Fundamentals of Medicinal Chemistry

CH 2 COCH 3 Ph OH OO H Ph OH OO H Ph OH OO H CH 2 C OH H CH 3 CH 2 C OH H CH 3 S-(−)-Warfarin OH CH 2 COCH 3 OO CH 2 COCH 3 Ph H ...

9.1.2 Biological factors affecting metabolism The metabolic differences found within a species are believed to be due to variati ...

9.1.3 Environmental factors affecting metabolism The metabolism of a drug is also affected by lifestyle. Poor diet, drinking, sm ...

Table 9.1 Some of the types of secondary pharmaceutical activity of metabolites. Note that not all the possible metabolic routes ...

9.4 Phase I metabolic reactions The main Phase I reactions are biological oxidations, reductions, hydrolyses, hydrations, deacet ...

Table 9.2 Examples of mixed function oxidase catalysed oxidations. Oxidation introduces or reveals new functional groups (shaded ...

Table 9.2 (continued) Type of reaction (groups) Example Dealkylation(methyl and ethyl secondary amines, tertiary amines,tertiary ...

azo groups and sulphoxides. The enzymes used to catalyse metabolic reductions are usually specific in their action. Many of them ...

utilized in a metabolic route. For example, the initial stage in the metabolism of L-dopa is decarboxylation. HO HO HO HO NH 2 N ...

Table 9.3 Phase II reactions. These normally produce pharmacologically inert metabolites but a few metabolites, such as N-acetyl ...

metabolite produced reaches the plasma. Alternatively, the metabolite may be administered separately when independent data conce ...

the drug. The rate of change of concentration of a metabolite (dM/dt) in the plasma is given by: dM=dt¼rate of formationrate of ...

metabolism is achieved by modifying the structure of the drug. These structural modifications may either make the analogue more ...

H 2 NHCOOCH 2 CH 2 N 2 N CONHCH 2 CH 2 N C 2 H 5 C 2 H 5 C 2 H 5 C 2 H 5 C 2 H 5 C 2 H 5 (a) Procaine Procainamide CH 3 CH 3 CH ...

9.8.2 Carrier prodrugs Carrier prodrugs are formed by combining an active drug with a carrier species to form a compound with th ...

9.8.3 The design of prodrug systems for specific purposes The introduction of a carrier into the structure of a drug to form a p ...

Improving patient acceptance Odour and taste are important aspects of drug administration. A drug with a poor odour or too bitte ...

and carrier. Once released, the hydrophilic drug is unable to recross the blood– brain barrier. The selected carrier must also b ...

9 .8. 3. 5 Minimizing side effects Prodrug formation may be used to minimize toxic side effects. For example, salicylic acid is ...

(continued) (7) The following scheme represents the hypothetical metabolic pathway of a drug. The figures in brackets are the ra ...