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Reaction of 3-aryl-1-(benzofuran-2-yl)-2-propen-1-ones 3a – c with malononitrile in the presence of sufficient amount of sodium alkoxide in the corresponding alcohol proceeds in a regioselective manner to afford 2-alkoxy-4-aryl-6-(benzofuran-2-yl)-3-pyridinecarbonitriles 4 – 37 , which also obtained by treating ylidenemalononitriles 6a – q with 2-acetylbenzofuran 1 in the presence of sufficient amount of sodium alkoxide in the corresponding alcohol. The new chemical entities showed significant vasodilation properties using isolated thoracic aortic rings of rats pre-contracted with norepinephrine hydrochloride standard technique. Compounds 11 , 16 , 21 , 24 and 30 exhibited remarkable activity compared with amiodarone hydrochloride the reference standard used in the present study. CODESSA-Pro software was employing to obtain a statistically significant QSAR model describing the bioactivity of the newly synthesized analogs ( N = 31, n = 5, R 2 = 0.846, R 2 cv OO = 0.765, R 2 cv MO = 0.778, F = 27.540. s 2 = 0.002). [ABSTRACT FROM AUTHOR]

Abstract: A variety of 2-alkoxy-4-aryl-6-(1H-benzimidazol-2-yl)-3-pyridinecarbonitriles 4a–r were prepared via either regioselective reaction of 3-aryl-1-(1H-benzimidazol-2-yl)-2-propen-1-ones 3 with malononitrile or ylidenemalononitriles 6 with 2-acetyl-1H-benzimidazoles 1 in the presence of sodium alkoxide in the corresponding alcohol. All the synthesized compounds showed significant vasodilation properties using isolated thoracic aortic rings of rats pre-contracted with norepinephrine hydrochloride standard technique. Compounds 4d, 4p, 4l, and 4f exhibited remarkable activity compared with prazosin hydrochloride, which was used as a reference standard in the present study. QSAR studies revealed a good predictive and statistically significant 3 descriptor model (r 2 = 0.913, , ). [Copyright &y& Elsevier]

New functionalized thiazol-benzimidazole derivatives were designed, synthesized and evaluated for their in vitro EGFR inhibiting activities. In vitro anti-breast cancer activity of the promising derivatives was also evaluated. The pro-apoptotic activity of the analogue 4a was evaluated against caspase-3, p53, Bax/Bcl-2 expression levels, cell cycle analysis as well as PARP-1 inhibition. QSAR analysis and molecular modelling studies were carried out representing the binding modes of the promising compounds in the active pocket of EGFR. • New thiazol-benzimidazole derivatives 4a-q have been synthesized. • Utilizing EGFR as a putative target, the new compounds 4a-q were evaluated in vitro as EGFR inhibitors. • The promising compounds (4a, 4b, 4d, 4f, 4h, 4i, 4j, 4m, 4n) were examined as anticancer agents against MCF-7 cancer cells. • Compound 4a was selected to study its effect on cell cycle and apoptosis induction as well as its pro-apoptotic activity against caspase-3, p53, Bax/Bcl-2 and PARP-1 expression levels. • QSAR and molecular modelling of 4a , 4d , 4h , 4i and 4n were also performed to elucidate their binding modes with amino acid residues of EGFR. Heterocyclic rings such as thiazole and benzimidazole are considered as privileged structures, since they constitute several FDA-approved drugs for cancer treatment. In this work, a new set of 2-(2-(substituted) hydrazinyl)-4-(1-methyl-1 H -benzo d imidazol-2-yl) thiazoles 4a-q were designed as epidermal growth factor receptor (EGFR) inhibitors and synthesized using concise synthetic methods. The new target compounds have been evaluated in vitro for their suppression activity against EGFR TK. Compounds 4n , 4h , 4i, 4a and 4d exhibited significant potency in comparison with erlotinib which served as a reference drug (IC50, 71.67–152.59 nM; IC50 erlotinib, 152.59 nM). Furthermore, MTT assay revealed that compounds 4j , 4a, 4f, 4h, 4n produced the most promising cytotoxic potency against the human breast cancer cell line (MCF-7) (IC50; 5.96–11.91 µM; IC50 erlotinib; 4.15 µM). Compound 4a showed promising activity as EGFR TK inhibitor as well as anti-breast cancer agent. In addition, 4a induced apoptotic effect and cell cycle arrest at G2/M phase preventing the mitotic cycle in MCF-7 cells. Moreover, 4a upregulated the oncogenic parameters; caspase-3, p53, Bax/Bcl-2 as well as it inhibited the level of PARP-1 enzyme. QSAR study was carried out for the new derivatives and it revealed the goodness of the models. Furthermore, molecular docking studies represented the binding modes of the promising compounds in the active pocket of EGFR. [ABSTRACT FROM AUTHOR]

A statistically significant QSAR model describing the bioactivity of bronchodilatory active 4 H -pyrano[3,2- c ]pyridine-3-carbonitriles ( N = 41, n = 8, R 2 = 0.824, R 2 cv = 0.724, F = 18.749, s 2 = 0.0018) was obtained employing CODESSA-Pro software. The bronchodilatory active 4 H -pyrano[3,2- c ]pyridine-3-carbonitriles 17 – 57 were synthesized through a facile approach via reaction of 1-alkyl-4-piperidones 1 – 4 with ylidenemalononitriles 5 – 16 in methanol in the presence of sodium. The bronchodilation properties of 17 – 57 were investigated in vitro using isolated guinea pig tracheal rings pre-contracted with histamine (standard method) and compared with theophylline (standard reference). Most of the compounds synthesized exhibit promising bronchodilation properties especially, compounds 25 and 28 . [ABSTRACT FROM AUTHOR]

N , N -Dimethyl- and N , N -diisopropyl-1-halo-2-methyl-l-propenylamines are readily available reagents for the mild deoxyhalogenation of alcohols and hydroxyacids. In this study we showed that the reactivity of the reagents can be tuned by varying the size of the alkyl groups on the reagents: the replacement of methyl by isopropyl groups led to a significant increase of reactivity. We then described a unified procedure for all deoxyhalogenations using the readily available α -chloroenamines as reagents with (bromination, iodination) or without (chlorination) an alkaline bromide or iodide. Finally, we showed that deoxyhalogenation reactions of secondary alcohols were highly stereospecific and generally occurred with inversion of configuration. Image 1 [ABSTRACT FROM AUTHOR]