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2000
Volume 25, Issue 13
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

Carbamate has been extensively used as a scaffold in the recent era of drug discovery and is a common structural motif of many approved drugs. The carbamate moiety's unique amide-ester hybrid (-O-CO-NH-) feature offers the designing of specific drug-target interactions. Despite the discovery of numerous carbamate derivatives that act on the endocannabinoid system (ECS), the development of clinically effective carbamates remains a challenge. In this review, we highlight the therapeutic potential of carbamate inhibitors of endocannabinoid degrading enzymes as a breakthrough in discovering neurotherapeutic drugs. We discuss the design strategies and medicinal chemistry aspects involved in developing carbamate-based molecular architectures that modulate the endocannabinoid signaling pathway by interfering with fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), and α/β-Hydrolase domain-containing 6 (ABHD6). Additionally, we highlight the dual activity profile of carbamates against FAAH and MAGL, FAAH and cholinesterase, and FAAH and TRPV1 channels. Furthermore, we illustrate the pharmacophores of -functionalized carbamates and N-cyclic carbamates that are crucial for FAAH and MAGL inhibitory activities, respectively.

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2025-12-29

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/content/journals/mrmc/10.2174/0113895575328120241107061303
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Promising Inhibitors of Endocannabinoid Degrading Enzymes Sharing a Carbamate Scaffold
Mini Rev Med Chem 25, 1008 (2025); https://doi.org/10.2174/0113895575328120241107061303
/content/journals/mrmc/10.2174/0113895575328120241107061303
/content/journals/mrmc/10.2174/0113895575328120241107061303
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  • Article Type:     Review Article
Keyword(s): Carbamate; endocannabinoid; fatty acid amide hydrolase; hypertension; monoacylglycerol lipase; neurotherapeutic

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