version date: 1 December 2006 of this exercise is to provide a geometrical and chemical overview of the substrate and inhibitor of great structural similarity. At the same time, it reinforces the importance of chemical transformations of a key substrate in a biochemical pathway when developing antimetabolite drugs Molecular dimensions and properties Varying the physical and chemical properties of metabolite has often been used in drug design to produce a structure analog such as antimetabolite(metabolite antagonism), required for inhibition of cellular growth and response process. Bioisosterism strategies are frequently used to convert a key substrate into an inhibitor, allowing extra binding interaction to a target enzyme. The substituent modifications can affect various parameters in a drug molecule such as the partition coefficient, electronic density, conformation, bioavailability, and its capacity to establish direct interaction in the receptor domain. Thus, both drug and substrate physical properties can be calculated and compared to give useful information on SARs. Important properties can be estimated in the Molecular Modeling Program, exemplified by partial charges, bond order, dipole moment, ionization potential, electron density distribution solubility, and thermodynamic properties. Some of the physical properties, including volume surface area, density, molecular length, and dipole moment, are affected by geometry, which depends on the minimization process. Additionally, appropriate orientation of the molecule in the x-y plane is required for molecular length comparisons <www.iupac.org/publications/cd/medicinalchemistry/>5 of this exercise is to provide a geometrical and chemical overview of the substrate and inhibitor of great structural similarity. At the same time, it reinforces the importance of chemical transformations of a key substrate in a biochemical pathway when developing antimetabolite drugs. Molecular dimensions and properties Varying the physical and chemical properties of metabolite has often been used in drug design to produce a structure analog such as antimetabolite (metabolite antagonism), required for inhibition of cellular growth and response process. Bioisosterism strategies are frequently used to convert a key substrate into an inhibitor, allowing extra binding interaction to a target enzyme. The substituent modifications can affect various parameters in a drug molecule such as the partition coefficient, electronic density, conformation, bioavailability, and its capacity to establish direct interaction in the receptor domain. Thus, both drug and substrate physical properties can be calculated and compared to give useful information on SARs. Important properties can be estimated in the Molecular Modeling Program, exemplified by partial charges, bond order, dipole moment, ionization potential, electron density distribution, solubility, and thermodynamic properties. Some of the physical properties, including volume, surface area, density, molecular length, and dipole moment, are affected by geometry, which depends on the minimization process. Additionally, appropriate orientation of the molecule in the x-y plane is required for molecular length comparisons. <www.iupac.org/publications/cd/medicinal_chemistry/> version date: 1 December 2006