Synthesis and Modeling Studies of Furoxan Coupled Spiro-Isoquinolino Piperidine Derivatives as NO Releasing PDE 5 Inhibitors

Abstract

Nitric oxide (NO) is considered to be one of the most important intracellular messengers that play an active role as neurotransmitter in regulation of various cardiovascular physiological and pathological processes. Nitric oxide (NO) is a major factor in penile erectile function. NO exerts a relaxing action on corpus cavernosum and penile arteries by activating smooth muscle soluble guanylate cyclase and increasing the intracellular concentration of cyclic guanosine monophosphate (cGMP). Phophodiesterase (PDE) inhibitors have potential therapeutic applications. NO hybridization has been found to improve and extend the pharmacological properties of the parental compound. The present study describes the synthesis of novel furoxan coupled spiro-isoquinolino-piperidine derivatives and their smooth muscle relaxant activity. The study reveals that, particularly 10d (1.50 ± 0.6) and 10g (1.65 ± 0.7) are moderate PDE 5 inhibitors as compared to Sidenafil (1.43 ± 0.5). The observed effect was explained by molecular modelling studies on phosphodiesterase.

Potential of NO donor furoxan as SARS-CoV-2 main protease (Mpro) inhibitors:in silicoanalysis

“…Moreover, Andrographolide (Enmozhi et al., 2020 ) and resveratrol (Wahedi et al., 2020 ) were found to be potential inhibitors of SARS-CoV-2 main protease. The 28 different nitric oxide donor furoxan derivatives coupled with benzhydrylpiperazine and spiro-isoquinolino-piperidine from our previous research work (Prabhuling et al., 2020 ; Pudukulatham et al., 2016 ) were selected for the current in silico analysis.…”

Recent Advances in the Synthesis and Biomedical Applications of Heterocyclic NO-Donors

“…The analogous reaction of 4-aryl-3-bromomethylfuroxans 50b with spiro[isoquinoline-4,4’]-piperidine derivative resulted in a formation of the tricyclic compounds 52 ( Scheme 28 ). All synthesized hybrids 52 demonstrated moderate to good vasodilating and antioxidant properties, while structures containing o -nitro- or o -methoxyphenyl substituents at the furoxan ring were moderate phosphodiesterase 5 (PDE 5) inhibitors as compared to the known pharmaceutical Sildenafil [ 95 ].…”

4,6-Dinitro-7-(thiazol-2-ylamino)benzo[c][1,2,5]oxadiazole 1-oxide

“…In the framework of the recent increasing attention paid to the synthesis of hybrid structures able to nitric oxide (NO) release, we report the synthesis of 4,6-dinitro-7-(thiazol-2-ylamino) benzo[c] [1,2,5]oxadiazole 1-oxide in mild conditions as a novel heterocyclic system incorporating furoxan and thiazole moieties of interest as a new potentially biologically active compound [16][17][18].…”