Recent advances in quinazoline/quinazolinone hybrid heterocycles in medicinal chemistry and their pharmacological diversification.

Rh(iii)-Catalyzed substituent enabled alkylation and alkenylation of 1,4-naphthoquinones with maleimides under acidic and basic conditions is described.

A novel series of indolyl oxoacetamide-quinazolinone hybrid analogues (9aa-9df) were designed, synthesized, and evaluated for their in vitro Pancreatic Lipase (PL) inhibitory potential that may lead to efficient anti-obesity agents....

A series of thiazolidinedione-indole hybrids are designed and synthesized as a potential inhibitor for pancreatic lipase (PL).

The rhodium(III)-catalyzed direct C−H addition and annulation of benzimidates and aldimines with β-(trifluoromethyl)-α,β-unsaturated ketones is described. This protocol provides the facile and efficient formation of various trifluoromethyl-containing indenamines or aminoindanes in moderate to high yields.I ndenes and indanes are very important carbocyclic derivatives that are found in various natural products and pharmaceutically active molecules. 1 Moreover, they find application in organometallics and material science. 2 In particular, aminoindene/indane derivatives have shown important biological activities, 3 such as glutamate receptor antagonist, calcium antagonist, and anti-Parkinson. In addition, trifluoromethyl-containing indane acts as a selective CB2 ligand (Figure 1). 4

Pancreatic Lipase (PL) is a key enzyme responsible for the digestion of 50%–70% of dietary triglycerides, hence its inhibition is considered as a viable approach for the management of obesity. A series of indole‐TZD hybrid analogues were synthesized, characterized and evaluated for their PL inhibitory activity. Knoevenagel condensation of various substituted indole‐3‐carboxaldehyde with substituted thiazolidinediones resulted in the formation of titled analogues. Analogues 6d and 6e exerted potent PL inhibitory activity (IC50‐6.19 and 8.96 µM, respectively). Further, these analogues exerted a competitive mode of PL inhibition. Moreover, molecular modelling studies were in agreement with the in vitro results (Pearson's r = .8682, p < .05). The fluorescence spectroscopic analysis further supported the strong binding affinity of these analogues with PL. A molecular dynamics study (20 ns) indicated that these analogues were stable in a dynamic environment. Thus, the present study highlighted the potential role of indole‐thiazolidinedione hybrid analogues as potential PL inhibitors and further optimization might result in the development of new PL inhibitory lead candidates.

Genus Alstonia is comprised of around 155 species throughout the world. Phytochemical screening of Alstonia genus has demonstrated the presence of diverse phytochemicals that include at least 800 distinct metabolites. The main classes of metabolites are alkaloids, iridoids, flavonoids, fatty acids, etc. Secondary metabolites from this genus also bring positive results when employed as anticancer, anti-spasmodic, antitussive, antiarthritic, antioxidant, etc. Alstonia boonei is listed as an antimalarial drug in African pharmacopoeia. In China, a formulation consists of A. scholaris leaves-Dengtaiye tablets are used for the treatment of cough and fever symptoms. Recently, A. scholaris leaves-derived indole alkaloids have been registered as an investigational new botanical drug (No. 2011L01436) and China Food and Drug Administration (CFDA) has approved its phase I/II clinical trials for the treatment of respiratory diseases. Pharmacokinetic and safety analysis of this botanical drug in healthy human subjects have revealed a safe profile under the dose regimen experiment. Apart from that, strictamine, an indole alkaloid isolated from A. scholaris exhibited a similar in vitro antiviral activity to that of acyclovir. The present chapter is mainly focused on the critical analysis of various secondary metabolites isolated from Alstonia (approximately 15 species). Apart from that, pharmacological, toxicological and intellectual property rights studies have also been included.

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