Premium
Computational‐Aided Design for Dopamine Prodrugs Based on Novel Chemical Approach
Author(s) -
Karaman Rafik
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01208.x
Subject(s) - prodrug , moiety , chemistry , dopamine , bioavailability , combinatorial chemistry , stereochemistry , pharmacology , biochemistry , medicine , endocrinology
The goal of this project was to design novel dopamine prodrugs for the treatment of Parkinson’s disease that can improve the overall biopharmaceutical profile of the current medications to enhance effectiveness and to ease the use of the medications. Based on Menger’s study and other’s kinetic studies on the cleavage reactions of some Kemp’s acid amides to the corresponding amines and anhydrides, DFT calculations were made to find a candidate to be used as an efficient dopamine prodrug. The proposed dopamine prodrugs have a carboxylic group as a hydrophilic moiety and a hydrocarbon skeleton as a lipophilic moiety, where the combination of both groups ensures a moderate hydrophilic lipophilc balance value. The potential prodrugs are expected to give better bioavailability than the parental drug owing to improved absorption. Furthermore, the proposed prodrugs are believed to be more effective than l ‐dopa because the latter undergoes decarboxylation in the periphery before reaching the blood–brain barrier. Additionally, the predicted prodrugs can be used in different dosage forms (I.V., S.C., tablets, and others) because of their potential solubility in organic and aqueous media. It is expected that the proposed prodrugs will undergo cleavage reactions to release the parental dopamine drug with half‐life time ( t ½ ) of 12–20 h.