Novel hydrazone moiety-bearing aminopyrimidines as selective inhibitors of epidermal growth factor receptor T790M mutant

Discovery of N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)phenyl)-N8-hydroxyoctanediamide as a Novel Inhibitor Targeting Cyclin-dependent Kinase 4/9 (CDK4/9) and Histone Deacetlyase1 (HDAC1) against Malignant Cancer

“…In Scheme , compound 4 was coupled to the diphenylmethanimine to obtain 8 , which was not necessary to further purify, and treated with concentrated HCl to obtain 20 . Compound 4 was heated with N 2 H 4 ·H 2 O in EtOH to give 21 . Compound 1c was condensed with 20 , 21 , ribociclib, 4-(aminomethyl)­anilinedihydrochloride, and tert -butyl (5-aminopyridin-2-yl)­carbamate to provide 22 , 23 , 24 , 26 , and 29 , respectively.…”

“…The residue was purified by silica gel column chromatography (petroleum ether−ethyl acetate, gradient 100:00 → 60:40) to obtain 1.45 g (65%) of 43 as a white solid, mp 64.9 °C. 1 (44). The title compound was prepared from compound 43 (336 mg, 1.5 mmol), compound 3e (461 mg, 1.65 mmol), Pd(OAc) 2 (8 mg, 0.04 mmol), BINAP (47 mg, 0.08 mmol), Cs 2 CO 3 (538 mg, 1.65 mmol), and 1,4dioxane (15 mL) using the procedure described for 5a−5f in 77% yield as a yellow solid, mp 131.6 °C.…”

Synthesis and Antitumor Activity of Novel 4-Aminoquinazoline Derivatives Containing Benzothiazole

“…The epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinases and plays a crucial role in cell proliferation, survival and differentiation via activation of downstream signaling pathways. [1][2] Quinazoline derivatives are important nitrogencontaining heterocycles [3] with a variety of pharmacological properties such as antimalarial, [4][5] antibacterial, [6][7] antiinflammatory, [8][9] anticonvulsant, [10][11] antihypertensive, [12] anti-diabetic, [13] cholinesterase inhibition [14][15] and antitumor. [16][17] Meanwhile, it can specifically block the auto-phosphorylation of the epidermal growth factor receptor and inhibit the epidermal growth factor receptor or its tyrosine kinase ultimately.…”

Rh2(OAc)4 Catalyzed Wittig-Type Olefination: A Facile Access to Alkylidene and Arylidene Malonates

“…The epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinases and plays a crucial role in cell proliferation, survival and differentiation via activation of downstream signaling pathways. [1][2] Quinazoline derivatives are important nitrogencontaining heterocycles [3] with a variety of pharmacological properties such as antimalarial, [4][5] antibacterial, [6][7] antiinflammatory, [8][9] anticonvulsant, [10][11] antihypertensive, [12] anti-diabetic, [13] cholinesterase inhibition [14][15] and antitumor. [16][17] Meanwhile, it can specifically block the auto-phosphorylation of the epidermal growth factor receptor and inhibit the epidermal growth factor receptor or its tyrosine kinase ultimately.…”