Novel heteroaryl phosphonicdiamides PTPs inhibitors as anti-hyperglycemic agents

Background Chronic and oral administration of benzylamine improves glucose tolerance. Picolylamine is a selective functional antagonist of the human adenosine A 2B receptor. Phosphonic diamide derivatives enhance the cellular permeability and in turn their biological activities. Methods A series of...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Daru 2014-12, Vol.22 (1), p.76-76, Article 76
Hauptverfasser: Sekhar, Kuruva Chandra, Syed, Rasheed, Golla, Madhava, MV, Jyothi Kumar, Yellapu, Nanda Kumar, Chippada, Appa Rao, Chamarthi, Naga Raju
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Background Chronic and oral administration of benzylamine improves glucose tolerance. Picolylamine is a selective functional antagonist of the human adenosine A 2B receptor. Phosphonic diamide derivatives enhance the cellular permeability and in turn their biological activities. Methods A series of heteroaryl phosphonicdiamide derivatives were designed as therapeutics to control and manage type2 diabetes. Initially defined Lipinski parameters encouraged them as safer drugs. Molecular docking of these compounds against Protein tyrosine phosphatase (PTP), the potential therapeutic target of type 2 diabetes, revealed their potential binding ability explaining their anti-diabetic activity in terms of PTP inhibition. Human intestinal absorption, Caco-2 cell permeability, MDCK cell permeability, BBB penetration, skin permeability and plasma protein binding abilities of the title compounds were calculated by PreADMET server. A convenient method has been developed for the synthesis of title compounds through the formation of 1-ethoxy-N,N’-bis(4-fluorobenzyl/pyridin-3-ylmethyl)phosphinediamine by the reaction of 4-fluorobenzylamine/ 3-picolylamine with ethyldichlorophosphite, subsequently reacted with heteroaryl halides using lanthanum(III) chloride as a catalyst. Results All the compounds exhibited significant in vitro anti-oxidant activity and in vivo evaluation in streptozotocin induced diabetic rat models revealed that the normal glycemic levels were observed on 12 th day by 9a and 20 th day by 5b , 5c , 9e and 9f. The remaining compounds also exhibited normal glycemic levels by 25 th day. Conclusion The results from molecular modeling, in vitro and in vivo studies are suggesting them as safer and effective therapeutic agents against type2 diabetes. Graphical Abstract Development of PTPs inhibitors.
ISSN:2008-2231
1560-8115
2008-2231
DOI:10.1186/s40199-014-0076-3