the corresponding key intermediates ( 2a–h ) depending on using of Williamson ether synthesis which was accomplished by stirring of p ‐nitrophenol in dimethylformamide with the appropriate benzyl bromide derivatives to afford the nitro derivatives in higher yields and high purity ( 1a–h ) . 4‐Benzyloxyanilines were synthesized through reduction of their corresponding nitro derivatives using Fe powder in NH 4 Cl and 70% ethanol (Scheme ). The reaction of ethyl acetoacetate, malononitrile, sulphur powder, and morpholine in water bath in a one pot procedure following Gewald procedures afforded the methyl 2‐amino‐3‐cyanothiophene‐5‐carboxylate precursor ( 3 ) in good yield and melting point as reported .…”

“…Elemental analyses were performed at the Regional Center for Mycology and Biotechnology, Al‐Azhar University. The key intermediates 1a–h , 2a – h [ 16–19], 3 were prepared according to the reported procedure.…”

Identification of a thienopyrimidine derivatives target by a kinome and chemical biology approach

“…Four of the thienopyrimidine analogues (5a-5d) exhibited good inhibitory activity against FLT3 (IC 50 range from 0.055 to 0.208 lM) with similar or improved activities compared to AC220, a selective FLT3 inhibitor (IC 50 = 0.120 lM). In addition to the kinase Paper Discovery of a novel series of thienopyrimidine as highly potent and selective PI3K inhibitors (Han et al 2015) mTOR/PI3Ka Paper Design, synthesis and docking studies of novel thienopyrimidine derivatives bearing chromone moiety as mTORa/ PI3Ka inhibitors (Zhu et al 2015) EGFR Paper Truncated structures used in search for new lead compounds and in a retrospective analysis of thienopyrimidine-abased EGFR inhibitors (Bugge et al 2015) Aurora A Paper Identification of new novel scaffold for Aurora A inhibition by pharmacophore modeling and virtual screening (Chavan et al 2014) Aurora B Paper A thienopyrimidine derivative induces growth inhibition and apoptosis in human cancer cell lines via inhibiting aurora B kinase activity (Li et al 2013) ErbB2…”

EFFECTIVE MICROWAVE SYNTHESIS OF BIOACTIVE THIENO[2,3-d]PYRTMIDINES

“…The thienopyrimidines occupy a special position among fused pyrimidines, along with some other pyrimidines containing an annelated five membered hetero aromatic ring; they are structural analogues of biogenic purines and can be considered as potential nucleic acid antimetabolites. Many of thienopyrimidines are found to exhibit a variety of biological activities like antimicrobial, 5 analgesic and ulcerogenic, 6 anti-inflammatory, [6][7][8] antitubercular, 9 EGFR inhibitors, 10 inhibition of cancer cell proliferation, 11 antagonism of α1 adrenoceptors, 12 adenosine receptor antagonists 13 and other wide range of biological activities. [14][15] Some recently reported thieno [2,3-d]pyrimidine derivatives have showed various biological activities (Fig.…”