ChemInform Abstract: Prodrug Approaches to the Improved Delivery of Peptide Drugs

Abstract

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Research Article: Computer‐Assisted Design of Pro‐drugs for Antimalarial Atovaquone

“…Recently, we have been engaged in investigating the driving force(s) responsible for significant accelerations in rate of some intramolecular processes that have been used as enzyme models and pro-drug hosts (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Using different molecular orbital calculation methods, we have explored: (i) the acid-catalyzed lactonization of hydroxy acids as studied by Cohen (16-21) and Menger (22)(23)(24)(25)(26)(27); (ii) the intramolecular proton transfer in rigid systems as investigated by ; and (iii) the S N 2-based cyclization as researched by Brown, Bruice and Mandolini (28)(29)(30)(31) arriving at the following conclusions: the driving force for rate enhancements in intramolecular processes can be attributable to proximity and ⁄ or steric effects, depending on the nature of the system, and the accelerations in rate for intramolecular reactions are a result of both entropy and enthalpy effects.…”

Prodrugs of aza nucleosides based on proton transfer reaction

“…Recently we have been researching the driving force(s) responsible for the accelerations in rate of some intramolecular processes that were utilized as enzyme models and pro-prodrug hosts [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Using DFT and ab initio calculation methods, we have explored: 1) the acid-catalyzed lactonization of the trimethyl-lock system and other hydroxy-acids as studied by Cohen [24][25][26][27][28][29] and Menger [30][31][32][33][34][35]; (b) the intramolecular proton-transfer from oxygen to carbon in some rigid systems as researched by Menger [30][31][32][33][34][35]; (c) the S N 2-based ring-closing reactions as investigated by Brown, Bruice and Mandolini [36][37][38][39] and (d) the proton transfer between two oxygen atoms in some of Kirby's acetals [40][41][42][43][44][45]…”

Density functional theory based quantitative structure-property relationship studies on coumarin-based prodrugs

“…This system has a cis-double bond which could facilitate the lactonization when an acyl group (R) is hydrolyzed by esterase (Scheme 1). To date, it has been used for the preparations of cyclic prodrugs of opioid peptides (5)(6)(7)(8), such as DADLE (9)(10)(11) and DADLE analogs (12), and peptidomimetics, such as an RGD (Arg-Gly-Asp) analog MK-383 (13,14). Moreover, this system was also applied in the design of non-peptide prodrugs such as meptazinol, and the prodrug of meptazinol has shown a 4-fold increase in oral bioavailability (15).…”