Synthesis and Evaluation of 2,2‐Dimethylchroman Derivatives as Inhibitors of ICAM‐1 Expression on Human Endothelial Cells

Abstract

in Wiley Online Library (wileyonlinelibrary.com).We herein report the synthesis of novel 2,2-dimethylchroman analogs and their effect on the modulation of tumor necrosis factor-a-induced expression of intercellular adhesion molecule-1 in human endothelial cells. These compounds were found to be potent inhibitors of tumor necrosis factor-a-induced expression of intercellular adhesion molecule-1 on human endothelial cells at very low concentration. The structure-activity relationship of these compounds has been studied. The IC 50 and maximum tolerable dose value of the lead compound 7d (X═NH, R═4Cl) of this study was found to be 9.5 and 150 mM, respectively. The present results indicate that our novel compound is potentially effective and therefore could be useful for further pharmaceutical studies.

Research Advancements on Fluorinated and Non-Fluorinated 4- Phenyl(thio)ureido-Substituted 2,2-Dimethylchromans Acting as Inhibitors of Insulin Release and Smooth Muscle Relaxants

“…The 2,2-dimethylchroman core structure is found in many biologically active natural compounds [1][2][3] as well as in synthetic compounds expressing multiple pharmacological activities [4][5][6][7][8][9]. The reference potassium channel opener cromakalim (1, Fig.…”

Deciphering Structure–Activity Relationships in a Series of 2,2‐Dimethylchromans Acting as Inhibitors of Insulin Release and Smooth Muscle Relaxants

“…The present study is an attempt to characterize the impact of the nature of substituentsi ntroduced at the 4-and 6-positions of 2,2-dimethylchromans on their capacities to inhibit insulin release from pancreatic b-cells or to relaxv ascular smooth muscle cells, both biological responses that are supposed to reflect interaction with specific ion channels. Chemical structureso fc romakalim (1;ast he most active enantiomer,l evcromakalim) and previously described 2,2-dimethylchromans (2)(3)(4)(5)(6)(7)(8) that act as inhibitors of insulinrelease and/or smooth musclerelaxants. Figure 1.…”

“…Molecules containing the 2,2-dimethylchroman core structure are the object of continual and intensive researchi nm edicinal chemistry.S uch heterocyclic scaffolds are known to be found in several biologically active naturalc ompounds [1][2][3] and also in synthetic compoundse xpressing multiple pharmacological activities. [4][5][6][7] In the context of the synthetic compounds, the well-known potassium channel openerc romakalim (1, Figure 1), an example of a4 ,6-disubstituted 2,2-dimethylchroman, has been am odel for the design of an impressive number of analogues, most of whichw ere developed as smooth muscler elaxants (vasodilators,b ronchodilators, oxytocic agents, etc.). [8][9][10] The myorelaxanta ctivity of cromakalim and of many analogues appearst ob erelated to the activation of potassium channels described as ATP-sensitive potassium channels (K ATP channels;A TP:a denosine triphosphate).…”