Add like
Add dislike
Add to saved papers

Designing Chromane Derivatives as α 2A -Adrenoceptor Selective Agonists via Conformation Constraint.

Enhancing the selectivity of alpha2 -adrenoceptor (α2A -AR) agonists remains an unresolved issue. Herein, we reported the design of an α2A -AR agonist using the conformation constraint method, beginning with medetomidine. The structure-activity relationship indicated that the 8-substituent of chromane derivatives exerted the most pronounced effect on α2A -AR agonistic activity. Compounds A9 and B9 were identified as the most promising, exhibiting EC50 values of 0.78 and 0.23 nM, respectively. Their selectivity indexes surpassed dexmedetomidine (DMED) by 10-80 fold. In vivo studies demonstrated that both A9 and B9 dose-dependently increased the loss of righting reflex in mice, with ED50 values of 1.54 and 0.138 mg/kg, respectively. Binding mode calculations and mutation studies suggested the indispensability of the hydrogen bond between ASP1283.32 and α2A -AR agonist. In particular, A9 and B9 showed no dual reverse pharmacological effect, a characteristic exhibited by DMED in α2A -AR activation.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

Related Resources

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app