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

Biomedicines

PrafullaB. Choudhari¹  ManishS. Bhatia¹  Ahmed Al-Harrasi²  TapanKumar Mohanta²  Swami Prabhuling³  ZubaidhaK. Pudukulathan³  Yasinalli Tamboli³ 

[1] Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur 416013, Maharashtra, India;Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Postal Code 616, Birkat Al Mouz, Nizwa, Oman;School of Chemical Sciences, SRTM University, Nanded 431606, Maharashtra, India;

关键词: nitric oxide;    furoxan;    PDE 5 inhibitors;    spiro-isoquinolino piperidine;   

DOI  :  10.3390/biomedicines8050121

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown