Latentiated drug latentiation

A seemingly complex heterocycle which on close examination is in fact a latentiated derivative of a salicylic acid shows antiinflammatory activity. It might be speculated that this compound could quite easily undergo metabolic transformation to a salicylate and that this product is in fact the active drug. Condensation of acid 134 with hydroxyl amine leads to the hydroxamic acid 135. Reaction of... 

Another type of therapeutically active molecule is one designed primarily with pharmacokinetics in mind (designed to be well absorbed and to enter the central compartment readily), which can then be converted to the therapeutically active molecule in the body. These are referred to as pro-drugs. This process, called latentiation, consists of the conversion of hydrophilic drugs into lipid-soluble drugs (usually by masking hydroxyl, carboxyl, and... 

Flufenamic acid (162) is a reasonably well-established NSAID (Non Steroidal Anti Inflammatory Drug). Alkylation of its potassiiini salt with the hydroxyethyl ethyl ether of ethylenechlo-rohydrin affords the latentiated derivative etofenamate (163) [41], Antiinflammatory activity is apparently retained when both rings in the fenamate series carry carboxyl groups. Thus, condensation of dichlorobenzoic acid 164 with anthranilic acid (165) by means of nucleophilic aromatic... 

Harper, N.J. Drug latentiation. In Progress in Drug Research Jucker, E., Ed. Birkhauser Basel, 1962 4, 221-294. 

Fig. 33.18 Cascade latentiation. A 2-Acyloxymethylbenzoic acids provide amides the lability of esters. ° ° B Substituted vinyl esters as lipophilic cascade carrier for carboxylic acid-containing drugs.

Various examples of this technique, know as "drug latentiation", have been documented by Harper (46) and more recently by Sinkula and Yalkowsky (47). Interestingly, Catsch (48) has suggested that the improved efficacy of certain EDTA-like chelating agents in promoting heavy metal excretion may be related to their ability to form internal esters with enhanced bioavailability e.g.. 

Carbenoxolone sodium was prepared essentially from considerations [506] of the concept of drug latentiation [507, 508] in order to secure a water-solubi-... 

Drug Latentiation 4, 221 (1962) Prof. Dr. N.J. Harper Head of the Department of Pharmacy, University of Aston, Birmingham 4, England... 

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