scholarly journals Design, Synthesis, Experimental and Theoretical Characterization of a New Multitarget 2-Thienyl-N-Acylhydrazone Derivative

2018 ◽  
Vol 11 (4) ◽  
pp. 119 ◽  
Author(s):  
Isadora Bastos ◽  
Pedro Pinheiro ◽  
Fanny Costa ◽  
Miguel Rocha ◽  
Carlos Sant’Anna ◽  
...  

Pulmonary arterial hypertension (PAH) is a chronic cardiovascular disease that displays inflammatory components, which contributes to the difficulty of adequate treatment with the available therapeutic arsenal. In this context, the N-acylhydrazone derivative LASSBio-1359 was previously described as a multitarget drug candidate able to revert the events associated with the progression of PAH in animal models. However, in spite of having a dual profile as PDE4 inhibitor and adenosine A2A receptor agonist, LASSBio-1359 does not present balanced potencies in the modulation of these two targets, which difficult its therapeutic use. In this paper, we describe the design concept of LASSBio-1835, a novel structural analogue of LASSBio-1359, planned by exploiting ring bioisosterism. Using X-ray powder diffraction, calorimetric techniques, and molecular modeling, we clearly indicate the presence of a preferred synperiplanar conformation at the amide function, which is fixed by an intramolecular 1,5-N∙∙∙S σ-hole intramolecular interaction. Moreover, the evaluation of LASSBio-1835 (4) as a PDE4 inhibitor and as an A2A agonist confirms it presents a more balanced dual profile, being considered a promising prototype for the treatment of PAH.

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Kristian A. Haanes ◽  
Alejandro Labastida-Ramírez ◽  
Kayi Y. Chan ◽  
René de Vries ◽  
Brian Shook ◽  
...  

2004 ◽  
Vol 504 (1-2) ◽  
pp. 55-59 ◽  
Author(s):  
Mary Kelly ◽  
Alexis Bailey ◽  
Catherine Ledent ◽  
Ian Kitchen ◽  
Susanna Hourani

2000 ◽  
Vol 14 (2) ◽  
pp. 81-89 ◽  
Author(s):  
Kiichi Ishiwata ◽  
Nobuo Ogi ◽  
Junichi Shimada ◽  
Hiromi Nonaka ◽  
Akira Tanaka ◽  
...  

2008 ◽  
Vol 18 (14) ◽  
pp. 4204-4209 ◽  
Author(s):  
Unmesh Shah ◽  
Claire M. Lankin ◽  
Craig D. Boyle ◽  
Samuel Chackalamannil ◽  
William J. Greenlee ◽  
...  

2008 ◽  
Vol 579 (1-3) ◽  
pp. 149-152 ◽  
Author(s):  
Mariangela Galluzzo ◽  
Anita Pintor ◽  
Antonella Pèzzola ◽  
Rosa Grieco ◽  
Franco Borsini ◽  
...  

2004 ◽  
Vol 1000 (1-2) ◽  
pp. 156-173 ◽  
Author(s):  
Liqun Yu ◽  
Martin C. Frith ◽  
Yutaka Suzuki ◽  
Robert A. Peterfreund ◽  
Tom Gearan ◽  
...  

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