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Graphical abstract A new series of fused carbazole–imidazoles 6a–w as potential α-glucosidase inhibitors was synthesized by one-pot two-step sequence. All the synthesized compounds were more active than acarbose as standard drug (IC 50 = 750.0 ± 1.5 µM) with IC 50 values in the range of 74.0 ± 0.7–298.3 ± 0.9 µM. Abstract Twenty three fused carbazole–imidazoles 6a–w were designed, synthesized, and screened as new α-glucosidase inhibitors. All the synthesized fused carbazole-imidazoles 6a-w were found to be more active than acarbose (IC 50 = 750.0 ± 1.5 µM) against yeast α-glucosidase with IC 50 values in the range of 74.0 ± 0.7–298.3 ± 0.9 µM. Kinetic study of the most potent compound 6v demonstrated that this compound is a competitive inhibitor for α-glucosidase (K i value = 75 µM). Furthermore, the in silico studies of the most potent compounds 6v and 6o confirmed that these compounds interacted with the key residues in the active site of α-glucosidase. [ABSTRACT FROM AUTHOR]

A new series of 6-amino-pyrido[2,3-d]pyrimidine-2,4-dione derivatives 3a – 3s were prepared via a facile and efficient reaction from α -azidochalcones and 6-amiouracils. The reactions were performed under mild conditions to produce the corresponding compounds in good to excellent yields. Obtained derivatives 3a – 3s were evaluated for α-glucosidase inhibitory activity and all of them exhibited excellent in vitro yeast α -glucosidase inhibition with IC 50 values ranging from 78.0 ± 2.0 to 252.4 ± 1.0 μM. For example, the most active compound 3o was around 10-fold more potent than acarbose, a standard drug (IC 50  = 750.0 ± 1.5 μM). Kinetic study of compound 3o revealed that it inhibited α -glucosidase in a competitive mode. Molecular modeling studies of the most active compounds 3o , 3i , 3e and 3m were also performed. [ABSTRACT FROM AUTHOR]

A facile, mild and efficient procedure for the synthesis of fully substituted pyrazolo[3,4- b ]pyridin-5-amines is reported. A mixture of an α -azidochalcone, a 5-aminopyrazole and t -BuOK was stirred in DMF at ambient temperature for 5 min to afford the corresponding pyrazolo[3,4- b ]pyridin-5-amines in good to excellent yields. [ABSTRACT FROM AUTHOR]

Efficient and facile protocols for the preparation of highly functionalized 1 H -imidazoles and 5 H -pyrrolo[1,2- c ]imidazoles are described. Heating a mixture of an α-azidochalcones and N,N,N′,N′ -tetramethyl guanidine under neat conditions gave the corresponding 2,4,5-trisubstituted 1 H -imidazole via Michael addition-cyclization in excellent yields. Subsequently, the prepared 1 H -imidazoles undergo addition-Wittig reaction with acetylenic esters in presence of triphenylphosphine in dichloromethane to afford 5 H -pyrrolo[1,2- c ]imidazoles in high yields. [ABSTRACT FROM AUTHOR]

A one-pot and three-component reaction is described for the preparation of 2,3-disubstituted isoindolin-1-ones. Heating a mixture of 2-formylbenzoic acid, a cyclic six-membered β-dicarbonyl compound, and a benzylamine under solvent-free conditions afforded the title compounds in good to excellent yields. The generality of the reaction was shown by the use of various β-dicarbonyl compounds including 1,3-cyclohexadione, dimedone, Meldrum’s acid, N , N -dimethylbarbituric acid, and some benzylamine derivatives. [ABSTRACT FROM AUTHOR]

An efficient, one-pot and three-component synthesis of a new series of 2-acyl-3,4,6-triaryl-1,4-dihydropyrazines is described. This two-step strategy involves treatment of phenacyl bromides and anilines to give the nucleophilic substitution intermediate followed by Michael-addition-cyclization to α -azidochalcones to afford the title compounds in high yields. [ABSTRACT FROM AUTHOR]

Angiogenesis, the formation of new blood vessels from the existing vasculature, is pivotal in the migration, growth, and differentiation of endothelial cells in normal physiological conditions. In various types of tumour microenvironments, dysregulated angiogenesis plays a crucial role in supplying oxygen and nutrients to cancerous cells, leading to tumour size growth. VEGFR-2 tyrosine kinase has been extensively studied as a critical regulator of angiogenesis; thus, inhibition of VEGFR-2 has been widely used for cancer treatments in recent years. Quinazoline nucleus is a privileged and versatile scaffold with a broad range of pharmacological activity, especially in the field of tyrosine kinase inhibitors with more than twenty small molecule inhibitors approved by the US Food and Drug Administration in the last two decades. As of now, the U.S. FDA has approved eleven small chemical inhibitors of VEGFR-2 for various types of malignancies, with a prime example being vandetanib, a quinazoline derivative, which is a multi targeted kinase inhibitor used for the treatment of late-stage medullary thyroid cancer. Despite of prosperous discovery and development of VEGFR-2 down regulator drugs, there still exists limitations in clinical efficacy, adverse effects, a high rate of clinical discontinuation and drug resistance. Therefore, there is an urgent need for the design and synthesis of more selective and effective inhibitors to tackle these challenges. Through the gathering of this review, we have strived to broaden the extent of our view over the entire scope of quinazoline-based VEGFR-2 inhibitors. Herein, we give an overview of the importance and advancement status of reported structures, highlighting the SAR, biological evaluations and their binding modes. [Display omitted] • Inhibitors of VEGFR-2 tyrosine kinase have been widely used for cancer treatments. • Quinazoline nucleus is a privileged and versatile scaffold with a broad range of pharmacological activity. • Advancement status of reported quinazoline-based inhibitors targeting VEGFR-2 (SAR and biological evaluations are depicted). [ABSTRACT FROM AUTHOR]

In an attempt to find new potent cytotoxic compounds, several mono- and bis-pyrazolophthalazines 4a-m and 6a-h were synthesized through an efficient, one-pot, three- and pseudo five-component synthetic approach. All derivatives were evaluated for their in vitro cytotoxic activities against four human cancer cell lines of A549, HepG2, MCF-7, and HT29. Compound 4e showed low toxicity against normal cell lines (MRC-5 and MCF 10A, IC 50 > 200 µM) and excellent cytotoxic activity against A549 cell line with IC 50 value of 1.25 ± 0.19 µM, which was 1.8 times more potent than doxorubicin (IC 50 = 2.31 ± 0.13 µM). In addition, compound 6c exhibited remarkable cytotoxic activity against A549 and MCF-7 cell lines (IC 50 = 1.35 ± 0.12 and 0.49 ± 0.01 µM, respectively), more than two-fold higher than that of doxorubicin. The binding properties of the best active mono- and bis-pyrazolophthalazine (4e and 6c) with HSA and DNA were fully evaluated by various techniques including UV–Vis absorption, circular dichroism (CD), Zeta potential and dynamic light scattering analyses indicating interaction of the compounds with the secondary structure of HSA and significant change of DNA conformation, presumably via a groove binding mechanism. Additionally, molecular docking and site-selective binding studies confirmed the fundamental interaction of compounds 4e and 6c with base pairs of DNA. Compounds 4e and 6c showed promising features to be considered as potential lead structures for further studies in cancer therapy. [ABSTRACT FROM AUTHOR]