Structure-activity relationships of thiazole and benzothiazole derivatives as selective cannabinoid CB2 agonists with
Aya E Ghonim1, Alessia Ligresti2, Alessandro Rabbito2
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, 11835, Egypt.
Abstract:
The strong therapeutic potential of CB2 receptor agonists for use as anti-inflammatory agents that lack psychiatric side effects has attracted substantial interest. We herein describe the rational design and synthesis of novel thiazole and benzothiazole derivatives and the evaluation of their binding affinity and functional activity on CB1 and CB2 receptors. The series with the general formula N-(3-pentylbenzo [d]thiazol-2(3H)-ylidene) carboxamide (compounds 6a-6d) exhibited the highest affinity and selectivity towards CB2 receptors with Kis in the picomolar or low nanomolar range, and selectivity indices (Ki hCB1/Ki hCB2) reaching up to 429 fold. Notably, these compounds also demonstrated an agonistic functional activity in cellular assays with EC50s in the low nanomolar range. More interestingly, compound 6d, the 3-(trifluoromethyl)benzamide derivative, exhibited remarkable protection against DSS-induced acute colitis in mice model.
Related Concept Videos
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
The direct-acting...
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
Local Anesthetics: Chemistry and Structure-Activity Relationship
Cholinergic Antagonists: Chemistry and Structure-Activity Relationship


