Carbamate group is mainly used for designing prodrugs to achieve first-pass and systemic stability against enzyme hydrolysis as the carbamate functionality is recognized by esterase enzymes. As compared to the ester functionality, the carbamate group shows a lesser lability towards enzyme hydrolysis, but a higher susceptibility than amides. Cyclic carbamates present a unique motif in the contemporary drug discovery and development owing to the presence of a polar, and sterically small, constrained Hydrogen-bonding acceptor atom. The metabolic stability of 5/6-membered cyclic carbamates are higher as compared to their acyclic counterparts as the former do not undergo metabolic ring opening under physiological conditions. Besides, the metabolic lability of acyclic carbamates is determined by the degree of substitution at the endocyclic/ exocyclic "N" atom, which further enables the design and development of various carbamate drugs or prodrugs. As such, the metabolic stability of carbamates follows the order: Cyclic carbamates > Alkyl-OCO-NH 2 » Alkyl-OCO-NHAcyl ∼ Alkyl-OCO-NHAryl ≥ Aryl-OCO-N(endocyclic) ∼ Aryl-OCO-N(Alkyl) 2
The benzoxazolone nucleus is an ideal scaffold for drug design, owing to its discrete physicochemical profile, bioisosteric preference over pharmacokinetically weaker moieties, weakly acidic behavior, presence of both lipophilic and hydrophilic fragments on a single framework, and a wider choice of chemical modification on the benzene and oxazolone rings. These properties apparently influence the interactions of benzoxazolone‐based derivatives with their respective biological targets. Hence, the benzoxazolone ring is implicated in the synthesis and development of pharmaceuticals with a diverse biological profile ranging from anticancer, analgesics, insecticides, anti‐inflammatory, and neuroprotective agents. This has further led to the commercialization of several benzoxazolone‐based molecules and a few others under clinical trials. Nevertheless, the SAR exploration of benzoxazolone derivatives for the identification of potential “hits” followed by the screening of “leads” provides a plethora of opportunities for further exploration of the pharmacological profile of the benzoxazolone nucleus. In this review, we aim to present the biological profile of different derivatives based on the benzoxazolone framework.
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