114362-54-8Relevant articles and documents
Discovery of Novel Pyrazolo[3,4- b] Pyridine Derivatives with Dual Activities of Vascular Remodeling Inhibition and Vasodilation for the Treatment of Pulmonary Arterial Hypertension
Hu, Liqing,Li, Lijun,Chang, Qi,Fu, Songsen,Qin, Jia,Chen, Zhuo,Li, Xiaohui,Liu, Qinglian,Hu, Gaoyun,Li, Qianbin
, p. 11215 - 11234 (2020)
Current pulmonary arterial hypertension (PAH) therapeutic strategies mainly focus on vascular relaxation with less emphasis on vascular remodeling, which results in poor prognosis. Hence, dual pathway regulators with vasodilation effect via soluble guanylate cyclase (sGC) stimulation and vascular remodeling regulation effect by AMP-activated protein kinase (AMPK) inhibition provide more advantages and potentialities. Herein, we designed and synthesized a series of novel pyrazolo[3,4-b] pyridine derivatives based on sGC stimulator and AMPK inhibitor scaffolds. In vitro, 2 exhibited moderate vasodilation activity and higher proliferation and migration suppressive effects compared to riociguat. In vivo, 2 significantly decreased right ventricular systolic pressure (RVSP), attenuated pulmonary artery medial thickness (PAMT), and right ventricular hypertrophy (RVH) in hypoxia-induced PAH rat models (i.g.). Given the unique advantages of significant vascular remodeling inhibition and moderate vascular relaxation based on the dual pathway regulation, we proposed 2 as a promising lead for anti-PAH drug discovery.
Discovery of pyrazolopyridones as a novel class of noncovalent DprE1 inhibitor with potent anti-mycobacterial activity
Panda, Manoranjan,Ramachandran, Sreekanth,Ramachandran, Vasanthi,Shirude, Pravin S.,Humnabadkar, Vaishali,Nagalapur, Kavitha,Sharma, Sreevalli,Kaur, Parvinder,Guptha, Supreeth,Narayan, Ashwini,Mahadevaswamy, Jyothi,Ambady, Anisha,Hegde, Naina,Rudrapatna, Suresh S.,Hosagrahara, Vinayak P.,Sambandamurthy, Vasan K.,Raichurkar, Anandkumar
, p. 4761 - 4771 (2014/07/07)
A novel pyrazolopyridone class of inhibitors was identified from whole cell screening against Mycobacterium tuberculosis (Mtb). The series exhibits excellent bactericidality in vitro, resulting in a 4 log reduction in colony forming units following compound exposure. The significant modulation of minimum inhibitory concentration (MIC) against a Mtb strain overexpressing the Rv3790 gene suggested the target of pyrazolopyridones to be decaprenylphosphoryl- β-d-ribose-2′-epimerase (DprE1). Genetic mapping of resistance mutation coupled with potent enzyme inhibition activity confirmed the molecular target. Detailed biochemical characterization revealed the series to be a noncovalent inhibitor of DprE1. Docking studies at the active site suggest that the series can be further diversified to improve the physicochemical properties without compromising the antimycobacterial activity. The pyrazolopyridone class of inhibitors offers an attractive non-nitro lead series targeting the essential and vulnerable DprE1 enzyme for the discovery of novel antimycobacterial agents to treat both drug susceptible and drug resistant strains of Mtb.
Synthesis and antibacterial activity of some novel pyrazolopyridine derivatives
Panda,Karmakar,Jena
, p. 1500 - 1508 (2012/01/05)
Eight pyrazolo[3,4-b]pyridine derivatives have been synthesized by Friedlaender condensation of 5-aminopyrazole-4-carbaldehyde with active methylene compounds in basic medium. These compounds have been screened for their antibacterial activity against two Gram-negative and two Gram-positive bacterium. Pyrazolopyridines having the carboxamide group at the 5-position showed moderate to good activity against P. aeruginosa, E. coli, S. pneumoniae, and B. cereus.
