Over expression of nucleotide pyrophosphatase (NPPs) activity is associated with chondrocalcinosis, osteoarthritis, type 2 diabetes, neurodegenerative diseases, allergies and cancer metastasis.

Benzothiazoloquinazolines are known to possess several interesting biological properties. Various arylated benzothiazoloquinazolines were synthesized from readily available 2‐bromo‐12H‐benzothiazolo[2,3‐b]quinazolin‐12‐one by palladium catalysed Suzuki‐Miyaura reactions in 43 – 85% yield. Synthesized derivatives were analysed regarding their in vitro inhibition activity towards monoamine oxidases A and B and showed significant inhibitory values in the micromolar range. Molecular modelling as well as PAINS studies on the binding interaction of most potent inhibitors with both isoforms were studied to verify the experimental results.

The combination of cyclocondensation with palladium catalysed cross‐coupling reactions, afforded a variety of 8‐functionalized benzothiazolo[3,2‐a]pyridimidin‐4‐ones in good to excellent yields. The anti‐proliferative potential of the synthetic compounds was evaluated in human cervical adenocarcinoma cells (HeLa) and hamster normal fibroblasts (BHK‐21). Three of the test derivatives exhibited the strongest cytotoxicity in HeLa cells with the median inhibitory concentration (IC50) of 0.93, 1.55 and 1.84 μM, respectively. Moreover, their anti‐proliferative effect was three times less strong in normal fibroblasts, asserting their possible anti‐cancer potential.

8‐Chloro‐3‐fluoro‐2‐methyl‐benzo[4,5]thiazolo[3,2‐a]pyrimidin‐4‐one was synthesized and employed in various palladium catalysed cross‐coupling‐reactions, including Suzuki‐Miyaura, Sonogashira and Buchwald‐Hartwig reactions, delivering 8‐aryl‐, 8‐alkynyl‐ and 8‐amino‐3‐fluoro‐2‐methyl‐benzo[4,5]thiazolo[3,2‐a]pyrimidin‐4‐ones in good to excellent yields. The synthesized derivatives were analysed for their monoamine oxidase (MAO−A and MAO−B) inhibitory potential. Most of the compounds exhibited moderate to good inhibitory activity towards MAO−A and/or MAO−B. Docking analysis was performed to verify the experimental results. Hence, 8‐substituted‐3‐fluoro‐2‐methyl‐benzo[4,5]thiazolo[3,2‐a]pyrimidin‐4‐ones might be potential lead compounds towards novel monoamine oxidase inhibitors.

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The Suzuki-Miyaura reaction of 2,6-dichloro-3-(trifluoromethyl)pyridine with 1 equiv of arylboronic acids resulted in site-selective formation of 2-aryl-6-chloro-3-(trifluoromethyl)pyridine. Due to electronic reasons, the reaction takes place at the sterically more hindered position. The selectivity was rationalised by DFT calculations. The one-pot reaction with two different arylboronic acids afforded 2,6-diaryl-3-(trifluoromethyl)pyridine containing two different aryl substituents. The reactions proceeded smoothly in the absence of phosphine ligands. In addition, Suzuki-Miyaura reactions of 2,6-dichloro-4-(trifluoromethyl)pyridine with one or two equivalents of arylboronic acids were carried out.

2‐Alkynyl‐ and 2‐aminobenzothiazolo[2,3‐b]quinazolin‐12‐ones have been synthesized by Palladium catalysed Buchwald‐Hartwig and Sonogashira reactions. Synthesized derivatives were further evaluated for their role as potential inhibitors of monoamine oxidase A and B (MAO−A and B) isozymes. Most compounds possess moderate to excellent inhibitory potential against MAO−A and MAO−B. The 2‐amino‐substituted derivatives show a significantly higher activity as compared to 2‐alkynyl‐ and previously reported 2‐aryl derivatives. Studied compounds might be employed as novel monoamine oxidase inhibitors and may provide insights for the development of new drug candidates against neurological diseases.