Molecular Modeling Studies on 11H-Dibenz[b,e]azepine and Dibenz[b,f][1,4]oxazepine Derivatives as Potent Agonists of the Human TRPA1 Receptor

Abstract

A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was performed on a series of the 11H-dibenz[b,e]azepine and dibenz[b,f][1,4]oxazepine derivatives as potent agonists of the human TRPA1 receptor. The CoMFA and CoMSIA models resulting from a 21 molecule training set gave r2cv values of 0.631 and 0.542 and r2 values of 0.986 and 0.981, respectively. The statistically significant models were validated by a test set of five compounds with predictive r2pred. values of 0.967 and 0.981 for CoMFA and CoMSIA, respectively. A systemic external validation was also performed on the established models. The information obtained from 3D counter maps could facilitate the design of more potent human TRPA1 receptor agonists.

Effect of dibenz(b,f)-1,4-oxazepine aerosol on the breathing pattern and respiratory variables by continuous recording and analysis in unanaesthetised mice

“…The role of Ca 2+ permeable, cation transient receptor potential (TRP) channels in airways of normal and disease conditions are gaining importance [ [23] , [24] , [25] ]. The TRP channels function as an important endogenous protective mechanism of the respiratory system by detecting noxious stimuli of various oxidative, chemical irritant and temperature stimuli, and ensure protection by physiological response.…”

1H and 13C NMR spectral assignments of novel flavonoids bearing benzothiazepine

“…The procedure used to assign the NMR data of derivative 8, [1,4]thiazepin-4-yl) naphthalen-1-ol was as follows: 28 carbon peaks were observed in the 13 C NMR spectrum. Of them, only one methylene peak at 36.1 ppm was observed in the DEPT experiments, which was the benzothiazepine-3 carbon (named C-bz3).…”

“…1(A)). [1][2][3][4] When two benzene rings are attached at the C-2 and C-4 positions, 2,4-diphenyl-2,3-dihydro-1,5-benzothiazepine containing a C6-C3-C6 skeleton can be derived ( Fig. 1(B)).…”

“…A variety of derivatives can be designed by modifying the positions of the double bond and benzene ring. 2,3-Dihydro-1,5-benzothiazepine (also known as 2,3-dihydro[b] [1,4]thiazepine) derivatives show diverse biological activities, including inhibitory effects on alpha-glucosidase, urease, cholinesterase, and butyrylcholinesterase, and agonistic activity toward the transient receptor potential ankyrin 1 (TRPA1) receptor ( Fig. 1(A)).…”

A Synthetic Overview of Benzoxazines and Benzoxazepines as Anticancer Agents

“…[20] Benzoxazepine groups have been identified to bind with microtubule assembly leading to exhibit anticancer activity. [21] Benzoxazepine derivatives are effective medicinally potent agents, considered lead molecules for future drug development, [22] like orexin receptor antagonists (Youssef et al 1996, [23] Bajaj et al 2004, [24] Kamei et al 2006, [25] Ai et al 2010, [26] Gijsen et al 2010, [27] Greene et al 2016, [28] ) have attracted vast attention of medicinal chemistry researchers. Within several benzoxazepine isomers, 1,4-and 1,5-benzoxazepine analogues are important due to their profound biological activities.…”